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Biomedical subjects

M Donahoe

Publications and source records attributed to M Donahoe.

16 recordsLinked to original sources
PubMed2000

Analysis of antibody response to Cryptococcus neoformans in five patients with AIDS and cryptococcosis by immunoblotting.

OBJECTIVES: The serological response of five patients with AIDS and cryptococcosis to non capsular antigens from Cryptococcus neoformans var. neoformans has been investigated. METHODS: Pressates of different isolates of C. neoformans were used as antigenic preparation for immunoblotting of patient samples. RESULTS: Multiple sera and cerebrospinal fluids sequentially collected from five AIDS patients with cryptococcosis showed a wide heterogeneity in antibody response with bands at 48. 43, 38 and 26 kD being present in all clinical samples of all five patients. The variation in banding patterns of the sequential samples from three patients was correlated with a decrease of the antigen titre and with an amelioration of the cryptococcal infection. CONCLUSIONS: We identified antibodies to four immunodominant non-capsular antigens, which might represent major target molecules of the humoral response of patients with cryptococcosis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group.

OBJECTIVES: Recent studies in animal models of sepsis-induced acute respiratory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA+GLA), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS. DESIGN: Prospective, multicentered, double-blind, randomized controlled trial. SETTING: Intensive care units of five academic and teaching hospitals in the United States. PATIENTS: We enrolled 146 patients with ARDS (as defined by the American-European Consensus Conference) caused by sepsis/pneumonia, trauma, or aspiration injury in the study. INTERVENTIONS: Patients meeting entry criteria were randomized and continuously tube-fed either EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 75% of basal energy expenditure x 1.3 for at least 4-7 days. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases were measured, and ventilator settings were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a measure of gas exchange. Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points. Clinical outcomes were recorded. Baseline characteristics of 98 evaluable patients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavages revealed significant decreases (approximately 2.5-fold) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet. Significant improvements in oxygenation (PaO2/FIO2) from baseline to study days 4 and 7 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients fed EPA+GLA compared with controls. Patients fed EPA+GLA required significantly fewer days of ventilatory support (11 vs. 16.3 days; p = .011), and had a decreased length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with controls. Only four of 51 (8%) patients fed EPA+GLA vs. 13 of 47 (28%) control patients developed a new organ failure during the study (p = .015). CONCLUSIONS: The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment, gas exchange, requirement for mechanical ventilation, length of intensive care unit stay, and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS.

Antioxidants↗
PubMed1998

Nutritional aspects of lung disease.

The relationships between dietary intake, ventilatory demand, and respiratory muscle function are now well recognized. Malnutrition in patients with advanced COPD is associated with adverse effects on respiratory muscle function leading to reduced muscle strength and premature mortality. The relationships between nutrient intake and the host inflammatory response are just beginning to be explored. This article summarizes current knowledge regarding the relationship between nutritional status and the lung.

Humans↗
PubMed1997

Nutritional support in advanced lung disease. The pulmonary cachexia syndrome.

Patients with advanced lung disease (ALD) demonstrate changes in body composition characteristically manifested by a progressive loss of body weight. The mechanisms of this pulmonary cachexia syndrome are multifactorial, and treatment must be comprehensive in nature. This article addresses our current knowledge regarding the relationship between nutrition and ALD.

Cachexia↗
PubMed1996

Elevated TNF-alpha production by peripheral blood monocytes of weight-losing COPD patients.

The inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta), have been associated with accelerated metabolism and protein turnover following exogenous administration in normal humans. We hypothesized that these inflammatory cytokines might contribute to the weight-losing process in patients with chronic obstructive pulmonary disease (COPD). COPD patients were identified prospectively as "weight losers" (WL; n = 10) if they reported > 5% weight loss during the preceding year or as "weight stable" (WS; n = 10) if their body weight fluctuated < or = 5%. Age-matched healthy volunteers were selected as the control group (C; n = 13). Monocytes were isolated from a peripheral blood sample, cultured, and exposed to lipopolysaccharide (LPS). The concentration of TNF-alpha and IL-1 beta in the monocyte supernatant was measured using a four layer enhanced ELISA. No significant difference in LPS-stimulated IL-1 beta production was found in the three study populations. However, LPS-stimulated TNF-alpha production (mean [range] ng/ml) by monocytes was significantly higher in the WL COPD patients (20.2 [6.3 to 44.8]), compared with WS patients (6.9 [1.5 to 16.6]), and C subjects (5.7 [0 to 61.8]). This difference was not maintained at 6 mo follow-up in the absence of ongoing weight loss. Definition of a causal relationship between TNF-alpha production and weight loss will require further understanding of the relationship between energy metabolism and TNF-alpha production in these patients.

Aged↗
PubMed1993

Indirect calorimetry with a hood: flow requirements, accuracy, and minute ventilation measurement.

Flow-dilution-based hood systems for indirect calorimetry eliminate the conventional mouthpiece or mask of sealed-circuit systems allow measurements with improved patient comfort. This feature is particularly relevant when measurements are made over long periods of time or are repeated often. The flow of air pulled through the hood into the calorimeter in these systems is necessary to clear CO2 from inside the hood. The errors in these systems are greater than those in the sealed-circuit systems and are proportional to the flow. We show that the CO2 concentration within the hood at steady state does not depend on hood size. We describe the accuracy in determination of O2 consumption (VO2), CO2 production, and respiratory exchange ratio with a hood system as a function of the accuracy of the O2 and CO2 analyzers and the water vapor in collected gas. For example, we show that if there is a 1% error in O2 concentration, the percent error in VO2 changes from 5% in a sealed circuit to 51% when a cleansing flow of 50 l/min is introduced. The error in VO2 caused by a 5% error in CO2 determination is 10.6% at this cleansing flow. Removal of 90% of the water vapor (instead of 100%) before analysis of the expired gas introduces a 15.8% error in VO2. By use of the equations described, the accuracy of any measurement system can be determined. In addition, we demonstrate that the measurement of ventilation, usually lost in a hood system, can be preserved using dual pneumotachographs and a sealed hood.

Air Movements↗
PubMed1993

Mechanisms of weight loss in chronic obstructive pulmonary disease.

The COPD patient population is susceptible to the onset of weight loss. The presence of this feature carries significant negative prognostic implications. Whether weight loss contributes to or is simply a marker of disease severity remains to be determined. Weight loss appears to result from an imbalance of metabolic demand and supply. The factors which produce this imbalance require further investigation.

Energy Intake↗
PubMed1992

Effects of growth hormone on diaphragmatic recovery from malnutrition.

A 25% weight loss was induced in adult Fisher 344 rats by nutritional deprivation. Subsequently, normal feeding was resumed. Refed animals were divided into three groups and received recombinant human growth hormone (rhGH) injections during 5 wk of refeeding, saline injections during 5 wk of refeeding, or 9 wk of refeeding without injections. The effects of nutritional deprivation and the various refeeding protocols on the cross-sectional areas (CSA) of each of the four types of myofibers [typed immunohistochemically with antibodies against four myosin heavy chain (MHC) isoforms known to be present in the rat diaphragm] were determined. Malnutrition decreased the CSA of myofibers containing MHC2X, MHC2B, and MHC2A (i.e., fast myofibers), with the greatest effect on muscle mass being due to the atrophy of fibers containing MHC2X. Fibers containing MHC beta/slow failed to undergo malnutrition-induced atrophy. Whereas refeeding for 5 wk in the absence of rhGH allowed the recovery of CSA of fibers containing MHC2A, fibers containing MHC2B and MHC2X remained smaller than fibers of similar type in control animals. In contrast, 5 wk of refeeding supplemented with rhGH returned all fiber CSAs to control values. Even when refeeding alone was extended to 9 wk to allow for weight stabilization, the CSA of the fibers containing MHC2B and MHC2X remained smaller than similar fibers in control muscle. Serum insulin-like growth factor, a marker of malnutrition (R. Reeves and J. Elders, J. Nutr. 109: 613-620, 1979), was significantly decreased after nutritional deprivation and returned to normal after 5 wk of refeeding and GH supplementation.

Animals↗
PubMed1992

Is loss of body weight in chronic obstructive pulmonary disease patients with emphysema secondary to low tissue oxygenation?

The available clinical information to date does not support the hypothesis that tissue oxygen debt is the primary cause of the wasting process in the chronic obstructive pulmonary disease (COPD) patient population. However, this should not deter the 'believers' of the hypothesis from further investigation. The information outlined above supports the need for reconsideration of this clinical problem. Tissue oxygen requirements and utilization is a complex interplay of multiple variables. Likewise, the assessment of nutritional status in the setting of oxygen therapy is complicated by shifts in body fluid compartments independent of changes in the fat-free mass (FFM). Utilization of newer techniques will be required to resolve the contribution of low tissue oxygenation to the wasting process. The continued development of noninvasive methods for the assessment of tissue metabolism, cardiac function, and tissue energy requirements will allow investigators to further clarify the relationship between tissue oxygenation and metabolism in patients with COPD. Clinical trials designed to examine this issue must recognize the multiple effects of oxygen on all aspects of nutrient utilization, including caloric intake, needs, and tissue delivery. Failure to address all aspects of this system will lead to continued debate regarding the etiology of weight loss in the COPD patient population.

Clinical Trials as Topic↗
PubMed1992

Physiologic effects of oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease. A randomized control study.

The association between severe nutritional depletion and chronic obstructive pulmonary disease (COPD) has long been recognized. A potential therapeutic benefit to nutritional support was previously suggested by us in a pilot investigation. Subsequent studies have reported conflicting results regarding the role of nutritional therapy in this clinical population. We report a randomized controlled study of nutritional therapy in underweight patients with COPD that combines an initial inpatient investigation (controlled nutritional support) with a prolonged outpatient follow-up interval. Provision of adequate calorie and protein support, adjusted to metabolic requirements, resulted in weight gain (intervention = +2.4 kg versus control -0.5 kg), improved handgrip strength (intervention = +5.5 kg-force versus control -6.0 kg-force), expiratory muscle strength (intervention = +14.9 cm H2O versus control -9.2 cm H2O), and walking distance (intervention = +429 feet versus control -1.0 foot). Inspiratory muscle strength was also improved (intervention = +11.4 cm H2O versus control +4.8 cm H2O) although this did not quite reach statistical significance. We conclude that provision of adequate nutrient supply under controlled conditions results in significant clinical improvements in the COPD patient population. However, the intervention is costly, time-intensive, and of limited therapeutic magnitude. More detailed work of alternative outpatient strategies combined with additional rehabilitative measures is indicated to delineate the full therapeutic potential of nutritional support for this clinical population.

Basal Metabolism↗
PubMed1990

Nutritional assessment and support in chronic obstructive pulmonary disease.

Malnourished COPD patients demonstrate energy requirements significantly above predicted needs especially during activity. Recognition of this altered metabolic state is essential to the design of any nutritional intervention program. This factor alone, however, cannot explain the wasting syndrome observed in these patients. The elevated demands appear to combine with recognized factors which act to limit caloric intake. Nutritional repletion with calorie and protein supply proportional to demand is associated with weight gain, nitrogen retention, and improvement in physiologic parameters of muscle strength. Greater success of outpatient nutritional repletion in this population is dependent on alternative feeding strategies to deal with those symptoms which limit caloric intake, especially during a disease exacerbation. Future clinical research must explore these strategies before an adequate assessment of the risk and cost-benefit ratio of nutritional intervention can be determined. Additional work is indicated in techniques to identify those patients who would benefit from calorie supplementation as well as techniques to monitor the response of these individuals. Information gathered from the continued study of this population of stable outpatients with COPD will have wide application to the entire COPD patient population. This includes those patients with respiratory failure on mechanical ventilation, where numerous complicating factors makes the study of nutritional intervention and respiratory muscle function difficult.

Body Constitution↗
PubMed1989

Oxygen consumption of the respiratory muscles in normal and in malnourished patients with chronic obstructive pulmonary disease.

Patients with severe chronic obstructive pulmonary disease (COPD) commonly experience weight loss. An increased energy expenditure for respiration might explain the increased caloric requirements and weight loss seen in this patient population. We measured the oxygen cost of augmenting ventilation (O2 cost) using an open circuit technique with dead-space stimulation of ventilation in nine normally nourished (greater than 90% ideal body weight) and in 10 malnourished (less than 90% ideal body weight) patients with COPD as well as in seven normal control subjects. O2 cost was significantly elevated in the malnourished patients with COPD (4.28 +/- 0.98 ml O2/L ventilation) relative to the normally nourished group (2.61 +/- 1.07) and the normal control subjects (1.23 +/- 0.51) (p less than 0.001). The measured resting energy expenditure (REEmeas) was also increased compared with predicted values (REEpred) in the malnourished population (REEmeas/REEpred = 94.57 +/- 6.21% for control subjects, 105.5 +/- 19.66% for normally nourished patients with COPD, and 119.4 +/- 11.69% for malnourished patients with COPD) (p less than 0.005). The malnourished population was characterized by a greater degree of hyperinflation (RV/TLC = 0.55 +/- 0.09 for normally nourished versus 0.69 +/- 0.06 for malnourished patients) and inspiratory muscle weakness (PImax = 51 +/- 16.5 for the normally nourished and 34 +/- 12.2 for the malnourished population). We conclude that malnourished patients with COPD are characterized by a relative increase in resting energy requirements and, specifically, increased energy requirements for augmenting ventilation. This increase in energy requirements may result from the increased mechanical work load associated with severe COPD and/or a reduced ventilatory muscle efficiency.

Aged↗
PubMedDate not supplied

Metabolic rate and weight loss in chronic obstructive lung disease.

Although weight loss is a common problem in chronic obstructive pulmonary disease (COPD), the precise cause of malnutrition in COPD patients is not known. The purpose of this study was to measure and compare resting energy expenditure (REE) in stable undernourished and adequately nourished COPD. REE was measured in normal, adequately nourished, and undernourished COPD patients by indirect calorimetry and then compared to predicted basal metabolic rate (BMR) calculated from the Harris-Benedict equation. We found that measured REE, compared to predicted, was significantly higher in the undernourished group, (1.15 +/- 0.02) and compared to the adequately nourished COPD (0.99 +/- 0.03) and normal groups (0.93 +/- 0.02) (p less than 0.0001). We conclude that there is a hypermetabolic state in stable malnourished COPD patients which may be a factor in weight loss. This elevated REE also needs to be taken into account when determining caloric requirements for COPD patients.

Adult↗
PubMedDate not supplied

Use of beta-human chorionic gonadotropin in gestational aging.

Quantitative radioimmunoassay (RIA) of the beta chain of human chorionic gonadotropin (B-hCG) in serum has been used to evaluate the gestational status of 99 normal early pregnancies in contrast to 29 ectopic, threatened, aborted and/or terminated cases. Quantitative measurement of serum B-hCG-RIA standardized against the second international standard (2dIS) accurately established age of normal pregnancies in utero up to but not after three weeks postconception and with an accuracy of plus or minus four days between the third and eighth week of gestation. Quantitative urinary hCG-RIA standardized against the 2dIS were not useful for gestational aging. Useful serum hCG-RIA were identically linear and parallel with the 2dIS, had negligible crossreactivity with LH, FSH and/or TSH, and had low nonspecific binding. Of 13 hCG-RIA evaluated, only assays having these latter characteristics were able to detect ectopic pregnancies, spontaneous abortions, and/or threatened pregnancies with up to 90 percent accuracy. However, some assays not standardized to the 2dIS gave over 200 percent error in hCG serum values. Thus, correct choice of quantitative B-hCG reagents is necessary for early pregnancy assessment.

Abortion, Incomplete↗