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Biomedical subjects

N Cohen

Publications and source records attributed to N Cohen.

At least 109 records · Page 6Linked to original sources

[Quinidine-induced rheumatic toxicity].

2 women with quinidine-induced lupus are presented. This condition is rare; only about 30 cases have been reported in the English literature. Both our patients had arthritis of the wrist, antinuclear antibodies with homogenous pattern and elevated ESR. Anti-double stranded DNA antibodies were present in 1 patient, and a petechial rash in the other. Complete resolution of arthritis occurred within a few days after quinidine withdrawal, but antinuclear antibodies persisted for several months.

Aged↗

Effects of thymectomy and tolerance induction on tumor immunity in adult Xenopus laevis.

Major-histocompatibility-complex homozygous partially inbred adults of the ff strain of Xenopus reject transplants of tumor cells of ff strain origin; ff tadpoles do not. Thymectomy, performed 5 days after fertilization, abrogated the adult tumor-rejection response suggesting that in this system tumor rejection is immunologically mediated by T cells. Thymectomy later in larval life did not alter tumor rejection, but it did reduce T-cell numbers. Tolerance to minor-histocompatibility(H) antigens segregating within the ff family, which was induced by grafting adult skin to metamorphosing larvae, did not affect the tumor-rejection capacity of the tolerant adult hosts. This suggests that the ff-2 tumor expresses (a) tumor-specific antigen(s). Immunization of larvae with tumor cells did not induce tolerance to skin grafts transplanted during adult life. Indeed, such grafts were rejected in accelerated fashion, suggesting that memory cells generated in the larvae persist through metamorphosis.

Animals↗

Changes in calcium transport in mammalian sperm mitochondria and plasma membranes caused by 780 nm irradiation.

BACKGROUND AND OBJECTIVE: Regulation of intracellular Ca2+ concentrations are very important in control of sperm motility and acrosome reaction. It was shown previously that low-power lasers in the visible and near-infrared range alter Ca2+ uptake by sperm cells. In the present work the effect of a 780 nm diode laser on Ca2+ uptake by sperm mitochondria and isolated plasma membrane vesicles is investigated. STUDY DESIGN/MATERIALS AND METHODS: Digitonin-treated spermatozoa and plasma membrane vesicles were irradiated with a 780-nm diode laser at various powers and energy doses, and Ca2+ uptake was measured by the filtration method. RESULTS: It was found that 780-nm irradiation inhibits Ca2+ uptake by the mitochondria but stimulates Ca2+ binding by sperm plasma membrane vesicles. The effect of light on Ca2+ uptake by plasma membrane vesicles in the absence of ATP was much larger than that measured in the presence of ATP. Addition of Ca2+ ionophore decreased the Ca2+ uptake by the irradiated membranes in the presence of ATP but enhanced it significantly in the absence of ATP. CONCLUSION: 780 nm light inhibits Ca2+ uptake by sperm mitochondria and enhances Ca2+ binding to sperm plasma membranes.

Animals↗

Conservative treatment for Brucella endocarditis.

Endocarditis is the most devastating complication of brucellosis. The accepted treatment for Brucella endocarditis (BE) is a combination of valve replacement and antibiotics. Conservative antibiotic treatment alone is not recommended by most authors, as it is considered ineffective, risking fatality. We describe a patient with BE, in whom antibiotic treatment alone resulted in complete recovery. On reviewing the literature, we found 12 additional such cases. We compared this group of 13 patients with data from 49 published cases treated with a combination of surgery and antibiotics, with a favorable outcome. Absence of congestive heart failure or a prosthetic valve, relatively mild extravalvular cardiac involvement, and a somewhat shorter disease history until initiation of treatment were characteristic of the group treated conservatively in comparison with patients who underwent surgery. In selected patients with BE, conservative antibiotic treatment may be a valid alternative to surgery.

Anti-Bacterial Agents↗

Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping.

Thiamine-responsive megaloblastic anemia, also known as "TRMA" or "Rogers syndrome," is an early-onset autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and sensorineural deafness, responding in varying degrees to thiamine treatment. On the basis of a linkage analysis of affected families of Alaskan and of Italian origin, we found, using homozygosity mapping, that the TRMA-syndrome gene maps to a region on chromosome 1q23.2-23.3 (maximum LOD score of 3.7 for D1S1679). By use of additional consanguineous kindreds of Israeli-Arab origin, the putative disease-gene interval also has been confirmed and narrowed, suggesting genetic homogeneity. Linkage analysis generated the highest combined LOD-score value, 8.1 at a recombination fraction of 0, with marker D1S2799. Haplotype analysis and recombination events narrowed the TRMA locus to a 16-cM region between markers D1S194 and D1S2786. Several heterozygote parents had diabetes mellitus, deafness, or megaloblastic anemia, which raised the possibility that mutations at this locus predispose carriers in general to these manifestations. Characterization of the metabolic defect of TRMA may shed light on the role of thiamine deficiency in such common diseases.

Alaska↗

Treatment of advanced pancreatic adenocarcinoma with 5-FU, leucovorin, interferon-alpha-2b, and cisplatin.

Previous laboratory and clinical studies support the ability of interferon (IFN) to enhance the antitumor properties of chemotherapy agents, including cisplatin and 5-fluorouracil (5-FU). A phase I-II clinical trial was initiated to treat several tumor types with IFN-alpha-2b, cisplatin, 5-FU, and leucovorin (LV), given daily for 5 days of a 28-day cycle. Because of preliminary results, this was continued as a phase II trial in 18 patients with metastatic adenocarcinoma of the pancreas. Each treatment day consisted of IFN 5 million u/m2 s.c. (maximum, 10 million U), CDDP 20 mg/m2 i.v. over 1 h, LV 20 mg/m2 i.v.p., and 5-FU 250-275 mg/m2 i.v.p. All patients had measurable disease with no prior chemotherapy for metastatic disease, and all had an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Six of the 16 patients evaluable for response had partial responses (PRs) (37.5%) with a median response duration of 4 months, and all responding patients survived > or = 8 months. Median survival of all 18 treated patients was 5 months. Severe gastrointestinal toxicity (nausea, diarrhea, or requirement for i.v. hydration) was common. Grade 4 hematologic toxicity was seen in six patients. The response rate observed is promising and supports the concept that IFN may potentiate the effects of standard chemotherapy agents. However, the toxicities observed with this dosage schedule were considerable and further studies are needed to develop a less toxic regimen.

Adenocarcinoma↗

Benign familial microcytic thrombocytosis with autosomal dominant transmission.

Familial thrombocytosis is an extremely rare disorder, so far reported in only a handful of families. In the majority of cases the characteristics were of essential thrombocythemia. Most patients presented with a platelet count above 800,000/mm3, were diagnosed as having a myeloproliferative disease, and some required chemotherapy. We describe a benign form of familial thrombocytosis with autosomal dominant inheritance in five healthy members of three generations of a family, all of whom had moderate thrombocytosis within the range 422,000-662,000/mm3, characterized by low mean platelet volume. A careful medical history and a 5-year follow up of the subjects did not reveal any untoward clinical development. This variant of familial thrombocytosis is therefore of a benign nature. Possible mechanisms linking thrombocytosis with platelet microcytosis in this family are discussed.

Adolescent↗

Influences on fit between psychiatric patients' psychosocial needs and their hospital discharge plan.

OBJECTIVE: The study examined factors that help determine a good or poor fit between the psychosocial support needs of hospitalized patients and the hospital's discharge plan. METHODS: The Mount Sinai Discharge Planning Inventory was completed weekly for 494 consecutive admissions to the hospital's adult inpatient psychiatric units. The resources that patients brought with them into the hospitalization in the areas of housing, entitlements, daily activities, and psychiatric treatment were recorded as well as the resources that would constitute an optimal discharge plan. Good or poor fit was operationally defined by the match between the optimal, first-choice plan and the implemented discharge plan. RESULTS: One-third of admissions were found to have an optimal fit on admission in all resource categories studied. For patients who entered the hospital with suboptimal resources, discharge planing was significantly more likely to establish clinically relevant psychiatric treatment options and to strengthen daily living activities than to change housing resources. Certain diagnoses and a history of drug abuse, criminality, violence, and treatment noncompliance were associated with poorer fits with first-choice disposition options. CONCLUSIONS: The Mount Sinai Discharge Planning Inventory provides a method to systematically evaluate discharge planning by tracking progress toward securing relevant posthospital care and support.

Activities of Daily Living↗

Psychoneuroimmunology.

This paper develops hypotheses regarding the interactions among stress, immunity, and chemical sensitivities and gives an overview of the questions and hypotheses generated by a working group exploring the application of psychoneuroimmunology to chemical sensitivities. Consideration is given to prospective longitudinal studies designed to find cases among at-risk exposed populations. Relevant immune parameters to be measured longitudinally and in challenge studies for patients with MCS are discussed. Immune system changes in response to the chronic stress of having MCS and as primary responses to chemical exposure also are considered.

Environment, Controlled↗

Chylothorax following median sternotomy.

Reports of chylothorax (CT) following median sternotomy are rare, amounting so far to 16 cases in the English literature, of which 6 were cases of postcoronary artery bypass grafting (CABG). This report deals with an additional case of a 70-year-old woman who developed left pleural chylous effusion following CABG. It is suggested that the incidence of this type of pleural effusion is considerably greater than the few cases hitherto reported. Moreover, as CT may produce serious pulmonary and/or pleural functional impairment, it is proposed that a diagnostic tap be performed more often in cases of post CABG pleural effusion and that preventive drainage be instituted when CT is diagnosed.

Aged↗

Erythrocyte Na+, K+ and Ca2+, Mg(2+)-ATPase activities in hypertensives on angiotensin-converting enzyme inhibitors.

OBJECTIVE: To investigate erythrocyte membrane Na+, K(+)- and Ca2+, Mg(2+)-ATPase activities in newly diagnosed hypertensive patients before and after 2, 4, and 6 months of treatment with enalapril or captopril as monotherapy. METHODS AND RESULTS: Na+, K(+)-ATPase activity (nmol ATP hydrolysed/min per mg protein) rose by 6 months of treatment in both groups when values were compared in each treated group over time (4.5 +/- 0.8 to 9.9 +/- 1.2; 4.9 +/- 0.8 to 10.5 +/- 1.7, respectively, p < 0.001 for both). When the treated groups were compared with controls at each period of time, Na+, K(+)-ATPase activity was higher at months 4 and 6 (p < 0.001) for both groups, respectively). Ca2+, Mg(2+)-ATPase activity (nmol ATP hydrolyzed/min per milligram protein) in the absence and in the presence of calmodulin increased in the enalapril (6.4 +/- 0.7 to 8.9 +/- 0.95, p < 0.05; 13.4 +/- 1.2 to 17.2 +/- 1.2, p < 0.05, respectively) and captopril (7.0 +/- 0.6 to 8.5 +/- 0.7; 14.4 +/- 1.1 to 16.0 +/- 1.0, p < 0.05, respectively) groups after 6 months of treatment compared within each treated group over time. When patient groups were compared with controls at time 0, 2, 4, and 6 months, the pump activity was higher in the treated groups at 6 months. CONCLUSION: The long-term enhancement of cell membrane Na+, K(+)-and Ca2+, Mg(2+)-ATPase activity associated with enalapril and captopril therapy may represent a specific effect of these agents or alternatively, a nonspecific outcome of blood pressure reduction.

Angiotensin-Converting Enzyme Inhibitors↗

Changes in calcium transport in mammalian sperm mitochondria and plasma membrane irradiated at 633 nm (HeNe laser).

The effect of light on calcium transport in mammalian sperm mitochondria and plasma membrane was studied. Digitonine-treated spermatozoa and plasma membrane vesicles were irradiated with an HeNe laser at various powers and energy doses and Ca2+ uptake was measured by the filtration method. It was found that there is an accelerated Ca2+ uptake by the mitochondria after low power HeNe irradiation and inhibition after high power. The flux of Ca2+ from the mitochondria was also examined and was found to be unaffected by the HeNe light. The ATP-dependent Ca2+ uptake by the bovine plasma membrane vesicles was not changed by the HeNe irradiation.

Animals↗

Increased lipid oxidation but normal muscle glycogen response to epinephrine in humans with IDDM.

The effects of physiological increments in epinephrine and insulin on glucose production (GP), skeletal muscle glycogen metabolism, and substrate oxidation were studied in eight insulin-dependent diabetes mellitus (IDDM) and nine control subjects. Epinephrine was coinfused for the final 120 min of a 240-min euglycemic, hyperinsulinemic clamp. In both groups, insulin increased glucose uptake, glycogen synthesis, and whole body carbohydrate (CHO) oxidation and inhibited GP (by 70-80%) and lipid oxidation (by approximately 50%), whereas epinephrine antagonized the effect of insulin on glucose uptake and glycogen synthesis. In contrast, GP increased in IDDM subjects (P < 0.02) but remained suppressed by insulin in controls. CHO oxidation fell (1.37 +/- 0.25 vs. 2.08 +/- 0.32 mg.kg-1.min-1) and lipid oxidation increased to baseline in IDDM subjects, with increments in plasma free fatty acids (FFA) and glycerol. In contrast, in controls, plasma FFA and glycerol remained suppressed and lipid oxidation decreased further with epinephrine (P < 0.005). Epinephrine completely reversed insulin's activation of muscle glycogen synthase in both groups. Thus, during hyperinsulinemia, the hepatic response to epinephrine in IDDM subjects may be dependent on activation of lipid oxidation. Skeletal muscle glycogen metabolism is exquisitely sensitive to epinephrine despite the presence of hyperinsulinemia.

Adult↗

Conditioning of cyclophosphamide-induced leukopenia in humans.

This study evaluated whether decrements in peripheral leukocyte counts induced by cyclophosphamide can be conditioned in humans. Ten subjects being treated for multiple sclerosis received four intravenous treatments with cyclophosphamide (unconditioned stimulus) paired with a conditioned stimulus. Subjects received conditioned stimulus plus 10 mg of cyclophosphamide during one of the next two treatments in a double-blind manner. Eight of 10 subjects (P = 0.044) displayed decreased peripheral leukocyte counts following conditioned stimulus. This change may have resulted from classical conditioning processes.

Adult↗

Effects of Various Modalities of Oral Furosemide Administration in Mild or Severe Congestive Heart Failure.

BACKGROUND: This study evaluated the optimal formulation (tablet vs solution) and frequency (once vs twice daily) of maintenance oral furosemide in compensated congestive heart failure (CHF). METHODS AND RESULTS: Eighteen patients with mild (group 1) and 18 with severe (group 2) CHF were studied. On 2 consecutive days each patient's individual fixed oral furosemide daily dosage was administered in tablet or solution in a crossover design. In an additional study, 14 patients with severe CHF received the daily dosage in tablet or solution form in two divided doses. Pharmacokinetic data were obtained in six randomly allocated patients of each group, during the once daily administration periods of either formulation. Twenty-four-hour urinary sodium and 12-hour volume were significantly greater in group 1 following furosemide solution versus tablets. In group 2, all parameters were comparable in response to single identical doses in tablets or solution, as well as to once versus twice daily administration of either formulation. These results coincided with a higher C(max) and a shorter t(max) following solution. CONCLUSIONS: A once-daily oral furosemide solution is more effective than the same dosage in tablet form in patients with mild, but not those with severe, CHF. In patients with severe CHF, the natriuretic and diuretic effects are similar whether oral furosemide in tablet or solution is administered in a once or twice daily schedule.

Journal Article↗

Atrial natriuretic peptide and plasma renin levels in assessment of mineralocorticoid replacement in Addison's disease.

Assessment of mineralocorticoid replacement therapy in Addison's disease relies on clinical features and laboratory measurements, including plasma renin and potassium. Previous studies have questioned the value of measuring the plasma renin concentration (PRC), particularly in the setting of fludrocortisone overreplacement. The aim of this study was to evaluate the usefulness of plasma atrial natriuretic peptide (ANP) measurements as a marker of sodium and volume status in Addison's disease. Fourteen patients with Addison's disease receiving their usual glucocorticoid doses were placed on various doses of fludrocortisone (FC; 0 mg, 0.05 mg, 0.1 mg and 0.2 mg) in random order for four 2-week periods. At the end of each period, blood pressure and clinical symptoms were assessed, and blood was drawn for measurement of PRC and ANP levels. PRC was significantly elevated in patients receiving placebo (54.2 +/- 57.9 ng/mL x h) compared with PRC in those receiving baseline FC (24.7 +/- 42.4 ng/mL x h), 0.1 mg FC (15.2 +/- 25.9 ng/mL x h), and 0.2 mg FC (5.5 +/- 5.7 ng/mL x h). ANP levels were measured by either an extraction method (ANP(ext)) or directly from plasma (ANP(dir)). ANP(dir) was significantly elevated at 0.2 mg FC (87.1 +/- 20.1 pg/mL) compared with baseline (63.3 +/- 8.1 pg/mL), placebo (56.1 +/- 5.5 pg/mL), 0.05 mg FC (60.5 +/- 16.0 pg/mL), and 0.1 mg FC (65.4 +/- 13.7 pg/mL) values. ANP(ext) was elevated in patients receiving 0.2 mg FC (42.7 +/- 41.8 pg/mL) compared with that in patients receiving placebo (7.9 +/- 5.4 pg/mL), 0.05 mg FC (16.2 +/- 11.2 pg/mL), or 0.1 mg FC (19.7 +/- 11.1 pg/mL). Our data suggest that PRC is of value in determining mineralocorticoid underreplacement, whereas ANP is a more sensitive index of FC overreplacement. ANP levels may, therefore, be complementary to PRC in adjustment of mineralocorticoid doses in the upper dose range, where clinical symptoms and signs appear to be of little value.

Addison Disease↗

Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects.

We compared the effects of oral vanadyl sulfate (100 mg/day) in moderately obese NIDDM and nondiabetic subjects. Three-hour euglycemic-hyperinsulinemic (insulin infusion 30 mU / m / min) clamps were performed after 2 weeks of placebo and 3 weeks of vanadyl sulfate treatment in six nondiabetic control subjects (age 37 +/- 3 years; BMI 29.5 +/- 2.4 kg/m2 ) and seven NIDDM subjects (age 53 +/- 2 years; BMI 28.7 +/-1.8 kg/m2). Glucose turnover ([3-3 H]glucose), glycolysis from plasma glucose, glycogen synthesis, and whole-body carbohydrate and lipid oxidation were evaluated. Decreases in fasting plasma glucose (by approximately 1.7 mmol/l) and HbAlc (both P < 0.05) were observed in NIDDM subjects during treatment; plasma glucose was unchanged in control subjects. In the latter, the glucose infusion rate (GIR) required to maintain euglycemia (40.1 +/- 5.7 and 38.1 +/- 4.8 micromol / kg fat-free mass FFM / min) and glucose disposal (Rd) (41.7 +/- 5.7 and 38.9 +/-4.7 micromol / kg FFM / min were similar during placebo and vanadyl sulfate administration, respectively. Hepatic glucose output (HGO) was completely suppressed in both studies. In contrast, in NIDDM subjects, vanadyl sulfate increased GIR approximately 82% (17.3 +/- 4.7 to 30.9 +/- 2.7 micromol / kg FFM / min, P < 0.05); this improvement in insulin sensitivity was due to both augmented stimulation of Rd (26.0 +/-4.0 vs. 33.6 +/- 2.22 micromol / kg FFM / min, P < 0.05) and enhanced suppression of HGO (7.7 +/- 3.1 vs. 1.3 +/- 0.9 micromol / kg FFM / min, P < 0.05). Increased insulin-stimulated glycogen synthesis accounted for >80% of the increased Rd with vanadyl sulfate (P < 0.005), but plasma glucose flux via glycolysis was unchanged. In NIDDM subjects, vanadyl sulfate was also associated with greater suppression of plasma free fatty acids (FFAs) (P < 0.01) and lipid oxidation (P < 0.05) during clamps. The reduction in HGO and increase in Rd were both highly correlated with the decline in plasma FFA concentrations during the clamp period (P < 0.001). In conclusion, small oral doses of vanadyl sulfate do not alter insulin sensitivity in nondiabetic subjects, but it does improve both hepatic and skeletal muscle insulin sensitivity in NIDDM subjects in part by enhancing insulin's inhibitory effect on lipolysis. These data suggest that vanadyl sulfate may improve a defect in insulin signaling specific to NIDDM.

Administration, Oral↗

Intestinal uptake and metabolism of fatty acids in the chick.

Uptake and metabolism of fatty acids in the duodenal mucosa of the chick was studied. In vitro incubations of a mucosal homogenate with 14C-oleic acid indicated that together with glycerides, water-soluble 14C compounds and 14CO2 were formed; the latter comprised approximately one quarter of metabolites formed. Studies in chickens introducing 14C-oleic acid into the duodenum and determining appearance of label in the cannulated pancreaticoduodenal vein and brachial artery indicated that similar processes occur in vivo, with both labeled glycerides and water-soluble compounds appearing in the blood. Quantitatively, metabolism of 14C-oleic acid to nonlipid compounds amounted to some 15% of the dose after 60 min. These findings suggest that a considerable portion of ingested fatty acids are metabolized before transport to the circulation.

Animals↗