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Biomedical subjects

S Klein

Publications and source records attributed to S Klein.

At least 145 records · Page 8Linked to original sources
PubMed1997

Lipolytic sensitivity to catecholamines in patients with human immunodeficiency virus infection.

Lipolysis is higher in patients with acquired immunodeficiency syndrome (AIDS) than in healthy control subjects. To evaluate whether this increase in lipolysis is related to increased beta-adrenergic sensitivity, we compared the lipolytic response to epinephrine (approximately 15 ng x kg(-1) x min(-1)) of six AIDS patients with that of six matched control subjects. Lipolysis was measured by infusion of [2H2]glycerol and [2H2]palmitate. The baseline rates of appearance of palmitate (2.06 +/- 0.21 compared with 1.45 +/- 0.07 micromol x kg(-1) x min(-1)) and glycerol (2.35 +/- 0.16 compared with 1.35 +/- 0.06 micromol x kg(-1) x min(-1)) were higher in AIDS patients (P < 0.05). The absolute increase in lipolysis, an indicator of the responsiveness to epinephrine, was not different between groups for the rate of appearance of palmitate (86 +/- 14 compared with 75 +/- 7 micromol x L(-1) x min(-1)) or glycerol (79 +/- 13 compared with 59 +/- 6 micromol x L(-1) x min(-1)). Plasma concentrations of epinephrine were not different between groups. Lipolysis was higher whereas the lipolytic response to epinephrine was normal in AIDS patients. Increased lipolytic sensitivity to catecholamines is not the cause of increased lipolysis in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Nutrition support in clinical practice: review of published data and recommendations for future research directions. Summary of a conference sponsored by the National Institutes of Health, American Society for Parenteral and Enteral Nutrition, and American Society for Clinical Nutrition.

In the last 30 years, marked advances in enteral feeding techniques, venous access, and enteral and parenteral nutrient formulations have made it possible to provide nutrition support to almost all patients. Despite the abundant medical literature and widespread use of nutritional therapy, many areas of nutrition support remain controversial. Therefore, the leadership at the National Institutes of Health, The American Society for Parenteral and Enteral Nutrition, and The American Society for Clinical Nutrition convened an advisory committee to perform a critical review of the current medical literature evaluating the clinical use of nutrition support; the goal was to assess our current body of knowledge and to identify the issues that deserve further investigation. The panel was divided into five groups to evaluate the following areas: nutrition assessment, nutrition support in patients with gastrointestinal diseases, nutrition support in wasting diseases, nutrition support in critically ill patients, and perioperative nutrition support. The findings from each group are summarized in this report. This document is not meant to establish practice guidelines for nutrition support. The use of nutritional therapy requires a careful integration of data from pertinent clinical trials, clinical expertise in the illness or injury being treated, clinical expertise in nutritional therapy, and input from the patient and his/her family. (Journal of Parenteral and Enteral Nutrition 21:133-156, 1997).

Cachexia↗
PubMed1997

Evaluation of protection by two endotoxin-neutralizing IgM monoclonal antibodies in different peritonitis models.

Two anti-core glycolipid (CGL) IgM monoclonal antibodies (mAbs 8-2 and 26-20), previously shown to display cross-reactivity with heterologous lipopolysaccharide (LPS) in vitro and to provide cross-protectivity against endotoxin challenge in vivo, were evaluated for their potential to protect mice against death from peritonitis caused by heterologous bacterial challenge. Without concurrent antibiotic treatment neither antibody was protective. Compared with a control mAb, prophylactic treatment with mAb 8-2 significantly increased the survival of gentamicin-treated mice challenged with the rough strain Salmonella minnesota Re595. Both mAb 8-2 and a control mAb, in combination with a suboptimal dose of ceftazidime, increased survival following challenge with the clinical isolate Escherichia coli O7:K1. In a model of mucin-enhanced peritonitis, neither mAb was protective against challenge with inocula of E. coli O7:K1, ranging from 10(2) to 10(4) bacteria. We conclude that protection of mice by anti-CGL mAb 8-2 against heterologous challenge is vitally dependent on concurrent treatment with antibiotics and that protection may not be attributable to the anti-CGL specificity of these antibodies.

Animals↗
PubMed1997

Regulation of plasma fatty acid oxidation during low- and high-intensity exercise.

In the present study we examined the hypothesis that fatty acid oxidation is less during high-intensity exercise than during moderate-intensity exercise because of inhibition of long-chain fatty acid entry into the mitochondria. Six volunteers exercised at 40% peak oxygen consumption (VO2peak) for 60 min and at 80% VO2peak for 30 min on two different occasions. [1-13C]oleate, a long-chain fatty acid, and [1-14C]octanoate, a medium-chain fatty acid, were infused for the duration of the studies. Lipids and heparin were infused during exercise at 80% VO2peak to prevent the expected decrease in plasma free fatty acid (FFA) concentration. Plasma oleate and total FFA availability were similar in the two experiments. Oleate oxidation decreased from 2.8 +/- 0.6 (40% VO2peak) to 1.8 +/- 0.2 mumol.kg-1.min-1 (80% VO2peak, P < 0.05), whereas octanoate oxidation increased from 1.0e-05 +/- 1.0e-06 (40% VO2peak) to 1.3e-05 +/- 5.1e-06 mumol.kg-1.min-1 (80% VO2peak, P < 0.05). Furthermore, the percentage of oleate uptake oxidized decreased from 67.7 +/- 2.8% (40% VO2peak) to 51.8 +/- 4.6% (80% VO2peak, P < 0.05), whereas the percentage of octanoate oxidized was similar during exercise at 40 and 80% VO2peak (84.8 +/- 2.7 vs. 89.3 +/- 2.7%, respectively). Our data suggest that, in addition to suboptimal FFA availability, fatty acid oxidation is likely limited during high-intensity exercise because of direct inhibition of long-chain fatty acid entry into mitochondria.

Adult↗
PubMed1997

An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein.

Six normal untrained men were studied during the intravenous infusion of a balanced amino acid mixture (approximately 0.15 g.kg-1.h-1 for 3 h) at rest and after a leg resistance exercise routine to test the influence of exercise on the regulation of muscle protein kinetics by hyperaminoacidemia. Leg muscle protein kinetics and transport of selected amino acids (alanine, phenylalanine, leucine, and lysine) were isotopically determined using a model based on arteriovenous blood samples and muscle biopsy. The intravenous amino acid infusion resulted in comparable increases in arterial amino acid concentrations at rest and after exercise, whereas leg blood flow was 64 +/- 5% greater after exercise than at rest. During hyperaminoacidemia, the increases in amino acid transport above basal were 30-100% greater after exercise than at rest. Increases in muscle protein synthesis were also greater after exercise than at rest (291 +/- 42% vs. 141 +/- 45%). Muscle protein breakdown was not significantly affected by hyperminoacidemia either at rest or after exercise. We conclude that the stimulatory effect of exogenous amino acids on muscle protein synthesis is enhanced by prior exercise, perhaps in part because of enhanced blood flow. Our results imply that protein intake immediately after exercise may be more anabolic than when ingested at some later time.

Adult↗
PubMed1997

Whole body leptin kinetics and renal metabolism in vivo.

Leptin metabolism was investigated in male Sprague-Dawley rats by use of 125I-labeled leptin plasma kinetic and arteriovenous balance studies. When conscious rats received bolus venous injections of 125I-leptin, intact (precipitable) leptin quickly disappeared from circulation in a biexponential manner during the 2-h experimental period. After substantial delay, most of the injected radioactivity appeared in the urine. The data were described by a two-compartment model, which postulated that plasma leptin exchanged with a nonplasma pool and that all of the tracer cleared from plasma appeared in urine or in a degraded form in plasma. The half-life of leptin was 9.4 +/- 3.0 min, and the leptin production rate was 3.6 +/- 1.2 ng 100 g fat-1.min-1. The left kidney extracted 21 +/- 1.5% of intact arterial 125I-leptin 5 min after femoral venous injection. Endogenous arterial leptin was reduced 21 +/- 8 and 18 +/- 12%, respectively, in simultaneously sampled left and right renal veins. Renal elimination appears to be the major elimination mechanism for leptin in normal rats, and the kinetic studies suggest that uptake of leptin by renal tissue rather than glomerular filtration is the predominant elimination mechanism.

Adipose Tissue↗
PubMed1997

Effects of in vivo culture of murine mammary adenocarcinoma cells on tumor and metastatic growth.

We studied the effect of tumoral microenvironments on metastatic phenotypes. Therefore, murine mammary adenocarcinoma cells cultured in vivo in diffusion chambers (DC) were implanted intraperitoneally in BALB/c mice. The behavior of DC-cultured cells was compared with that of cells obtained from tumors growing subcutaneously or intraperitoneally and from primary cultures in vitro of the former. DC-cultured and control cells were inoculated into normal mice to evaluate their tumorigenicity and metastasizing ability. We found that DC-cultured cells were less tumorigenic and metastatic both in spontaneous and in experimental metastasis assays. The host response to tumor progression resulted in an early leukocytosis, probably due to the overproduction of a hematopoietic factor by the tumor cells. Finally, it was found that DC-cultured cells produced lower levels of urokinase-type plasminogen activator activity, while no differences were found in the metalloproteinase production compared to cells obtained from a tumor growing subcutaneously.

Adenocarcinoma↗
PubMed1997

Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo.

We measured arterio-venous differences in concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) across a sc adipose tissue bed in the postabsorptive state in 39 subjects [22 women and 17 men; median age, 36 yr (interquartile range, 26-48 yr); body mass index, 31.8 kg/m2 (range, 22.3- 38.7 kg/m2); percent body fat, 28.7% (range, 17.6-50.7%)]. A subgroup of 8 subjects had arteriovenous differences measured across forearm muscle. Thirty subjects were studied from late morning to early evening; 19 ate a high carbohydrate meal around 1300 h, and 11 continued to fast. We found a greater than 2-fold increase in IL-6 concentrations across the adipose tissue bed [arterial, 2.27 pg/mL (range, 1.42-3.53 pg/mL); venous, 6.71 pg/mL (range, 3.36-9.62 pg/mL); P < 0.001], but not across forearm muscle. Arterial plasma concentrations of IL-6 correlated significantly with body mass index (Spearman's r = 0.48; P < 0.01) and percent body fat (Spearman's r = 0.49; P < 0.01). Subcutaneous adipose tissue IL-6 production increased by the early evening (1800-1900 h) in both subjects who had extended their fasting and those who had eaten. Neither deep forearm nor sc adipose tissue consistently released TNF alpha [across adipose tissue: arterial, 1.83 pg/mL (range, 1.36-2.34 pg/mL); venous, 1.85 pg/mL (range, 1.44-2.53 pg/mL); P = NS: across forearm muscle: arterial, 1.22 pg/mL (range, 0.74-2.76 pg/mL); venous, 0.99 pg/mL (range, 0.69-1.70 pg/mL); P = NS]. Although both IL-6 and TNF alpha are expressed by adipose tissue, our results show that there are important differences in their systemic release. TNF alpha is not released by this sc depot. In contrast, IL-6 is released from the depot and is thereby able to signal systemically.

Abdomen↗
PubMed1997

Increased plasma leptin concentration in end-stage renal disease.

Leptin is a 16-kDa protein recently identified as the obese gene product involved in body weight regulation. Administration of recombinant leptin to ob/ob mice, which have a genetic defect in leptin production, reduces food intake and increases energy expenditure. Leptin is synthesized by fat cells, and in normal humans, plasma concentrations are proportional to adiposity. The physiological actions and the degradation pathways of leptin in humans are unknown. We investigated renal elimination of leptin by comparing plasma leptin concentrations in end-stage renal disease (ESRD) patients with normal controls. Our hypothesis was that if renal filtration is a significant route of elimination, the hormone would accumulate in ESRD patients. Mean plasma levels in 141 ESRD patients (26.8 +/- 5.7 and 38.3 +/- 5.6 micrograms/L for males and females, respectively) were significantly higher (P < 0.001) than mean values obtained in normal controls (11.9 +/- 3.1 and 21.2 +/- 3.0 micrograms/L for males and females, respectively). Leptin concentrations in ESRD patients correlated directly with body mass index (BMI; r = 0.77 for men and 0.78 for women). The rate of increase in leptin concentrations with BMI was significantly greater in ESRD patients (5.5 and 6.6 micrograms/L/U BMI for men and women, respectively) than in normal controls (1.4 and 2.6 micrograms/L/U for men and women, respectively). Pre- and postdialysis leptin levels in hemodialysis patients were similar. Western blot of plasma from ESRD patients with high leptin levels showed bands corresponding to the intact protein (16 kDa) with no lesser or greater molecular mass species observed. Leptin concentrations in patients with ESRD did not correlate with measures of residual renal function (serum creatinine, beta 2-microglobulin, PTH, or GH levels). Similarly, we found no correlation between leptin levels and the number of years patients had been on dialysis or with recent weight changes. We conclude that intact leptin is increased in ESRD patients, but does not appear to cause decreased weight. As leptin levels did not correlate with residual renal function, increased production may account for the high levels observed.

Adult↗
PubMed1997

Leptin production during moderate-intensity aerobic exercise.

Leptin, the protein product of the ob gene, may be involved in the regulation of energy balance. Although a clear relationship between energy intake and plasma leptin concentrations has been demonstrated in humans, little is known about the effect of exercise on leptin metabolism. In the present study, we evaluated abdominal adipose tissue leptin production in vivo by arteriovenous balance at rest and during 60 min of moderate-intensity cycle ergometer exercise (50% of maximal heart rate) in five sedentary male subjects (mean age 38.4 +/- 1.7 yr, body mass index (28.4 +/- 4.2 kg/m2). Blood samples were taken simultaneously from an abdominal vein, draining sc adipose tissue, and a radial artery, at rest and every 10 min during exercise. Adipose tissue blood flow was determined by the xenon washout technique. Plasma leptin concentrations did not change throughout exercise and were the same as the values obtained during resting conditions. Average net adipose tissue leptin production rates during exercise (3.07 +/- 0.89 ng/100 g-1.min-1) also were similar to resting values (3.86 +/- 0.95 ng/100 g-1.min-1). These results demonstrate that plasma leptin concentrations and leptin production do not change during an acute bout of moderate-intensity aerobic exercise.

Adipose Tissue↗
PubMed1997

Endograft repair of an aortic pseudoaneurysm following gunshot wound injury: impact of imaging on diagnosis and planning of intervention.

PURPOSE: To describe the endovascular treatment of a gunshot injury to the visceral aorta and the role of various imaging modalities in the staging and planning of the endograft procedure. METHODS AND RESULTS: The bullet entered the aorta posteriorly beneath the origin of the superior mesenteric artery and traversed the wall in a tangential manner entering the lumen proximal to the renal arteries. Intravascular ultrasound (IVUS) imaging and spiral computed tomography (CT) identified the injury that the initial angiograms failed to demonstrate. Combined use of IVUS and CT imaging enabled observation of the evolution of a pseudoaneurysm until an interval when endograft exclusion was possible. A stent-graft was customized based on precise IVUS and CT dimensional data and implanted successfully through an arteriotomy in the common femoral artery 3 weeks after the initial injury. Three-month follow-up imaging demonstrated continued exclusion of the pseudoaneurysm, and the patient remains well at 16 months. CONCLUSIONS: IVUS and spiral CT scans were instrumental in identifying an arteriographically undetected aortic injury. The combined imaging modalities also helped determine the timing for the endovascular procedure and provided the precise measurements for device fabrication and deployment.

Adult↗
PubMed1997

Detection of axillary lymph node metastasis of breast carcinoma with technetium-99m sestamibi scintimammography.

Several investigators have advocated management of breast cancer patients without axillary dissection, obviating the morbidity associated with this procedure. Approximately 30-40 per cent of all patients with breast carcinoma will have lymph node metastasis. Axillary dissection offers no therapeutic benefit to node-negative patients, and it may lead to unnecessary morbidity. It is apparent that a noninvasive test to determine the presence of axillary metastases may obviate the need for axillary dissection. The aim of this study was to determine the role of scintimammography (SMM) with technetium-99m sestamibi in the detection of axillary node metastasis in breast carcinoma. Thirty-one women with the diagnosis of breast carcinoma who had SMM and axillary lymphadenectomy were included. SMM was done following an intravenous injection of 20 mCi of Tc-99m sestamibi. Planar scintigraphic imaging was acquired in a lateral prone and an anterior view of the breasts for the evaluation of the axilla. SMM scans were interpreted by two nuclear medicine physicians blinded to the clinical presentation and histologic results. The correlation of SMM with histologic assessment showed a sensitivity of 75 per cent, specificity of 82 per cent, positive predictive value of 88 per cent, and negative predictive value of 64 per cent. The interobserver correlation of SMM interpretation between the two nuclear medicine physicians showed good agreement, with kappa = 0.49. Consistency in the interpretation of Tc-99m SMM was obtained when two independent radiologists reviewed the studies. Based on these data, we are unable to show that SMM is a reliable test for the detection of axillary metastases in patients with breast cancer. However, a high positive value of 88 per cent is encouraging and deserves further study.

Adult↗
PubMed1997

The role of barium enema in colostomy closure in trauma patients.

Recently, the routine use of barium enema preceding colostomy closure in trauma patients has been challenged. It has been argued that the nature of the injury should be apparent from the initial laparotomy and that the likelihood of finding an unsuspected colonic lesion in the young, previously healthy patients who constitute the majority of trauma patients is very small. We retrospectively reviewed 124 consecutive cases of patients who received colostomy takedowns for trauma. One hundred six of the patients had preoperative barium enema evaluation. 87.1 per cent of the examinations were negative, with a subsequent stoma closure complication rate of 20.4 per cent. Of the 13 positive barium enemas, 9 were falsely positive. These patients had a higher stoma closure complication rate of 39 per cent, a fact that could not be explained on the basis of their abnormal studies. The 18 patients who did not have barium enema performed did not have an increase in complications (17.6%). Barium enema failed to uncover unsuspected pertinent diagnoses, often added unnecessary delays and expense, and in no case changed the operative management. Contrast studies were found to be useful in defining anatomy in cases of known fistulas and when the takedowns were performed without the benefit of operative reports from the previous surgery.

Adolescent↗
PubMed1997

Analysis of multichannel patch clamp recordings by hidden Markov models.

Conventional methods of analysis do not allow the kinetics of patch clamped ion channels to be completely determined if more than one channel is present in the patch. This hinders investigations on small ion channels as well as on channel cooperativity and the homogeneity of channel populations. We present a method to extract the rate constants and current amplitudes for each individual channel from multichannel patches by a one-step procedure. For this purpose, the current record is modeled by the superposed Markov processes of the opening and closing of each channel that is contaminated by noise (Hidden Markov Model). Channel parameters are obtained by maximum likelihood methods. Because the parameters can be calculated directly from the unfiltered record, the dwell time and missed event problems are widely diminished. Confidence bounds for the estimated parameters are given. Statistical tests to decide whether channels switch identically and/or independently are introduced. The application of the method is demonstrated with simulated data.

Biometry↗
PubMed1997

Treatment of cirrhotic rats with L-ornithine-L-aspartate enhances urea synthesis and lowers serum ammonia levels.

CCl4-induced cirrhosis of rats was used for studying the influence of L-ornithine-L-aspartate (OA) on hyperammonemia. OA given to cirrhotic rats (2 g/kg daily) for 2 wk slightly increased net body weight and led to a significant increase in plasma urea levels and a decrease in plasma ammonia levels. Serum concentrations of glutamate, glutamine and arginine decreased significantly. In the livers of the OA-treated rats the activities of carbamoylphosphate synthetase I and arginase increased by 30 and 40%, respectively, approaching normal levels. No change in the activities of the other urea cycle enzymes as well as of glutamate dehydrogenase, glutaminase and glutamine synthetase was found. The negative correlation between glutamine synthetase activity and plasma ammonia levels reported previously for cirrhotic rats (Gebhardt and Reichen, Hepatology 20:684-691, 1994) was corroborated for cirrhotic animals not treated with OA, but was no longer apparent in OA-treated cirrhotic rats. Despite this improvement, plasma ammonia levels still varied considerably reflecting the variable accessibility and activities of glutamine synthetase in cirrhotics. Cultured hepatocytes from the two groups of rats showed a similar stimulation of urea production by addition of ammoniumacetate and/or OA to Hanks' buffered salt solution. In Williams medium E, however, the hepatocytes from the OA group produced significantly more urea than those from controls. These results suggest that treatment of cirrhotic rats with OA considerably improves urea production favoring the detoxification of ammonia that, however, is still limited by the severe alterations in liver architecture that are not influenced by OA in a 2-wk period.

Amino Acids↗
PubMed1997

Preinjury family environment as a determinant of recovery from traumatic brain injuries in school-age children.

Previous studies of childhood traumatic brain injury (TBI) have emphasized injury-related variables rather than environmental factors as predictors of recovery. We addressed this concern using data collected during a prospective study of children with either TBI or orthopedic injuries (OI) and their families. Participants included 53 children with severe TBI, 56 with moderate TBI, and 80 with OI, all from 6 to 12 years of age at the time of injury. Measures of the preinjury family environment were collected shortly after the injury (baseline). Child cognitive and behavioral outcomes were assessed at baseline and at 6- and 12-month follow-ups. Individual growth curve analyses showed that measures of the preinjury family environment consistently predicted both the level of cognitive and behavioral functioning at 12 months postinjury and the rate of intraindividual change during the 12-month follow-up period, even after taking into account group membership and injury severity. In some cases, the preinjury family environment was a significant moderator of the effect of TBI, buffering its impact in high-functioning families and exacerbating it in low-functioning families. Thus, preinjury environmental factors predict recovery following TBI in children, even after accounting for injury-related variables.

Brain Injuries↗
PubMed1996

Human evoked potentials to long duration vibratory stimuli: role of muscle afferents.

Tonic vibratory stimuli of 1000 ms duration and different frequencies were delivered to muscles of the forearms of young human subjects. Evoked potentials (EPs) were recorded from 29 scalp channels and revealed phasic highly lateralised and focally distributed EPs during the first 100 ms of the recording epoch that could be adequately modelled with a single point dipole source located in the vicinity of the central sulcus contralateral to the stimulated arm. A later negativity with an onset of about 400 ms and a duration of about 800 ms was found to be symmetrically distributed over fronto-central regions. This negativity is interpreted in terms of cortical activation beyond the primary sensory fields and could be related to the kinaesthetic phenomena experienced during muscle vibration.

Adult↗