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BETTER NUTRITIONAL STATUS AS MEASURED BY THE MINI NUTRITIONAL
ASSESSMENT TOOL IS ASSOCIATED WITH INCREASED IMMUNE RESPONSE
IN ELDERLY NURSING HOME RESIDENTS WITH PRESSURE ULCERS
JAN ELIZABETH HUDGENS
A THESIS PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF SCIENCE
UNIVERSITY OF FLORIDA
Jan Elizabeth Hudgens
I would like to thank my parents, Vicki and Jerry Streeter for their kindness and
generosity. I would also like to thank them for their reassurance that there was life after
graduate school, and that one day I would live it. I would like to thank my long-time lab
mates, CJ Nieves and Suzie Cole, for their incredible work ethic, for the camaraderie they
showed me during thick and thin, and for being two of the nicest people I know. I would
like to thank Kelli Herrlinger-Garcia for all the time and energy she spent sitting by my
side at the computer or the workbench, for her excellent working knowledge of
laboratory techniques and procedures, and for her down-to-earth good nature. I would
like to thank Dr. Joyce Stechmiller for serving on my supervisory committee; and
providing me the opportunity to do research with the elderly, which was a very rewarding
experience. I would also like to thank her for her encouragement and being available
when I needed it most. I would like to thank Dr. Elaine Turner for serving on my
supervisory committee, for her personal kindness, and for her keen sense of humor. Most
of all, I would like to thank Dr. Bobbi Langkamp-Henken, my graduate advisor and
committee chairperson, for her continuous encouragement and support during my work
as a graduate student. Her knowledge and patience were great inspirations, and she
served as a role model for the kind of professional I would one day like to become. It
was a true pleasure to work in her lab.
TABLE OF CONTENTS
A C K N O W L E D G M E N T S ............................................................................................. iii
T A B L E O F C O N T E N T S..................................................................... ......................iv
L IST O F T A B L E S ...................................................................... vi
LIST OF FIGURES ................................................................ ............. vii
A B STR A CT .......... ....... ................................................................... viii
1 INTRODUCTION .................................... ........................... ............. 1
2 REV IEW OF LITERA TURE ............................................................ .............. 4
Current Methods of Nutritional Assessment ............. ..........................................4
The Mini-Nutrition Assessment (MNA) ........... ................................ ..............5
V alidation of the M N A ............................................................ ...........7
E explanation of studies......................................................... ............ ..7
Stu dy fin d in g s................................ ... ........ ................... 8
Comparison of the MNA with Other Nutrition Assessment Tools ........................9
T he M N A vs. the SG A ............................................................. .............. ... 9
The MNA vs. Determine Your Health Checklist (NSI) ............................9.
Importance of MNA.............. .................. ...................... 10
Identifying comorbidities of malnutrition........................................... 11
Pressure ulcers and nutrition ................................................................ .. 12
Improving prognosis through intervention............................................ 13
Immune Function............................... ......................... 14
M alnutrition and Immune Function................. .................. ...... ... .............. 14
Total lymphocyte count (TLC) and lymphocyte proliferation................... 15
N eutrophils ................. ................. ........................... ........... 16
Delayed-type hypersensitivity ............................................ .............. 17
Aging and Im mune Function ........................................................... ........ 17
Purpose for Study ................................... .......................... ............ 18
3 STUDY DESIGN AND M ETHODS .............................................. .............. 21
Inclusion/Exclusion C riteria.............................................. ............................. 21
Sam ple Collection................................................ 21
Im m une Function T ests................................................................. ............... .. 22
Isolation of neutrophils and lymphocytes from whole blood.....................22
Lymphocyte proliferation assay ......................................... ...............22
Whole blood proliferation assay ....................................... ...............24
N eutrophil oxidative burst assay: .................................................... ......24
Delayed-type hypersensitivity (DTH) test .............................................26
T he M N A A dm inistration ......................................................................... ..... .. 27
S statistic s ........................................................................... 3 1
4 R E SU L T S ............................................ ............................ 33
The MNA as a Measure of Nutritional Status.........................................................33
Comparison of the MNA with Immune Parameters ..............................................34
5 D ISCU SSION ............................................................................ 43
6 C O N CLU SIO N ..................................................................................................47
A PRESSURE ULCER STAGES....................................................... ..... ......... 48
B MINI NUTRITIONAL ASSESSMENT......................... ............. 49
C THE RJL SYSTEMS ELECTRODE PLACEMENT .............. .............. 50
L IST O F R E FE R E N C E S ......... ................................................................................. 5 1
BIO GRAPH ICAL SKETCH ................................................. .............................. 59
LIST OF TABLES
3-1 Percentage of total body weight values for weight adjustment for amputees .........32
4-2 Characteristics of 24 subjects included in the study ............................................36
LIST OF FIGURES
2-1 Overview of age-related phenomena in relation to odor perception....................... 19
2-2 Relationships among nutrition, pressure ulcers, and immunity............................20
4-1 Nutritional parameters contained within the MNA vs. MNA score .....................37
4-2 Measures of BIA vs. MNA score ............................................................ 38
4-3 A lbum in vs. M N A score............................................. .............................. 39
4-4 Total lymphocyte count vs. M NA score...................................... .............. 39
4-5 Lymphocyte proliferation vs. MNA score..........................................................40
4-6 Whole blood proliferation vs. MNA score.........................................................41
4-7 Neutrophil burst (normalized) vs. MNA score ....................................................42
A -1 Pressure ulcer stages ............................................................... 48
C-1 The RJL systems electrode placement ........................................ .............. 50
Abstract of Thesis Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Master of Science
BETTER NUTRITIONAL STATUS AS MEASURED BY THE MINI NUTRITIONAL
ASSESSMENT TOOL IS ASSOCIATED WITH INCREASED IMMUNE RESPONSE
IN ELDERLY NURSING HOME RESIDENTS WITH PRESSURE ULCERS
Jan Elizabeth Hudgens
Chair: Bobbi Langkamp-Henken
Department: Food Science and Human Nutrition
A decline in immune function occurs with age and this decline is exacerbated by
malnutrition. Clinical studies demonstrate that moderate to severe malnutrition can be
observed in 30 to 50% of geriatric hospitalized patients, and malnutrition is a condition
associated with greater susceptibility to infection, longer hospital stay, and increased
mortality. Through detection of malnutrition and impaired immune function in the
elderly, early intervention may reduce the risk of these negative consequences.
Unfortunately, malnutrition and impaired immune function often go unrecognized
in the elderly because of a lack of assessment methods. To partially combat this, the
Mini-Nutrition Assessment (MNA) was developed as an efficient and economical
assessment technique for elderly individuals. This assessment technique, which has been
validated in both France and the United States for use in persons 65-90 years of age, is a
comprehensive evaluation that is composed of four major parts: anthropometric
measurements, dietary questionnaire, global assessment, and subjective assessment.
The purpose of this investigation was to identify a relationship between MNA score
and immune response in elderly nursing home residents with pressure ulcers. The
variables assessed were whole blood and lymphocyte proliferation, neutrophil respiratory
burst, and delayed-type hypersensitivity (DTH). Based on MNA score, subjects were
classified as malnourished (n=13, MNA score<17), at risk for malnutrition (n=7, MNA
score=17-23.5), or well-nourished (n=4, MNA score>23.5); and nutrition status was
compared to each immune parameter using the Kruskall-Wallis test.
Whole blood proliferation was significantly greater in the at-risk subjects compared
to the malnourished subjects with both pokeweed [median (25t, 75th percentile), 1.8 (1.0,
2.2) vs. 0.6 (0.3, 1.0) dpm/cell, (p=0.017)]; and concanavalin-A [2.8 (2.3, 5.4) vs. 1.7
(0.9, 2.0) dpm/cell, (p=0.031)] mitogen, respectively. Normalized respiratory neutrophil
burst was significantly greater in the well-nourished subjects than in the malnourished
subjects [1.4 (1.2, 1.5) vs. 0.7 (0.5, 0.9), p=0.017].
The number of subjects who responded to at least one antigen was 3 of 4 (75%), 2
of 7 (28.6%), and 4 of 13 (30.8%), for well-nourished, at risk, and malnourished,
respectively. These results were not significant. Additionally, there was no significant
difference among groups in lymphocyte proliferation with concanavalin-A, pokeweed, or
phytohemagglutinin mitogen. These data suggest that in elderly nursing home residents
with pressure ulcers, a greater MNA score (indicative of better nutritional status) is
associated with greater immune responses.
The prevalence of malnutrition increases with age, and is most common in the
institutionalized (1,2). Malnutrition is still the most neglected problem in the elderly (3),
because of inadequate nutrition training of healthcare professionals (4) and lack of
validated screening methods (5),and also because of the challenge of distinguishing
malnutrition from the aging process itself (6).
Malnutrition is a condition associated with greater susceptibility to infection,
decreased wound healing, longer hospital stay, and increased mortality (1,2,6,7). Several
studies have shown correlations between nutritional status and immune function (8,9).
Other intervention trials demonstrate increased immune function with improved
nutritional status, further solidifying this relationship (10,11).
The decline in immune function associated with malnutrition may further
exacerbate a decline in nutritional status. It is easier to halt this downward spiral through
nutritional repletion in elderly at risk of malnutrition than in those who are severely
malnourished (12,13) because the immune system is not yet severely affected. Therefore,
accurate nutrition-assessment tools are needed to determine the nutritional state of elderly
individuals and to implement care before nutritional and immunological deteriorations
The MNA was developed in the early 1990s as a quick, economical, non-invasive
nutrition assessment tool (14). It was validated for use in the elderly through two
successive studies in France in elderly institutionalized populations, by comparing MNA
score to biochemical indices, anthropometric measurements, and clinician assessment. A
third study further validated the MNA by repeating these methods in an independently
living population in New Mexico (15).
Many studies show significantly higher mortality in malnourished patients when
compared to their well-nourished counterparts, regardless of nutrition assessment method
used (16-18). The MNA has been shown to be predictive of mortality when the score
achieved is less than 17, which categorizes the subject as malnourished (4).
Given that the MNA has demonstrated high sensitivity in detecting malnutrition in
elderly institutionalized individuals (14,15,19), it is a logical assumption that MNA score
will be associated with several immunological markers in a similar population. If true,
this would be a significant finding because impaired immune function in the elderly often
leads to a fatal outcome (9). Only a few studies to date have compared MNA with
immune function (9,20), and further compared these factors in independent-living elderly
with pressure ulcers (21,22), yet no studies have examined this relationship in
institutionalized elderly with pressure ulcers (a more vulnerable population).
Impaired immune function has been linked to inadequate food intake in many
studies (23-26), and normalization of immune parameters has been seen on refeeding
(27,28). Elderly often suffer from inadequate protein and calorie intake, and this is
worsened with institutionalization (1,2,29). Protein malnutrition is a contributing factor
in the development of pressure ulcers (30); and undernutrition has further been linked to
immunocompentence and poor wound healing (31). The MNA has been shown to
anticipate nutritional decline before the physiology of immune function is distorted (9).
This ability of the MNA may allow practitioners to prevent immune function decline
through identification ofundernutrition and intervention through nutritional
Therefore, the aim of this investigation was to identify a relationship between
MNA score and immune status as defined by immunological assays in elderly nursing
home residents with pressure ulcers. The assays performed were respiratory neutrophil
burst, lymphocyte proliferation, and delayed-type hypersensitivity.
REVIEW OF LITERATURE
Current Methods of Nutritional Assessment
Currently, valid and reliable screening tests are used in geriatric assessment of
cognitive problems (Mini Mental State Exam), autonomy (KATZ ADL), gait and balance
(Tinetti Performance oriented Mobility assessment), and depression (geriatric depression
scale) (32,33). Yet very few reliable tools exist to assess nutritional status in seniors.
Additionally, the tools that do exist are extensive, complex, and costly. No gold standard
exists for determining nutritional status (34). The development of malnutrition can be
described as a continuum, starting with inadequate food intake, and resulting in decreased
anthropometric and biochemical values (5). Therefore, anthropometric measures and
biochemical parameters have traditionally been used to assess level of nutrition (35).
One current method to determine nutritional status is the Comprehensive Geriatric
Assessment (CGA), which is a multi-dimensional diagnostic process used for long-term
care planning (33). The CGA format varies among institutions, but usually incorporates at
least four major domains: medical status, functional status, psychological function, and
Other tools were developed in which weighted scoring rates the individual at low,
moderate, or high risk for malnutrition. Chandra and colleagues designed a 14-question
screening tool to assess nutritional status in elderly Canadian patients (36).
The Determine Your Nutritional Health Checklist was developed as part of the US
Nutrition Screening Initiative (NSI), a collaborative effort between the American Dietetic
Association, the American Academy of Family Physicians, and the National Council of
Ageing (6). It is composed of 10 yes-or-no items that are given different weights,
associated with the nutritional health of the elderly. The cumulative score can range from
zero to 21, and seniors are categorized at high (score >6), moderate (score of 3-5), or low
(score of 0-2) nutritional risk (6). The checklist is not a diagnostic tool, but a
self-administered screening assessment, designed to identify elderly at risk of malnutrition
(37). Few studies have validated the checklist (38-40).
The subjective global assessment (SGA) was originally developed for use in
gastrointestinal surgery patients, but has been used in many different groups including the
geriatric population. The SGA includes questions about weight loss, changes in dietary
intake, gastrointestinal disturbances, and functional capacity. The physical exam section of
the tool assesses subcutaneous tissue loss, muscle emaciation, and presence of edema.
Results of the interview and physical exam are used to subjectively classify the senior as
either well-nourished (SGA A), moderately malnourished (SGA B), or malnourished (SGA
C). The SGA has a high degree of interrater agreement, and is a particularly useful method
of identifying protein-energy malnutrition (18).
The Mini-Nutrition Assessment (MNA)
Few methods of assessment existed before the introduction of the MNA. The MNA
was developed through collaboration between the Toulouse University Hospital in France,
the Medical School of New Mexico in the United States, and Nestle Research Centre in
Switzerland (4). It was created in the early 1990s by researchers Vellas, Garry, Guigoz,
and Albarede as a quick, economical, and noninvasive method of assessing nutritional
status of the elderly when they enter hospitals or institutions, and monitoring any
nutritional changes during their stay (5). This evaluation tool is composed of simple
measurements and a battery of questions which, when answered, provide a score out of
thirty points in order to categorize the nutritional status of the person assessed (41). The
MNA is administered in two parts. Part 1 is a screening questionnaire and takes only a few
minutes to administer. Out of a maximum score of 14, individuals who score >12 are
considered well-nourished, and do not need further assessment. Individuals who score <11
are considered at risk for malnutrition, and are given Part 2 of the test, which is an
assessment that awards a maximum of 16 points (Appendix A). On completion of the
assessment stage, the score is added back to the screening score to achieve a total MNA
score. Scoring categories are as follows (42):
* Malnourished: Scoring less than 17 points.
* At risk for malnourishment: Scoring between 17 and 23.5 points.
* Well-nourished: Scoring greater than 23.5 points.
The MNA fulfills many criteria for both screening and diagnostic measures, meaning
that it identifies those at risk for nutrition and can be used to determine outcome (42). It is
composed of four major sections (43,44) that include both screening and assessment
questions. Each section of the MNA is listed below, and possible scores for each section
are listed in parentheses.
* Anthropometric measurements: BMI (0, 1, 2, 3), mid arm circumference (0.0, 0.5, 1.0),
calf circumference (0, 1), and weight loss during the last three months (0, 1, 2, 3).
* Global evaluation: independence at home (0, 1), medications taken per day (0, 1),
psychological stress or acute disease in the last tree months (0, 1), mobility (0, 1, 2),
neuropsychological problems (0, 1, 2), skin lesions or ulcers (0, 1).
* Dietary assessment: number of meals/day (0, 1, 2), consumption of dairy products (0.0,
0.5, 1.0), intake of fruits and vegetables (0, 1), recent decline in food intake (0, 1, 2),
Fluid intake (0.0, 0.5, 1.0), mode of feeding (0, 1, 2).
* Subjective self-assessment: Nutritional problems (0, 1, 2), health status compared to
people the same age (0.0, 0.5, 1.0).
Validation of the MNA
Explanation of studies
The MNA has been validated for use with the elderly by three successive studies.
The first study was completed in Toulouse, France in 1991 in 155 elderly nursing home
subjects whose nutritional status ranged from very healthy to malnourished. In 1993, a
second study was completed in Toulouse with 120 subjects in a similar population. The
Albuquerque 1993 study was based in New Mexico, and used 347 independent-living
elderly (also 65 y or older), who were already participants in the New Mexico aging
process study, to further validate the MNA (15). The New Mexico Aging Process study
was a longitudinal study that examined nutrition and health status in the independent-living
elderly over time. In all three studies, both the very frail and the very active were included.
Overall, more than 600 individuals were enrolled (14).
The MNA was validated in all three studies by two principle criteria. First, a
comprehensive Nutrition Assessment was performed on each participant by a researcher.
Anthropometrics were taken, such as height, weight, body mass index (BMI), and skin fold
measurements. An evaluation of diet was accomplished using a diet history, 3-day record,
interview, and food frequency checklist. Additionally, the following biological markers
were measured and used as the gold standard for nutritional health: albumin, prealbumin,
transferring, retinol-binding protein, C-reactive protein, ceruloplasmin, cholesterol,
triglycerides, vitamins A, D, E, B1, B2, B6, B12, folate, copper, zinc, hematocrit,
hemoglobin, and blood cell count.
Second, two physicians trained in nutritional assessment independently assessed each
patient without knowing their MNA score. Both of the physician assessments and the
detailed nutrition assessment were compared to the MNA score received by the patient.
The specificity of the MNA was determined by cross-classification of the two
Toulouse studies using equations from the discriminant analysis (14). These results
showed the MNA could correctly identify 70-75% of individuals as normal or
malnourished without the use of biochemical indices. The rest of the population (25-30%)
fell in the buffer zone between well-nourished and malnourished, and would need
biochemical indices or clinical evaluation to classify further. In order to set the threshold
values for the MNA, scores were cross-tabulated with albumin levels of the subjects from
the Toulouse studies. All subjects with inflammation, as determined by C-reactive protein
>20 mg/L were excluded. In this manner, the scores were determined for well-nourished
(>24), at risk for malnutrition (17-23.5), and malnourished (<17).
In both Toulouse studies, there was a strong correlation between several nutritional
markers (transthyretin, serum folate, and vitamin D), energy intake, and MNA score in both
males and females. Additionally, an association between a low MNA score and mortality
at three months and one year was also found. Overall, the test was found to be 96%
sensitive (in the ability to detect malnutrition) and 98% specific (in the ability to classify
The New Mexico Ageing Process Study examined the nutritional status of
independent-living elderly in America. Half of this study population was between the ages
of 75 and 85 y(with 10% being older than 85 y). Even though this group was
independent-living, and therefore, considered to be healthier than the institutionalized
elderly, almost 20% were found to be at risk for malnutrition. The at risk group had a
lower mean dietary intake than the well-nourished group, yet both albumin levels and BMI
were within the normal range (15). The results of the New Mexico Aging Process Study
showed a correlation between a high MNA score (27-30) and successful aging (45).
Comparison of the MNA with Other Nutrition Assessment Tools
The MNA vs. the SGA
Barone and associates compared the SGA with the MNA in the detection of
malnutrition over 60 days in 43 elderly hospitalized patients (age greater than 65 years) in
Australia. There was no significant difference in the percentage of people identified as
malnourished between SGA and MNA; however, the MNA identified a greater proportion
of malnourished patients across the time intervals, suggesting a significantly more
(P=0.005) sensitive degree of detection (2). The findings supported claims of other authors
that the SGA cannot be used to monitor changes in nutritional status secondarily to the
tool's subjective nature and nonquantitative data analysis. On the contrary, the MNA
assesses patients quantitatively, which allows easier long-term monitoring of nutritional
status. The MNA also has good interrater reproducibility in the institutionalized elderly
(5). The SGA shows a lower interrater agreement than the MNA when used in elderly
populations because it was validated for use in all hospitalized patients, whereas the MNA
was specifically designed and validated for use in an elderly population (46). Overall, the
MNA was considered to be a more appropriate nutritional assessment tool than the SGA in
an elderly population (2).
The MNA vs. Determine Your Health Checklist (NSI)
The MNA was compared to the Determine Your Health Checklist (47) as a predictor
of morbidity and mortality in an elderly independent-living Danish population. It was
reported that the NSI was a poor indicator of mortality, but individuals classified as
"at-risk" by the MNA had a significantly higher mortality rate and a greater incidence of
chronic disease when compared to the well-nourished group (6).
Importance of MNA
One advantage of the MNA is that it does not require measurements that are difficult
to assess, such as blood values, but MNA score has still been shown to correlate with many
aspects of health (2). Many studies show significantly higher mortality in malnourished
elderly when compared to their well-nourished counterparts (16-18). Studies also show
that malnutrition, as determined by the MNA score, is very predictive of mortality
compared to seniors classified at risk or well-nourished by the same tool (4). This is
important because the prevalence of malnutrition, relatively low in independent-living
elderly (1-9%), rises considerably (20-75%) in hospitalized or institutionalized elderly (1).
Moreover, undernutrition may be difficult to distinguish from the aging process itself
(6,38), and physicians tend to overlook malnutrition due to their meager training in
nutritional assessment (4).
Malnutrition as determined by the MNA is associated with several biological markers
of malnutrition, specifically hematocrit and hemoglobin (9). Furthermore, Schiffrin and
colleagues showed that by categorizing subjects by albumin level (<35 g/L, 35-40 g/L, and
>40 g/L, respectively), PHA (phytohemagglutinin; a T-cell mitogen) stimulated
lymphocyte proliferation was significantly less in the group with albumin <35g/L. This is
a significant finding because malnutrition is still one of the most neglected problems in
geriatric medicine (3) and impaired immune function in the elderly population often leads
to a fatal outcome (9).
Based on these research studies, elderly nursing home residents are at a much greater
risk for malnutrition and impaired immune function than the general population. More
importantly, the term "at-risk" implies that without intervention, the population so noted
will progress to a more severely malnourished or immune compromised state (38).
Therefore, reliable assessment tools are needed to identify elderly at-risk of malnutrition.
The MNA has been validated through successive studies to assess nutritional status in
elderly persons (15). A recent study completed in two long-term geriatric units in Spain,
found the MNA to be reliable in terms of internal consistency and in terms of interobserver
test-retest reliability (48).
Identifying comorbidities of malnutrition
Malnutrition has been associated with many comorbidities of malnutrition. A study
conducted in independent-living elderly showed a direct association between moderate
score (defined at risk) on the MNA with lower BMI, energy intake, functional, and mental
abilities compared to seniors who were categorized as well-nourished (41). More
specifically, Havlik and associates demonstrated that the increase in functional limitations
associated with aging often impairs ability to grocery shop and prepare food (49).
Covinsky and colleagues discovered malnourished elderly were more likely to be
dependent in at least one activity of daily living (ADL) after hospital discharge, resulting in
a higher probability of nursing home use in the year following hospitalization (18).
Griep and colleagues discovered a relationship between poorer health, poorer odor
perception, fewer natural teeth and being at risk for malnutrition based on an MNA score of
less than 24. Many studies show that odor perception decline can cause changes in food
consumption and decreased food appreciation (50). Poor oral health is often seen in the
elderly and plays a large role in food intake (Figure 1). For example, dental caries,
ill-fitting dentures and missing teeth often hinder mastication, furthering risk of
Pressure ulcers and nutrition
A pressure ulcer is a wound that often arises from too much pressure on the skin;
however, it can also occur from friction by rubbing against an object (e.g. bed sheet). In
long-term care facilities, pressure ulcers often arise as a result of the resident not being
turned, cleaned, or fed as often as the ideal standard of nursing would dictate.
Nutritional status also plays a large role in skin integrity. Protein malnutrition can
alter dermal extracellular matrix turnover, increasing risk for pressure ulcer development
(53). Protein requirements are higher in stressed populations secondary to hypermetabolic
state, and are necessary for wound healing (53,54). Additionally, many nutrients play a
role in wound healing; vitamin C is necessary for collagen synthesis, vitamin A enhances
epithelialization, and zinc is vital for cell mitosis and proliferation (7). Wissing and
colleagues demonstrated the relationship between ulcers and nutrition by correlating
reduced MNA score in seniors with open ulcers, and an increase in MNA score upon
healing (21). Severity of the pressure ulcer is determined by "stage", or how deeply the
wound penetrates the tissue (see Appendix A).
In addition to diminished quality of life, pressure ulcers are a financial burden to
health institutions. In 1993, one study concluded physician and hospital cost for treating a
pressure ulcer patient was $230,575 (55). The same study estimated that for the
approximately 34,000 seniors with pressure ulcers in the United States, that total charges
run over 800 million dollars annually, and expense increases with pressure ulcer stage (56).
Identifying seniors at risk of malnutrition and intervening prior to ulcer formation would
not only reduce costs, but could also improve quality of life.
Improving prognosis through intervention
One prospective, randomized controlled study demonstrated the effectiveness of
nutrition intervention in 88 elderly nursing home residents at risk for malnutrition (57).
Nutritional status was determined at Day 0, 30, and 60 by a 3-day diet record and
simultaneous evaluation by the MNA. Subjects were then divided into 4 groups according
to their MNA score. Those with a score >24 (well-nourished) did not receive supplement.
Those with a score between 17 and 23.5 (at risk) were randomized into one of two groups.
One group received supplementation, and the other did not. The group with MNA scores <
17 (malnourished) also received oral supplements. Resident compliance with oral
supplements was good.
The majority of the residents receiving oral supplements improved their MNA score
and increased their weight significantly by 1.4+0.5kg. The well-nourished and at risk
group that did not receive supplementation did not change in MNA score or weight.
Intervention supplementation was shown to be successful in improving weight and
increasing MNA score in malnourished and at-risk elderly nursing home resident (57).
Some studies suggest the need for intervention. Several clinical studies have shown
increased post-operative morbidity and mortality in seniors over 60 years of age (58,59).
This risk was found to be exacerbated by malnutrition (60). When the MNA was used in a
preoperative setting, 9% of the subjects were found to be malnourished, and 5% were at
risk of malnutrition. These results suggest a need for pre-operative nutrition that might
reduce morbidity and mortality risk (61).
Intervention could also reduce weight loss, which is associated with increased risk
for morbidity and mortality compared to weight gain or maintenance (62). Additionally,
weight loss often reduces functional activity, and has been associated with depressed
immunity, which also increases risk of morbidity and mortality (63).
In a study of 120 hematology patients, malnutrition did not appear to be more
prevalent than in the normal elderly population when assessed using the MNA; however,
the authors agreed that the MNA was an important tool for use in this population, because
nutritional influence could influence the outcome of the disease (64).
In conclusion, many studies have shown the relationship of impaired nutritional
status with increased risk for morbidities and mortality, suggesting an opportunity for
intervention to reduce these risks. Overall, prevention of malnutrition is more successful
than treatment (65).
Malnutrition and Immune Function
Malnutrition can impair the immune system through a number a mechanisms,
including impairment of antigen presenting cells and proliferative responses and reduction
of phagocytic and cytolytic ability (66). In fact, suboptimal nutrition is believed to
contribute to immune senescence (11).
Elderly are at risk for protein energy malnutrition (29), which has been associated
with impairment of cell-mediated immunity, phagocyte function, complement system, and
cytokine production (27). Chandra stated immunocompetence results from deficiencies in
vitamin A, beta-carotene, folic acid, vitamin B6, vitamin B12, vitamin C, and vitamin E.
Research has shown that these immune function impairments can be reversed with feeding.
Allende and associates noted a normalization of total lymphocytes and lymphocyte
proliferation upon refeeding in anorexic patients (28).
Malnutrition as defined by the MNA seems to anticipate change in nutritional
markers before the physiology of immune response is overwhelmingly altered (9),
presenting an opportunity for intervention if the malnutrition is identified. Schiffren and
associates found significantly lower hemoglobin and hematocrit levels in malnourished vs.
well-nourished subjects as determined by the MNA even though total lymphocyte count
(TLC) and lymphocyte proliferative response were not significantly different between
groups (9). These researchers concluded that although the malnourished groups showed
markers of malnutrition, these were not severe enough to alter immune status.
Total lymphocyte count (TLC) and lymphocyte proliferation
TLC is a sensitive, but not specific, indicator of nutritional status that correlates with
morbidity and mortality (67); however, it can be affected by several other factors, such as
aging and infection (11,66,68). TLC is calculated by multiplying the white blood cell
count by percentage of lymphocytes. Normal, mild, moderate, and severe nutritional
depletion are associated with lymphocyte counts of >1800mm3, 1500-1800 mm3, 900-1500
mm3, and <900 mm3, respectively (69).
The ability to mount a proliferative response has also been associated with nutritional
state. Impairment of T-lymphocyte proliferation has been seen in nursing home residents
as defined by MNA score (11,70), and albumin levels (9), yet few studies examine
T-lymphocyte proliferative response in a pressure ulcer population (71). It is important for
clinicians to understand the impact a pressure ulcer has on the immune system, so they can
provide patient better care.
Immune senescence also may play a role in lymphocyte proliferation. T-lymphocyte
proliferation is one immune response that has been shown to decrease with age from 20-70
years of age, and plateau after 70 (72,73). A study involving 403 independent-living
elderly (70-106 years) revealed 18% were incapable of mounting a proliferative response to
PHA, ConA (a T-cell mitogen), and PW (a T and B-cell mitogen), and this decreased
response was associated with a mortality risk two times greater than in positive responders
(74). Individuals who demonstrated <10% of the mean response of the young control to
PHA, PW and ConA were classified as negative responders. The authors concluded that
decreased proliferative response may have been due to an underlying disease; however,
when this variable was excluded, the negative responders still had a higher mortality rate
when compared to the positive responders. This study suggested that decreased
lymphocyte proliferation to mitogens is a "marker of physiologic aging" and might be a
predictor of death in the elderly (74).
Neutrophils are the most abundant white blood cell (50-70%) and are primarily
responsible for destroying foreign microbes through phagocytic processes (66). When
neutrophils are stimulated by cytokines, they migrate to the infected area and engulf
foreign microbes. Once the microbe is inside the neutrophil, it is dissolved by the
discharge (degranulation) of highly reactive oxides (including superoxide anions, hydrogen
peroxide, hydroxyl radicals, and hypochlorous acid) into the phagocytic vacuole (66).
Neutrophil activity can be measured many ways. One method is called a neutrophil
respiratory burst test (NBT). NBT is accomplished by stimulating neutrophils in the
presence of a reducible compound (often ferricytochrome c) that changes color upon
reduction. This color change is then detected spectrophotometrically (75). It has been
suggested that aging may negatively effect neutrophil function (76). Conversely, one
recent study found no significant difference in neutrophil function in elderly without
infection compared to their infected counterparts and the young control (77). Although it is
still controversial whether age plays a role in neutrophil dysfunction, it is generally
accepted that nutritional status has a great impact on neutrophil function in both animals
(23) and humans (25).
Delayed-type hypersensitivity (DTH) is a measure of in vivo immune function and is
often administered to nursing home residents in the form of a tuberculosis test. A positive
response to DTH testing indicates previous exposure to the antigen and the production of
memory cells. Inability to produce a DTH reaction has been associated with increased
mortality in consecutive studies (78,79).
One limitation of DTH is that malnutrition may result in energy regardless of
previous exposure (80). The antigens used in this study are Candida albicans, mumps
antigen, and tetanus toxoid. These antigens were chosen because of their common
exposure in this population, from either the environment or vaccination. Since it was
known that most of the observed population had been previously exposed to these antigens,
it was expected that most of the subjects would show a positive response, and a negative
response may possibly be attributed to malnutrition.
Aging and Immune Function
Immunosenescence can be defined as "a state of dysregulated immune function that
contributes to increased susceptibility of the elderly to infection (81)." By the age of 40
years, there is a 90% complete involution of the thymus.
Decreased immune function in the elderly has been studied in an effort to determine
its etiology. While the exact etiology remains unclear, some mechanisms are understood,
as explained by Schiffrin and colleagues (9):
An altered (impaired) immune response has previously been detected in elderly
individuals. Several investigators have suggested that this impaired immune function
is caused by a basic defect in receptor signaling of immune cells and an altered
capacity to respond to antigen-dependent activation signals. In fact, any immune
response implies the activation and expansion (proliferation) of antigen-specific cells,
and it has been reported that with aging a smaller number of immune cells enters the
cell cycle upon antigen or mitogen stimulation. Two major mechanisms could be
responsible for this observation: (i) a different distribution of lymphocyte subsets
with the aging process owing to an abnormal lymphopoietic function, including
cellular maturation, and (ii) an intrinsic cellular deficiency resulting in an abnormal
response to activation signals.
Although the etiology of immunosenescence may still be unclear, it is known that
responses to vaccination are diminished in the elderly. Burns and Goodwin found a
40-150-fold increase in the rate of influenza infection in elderly individuals with chronic
illnesses such as diabetes, emphysema, or chronic renal insufficiency (82). Chronic
illnesses may go undiagnosed in the elderly, which presents the complication of enrolling
"apparently healthy" seniors into research studies. The SENIEUR protocol was developed
by a the EURAGE Concerted Action Programme on Ageing of the European Community.
This protocol describes exclusion criteria in effort to observe only the "truly healthy"
elderly population, and standardize subject selection between studies investigating the
interaction between aging and immune dysregulation (83).
The SENIEUR protocol elucidated one very important fact: Immune senescence
does not happen to everyone, and often it exists concurrently with other comorbidities (83).
Given that many studies have demonstrated the relationship between poor nutritional status
and declined immune function (11,66,68,70,74) one could argue that poor nutrition is a
preventable comorbidity to immune senescence.
Purpose for Study
In general, there is a greater occurrence of malnutrition in the elderly population, but
most predominately in elderly who have been hospitalized or institutionalized (13,84). If
we define nutrition as "decreased nutrient reserves," malnutrition is found in up to 15% of
the independent-living elderly, whereas the incidence of malnutrition rises to 25-60% in the
institutionalized elderly (44). Malnutrition has been shown to develop as a result of
diminished odor perception associated with age (50), which can then effect nutrient intake
from diminished food appreciation (Figure 1). A decline in nutritional parameters (e.g.
hemoglobin, hematocrit) has been associated with the presence of pressure ulcers.
Furthermore, a distinct relationship has been identified between nutritional status, immune
response, and pressure ulcers, as shown in Figure 2.
Due to the relationship between malnutrition, pressure ulcers, and immune function
decline, we would anticipate impaired nutritional and immunological status in a pressure
ulcer population, which would be further compounded by institutionalization. Therefore,
the purpose of this study is to identify a relationship between parameters of immune
function and score achieved on the MNA. If a relationship does exist, the MNA could be
used clinically as a quick, economical, non-invasive method of predicting immune function
decline. By repleting nutritional status in subjects identified at risk of malnutrition by the
MNA, a decline in immune function can be avoided, and risk of mortality decreased.
Medicatio Odor Perception
Health Status Dental state
Nutritional status Nutrient intake (food consumption)
Figure 2-1. Overview of age-related phenomena in relation to odor perception. Griep, M.
I., Mets, T. F., Collys, K., Verte, D., Verleye, G., Ponjaert-Kristofferson, I, and
Massart, D. L. (1999) MNA and odor perception. Nestle Nutr Workshop Ser
Clin Perform Programme 1: 41-59.
Malnutrition 4 Infecti
Figure 2-2. Relationships among nutrition, pressure ulcers, and immunity
STUDY DESIGN AND METHODS
Data for this cross-sectional study were collected prospectively and represent the
baseline data from an interventional trial. MNA score was assessed for each enrolled
subject. Venous blood was collected to determine total lymphocyte count (TLC), serum
albumin, and immune function studies. Bioelectrical impedance analysis (BIA) was
performed on each patient to assess body composition.
Thirty nursing home residents from the Lake City Veterans Administration (VA)
Nursing Home, Lake City, Florida were recruited for the study. Eligible subjects were 65
years of age or older, and had a stage II or more severe pressure ulcer. Residents were
excluded if they were receiving immunosuppressive medications, suffered from egg or
thimersal allergies, had diabetes treated by insulin, or an immune deficiency disease.
Additionally, residents with renal or hepatic failure were excluded due to the protein load
of the intervention product for the larger study.
A 30 mL blood sample was drawn at 9 AM and collected in three 10 mL sodium
heparin Vacutainers (Becton Dickenson, Franklin Lakes, NJ). The Lake City VA
laboratory completed the CBC with differential and serum albumin on one of the 10 mL
tubes. The remaining two 10 mL tubes were transported to Gainesville, Florida where
they were processed for neutrophil burst and lymphocyte proliferation assays.
Immune Function Tests
Isolation of neutrophils and lymphocytes from whole blood
Two 10 mL sodium heparin Vacutainers of whole blood were received per patient.
To isolate the leukocyte-rich plasma (LRP) layer, whole blood was mixed with dextran
(Accurate Chemical and Scientific Corp., Westbury, NY) solution (6% w/v dextran 500 +
9% w/v NaC1) in a 9:1 ratio and allowed to stand at room temperature for 40 minutes.
During this period, prepare a final concentration of 1.077 g/mL of Optiprep (Accurate
Chemical and Scientific Corp., Westbury, NY) in 0.85% sodium chloride (NaC1),
containing 1 mM ethylenediamine tetra acetic acid (EDTA), 20 mM HEPES, pH 7.4: a
1.095 g/mL Optiprep in the same buffer. A density gradient was then prepared for each
sample consisting of 4 mL of the 1.077 g/mL Optiprep prepared above layered on top of
4 mL of the 1.095 g/mL Optiprep solution.
After 40 minutes, the dextran caused red blood cells (RBC) to settle to the bottom
of the tube and the top LRP fraction was layered on the prepared density gradient. The
layered sample was then centrifuged in a 15 mL conical tube at 800 x g for 30 minutes in
a Jouan C312 Centrifuge without brake (Jouan, Inc., Winchester, VA). Centrifugation
results in the formation of 2 distinct bands: the upper band contains lymphocytes and the
lower band contains neutrophils. The lymphocyte layer was removed using a sterile
fine-tip transfer pipette and placed in a 50 mL conical tube. The neutrophil layer was
also removed using a sterile fine-tip transfer pipette and placed in a separate 50 mL
Lymphocyte proliferation assay
Isolated lymphocytes were re-suspended in 20 mL of RPMI-wash (RPMI-1640
containing 50 pLM 2-mercaptoethanol, 2 mM L-glutamine, 50 units /mL penicillin, 50
pg/mL streptomycin, and 25 mM HEPES buffer, Cellgro, Herndan, VA) and centrifuged
in the Jouan C312 centrifuge for 15 min at 400 x g. The supernatant was removed and
the pellet was washed twice with RPMI-wash using the same procedure as above. After
the final wash, the supernatant was removed and the pellet was re-suspended in 1 mL of
RPMI-complete [RPMI wash (as described above) supplemented with 10% VSP
(Human serum gamma depleted/heat inactivated); Biocell Laboratories, Inc., Ranch
Dominguez, CA]. Cells were quantified using a hemocytometer, and then adjusted to a
stock concentration of 4 x 106 cells/mL in RPMI-complete.
In a 96-well round bottom culture plate, cells were plated at a concentration of 2.0
x 105 cells/well and a final volume of 200 pil/well. Cells were stimulated with a final
concentration of 10 [ig/mL phytohemagglutinin (PHA, a T-cell mitogen), 1 [ig/mL
pokeweed (PW, a T and B-cell mitogen), and 12.5 [ig/mL concanavalinA (ConA, a T-
Cell mitogen) and the remaining wells served as controls with RPMI complete and cells
only. The final concentrations for PHA, ConA, and PW were used because they were
found through experimentation in our lab to evoke the greatest response in our elderly
Cells were then incubated for 66 hours in 5% CO2 at 370C. After a 66-hour
incubation, 1 [tCi ofH3-thymidine in RPMI-wash (specific activity 20 Ci/mmol: NEN
Life Science Products, Inc., Boston, MA) was added to each well and then each well was
harvested 6 hours later. Cells were harvested onto glass filter paper using a Skatron Cell
Harvester (Denton Harbor, MI) and filter paper was placed into scintillation tubes
containing 5 mL of Scinti-Safe scintillation fluid (Fisher Scientific, Suwannee, GA).
Samples were then counted using a Beckman Scintillation counter LS6000SC (Beckman,
CA). The average counts per minute (cpm) minus the average unstimulated counts were
divided by 0.6 to compensate for the 60% efficiency of our liquid scintillation counter for
3H. Data are reported in disintegrations per minute (dpm).
Whole blood proliferation assay
In a 15 mL conical tube, 1 mL of patient whole blood was mixed with 3 mL
RPMI-wash (see above description) resulting in a 1:4 dilution. In a 96-well plate, cells
were stimulated with a final concentration of 10 pg/mL PHA, 1 CIg/mL PW, and 12.5
pg/mL ConA and the remaining wells served as controls with RPMI complete and cells
only. Each well was adjusted to a final volume of 200 pjl/well with RPMI complete, and
200 jpl of sterilized Milli-Q water was added to each well that was empty after all other
wells had been plated. Cells were then incubated for 72 hours in 5% C02 at 370C. After
a 72-hour incubation, 1 ptCi ofH3-thymidine in RPMI-wash (specific activity 20
Ci/mmol: NEN Life Science Products, Inc.) was added to each well and then each well
was harvested 24 hours later. Cells were harvested onto glass filter paper using a Skatron
Cell Harvester (Denton Harbor, MI) and filter paper was placed into scintillation tubes
containing 5 mL of Scinti-Safe scintillation fluid (Fisher Scientific). Samples were then
counted using a Beckman scintillation counter. The average counts per minute (cpm)
minus the average unstimulated counts divided by 0.6 to compensate for the 60%
efficiency of our liquid scintillation counter for 3H. The data are reported as dpm.
Neutrophil oxidative burst assay
The neutrophils isolated from the whole blood by density gradient centrifugation
were washed with 0.85% NaCl containing ImM EDTA and 20 mM HEPES, pH 7.4.
This was centrifuged for 10 minutes at 260 x g in the Joan C312 centrifuge. IfRBC
contamination was noted in the pellet, 3 mL lysing buffer (0.83% NaC1 with 10mM
HEPES, pH 7.0) was added and the sample was incubated at 370C for 7 minutes. After
lysing, the sample was centrifuged at 260 x g for 10 minutes and the resulting pellet was
washed in 10 mL Hank's Balanced Salt Solution without Mg2+ or Ca2+ (Mediatech, Inc.,
Herndon, VA) and centrifuged at 350 x g for 10 minutes. The supernatant was removed
and 1 mL of glucose (Sigma, St. Louis, MO) in Dulbecco's Phosphate-Buffered Saline
(DPBS) (Ig/L) was added to the pellet and the neutrophils were counted in a Beckman
Coulter Instrument (Coulter Corporation, Miami, FL). Neutrophil concentration was
adjusted to 5.0 x 106 cells/mL. Fifty microliters of neutrophils were plated for a final
concentration of 2.5 x 105 cells/well in a 96-well flat bottom plate. To each well was
added 100 jpl DPBS with glucose (as prepared above); 10 jpl of ICjg/mL phorbol
12-myristae 13 acid (PMA; Sigma, St. Louis, MO) in DPBS with glucose, and 10 Pl of
18.6 mg/mL ferricytochrome c, horse heart muscle (Sigma, St. Louis, MO).
The neutrophil oxidative burst was measured by a colorimetric kinetic assay using
UV Max (Molecular Devices, Sunnyvale, CA). Each well, therefore, contains cell
suspension from a subject, media and substrate for those cells (DPBS + glucose solution),
a stimulator of T and B lymphocytes (PMA), and an iron-containing molecule that
changes color upon oxidation. When the neutrophils are stimulated in vitro they produce
highly reactive oxides that are used to kill bacteria engulfed by the neutrophil or are
secreted to clear microbes that are too large for the neutrophil to engulf. These oxidative
agents made by the neutrophil include superoxide anions, hydrogen peroxide, hydroxyl
radicals, and hypochlorous acid. These agents reduce the iron molecule in
ferricytochrome, causing a color change that is measured as a change in absorbance by
the UV Max instrument.
In theory, healthier neutrophils will react more readily to an outside stimulant
(PMA, in this case), and therefore cause a greater color change over a shorter period of
time. The plates were read for thirty minutes total; however, the reaction occurred at the
highest linear change in Vmax from 3 to 10 minutes; for this reason, the 3 to 10 minute
data are reported and compared between subjects. Results were normalized with a
young control to account for any variation in assay technique. A young control (25-40 y)
was an individual without any overt medical complication. Young control blood was
drawn the same day and time as subjects, and processed concurrently with subject blood.
Delayed-type hypersensitivity (DTH) test
DTH testing was completed with the use of three antigens and a saline control
purchased from ALK-Abello (Round Rock, Texas); these antigens were Candin (Candida
albicans), MSTA (mumps antigen), and tetanus toxoid. These antigens were chosen
because of their common exposure in this population. All three antigens and the control
were injected intradermally. Candin and MSTA were purchased ready to use, but the
tetanus toxoid was mixed in a 1:10 dilution with sterile 0.9% normal saline and 0.4%
phenol mixture (ALK-Abello). Induration (swelling) was measured at 48 and 72 hours
post administration. Subjects were classified as responding if they had a minimum
induration of 5 mm to any of the 3 antigens at either time point, or anergic if they did not
respond to any of the antigens. Measurements were taken by averaging the two widest
points of the induration. Erythema (redness) without induration was considered not
significant. Total induration was calculated by adding the diameter of all positive
The MNA Administration
The MNA, as developed by Guigoz and associates, leaves much room for
professional judgment (Appendix B). To maintain consistency between interviewers,
interpretation and clarification of several questions of the MNA were developed, and
patients were assessed according to these definitions. It is important to note that the
decisions made to clarify these MNA questions may not have been the same decisions
made by the researchers who validated the MNA; however, all researchers in our study
wanted continuity of assessment, and we felt question clarification would help achieve
this. Either a researcher or a research assistant who had been trained to use the tool
administered the MNA. The question clarifications are listed below and justifications for
these adjustments are:
Question 1 asks if food intake has declined over the past three months due to loss
of appetite, digestive problems, chewing or swallowing difficulties. Subjects received
full points if there was no decline in food intake over the past three months, and zero
points if food intake had severely declined. All researchers involved agreed that it would
be more pertinent to determine caloric intake rather than appetite to assess nutritional
status. Appetite may not necessarily affect intake, especially in an institutionalized
setting where residents receive assistance with meals and are constantly monitored by a
Question 3 assesses mobility, but level of mobility is poorly defined. Clarification
of this question was as follows: Patients received no points if they were in contracture or
could not hold themselves up if placed in a chair. Subjects received a score of 1 if they
were mobile but chose not to leave their room or the subject was able to get out of bed
with assistance or independently but did not leave the nursing home. Subjects received a
full score if they were able to leave the nursing home and were mobile once in their
wheelchair or walker (either with assistance or independently). Some studies have shown
that persons with decreased mobility are at risk for poor diets (22). This is unlikely in an
institutional setting where food is prepared for and delivered to the residents.
Question 6 pertained to body mass index (BMI). Weights were obtained from the
patient's chart. For amputees, BMI's were calculated using an adjusted body weight
through a method by Lee and Nieman (1996):
Adjusted body weight = (measured weight)/(100-% of amputation) (3-1)
Table 1 represents percentage of total body weight values for weight adjustment of
All heights were calculated through knee height measurement using a knee height
caliper (Ross, Columbus, OH). Subjects were asked to lie in a supine position and bend
both the left knee and left ankle at 900. The fixed blade was placed under the heel of the
left foot while the sliding blade was pressed down against the thigh distal to the patella.
The shaft of the caliper was in line with long bone in the lower leg (tibia) and crossed
over the lateral malleolus. The locking lever was pushed away from the blades to hold the
measurement and was read through the viewing window to the nearest 0.1 cm. Two
measurements were made in immediate succession, and the average measurement was
Actual stature was estimated by inserting the knee height into the following
equations 3-2 by Chumlea (Chumlea, W. C. et al in Nutritional assessment of the elderly
through anthropometry, 1987), and patients older than the equation's defined age range
were still assess with the same equation:
White male (age 60-90 yr.): [KH (cm) x 2.08] + 59.01
Black male (age 60-80 yr.): [KH (cm) x 1.37] + 95.79
White female (age 60-80 yr.): [KH (cm) x 1.91] [Age (yr.) x 0.17] + 75
Black female (age 60-80 yr.): [KH (cm) x 1.96] + 58.72 (3-2)
Question 8 asks if the subject takes more than 3 prescription drugs per day. In
many nursing home settings, any medication is considered a prescription drug because it
must be ordered by a physician, including over the counter medications like aspirin. For
clarification, prescription drugs were defined as medications not available over the
counter to the general public.
Question 10 asks how many full meals a subject eats per day. A full meal was
considered to be 75% or more of a meal. Subjects received full points if they were eating
three meals per day or of they were receiving 100% of their energy need though a feeding
tube alone, through a tube feeding and oral diet, or through meals and between meal
Questions 11, 12, and 13 are designed to assess intake of protein, fruits and
vegetable, and fluids, respectively. Patients received full points for each question if they
were meeting nutrient needs via tube feeding.
Question 14 was designed to assess the subject's mode of feeding. The patient
receives no points if unable to self-feed without assistance. Previous research has shown
a correlation between MNA score and need for public help with activities of daily living
(41); however, in an institutionalized setting, subjects receive additional help with all
meals, and often receive supplements between meals. For these reasons, the researchers
agreed to assign no points only if the patient completely refuses to eat.
Questions 15 and 16 are self-perception questions regarding health, and the subject
answers them. If subjects could not answer questions independently, due to either
cognitive impairment or physical impediment, the primary caregiver for that resident was
Question 17 requires the researcher to measure the subject's mid-arm
circumference. To maintain consistency between researchers, the following protocol was
followed: Patients were asked to lie in a supine position with their arms at rest by their
sides. A tape measure was used to determine the mid-point of the arm by measuring the
distance between the acromial surface of the scapula (bony protrusion surface of the
upper shoulder) and the olecranon process of the elbow (bony point of the elbow on the
back of the arm). The mid-point was marked with a black marker. The tape measure was
then positioned at the previously marked mid-point on the upper arm and tightened
snugly, but not tight enough to cause indentation of the skin. Measurements were
repeated twice and average was recorded.
Question 18 requires the researcher to measure mid calf circumference. Again, to
maintain consistency between researchers, the following protocol was followed: The
subject was asked to lie in a supine position, with one knee bent at a 900 angle while their
foot rested on the bed. The assessor visually verified the 900 angle with a cardboard
cutout of a right triangle by holding the triangle up to the subject's knee. The assessor
then subjectively chose the largest circumference of the calf and placed a measuring tape
around this area to determine the calf circumference in centimeters. Measurements were
repeated twice, and the average of the two measurements was recorded.
BIA was measured using the RJL Fluid and Nutrition System developed by RJL
Systems, Inc (RJL Systems, Clinton, MI). Subjects were excluded from the procedure if
they had an amputation. Hydration status was screened before enrollment by completing
a comprehensive metabolic panel on each subject, followed by fluid or electrolyte
replacement if necessary. Hydration status was not assessed the day BIA was completed,
which may be another limitation to the study.
All jewelry was removed from the subject. Subjects were placed in a supine
position on a non-conductive surface with arms 300 from the body and legs slightly apart.
The subject was instructed to lie quietly during the procedure, and the tester explained the
testing procedure to the patient, as it was completed.
The subject's right sock was removed and the electrode sites were swabbed with
alcohol. Electrodes and cables were attached according to the illustration (Appendix C).
Once the subject was relatively still, the current was turned on, and the resistance and
reactance measurements were recorded. The recorded values for resistance and reactance
were entered into the Cyprus software program (RJL Systems, Clinton, MI) along with
age, weight obtained from chart, and height calculated from knee height measurement.
The Cyprus program then displayed body composition results.
Statistical analysis for neutrophil respiratory burst, lymphocyte and whole blood
proliferation was performed using the Kruskall-Wallis test with significance taken at
p<0.05. Post-hoc analyses were accomplished using Dunn's Multiple Comparison Test.
Number of responders to DTH was analyzed using a chi-squared test for independence.
Box Plots are given for all data except BIA measures (total body water, fat pounds,
fat percentage, and phase angle). BIA measures are reported as scatter plots because "n"
was too small in the well-nourished group to report in a box plot. Each box is set up so
that the bottom of the box represents the 25th percentile and the top of the box represents
the 75th percentile. The horizontal line inside the box is the mean. The median can be
estimated by finding the point equidistant from the bottom (25th percentile) and the top
(75th percentile) of the box and drawing a horizontal line through it so that it bisects the
box. The whisker extending from the top of the box represents the top quartile
(75-100%), and the highest horizontal line on the top whisker represents the highest data
point. The whisker below the box represents the lowest quartile (0-25th%) and the
lowest horizontal line on the whisker represents the smallest data point.
Table 3-1. Percentage of total body weight values for weight adjustment of amputees
Body part Percent (%) of total body weight
Below knee 7.1
Entire leg 18.5
Below elbow 3.1
Entire arm 6.5
Lee, R. D. & Neiman, D. C. (1996) Nutritional Assessment, 2 ed. McGraw-Hill
Companies. New York, NY.
Thirty nursing home residents were recruited for this study. Of the thirty residents
recruited, five dropped out prior to initiating the study protocol. Reasons for drop out
included discharge to home (n=l), MD request (n=l), blood draw refusal (n=2), and two
patients did not meet inclusion criteria. The final number of residents included in the
study was 24. Subjects were categorized by MNA score as malnourished (score <17), at
risk for malnutrition (score =17-23.5), and well-nourished (score >23.5). Demographics
for the 24 residents who met inclusion criteria are listed by MNA category in Table 2.
The MNA as a Measure of Nutritional Status
Figure 4-1 shows the nutritional parameters of the MNA. There was no difference
in height among the three groups (data not shown). In Figure 4-1A, BMI was
significantly (p=0.0044) lower in malnourished subjects compared to well-nourished
subjects. Figure 4-1B shows no significance among groups in mid-arm circumference.
Body weight was significantly (p=0.0164) greater in well-nourished residents when
compared to their malnourished counterparts (Figure 4-1C). Mid-calf circumference was
also significantly (p=0.0283) greater in well-nourished versus malnourished residents
Nutritional parameters that are not components of the MNA include BIA, albumin,
hematocrit, and hemoglobin. Figure 4-2 compares measures of the BIA with score
achieved on the MNA. The measures shown versus MNA score are total body water
(Figure 4-2A), phase angle (Figure 4-2B), fat percentage of body weight (Figure 4-2C),
and pounds of body fat (Figure 4-2D). The only significant component of the BIA was
total body water, which was significantly (p=0.0221) lower in the malnourished
compared to both the well-nourished and the at-risk group. There also appeared to be a
trend toward greater pounds of body fat in residents with increased MNA score
(p=0.1049); however, this trend did not reach significance. There was no significant
difference among groups for fat percentage or phase angle.
Figure 4-3 compares serum albumin level and MNA category. There was no
significant difference (p=0.2837) between the groups; however, one of the residents in
the well-nourished category had an unusually low albumin number. One week after
completing the MNA, he was diagnosed with renal insufficiency. This resident refused
nephrology consultation to determine the exact etiology of his renal insufficiency,
therefore his condition during enrollment remains unknown; however, pre-existing
nephrotic syndrome would explain the unexpectedly low albumin level for a patient
classified as otherwise well-nourished. If this resident's data had been excluded, the
results would have almost been significant (p=0.0563). Hemoglobin and hematocrit
levels were not significant among groups in our study (data not shown).
Comparison of the MNA with Immune Parameters
The immune parameters observed in this study were TLC, DTH, lymphocyte and
whole blood proliferation, and neutrophil respiratory burst. Figure 4-4 compares TLC
with MNA. There was no significant difference among the groups.
The number of DTH responders for the well-nourished, at risk, and malnourished
groups were 3 of 4 (75%), 2 of 7 (28.6%), 4 of 13 (30.8%). These results were not
significantly different among groups.
Figure 4-5 compares lymphocyte proliferation to three different mitogens, and the
level of responders for each MNA group. Of the 24 residents included in this study, four
residents are not included in any of the lymphocyte proliferation or responder data. One
resident withdrew from the study prior to the blood draw. Two residents did complete a
blood draw, however, they were excluded due to a different cell separation technique in
the protocol, which we used for these first two residents only. We were unable to collect
lymphocyte proliferation data for another resident because the young control had an
insufficiently low lymphocyte yield for that particular day. Finally, a fifth resident only
had data for PHA mitogen because of complications isolating the lymphocytes, which
resulted in insufficient cells to plate with all three mitogens. Lymphocyte proliferation
data is shown with stimulation with PHA (Figure 4-5A), PW (Figure 4-5B), and ConA
(Figure 4-5C). Figure 4-5D shows the level of response to stimulation compared to the
Lymphocyte proliferation to the three mitogens and responder data were not
significant; however, with PHA stimulation, a major outlier in the at risk group may have
been responsible, as removing this outlier would result in a significant difference between
malnourished and at risk groups as well as at risk and well-nourished groups. If this
subject were omitted the p value would become (p=0.0052). Additionally, the exclusion
of this outlier would result in a significant (p=0.0387) difference between malnourished
and at-risk groups for PW.
Figure 4-6 compares whole blood stimulated with three separate mitogens with
score achieved on the MNA. Figure 4-6A represents whole blood proliferation with
PHA, which was not significant among groups. Whole blood proliferation was found to
be significantly lower in the malnourished subjects with both PW (p=0.031) and Con A
(P=0.017) mitogen compared to the at-risk groups (Figures 4-6B and 4-6C).
Figure 4-7 compares normalized respiratory neutrophil burst with MNA score.
Malnourished subjects were significantly (p=0.017) lower than their well-nourished
Table 4-2:Characteristics of 24 subjects included in the study
Mini Nutrition Assessment Score (median)
<17 (13) 17-23.5 (19) >23.5 (24) p-value
n (%) 13 (54%) 7 (29%) 4 (17%) ns
Median MNA score 24 (24, 25) 19 (17.5, 22) 12.5 (10.3, 14.5)
(25th, 75th percentile)
Age+SEM 79.2+1.8 80.6+2.8 75.3+1.9 ns
Caucasian 5 3 4 ns
African American 8 4 0 ns
M 13 7 3 ns
F 0 0 1 ns
Ulcer Stage 4 (1.5-3) 3 (3-4) 2 (2.5-4) ns
(Median+25, 75 percentile)
Number of Ulcers+SEM 3.3+0.5 2.6+0.8 2.3+0.8 ns
(UJO) aoueJajLunoJio wje-pi~j
S (tUI6y ) wIR
(we) eouGejJWlnojJ! JIez
*4 I 4
4 4 4
b6 J 6
I%- wo 4 0
4 4 -4 f4
V c P
('1 laSt Apo8 legOj.
Figure 4-3. Albumin vs. MNA score
Figure 4-4. Total lymphocyte count vs. MNA score
0 M M M M 0 0 M
%%%% w M M A 0 d
M M M M M M M M I
M M M M M
M M M
M M M
(wdp) Md 41W1
(wdp) VHd 4l!M
esuodseaJ jo l8A-
(wdp) vuoo qMm
2 j 6-
E 5 ----------------
0 >23.5 17-23.5 <17
B O 4
|. o o-----I--^
>23.5 17-23.5 <17
0 5.0- #--
S-6 >23.5 17-23.5 <17
>-2.5- MNA score
Figure 4-6. Whole blood proliferation vs. MNA score. A) Whole blood proliferation
with PHA vs. MNA score. B) Whole blood proliferation with PW vs. MNA
score. C) Whole blood proliferation with ConA vs. MNA score. # p<0.05 vs.
at risk (17-23.5 MNA score)
>23.5 17-23.5 <17
Figure 4-7. Neutrophil burst (normalized) vs. MNA score. p<0.05 vs. well-nourished
(>23.5 MNA score)
The hypothesis of this study was that there would be a relationship between
immune parameters and score achieved on the MNA. Our results did show a significant
decline in some immune parameters with malnutrition, as defined by the MNA. For
instance, malnourished subjects had significantly decreased whole blood proliferation
with Con A (p=0.017) and PW (p=0.031) mitogens compared to subjects who were only
at-risk for malnutrition. Additionally, respiratory neutrophil burst was significantly
(p=0.017) impaired in malnourished subjects when compared to their well-nourished
On the contrary, lymphocyte proliferation data showed no significant difference
between MNA groups, even though we found a significant difference in whole blood
proliferation with MNA score. It is important to note that whole blood proliferation is a
stimulation of lymphocytes within whole blood, which provides an environment that may
more closely mimic in vivo conditions. However, under these conditions, change in
whole blood lymphocyte proliferation with malnutrition cannot be directly attributed to a
change in lymphocyte function. In fact, because there was no effect of malnutrition on
lymphocyte proliferation when lymphocytes were separated from other cell populations
and the subject's serum, it is possible that non-lymphocyte factors were responsible for a
decreased proliferative response in the whole blood sample.
The number ofDTH responders for the well-nourished, at risk, and malnourished
groups were 3 of 4 (75%), 2 of 7 (28.6%), and 4 of 13 (30.8%), respectively. These
results were not significantly different between groups, most likely due to the small
sample size. However, even though these results were not significant, it is still
interesting to note that the malnourished and at risk subjects were only half as likely to
respond to DTH testing than the well-nourished subjects.
The only significant component of the BIA was total body water, which was
(p=0.0221) lower in malnourished subjects compared to both the well-nourished and the
at-risk groups. This may suggest that malnourished patients are slightly dehydrated.
Furthermore, if malnourished persons are dehydrated, this would falsely elevate albumin,
hemoglobin, and hematocrit levels, making them not significantly different from the
well-nourished or at risk patients, as was observed. Of course, another limitation to this
study is that we did not reassess patient hydration status prior to completing BIA.
An assumption of this study was that the MNA is a sensitive indicator of nutritional
status in the elderly as demonstrated through previous trials (14,15). To check that this
assumption was correct, hematocrit, hemoglobin, and albumin were measured in each
subject. In addition, MNA score was compared to nutritional parameters contained
within the MNA. Our results were consistent with previous findings that MNA score is
associated with nutritional parameters contained within the MNA (e.g. BMI, body
weight, and calf circumference). Furthermore, our results confirmed this association in a
pressure ulcer population. This is significant because body weight is a predictor of
mortality in this population (85). However, our results showed there were no significant
differences among MNA groups in hematocrit or hemoglobin even though previous
findings have shown significant associations between these values and MNA score (9).
Furthermore, there were no differences among groups for albumin, which may have been
due in part to the suggested dehydration in malnourished subjects as suggested by total
body water results. Dehydration in the malnourished group may have falsely elevated
albumin levels and erased any significant difference from albumin levels in
More than likely, the observed population was in a state of chronic inflammation
from the presence of pressure ulcers. Previous studies show depressed levels of both
hematocrit and hemoglobin in patients with chronic inflammation (54,86,87). Anemia
from chronic inflammation is characterized by normal iron stores in the
reticuloendothelial system, and is believed to result from the inability to access these
stores (88,89). The overall average hematocrit and hemoglobin levels in our studied
population demonstrate this inflammatory state. The overall average hematocrit value
was 32.1%, which is significantly below the deficient levels of<36% for females and
<41% for males (90). To further demonstrate the level of deficiency in this group, it is
important to note that there was only one female in the observed population.
Hemoglobin was also deficient in this group ( =10.6 g/dL) compared to acceptable levels
in males (>13.5 g/dL) and females (>12 g/dL). It is important to note that hemoglobin
and hematocrit are not measures of nutrition alone. In fact, hemoglobin and hematocrit
levels can be affected by age, exercise, and disease.
In addition to low hematocrit and hemoglobin, the observed population displayed
hypoalbuminemia. This finding was consistent with other studies that observed
depressed albumin levels in seniors with pressure ulcers (53,54). The average albumin
for the entire group was 3.1 g/dL, which is considered mild depletion (90), although
research shows this is a result of decreased hepatic albumin synthesis, and not serum
protein leakage from the wound site (54). Furthermore, C-reactive protein (CRP), a
marker of inflammation, has been indirectly associated with albumin levels (54).
Although we were unable to measure CRP in our study, it may be that CRP levels were
elevated, and the low albumin in our residents may partially be a result of inflammation
from a chronic disease, or, the pressure ulcer itself (18,91). Thus, if the entire observed
population is in an inflammatory state, then albumin, hemoglobin, and hematocrit may
not be good measures of nutritional status.
Nutritional status for all residents was measured in this study using prospective
clarifications of INA questions. The MNA assesses nutritional status within the past
three months. However, not all residents enrolled in this study had been at the Lake City
VA medical center for this amount of time. If the resident's home care had been
assessed, it is likely their MNA score would have been lower because they would not
have been receiving specialized care. Therefore, this was a limitation to the study.
Yet, another limitation of the study was the size of the studied population. Our
sample size was too small to assume Gaussian distribution, and more than likely, a larger
"n" would have shown significance where our study only found trends. Furthermore, out
of 25 seniors examined, only four were considered to be well-nourished, thus creating
unequally sized groups for comparison. In retrospect, the small number of
well-nourished subjects with pressure ulcers should have been expected because poor
nutritional status is a risk factor for pressure ulcer development. Future studies may want
to consider a larger study size. This would more than likely increase significance among
MNA groups, as well as correct for unequally sized groups for comparison.
In conclusion, the results of this study suggest the MNA can be used to determine
level of immune function parameters in elderly nursing home residents with pressure
ulcers. This may be due in part to the interrelationship between nutrition and immunity.
Malnutrition and declining immune function are intertwined, accelerating each
other to a vicious downward spiral that can only be stopped through nutritional
intervention. MNA score is a predictor of nutritional decline in pressure ulcer patients,
and decreased MNA score is associated with increased morbidity and mortality. Since
MNA score is related to decreased immune function, this may partially help explain the
reason decreased MNA score is related to increased morbidity. Because elderly with
pressure ulcers are more likely to be nutritionally deficient, nutritional intervention is
PRESSURE ULCER STAGES
Figure A-1. Pressure ulcer stages. Reprinted with permission from "Pressure Ulcers in
Adults: Prediction and Prevention" Clinical Practice Guideline Number 3,
Description of Stages
* Stage 1: The ulcer appears as a defined area of persistent redness in lightly
pigmented skin, whereas in darker skin tones, the ulcer may appear with persistent
red, blue, or purple hues. Warmth, edema, induration, or hardness may also be
* Stage 2: Partial thickness skin loss involving epidermis, dermis, or both. The ulcer
is superficial and presents clinically as an abrasion, blister, or shallow crater.
* Stage 3: Full thickness skin loss involving damage to or necrosis of subcutaneous
tissue that may extend down to, but not through, underlying fascia. The ulcer
presents clinically as a deep crater with or without undermining of adjacent tissue.
* Stage 4: Full thickness skin loss with extensive destruction, tissue necrosis, or
damage to muscle, bone, or supporting structures (e.g., tendon, joint capsule).
Undermining and sinus tracts also may be associated with Stage 4 pressure ulcer.
MINI NUTRITIONAL ASSESSMENT
Last name: First name: Sex: Date:
Age: Weight, kg: Height, cm: 1.0 Number:
Complete the screen by filling m the boxes with the appropriate numbers.
Add the numbers for the screen. If score is I1 or less, continue with the assessment to gain a Malnutrition Indicator Score.
A Has food intake declined over the past3 months
due to loss of appetite, digestive problems,
chewing or swallowing difficulties?
0 = severe loss of appetite
1 = moderatelossofappette
2 = no loss of appetite
B Weight loss dunng lastmonths
0 = weightlossgreaterthan3kg(6,61bsl
1 = does notknow
2 = weight loss between 1 and 3 kg (2.2 and 6.6 Ibs)
3 = noweightioss
0 = bed or chairbound
1 = ableto get outofbed/chairbutdoes notgo out
2 = goesout E
D Has suffered psychological stress or acute
disease in the past months
0 = yes 2 = no E
E Neuropsychological problems
0 = severe dementia ordepression
1 = milddementia
2 = no psychological problems I
F Body Mass Index (BMI) (weight in kg /(heigntin mP
0 = BMllessthanl9
1 = BMI19tolessthan21
2 = BMI21tolessthan23
3 = BMI23orgreater
Screening score (subtotal max. 14 points
12points orgreater Normal-not atnsk-
no need to complete assessment
11 points or oelow Possible malnutrition- continue assessment
G Lives independentlylnoin a nursing home or hospital)
D = no 1 = ves
H Takes more than 3 prescription crugs per day
0 = yes 1 no
1 Pressure sores or skin ulcers
0 = yes 1 = no
(et ilgaq :pas B c0 o i: 94 ina u tntona Assessmetm cranet: aassessment al olr
115 5q9 h . ....... .. ..... ... ..
ubernloes 'ro auat o t noe s earno jmoeasernai r ren srrmenao ont anr
he MNo *nr Jrirccw lo: s .oo r "lnaislssmnlo ondderogmenl o C Sih nena oornorn
he aNA Ie o el nrolson l s sessmeni A rv searm ai racnl. Ie nr s v wn lrl
1 Gar- PJ and Gu czci lors reistle Nul I on ,Vcr:snap kres h nca & Peaformance Pro
Soceie eaes Proaults Nestle S A. .'evey Switzerlana. Traoemarx Owners
J How many full meals does the patient eat daily?
0 = meal
2 = meals
K Selected consumption markers for protein intake
At least one serving of dairy products
(milk, cheese, yogurt) per day? yes no
Two or more serving of legumes
or eggs per week? yes no -
Meat, fish orpouitryeveryday yes n no
1.0= f3yes e
L Consumestwo or more servings
of fruits or vegetables per day?
0 = no 1 = yes
M How much fluid (water, julce, coffee,tea,mlik...J
is consumed oer day?
05= 3to 5cups
1.0= morethan5cups _. -
0 = unable toeatwithoutassistance
1 =self-fedwithsome difficulty
2 = sef-fed without any problem T
0 Self view of nutritional status
0 = view self as being malnourished
I = is uncertain of nutritional state
2 = views self as having no nutritional problem
P In comparison with other people of the same age,
how do they consider their health status?
Q Mid-arm circumference MAC) in cm
0.0= MAC essthan21
0.5= MAC 21 to22
1.0= MAC22orgreater _._!
R Calf circumference (CCI in cm
0 = CClessthan31 1 = CC 31 orgreater
Assessment max. 16 oints
Total Assessment (max 30 points)
Malnutrition Indicator Score
17 to 23.5 points at nsk of malnutrition
Lessthan 17 points malnourished
THE RUDOLPH J. LIEDTKE (RJL) SYSTEMS ELECTRODE PLACEMENT
ecing electrode Delecdu elert onde
e is Iplme. on d ale is pliredl onl
IIinaiI-ry lue miniihi ian line
crlig the iihinr p Imjisrilwte r e
d II ue omi il le tmaUl mielleaJ "l
eri ide of w istl i bolle onl big loe
ide of tuldel
Red lemls iPh&t hand
aInd on Ihe 1 Siawial eleclnole
I joint of lle is pI)Lq oil Hie
(dle fiiger bIas' o ile epo Ld Lt' e -W RJ_
Figure C-1. The RJL systems electrode placement.
LIST OF REFERENCES
1. Arnaud-Battandier, F., Lauque, S., Paintin, M., Mansourian, R., Vellas, B. J. &
Guigoz, Y. (1999) MNA and nutritional intervention. Nestle Nutr Workshop Ser.
Clin. Perform Programme 1: 131-138.
2. Barone, L., Milosavljevic, M. & Gazibarich, B. (2003) Assessing the older
person: Is the MNA a more appropriate nutritional assessment tool than the SGA?
The Journal of Nutrition, Health, and Aging 7: 13-17.
3. Oster, P., Rost, B. M., Velte, U. & Schlierf, G. (1999) Comparative nutrition
evaluation with the Mini Nutritional Assessment and the Nutritional Risk
Assessment Scale. Nestle Nutr. Workshop Ser. Clin. Perform Programme 1: 35-
4. Company, B., di Castri, A., Plaze, J. M. & Arnaud-Battandier, F. (1999)
Epidemiological study of malnutrition in elderly patients in acute, sub-acute and
long-term care using the MNA. The Journal of Nutrition, Health, and Aging 3:
5. Vellas, B. J., Guigoz, Y., Garry, P. J., Nourhashemi, F., Bennahum, D., Lauque,
S. & Albarede, J. L. (1999) The Mini nutritional Assessment (MNA) and its use
in grading the nutritional state of elderly patients. Nutrition 15: 116-122.
6. Beck, A. M., Ovesen, L. & Osler, M. (1999) The 'Mini Nutritional Assessment'
(MNA) and the 'Determine Your Nutritional Health' Checklist (NSI Checklist) as
predictors of morbidity and mortality in an elderly Danish population. British
Journal of Nutrition 81: 31-36.
7. Trujillo, E. B. (1993) Effects of nutritional status on wound healing. J Vasc. Nurs.
8. Gerber, V., Krieg, M. A., Cornuz, J., Guigoz, Y. & Burckhardt, P. (2003)
Nutritional status using the Mini Nutritional Assessment questionnaire and its
relationship with bone quality in a population of institutionalized elderly women.
The Journal of Nutrition 7: 140-145.
9. Schiffrin, E. J., Guigoz, Y., Perruisseau, G., Blum, S., Delneste, Y., Mansourian,
R., Vellas, B. J. & Blancher, A. (1999) MNA and immunity: Nutritional status
and immunological markers in the elderly. Nestle Nutr. Workshop Ser. Clin.
Perform Programme 1: 23-33.
10. Wouters-Wesseling, W., Rozendaal, M., Snijder, M., Graus, Y., Rimmelzwaan,
G., de Groot, L. & Bindels, J. (2002) Effect of a complete nutritional supplement
on antibody response to Influenza vaccine in elderly people. J. Gerontol. A Biol.
Sci. Med. Sci.57A: M563-M566.
11. Fulop, T., Jr., Wagner, J. R., Khalil, A., Weber, J., Trottier, L. & Payette, H.
(1999) Relationship between the response to influenza vaccination and the
nutritional status in institutionalized elderly subjects. J. Gerontol. A Biol. Sci.
Med. Sci. 54: M59-64.
12. Hall, K., Whiting, S. & Comfort, B. (2000) Low nutrient intake contributes to
adverse clinical outcomes in hospitalized elderly patients. Nutrition Reviews 58:
13. Vellas, B. J., Guigoz, Y., Baumgartner, M., Garry, P. J., Lauque, S. & Albarede,
J. L. (2000) Relationship between nutritional markers and the Mini-Nutritional
Assesssment in 155 older persons. Journal of the American Geriatric Society 48:
14. Guigoz, Y. & Vellas, B. J. (1999) The Mini Nutritional Assessment (MNA) for
grading the nutritional state of elderly patients: Presentation of the MNA, History
and validtion. Nestle Nutr. Workshop Ser. Clin. Perform Programme 1: 3-11.
15. Garry, P. J., Goodwin, J. S., Hunt, W. C., Hooper, E. M. & Leonard, A. G. (1982)
Nutritional status in a healthy elderly population: dietary and supplemental
intakes. American Journal of Clinical Nutrition 36: 319-331.
16. Sullivan, D. H., Patch, G. A., Walls, R. C. & Lipschitz, D. A. (1990) Impact of
nutritional status in a select population of geriatric rehabilitation patients.
American Journal of Clinical Nutrition 51: 749-758.
17. Persson, M. D., Brismar, K. E., Katzarski, K., S., Nordenstrom, J. & Cederholm,
T. E. (2002) Nutritional status using Mini Nutrtional Assessment and Subjective
Global Assessment predict mortality in geriatric patients. Journal of the American
Geriatric Society 50: 1996-2002.
18. Covinsky, K. E., Martin, G. E., Beyth, R. J., Justice, A. C., Sehgal, A. R. &
Landefeld, C. S. (1999) The relationship between clinical assessments of
nutritional status and adverse outcomes in older hospiatlized medical patients.
Journal of the American Geriatric Society 47: 532-538.
19. Donini, L. M., de Felice, M. R., Tassi, L., de Bernardini, L., Pinto, A., Giusti, A.
M. & Cannella, C. (2002) A "proportional and objective score" for the Mini
Nutritional Assessment in long-term geriatric care. The Journal of Nutrition,
Health, and Aging 6: 141-146.
20. Khavinson, V. K. & Solovieva, D. V. (1999) Role of immune status in MNA in
the elderly. In: Institute of Bioregulation and Gerontology, St. Petersburg.
21. Wissing, U., Ek, E. C. & Unosson, M. (2001) A follow-up study of ulcer healing,
nutrition, and life-situation in elderly patients with leg ulcers. The Journal of
Nutrition, Health, and Aging 5: 37-42.
22. Wissing, U. & Unosson, M. (1999) The relationship between nutritional sttus and
physical activity, ulcer history and ulcer -related problems in patients with leg and
foot ulcers. Scand. J. Caring Sci. 13: 123-128.
23. Ikeda, S., Saito, H., Fukatsu, K., Inoue, T., Han, I., Furukawa, S., Matsuda, T. &
Hidemura, A. (2001) Dietary restriction impairs neutrophil exudation by reducing
CD11b/CD18 expression and cytokine production. Arch. Surg. 136: 297-304.
24. Lesourd, B. & Mazari, L. (1999) Nutrition and immunity in the elderly.
Proceedings of the Nutrition Society 58: 685-695.
25. Walrand, S., Moreau, K., Caldefie, F., Tridon, A., Chassagne, J., Portefaix, G.,
Cynober, L., Beaufrere, B., Vasson, M. P. & Boirie, Y. (2001) Specific and
nonspecific immune responses to fasting and refeeding differ in healthy young
adult and elderly persons. American Journal of Clinical Nutrition 74: 670-678.
26. Marcos, A., Nova, E. & Montero, A. (2003) Changes in the immune system are
conditioned by nutrition. European Journal of Clinical Nutrition 57: S66-S69.
27. Chandra, R. (1997) Nutrition and the immune system: an introduction. American
Journal of Clinical Nutrition 66: S460-S463.
28. Allende, Corell, Manzanares, Madruga, Marcos, Madrono, Lopez-Goyanes,
Garcia-Perez, Moreno, Rodrigo, Sanz & Arnaiz-Villena (1998)
Immunodeficiency associated with anorexia nervosa is secondary and improves
after refeeding. Immunology 94: 543-551.
29. Campbell, W. W., Trappe, T. A., Wolfe, R. R. & Evans, W. J. (2001) The
Recommended Dietary Allowance for protein may not be adequate for older
people to maintain skeletal muscle. J. Gerontol. A Biol. Sci. Med. Sci. 56: M373-
30. Pinchcofsky-Devin, G. D. & Kaminski, M. V. (1986) Correlation of pressure
sores on nutritional status. Journal of American Geriatric Society 34: 435-440.
31. Barbul, A., Lazarou, S. A., Efron, D. T., Wasserkrug, H. L. & Efron, G. (1990)
Arginine enhances wound healing and lymphocyte immune responses in humans.
Surgery 108: 331-336.
32. Guigoz, Y., Vellas, B. J. & Garry, P. J. (1996) Assessing the nutritional status of
the elderly: the Mini Nutritional Assessment as part of the geriatric evaluation.
Nutr. Rev. 54: S59-S65.
33. Rubenstein, L. Z., Harker, J. O., Guigoz, Y. & Vellas, B. J. (1999)
Comprehensive Geriatric Assessment (CGA) and the MNA: An overview of
CGA, nutritional assessment, and development of a shortened version of the
MNA. Nestle Nutr. Workshop Ser. Clin. Perform Programme 1: 101-115.
34. Klein, S., Kinney, J., Jeejeebhoy, K., Alpers, D., Hellerstein, M., Murray, M. &
Twomey, P. (1997) Nutrition support in clinical practice: review of published data
and recommendations for future research directions. American Journal of Clinical
Nutrition 66: 683-706.
35. Azad, N., Murphy, J., Amos, S. S. & Toppan, J. (1999) Nutrition survey in an
elderly population following admission to a tertiary care hospital. C.M.A.J. 161:
36. Chandra, R., Imbach, A., Moore, C., Skelton, D. & Woolcott, D. (1991) Nutrition
in the elderly. C.M.A.J. 145: 1475-1487.
37. Dwyer, J. (1991) Screening older American's nutritional health: current practices
and future possibilities. In: NSI, p. 28, Washington.
38. Coulston, A. M., Craig, L. & Coble Voss, A. (1996) Meals-on-wheels applicants
are a population at risk for poor nutritional status. Journal of the American
Dietetic Association 96: 570-573.
39. Posner, B. M., Jette, A. M., Smith, K. W. & Miller, D. R. (1993) Nutrition and
health risks in the elderly: the nutrition screening initiative. Am. J. Public Health
40. Sahyoun, N., Jaques, P. F., Dallal, G. E. & Russell, R. M. (1997) Nutrition
screening initiative checklist may be a better awareness/educational tool than a
screening one. Journal of the American Dietetic Association 97: 760-764.
41. Beck, A. M., Ovesen, L. & Schroll, M. (2001) A six months' prospective follow-
up of 65 + -y-old patients from general practice classified according to nutritional
risk by the Mini Nutritional Assessment. European Journal of Clinical Nutrition
42. Murphy, M. C., Brooks, C. N., News, S. A. & Lumbers, M. L. (2000) The use of
the Mini-Nutritional Assesment (MNA) tool in elderly orthopaedic patients.
European Journal of Clinical Nutrition 54: 555-562.
43. Guigoz, Y., Lauque, S. & Vellas, B. J. (2002) Identifying the elderly at risk for
malnutrition. The Mini Nutritional Assessment. Clin. Geriatr. Med. 18: 737-757.
44. Rubenstein, L. Z., Harker, J. O., Salva, A., Guigoz, Y. & Vellas, B. J. (2001)
Screening for undernutrition in geriatric practice: Developing the Short-Form
Mini-Nutrition Assessment (MNA-SF). J. Gerontol. A Biol. Sci. Med. Sci. 56A:
45. Scheirlinckx, K., Vellas, B. J. & Garry, P. J. (1999) The MNA score in people
who have aged successfully. Nestle Nutr. Workshop Ser. Clin. Perform
Programme 1: 61-65.
46. Deurksen, D. R., Yeo, T. A., Siemens, J. L. & O'Connor, M. P. (2000) The
validity and reproducibility of clinical assessment of nutritional status in the
elderly. Nutrition 16: 740-744.
47. (1991) Nutrition Screening Manual for Professional Caring for Older Adults.
Nutrition Screening Initiative, Washington, D. C.
48. Bleda, M. J., Bolibar, I., Pares, R. & Salva, A. (2002) Reliability of the Mini
Nutritional Assessment (MNA) in institutionalized elderly people. The Journal of
Nutrition 6: 134-137.
49. Havlik, R. J., Liu, B. M., Kovar, M. C., Suzman, R., Feldman, J. J., Harris, T. &
Nostrand, J. V., eds. (1987) Health Statistics on Older Persons, Rockville.
50. Griep, M. I., Mets, T. F., Collys, K., Verte, D., Verleye, G., Ponjaert-
Kristofferson, I. & Massart, D. L. (1999) MNA and odor perception. Nestle Nutr.
Workshop Ser. Clin. Perform Programme 1: 41-59.
51. Shay, K. S. & Ship, J. A. (1995) The importance of oral health in the older
patient. Journal of American Geriatric Society 43: 1414-1428.
52. de Baat, C., Kalk, W. & Schuil, G. R. E. (1993) The effectiveness of oral hygeine
programmes for elderly people. Gerodontology 10: 109-113.
53. Perier, C., Granouillet, R., Chamson, A., Gonthier, R. & Frey, J. (2002)
Nutritional markers, acute phase reactants and tissue inhibitor of matrix
metalloproteinase 1 in elderly patients with pressure sores. Gerontology 48: 298-
54. Fuoco, U., Scivoletto, G., Pace, A., Vona, V. U. & Castellano, V. (1997) Anaemia
and serum protein alteration in patients with pressure ulcers. Spinal Cord 35: 58-
55. Granick, M. S., McGowan, E. & Long, C. D. (1998) Outcome assessment of an
in-hospital cross-functional wound care team. Plastic and Reconstructive Surgery
56. Bergstrom, N., Allman, R. N. & Alvarez, O. (1994) Treatment of pressure ulcers.
In: Agency for healthcare policy and research, Rockville.
57. Lauque, S., Arnaud-Battandier, F., Mansourian, R., Guigoz, Y., Paintin, M.,
Nourhashemi, F. & Vellas, B. J. (2000) Protein-energy oral supplementation in
malnourished nursing-home residents. Age and Ageing 29: 51-56.
58. Barlow, A. P., Zarifa, Z. & Shillito, R. G. (1989) Surgery in a geriatric
population. Ann. R. Coll. Surg. Engl. 71: 110-114.
59. Edwards, A. K., Seymour, D. G., McCarthy, J. M. & Crumplin, M. K. H. (1996)
A 5-year survival study of general surgical patients aged 65 years and over.
Anaesthesia 51: 3-10.
60. Mullen, J. L., Buzby, G. P., Matthews, D. D. & Smale, B. F. (1980) Reduction of
operative morbidity and mortality by combined preoperative and postoperative
nutritional support. Ann. Surg. 192: 604-613.
61. Cohendy, R., Gros, T., Arnaud-Battandier, F., Tran, G., Plaze, J. M. & Eledjam, J.
J. (1999) Preoperative nutritional evaluation of elderly patients: the Mini
Nutritional Assessment as a practical tool. Clin. Nutr. 18: 345-348.
62. Chumlea, W. C., Vellas, B. J. & Guo, S. S. (1998) Malnutrition or healthy
senescence. Proc. Nutr. Soc. 57: 593-598.
63. Chumlea, W. C., Hall, G., Lilly, F., Siervogel, R. M. & Guo, S. S. (1999) The
Mini Nutritional Assessment and body composition in healthy adults. Nestle Nutr.
Workshop Ser. Clin. Perform Programme 1: 13-21.
64. Bauduer, F., Scribans, C., Dubernet, E. & Capdupuy, C. (2003) Evaluation of the
nutritional status of patients over 60-years admitted in a hematology department
using the mininutritional assessment (MNA). A single centre study of 120 cases.
The Journal of Nutrition, Health, and Aging 7: 179-182.
65. Ek, E. C., Unosson, M., Larsson, J., Ganowiak, W. & Bjurulf, P. (1996) Interrater
variability and validity in subjective nutritional assessment of elderly patients.
Scand. J. Caring Sci. 10: 163-168.
66. Langkamp-Henken, B. & Wood, S. M. (1998) Evaluating Immunocompetence.
In: Contemporary Nutrition Support Practice (Matarese, L. E. & Gottschlich, M.
M., eds.), pp. 65-76. W. B. Saunders, Philadelphia.
67. Lewis, R. T. & Klein, H. (1979) Risk factors in postoperative sepsis: significance
of preoperative lymphocytopenia. J. Surg. Res. 26: 365-371.
68. Stephensen, C. B. (2001) Examining the effect of a nutrition intervention on
immune function in healthy humans: What do we mean by immune function and
who is really healthy anyway? American Journal of Clinical Nutrition 74: 565-
69. Shopbell, J. M., Hopkins, B. & Shronts, E. P. (2001) Nutrition Screening and
Assessment. Hunt Publishing Company.
70. Keithley, J. K. (1982) Wound healing in malnourished patients. A.O.R.N. Journal
71. Langkamp-Henken, B., Herrlinger-Garcia, K. A., Stechmiller, J. K., Nickerson-
Troy, J. A., Lewis, B. & Moffatt, L. (2000) Arginine supplementation is well
tolerated but does not enhance mitogen-induced lymphocyte proliferation in
elderly nursing home residents with pressure ulcers. Journal of Parenteral and
Enteral Nutrition 24: 280-287.
72. Murasko, D., Weiner, P. & Kaye, D. (1987) Decline in mitogen induced
proliferation of lymphocytes with increasing age. Clin. Exp. Immunol. 70: 440-
73. Murasko, D., Nelson, B. J., Silver, R., Matour, D. & Kaye, D. (1986)
Immunologic response in an elderly population with a mean age of 85. Am. J.
Med. 81: 612-618.
74. Murasko, D., Weiner, P. & Kaye, D. (1988) Association of lack of mitogen-
induced lymphocyte proliferation with increased mortality in the elderly. Aging:
Immunology and Infectious Disease 1: 1-6.
75. Clark, R. A. & Nauseef, W. M. (1996) Isolation and functional analysis of
neutrophils. In: Current protocols in immunology, pp. 7.23.21-27.23.17. Wiley,
76. Corberand, J., Ngyen, F. & Laharrague, P. (1981) Polymorphonuclear functions
and aging in humans. Journal of American Geriatric Society 29: 391-397.
77. Angelis, P., Scharf, S. & Christophidis, N. (1997) Effects of age on neutrophil
function and its relevance to bacterial infections in the elderly. J. Clin. Lab.
Immunol. 49: 33-40.
78. Christou, N. V., Meakins, J. L., Gordon, J., Yee, J., Hassan-Zahraee, M., Nohr, C.
W., Shizgal, H. M. & MacLean, L. D. (1995) The delayed hypersensitivity
response and host resistance in surgical patients. Annals of Surgery 222: 534-548.
79. Christou, N. V. (1985) Host-defense mechanisms in surgical patients: a
correlative study of the delayed hypersensitivity skin-test response, granulocyte
function and sepsis. The Canadian Journal of Surgery 28: 39-49.
80. Hersh, E. M., Gutterman, J. U. & Mavligit, G. (1973) Host defense, chemical
immunosuppression, and the transplant recipient. Transplant proc. 5: 1191-1195.
81. Castle, S. C. (2000) Clinical relevance of age-related immune function. Clinical
Infectious Diseases 31: 578-585.
82. Burns, E. A. & Goodwin, J. S. (1997) Immunodeficiency of aging. Drugs Ageing
83. Ligthart, G. J., Corberand, J. X. & Fournier, C. (1984) Admission criteria for
immunogerontological studies in man: the SENIEUR protocol. Mech. Ageing
Dev. 28: 47-55.
84. Gazzotti, C., Albert, A., Pepinster, A. & Petermans, J. (2000) Clinical usefulness
of the Mini Nutritional Assessment (MNA) scale in geriatric medicine. The
Journal of Nutrition 4: 176-181.
85. Thomas, P., Hazif-Thomas, C. & Clement, J. P. (2003) Influence of
antidepressant therapies on weight and appetite in the elderly. The Journal of
Nutrition, Health, and Aging 7: 166-170.
86. Hirsch, G. H., Menard, M. R. & Anton, H. A. (1991) Anemia after traumatic
spinal cord injury. Arch. Phys. Med. Rehab. 72: 195-201.
87. Perkash, A. & Brown, M. (1986) Anemia in patients with traumatic spinal cord
injury. J. Am. Parapalegia Soc 9: 10-15.
88. Roberts, F. D., Hagerdon, A. B., Slocumb, C. & Owen, L. A. (1963) Evaluation
of the anemia of rheumatoid arthritis. Blood 21: 470-476.
89. Cartwright, G. E. (1966) The anemia of chronic disorders. Semin. Hematol. 3:
90. Whitney, E. W. & Rolfes, S. R. (1999) Understanding Nutrition, 8 ed.
West.Wadsworth Publishing, Belmont.
91. Hedlund, J. U., Hansson, L. O. & Ortqvist, A. B. (1995) Hypoalbuminemia in
hospitalized patients with community-acquired pneumonia. Arch. Intern. Med.
Jan Hudgens is a native Floridian, and has resided in Gainesville, Florida for most
of her life. Her early interest in science led her to volunteering opportunities in multiple
organizations, including North Central Florida AIDS Network, Shands Teaching hospital,
and numerous nursing homes throughout Gainesville, Florida. At 16 years of age, she
began working with the Florida Institutional Review Board of Gainesville, Florida, until
her admission to college in 1997. Jan attended the University of Florida where she
graduated cum laude in May of 2001 with a B.S. in Food Science and Human Nutrition
and a specialization in Dietetics. She was accepted into the combined Master of
Science/Dietetic Internship program later that year, and was awarded a departmental
teaching assistantship based on her previous academic achievements. While in graduate
school, Jan worked under the supervision of Dr. Bobbi Langkamp-Henken, and assisted
in the orchestration of several human studies. In the future, Jan plans to obtain a
doctorate in Human Anatomy, and teach at the graduate level.