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Biomedical subjects

B Dworkin

Publications and source records attributed to B Dworkin.

At least 19 recordsLinked to original sources

Impact of post-synaptic block of neuromuscular transmission, muscle unloading and mechanical ventilation on skeletal muscle protein and mRNA expression.

To analyse mechanisms of muscle wasting in intensive care unit patients, we developed an experimental model where rats were pharmacologically paralysed by post-synaptic block of neuromuscular transmission (NMB) and mechanically ventilated for 9+/-2 days. Specific interest was focused on the effects on protein and mRNA expression of sarcomeric proteins, i.e., myosin heavy chain (MyHC), actin, myosin-binding protein C (MyBP-C) and myosin-binding protein H (MyBP-H) in fast- and slow-twitch limb, respiratory and masticatory muscles. Muscle-specific differences were observed in response to NMB at both the protein and mRNA levels. At the protein level, a decreased MyHC-to-actin ratio was observed in all muscles excluding the diaphragm, whereas at the mRNA level a decreased expression of the dominating MyHC isoform(s) was observed in the hind limb and intercostal muscles, but not in the diaphragm and masseter muscles. MyBP-C mRNA expression was decreased in the limb muscles, but it otherwise remained unaffected. MyBP-H conversely increased in all muscles. Furthermore, we found myofibrillar protein and mRNA expression to be affected differently when comparing NMB animals with peripherally denervated (DEN) ambulatory rats. We report that NMB has both a larger and different impact on muscle, at the protein and mRNA levels, than DEN has.

Animals↗

Liver function in early Lyme disease.

To evaluate the frequency, pattern, and severity of liver function test abnormalities in patients with Lyme disease associated with erythema migrans (EM), 115 individuals with no other identifiable cause for liver function test abnormalities who presented with EM between July 1990 and September 1993 were prospectively evaluated. For individuals with abnormal liver function tests, common causes of hepatitis, including hepatitis A, B, and C, were excluded. A local control group was used for comparison. Forty-six (40%) patients had at least one liver test abnormality, and 31 (27%) had more than 1 abnormality compared with 19 (19%) and 4 (4%) of controls, respectively (P < .01 for each comparison). gamma-Glutamyl transpeptidase (28%) and alanine transaminase (ALT) (27%) were the most frequently elevated liver function tests among Lyme disease patients. Anorexia, nausea, or vomiting was reported by 30% of patients, but did not occur more frequently in patients with elevated liver function tests compared with those with normal values. Patients with early disseminated Lyme disease were more likely to have elevated liver function studies (66%) compared with patients with localized disease (34%) (P = .002). After antibiotic treatment, elevated liver function tests improved or resolved in most patients. Liver function test abnormalities are common in patients with EM but were mild, most often not associated with symptoms, and improved or resolved by 3 weeks after the onset of antibiotic therapy in most patients.

Adult↗

Behavioral treatment of scoliosis and kyphosis.

A behavioral treatment of scoliosis and kyphosis was tested with 27 adolescent patients (19 scoliosis, eight kyphosis patients) to determine in which cases the conspicuous and restraining brace treatment could be replaced. In 22 compliant patients, posture biofeedback (PB) was highly effective compared to five non-compliant patients. Biologically more mature scoliosis patients (menarche at the beginning of treatment) seemed to profit more from PB. With kyphosis patients the PB treatment resulted in rapid straightening of the spine and removal of structural deformities of Scheuermann's disease. PB may serve as an unobtrusive yet effective treatment alternative for both juvenile scoliosis and kyphosis.

Adolescent↗

Low-dose dexamethasone as adjunctive therapy for disseminated Mycobacterium avium complex infections in AIDS patients.

Five human immunodeficiency virus-infected patients with disseminated Mycobacterium avium complex infection had progressive weight loss and persistent fever despite multidrug antimycobacterial therapy. These patients were given daily low-dose oral dexamethasone (typically 2 mg/day) as adjunctive therapy. All had substantial and sustained weight gain (12 to 50% of pre-steroid treatment body weight [P < 0.03]), reduction in fever, and an improved sense of well-being. The serum albumin level increased during dexamethasone therapy (from 3.06 +/- 0.59 g/dl [mean +/- standard deviation] to 3.9 +/- 0.22 g/dl [P < 0.01]), while the serum alkaline phosphatase level fell (from 368 +/- 247 U/liter to 128 +/- 43.6 U/liter [P < 0.04]). Further studies of the potential role for corticosteroids in the management of disseminated M. avium complex infections in human immunodeficiency virus-infected patients are warranted.

AIDS-Related Opportunistic Infections↗

Cigarette smoking, blood lipids, and baroreceptor-modulated nociception.

Activation of arterial blood pressure has been shown to influence higher central nervous activity. In animals, induction of sleep-like states and increases of seizure and pain thresholds in response to baroreceptor stimulation have been reported. In certain human groups, mechanical stimulation of the carotid baroreceptors also increases pain thresholds. The present paper examines the hypothesis that smokers show baroreceptor dependent antinociception as compared to non-smokers. It is speculated that one effect which rewards smoking is the nicotine induced phasic blood pressure increase which leads to baroreceptor stimulation and dampens pain perception. One hundred and twenty subjects were investigated using a recently developed mechanical baroreceptor stimulation technique and an electrical pain stimulus. The group of heavy smokers showed the predicted effect: their pain thresholds were enhanced during conditions of increased baroreceptor activity as compared to the control condition. The group of medium, light and non-smokers, however, did not show this effect. Neither blood lipid levels nor diastolic or systolic blood pressure paralleled the group differences on baroreceptor dependent antinociception. In heavy smokers, the nicotine induced phasic blood pressure increases might have baroreceptor dependent pain dampening effects, which might be among the reinforcing qualities of smoking.

Adult↗

Liver diseases unique to pregnancy.

Severe liver diseases occur in less than 0.1% of pregnancies. Accurate diagnosis and appropriate therapy are essential to the health and survival of both the mother and fetus. Because of their low incidence and the fact that most pregnant women are cared for primarily by their obstetricians, gastroenterologists only infrequently encounter these diseases. This review is intended to update the practicing gastroenterologist on the complex spectrum of liver diseases unique to pregnancy.

Female↗

Severe intrahepatic cholestasis in patients treated with recombinant interleukin-2 and lymphokine-activated killer cells.

Immunotherapy with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells (LAK) has become a new form of therapy that has been shown to induce remissions in patients with renal cell carcinoma and melanoma. Despite encouraging results, this form of therapy has been associated with increasing toxicity, often requiring therapy in an intensive-care unit. In this report severe intrahepatic cholestasis occurred in two patients receiving rIL-2 and LAK cells. This form of cholestasis appeared to be directly related to rIL-2 administration at a doses of 2 x 10(6) U/m2 and 3 x 10(6) U/m2 t.i.d. A liver biopsy showed moderate hepatocellular bile stasis, with lobular and portal inflammation. All other studies for potential cause of this cholestasis were negative, including studies for metastatic disease. When therapy was discontinued, evidence for cholestasis and bile stasis resolved. We conclude that rIL-2 is a drug with a potential to induce severe hepatic injury that is reversible upon cessation of therapy with rIL-2. Further care should be exercised when rIL-2 is administered to patients with abnormal liver function.

Adult↗

Common nutritional disorders in the elderly: atypical manifestations.

Nutritional problems are commonly seen in elderly persons living in both community and institutional settings. Multiple interacting medical problems, age-related physiological changes, and low socio-economic status are just some of the factors placing the older person at greater risk for nutritional problems. Nutritional inadequacies often have a slow and insidious onset; many of the presenting features mimic changes of normal aging. Absence of clear-cut signs and symptoms may easily lead to a delay in the diagnosis of these potentially serious yet easily reversible conditions. Practicing physicians need to keep in mind the atypical presentation nutritional deficiencies may have in old age.

Aged↗

Campylobacter pyloridis degrades mucin and undermines gastric mucosal integrity.

The role of Campylobacter pyloridis, a spiral bacteria associated with gastritis and peptic ulcers in weakening the mucus component of gastric mucosal barrier was investigated. The colonies of bacteria, cultured from antral mucosal biopsies of patients undergoing gastroscopy, were washed with saline, passed through sterilization filter and the filtrate was examined for protease and glycosylhydrolase activities. The obtained results revealed that the filtrate exhibited a strong proteolytic activity not only towards the typical protein substrates such as albumin but also towards gastric mucin. Optimum enzymatic activity for degradation of mucin was attained at pH 7.0 and the protease activity was found in a low m.w. (less than 50K) protein fraction. The filtrate showed little glycosylhydrolase activity and did not cause the hydrolysis of mucin carbohydrates. The data suggest that C pyloridis infection weakens the gastric mucosal defense by causing proteolytic degradation of mucin component of the protective mucus layer.

Campylobacter↗

Diminished blood selenium levels in renal failure patients on dialysis: correlations with nutritional status.

Selenium deficiency has been implicated as contributing to the development of cardiovascular disease, skeletal muscle myopathy, anemia, increased cancer risk, and deranged immune function. Since these problems may also be associated with renal failure, and the kidney plays an important role in selenium homeostasis, we measured selenium and compared it with nutritional status in 24 stable hemodialysis patients, 12 chronic intermittent peritoneal dialysis patients, and 29 healthy controls. Whole blood and plasma selenium was determined by a spectrofluorometric method. For whole blood the mean (+/- SD) selenium levels were 0.11 +/- 0.02 micrograms/ml in controls vs. 0.071 +/- 0.01 micrograms/ml in hemodialysis cases and 0.052 +/- 0.006 micrograms/ml in peritoneal dialysis (p less than 0.005). Significant decreases were seen also for plasma and red blood cell selenium in all groups respectively. Pre- and postdialysis plasma and whole blood selenium levels showed no significant changes in both dialysis groups. However, predialysis residual peritoneal fluid did contain selenium (0.029 +/- 0.005 micrograms/ml). Some evidence of protein-energy undernutrition was noted in both dialysis groups compared with controls. However, no significant differences in nutritional parameters were noted between hemodialysis and peritoneal dialysis patients. When all groups were combined, significant correlations were found between whole blood selenium and serum albumin (r = 0.61; p less than 0.001), triceps skin fold in females (r = 0.62; p less than 0.001), and midarm muscle circumference in males (r = 0.71; p less than 0.001). We conclude that low blood selenium is present in renal failure patients undergoing hemodialysis. This abnormality is even greater in peritoneal dialysis cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Persistence of multiply antibiotic-resistant Campylobacter jejuni in a patient with the acquired immune deficiency syndrome.

Chronic diarrhea due to Campylobacter jejuni has been described in patients with hypogammaglobulinemia. A patient with the acquired immune deficiency syndrome (AIDS) and normal total serum immunoglobulins had persistent diarrhea and C. jejuni on stool culture for seven and a half months despite repeated antibiotic therapy. Antibiotic sensitivity studies revealed the C. jejuni to be multiply antibiotic-resistant. Evaluation of the mechanism of resistance showed the organism harbored a conjugative plasmid capable of transferring resistance to tetracycline, but not to other antibiotics. It is concluded that C. jejuni infection may rarely result in chronic diarrhea in patients with AIDS. The combination of an immune deficiency state including abnormal B cell function previously described in AIDS and multiple antibiotic resistance may have contributed to the persistence of the organism in this case.

Acquired Immunodeficiency Syndrome↗

Low blood selenium levels in alcoholics with and without advanced liver disease. Correlations with clinical and nutritional status.

Selenium deficiency has been implicated as a cause of hepatic injury, possibly from accentuated lipoperoxidation due to decreased activity of the selenoenzyme, glutathione peroxidase. Because of possible clinical and biochemical links between selenium and alcohol, we performed nutritional assessment and assayed red blood cell, plasma, and whole blood selenium by spectrofluorometry in 27 normals (group I), 30 asymptomatic alcoholics on admission to a detoxification unit, (group II) and 16 alcoholics with severe liver disease (group III). We found a mean (+/- SD) whole blood selenium of 0.109 micrograms/ml +/- 0.014 for group I vs 0.076 +/- 0.010 for group II (P less than 0.001), and 0.047 +/- 0.006 for group III (P less than 0.001 vs group I and II). For plasma, the mean (+/- SD) selenium was 0.095 micrograms/ml +/- 0.016 for group I versus 0.065 micrograms/ml +/- 0.012 in group II and 0.038 micrograms/ml +/- 0.007 in group III (All P less than 0.001). Calculated red blood selenium levels were also significantly reduced in alcoholics versus controls. Whole blood and plasma selenium correlated directly with serum albumin. For whole blood selenium versus albumin, r = 0.73 (P less than 0.01), and for plasma selenium versus albumin, r = 0.71 (P less than 0.01). A significant inverse correlation was noted between whole blood selenium and the height of the total serum bilirubin (r = -0.46), alkaline phosphatase (r = -0.50), and AST (r = -0.51) (P less than 0.01 for all). Among alcoholics admitted for detoxification, selenium was diminished despite the absence of severe malnutrition, as determined by standard nutrition assessment parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Behavioral method for the treatment of idiopathic scoliosis.

Idiopathic scoliosis was treated by an automated portable posture-training device that incorporated precise behavioral principles and enabled therapeutic training to be given in the patients' normal environment throughout the entire day. Twenty-one patient-years of training were completed with a group of 12 adolescent girls selected as being imminently likely to require a brace because of the way their spinal curves had been progressing. As an alternative to conventional brace therapy, patients found the posture-training device considerably less physically restraining and more cosmetically acceptable. Most patients wore it 23 hr per day for at least 1 year and adapted well to the constant physical and psychological presence of the instrument. For 10 patients, the outcome was entirely successful; they were discharged from this pilot study as satisfactorily corrected. Progression of the scoliotic curve was arrested; in fact, there was an average slight improvement in the Cobb angle (a measure of spinal curvature) as measured by x-ray radiography.

Adolescent↗

The analgesic effects of aspirin and placebo on experimentally induced tooth pulp pain.

We examined the relative analgesic potency of aspirin and placebo in a within-subject-repeated-measure experiment using a precision tooth pulp stimulation technique with long-term stability (r = 0.93) for more than two months between measures. The attenuation of pain perception was evaluated using a standardized magnitude estimation procedure and constructing an individual psychophysical function for each trial. The data were fit equally well by either a straight line (Y = mX + b) or a power function (Y = mXa + b). Using the line fit and distribution insensitive conservative statistical tests, the effect of each treatment was compared to baseline and the treatments were compared to each other. In randomized, double-blind trials we found reliable effects of both aspirin (p less than 0.001) and placebo (p less than 0.001) but no difference (p = 0.08) between these two treatments. However, on an individual basis, 12 of 17 subjects displayed a larger analgesic response to aspirin than to placebo (p less than 0.05).

Adolescent↗

Gastrointestinal manifestations of the acquired immunodeficiency syndrome: a review of 22 cases.

Patients with acquired immunodeficiency syndrome (AIDS) frequently have diarrhea and weight loss. We prospectively examined the upper and lower gastrointestinal tracts in 22 AIDS patients, although severe medical problems often precluded full evaluation. Ninety-six percent (21 of 22) lost weight, and 55% (12 of 22) had diarrhea. The mean (+/- SD) weight loss was 34 +/- 19 lb. Steatorrhea was found in 4 of 14 patients, and D-xylose tests were abnormal in 8 of 14 patients. Mean serum albumin was 3.3 +/- 0.8 g/dl. A significantly diminished plasma selenium level, which can influence immune function, was noted in these AIDS patients. Gastrointestinal infections were identified in 45% of patients. Although diarrhea and malabsorption were more common in the infected group, weight loss and albumin were similar in those with and without demonstrated infections. Flexible sigmoidoscopy showed that of 15 patients, there were two with Kaposi's sarcoma, 10 normals, and three with nonspecific endoscopic changes of colitis. Infection was documented in all patients with colitis. Panendoscopy of the upper gastrointestinal tract was positive for AIDS-related pathology in five of 10 patients, including two with Kaposi's sarcoma, one with Candida esophagitis, one with herpetic esophagitis, and one with gastroduodenitis (biopsy positive for cryptosporidia); five patients had a normal-appearing tract. Small bowel or colonic biopsies frequently showed nonspecific inflammatory changes, although pathogens were identified in six patients (27% of all biopsies). We conclude that a wide variety of gastrointestinal pathology, which includes infectious agents, neoplasms, and inflammatory changes, may occur in AIDS patients. Therefore, AIDS patients, particularly those with diarrhea or weight loss, deserve an intensive evaluation for remediable lesions of their gastrointestinal tracts.

Acquired Immunodeficiency Syndrome↗

Intravenously administered amino acids with either dextrose or lipid as nutritional support in surgical patients.

The relative efficacy of exogenous fat or glucose in preserving lean body mass in surgical patients is controversial. In this study, peripheral intravenously administered amino acids with either lipid or dextrose were given to well nourished patients undergoing elective total cystectomy and ileal diversion. Patients were well matched for age, sex, nutritional status and degree of operative stress. Twenty-eight patients received 1.2 grams per kilogram per day of amino acids plus either dextrose (440 kilocalories per day) (17 patients) or 10 per cent fat emulsion (550 kilocalories per day) (11 patients) for three days preoperatively and seven days postoperatively. No significant differences between the groups were noted in mean nitrogen balances during the preoperative and postoperative periods or in the mean cumulative adjusted (for change in blood urea nitrogen and body weight) nitrogen balances for the total study time. Mean nitrogen excretion per 100 nonprotein calories infused was also similar. Changes in mean body weight, blood urea nitrogen, serum glucose and serum albumin were similar in the two groups. No deaths or major infectious complications occurred in either group. In well nourished patients matched for age, sex, nutritional status and degree of operative stress, the addition of either hypocaloric fat or dextrose to intravenously infused amino acid solutions resulted in an equivalent metabolic and clinical outcome.

Aged↗

Primary gastric lymphoma. A review of 50 cases.

The records of 50 patients with localized primary gastric lymphoma were reviewed and clinical and prognostic factors characterized. Pathologic material was reclassified according to Rappaport's, Lukes-Collins, and Lennert's Kiel classifications. Factors with the greatest prognostic significance included initial stage as determined by surgery and pathology, absolute tumor size, degree of penetration through the stomach wall, and histologic grade of the lymphoma. After surgical resection for cure, the overall 5-year disease-free survival was 47%. For stage I disease, this was 78% vs 29% for stage II (P = 0.006). Patients with lymphomas less than 5 cm in diameter had 58% 5-year disease-free survival vs 32% for those with tumors greater than 10 cm (P = 0.06). Full-thickness penetration decreased 5-year survival from 75% to 38% (P = 0.06). Patients with histologically low-grade lymphomas had a better prognosis than those with high-grade lymphomas. The most significant correlation of histology to survival was seen with the Kiel classification with a 5-year survival of 39% for centroblastic polymorphous lymphoma vs 66% for LP immunocytoma. When lymphoma recurred it developed outside the abdomen in a majority of patients. The addition of abdominal radiation therapy to surgical resection made no significant impact on survival for either stage I or II disease.

Adult↗