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Biomedical subjects

E Cohen

Publications and source records attributed to E Cohen.

At least 109 records · Page 6Linked to original sources
PubMed1996

Fish oils and low-molecular-weight heparin for the reduction of restenosis after percutaneous transluminal coronary angioplasty. The EMPAR Study.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is complicated by restenosis within 6 months in > 40% of patients. Theoretical, animal experimental, and human epidemiological and clinical trial findings have suggested that fish oils (n-3) might reduce restenosis. Low-molecular-weight heparin (LMWH) has reduced cellular proliferation and restenosis in several experimental systems. METHODS AND RESULTS: We randomized 814 patients to fish oils (5.4 g n-3 fatty acids) or placebo a median of 6 days before PTCA and continued for 18 weeks. At the time of sheath removal, 653 patients with at least one successfully dilated lesion were randomized to LMWH (30 mg SC BID) or control for 6 weeks in a 2 x 2 factorial design. Follow-up with quantitative coronary angiography (QCA; target, 18 weeks) was interpretable on 96% of these patients. Restenosis rates per patient were for n-3, 46.5%; placebo, 44.7%; LMWH, 45.8%; and control, 45.4%. Restenosis rates per lesion were for n-3, 39.7%; placebo, 38.7%; LMWH, 38%; and control, 40.4%. At follow-up QCA, mean minimal lumen diameters were (mm) for n-3, 1.12; placebo, 1.10; LMWH, 1.12; and control, 1.10. Fifteen percent of patients permanently discontinued n-3/placebo before study completion, and 21% of patients discontinued LMWH early. There were no significant differences in the occurrences of ischemic events. Bleeding was more common with LMWH, usually was mild, and led to early discontinuation of study medication in only 0.9% of patients. Gastrointestinal side effects were more common in patients receiving n-3 than placebo. CONCLUSIONS: There is no evidence for a clinically important reduction of PTCA restenosis in this trial by either n-3 or LMWH. Evaluation of the results for n-3 in the context of previously published data on the reduction of PTCA restenosis indicates that n-3 is not efficacious and that further trials are unwarranted.

Adult↗
PubMed1996

Cisplatin-based chemotherapy in renal transplant recipients. A case report and a review of the literature.

BACKGROUND: Renal transplant recipients have a high incidence of cancer. The main side effect of cisplatin, nephrotoxicity, has special implications in renal transplant recipients. This is particularly true in view of the routine use of cyclosporine as an immunosuppresant. Nephrotoxicity is also one of the main side effects of cyclosporine. METHODS: We report a patient with a renal allograft who was receiving cyclosporine for immunosuppression and developed metastatic transitional cell carcinoma of the bladder and was treated with cisplatin-based chemotherapy. The literature regarding cisplatin-containing chemotherapy in patients with different cancers and a single transplanted kidney is reviewed. RESULTS: The patient received four cycles of methotrexate, vinblastine, doxorubicin, and cisplatin while on continuous cyclosporine therapy. His renal function remained stable. He responded to chemotherapy initially, but this response was short. Ten patients with renal transplants and cancer who were treated with cisplatin have been reported previously. Two were maintained on cyclosporine for immunosuppression throughout chemotherapy. No patient developed renal failure during or shortly after administration of cisplatin. Two of five patients treated for testicular cancer developed renal failure at 3 and 6 years after completion of chemotherapy. However, in both cases the cause of renal failure was attributed to chronic rejection of the transplanted kidney. CONCLUSION: Renal transplant recipients usually tolerate cisplatin-based chemotherapy well. It should be offered to patients with potentially curable cancer (e.g., germ cell tumor). This case and a review of the literature suggest that these patients retain baseline renal function even if cisplatin-based chemotherapy and cyclosporine are given simultaneously.

Adult↗
PubMed1996

Antenatal diagnosis of short-limb dwarfism: sonographic approach.

Based on the findings in 12 patients with skeletal dysplasia diagnosed antenatally, the authors propose a tailored approach to the evaluation of foetuses with shortened long bones, depending on the time of discovery, the degree of shortening and the associated findings. During the second trimester, a very short femur [2 standard deviations (SD) - 5 mm and less] most probably corresponds to a bone dysplasia, although the differential diagnosis is mainly early intra-uterine growth retardation, and the foetal skeleton should be surveyed completely in order to find supplementary features suggestive of dwarfism. Anomalies of long bones in their shape, thickness or contour, or spinal ossification disorders or undermineralisation (best evaluated at the level of calvarial bones) are most helpful in determining the type of dysplasia. A short femur (between 2 SD and 2 SD - 4 mm) may indicate growth retardation, a chromosomal anomaly or dwarfism. Follow-up examinations are mandatory in order to differentiate between them. During the third trimester a very short femur may indicate a bone dysplasia and the work-up should be the same as in the second trimester. A short femur may correspond to dwarfism of late development, a growth-retarded foetus or constitutional shortness. Various ratios, especially that of the femur/foot, are helpful in differentiating between them. In case of previous family history, a short or very short femur usually indicates recurrence of the dwarfism. In all cases of antenatal diagnosis, confirmation of the sonographic findings should be obtained either by foetal or neonatal radiographs. The approach proposed by the authors should provide sufficient information to counsel the family not only for the ongoing pregnancy but also for subsequent ones.

Bone and Bones↗
PubMed1996

Cytotoxicity of nimbolide, epoxyazadiradione and other limonoids from neem insecticide.

Neem seed preparations contain not only azadirachtin as the active insect antifeedant or growth regulator but also a variety of their limonoids, some of which are cytotoxic to N1E-115 neuroblastoma (mouse), 143B.TK- osteosarcoma (human) and Sf9 (insect) cultured cell lines. The most potent of these limonoids is nimbolide with an IC50 ranging from 4 to 10 microM, and averaging 6 microM for the three cell lines. Other limonoids of decreasing potency and their average IC50 values (microM) are epoxyazadiradione 27 microM, salannin 112 microM, and nimbin, deacetylnimbin and azadirachtin each >200 microM (practically nontoxic). Nimbolide at 10 microM acts rapidly in the neuroblastoma cells to induce blebbing associated with disruption of plasma membranes almost instantaneously and 50% loss of cell viability with 30 min. At 5 microM nimbolide, the cells become elongated and assume a neuronal shape accompanied by spikes and lamellipodia within 1-2 hr followed shortly thereafter by extensive cytological changes and and vacuolization associated with irreversible processess leading to cell death. Calcium is apparently not involved the cytotoxic effect since a calcium-free medium, leading to profound morpholigical changes, does not alter the sensitivity to nimbolide. In contrast, epoxyazadiradione requires higher concentrations and a few hr for 50 % viability loss without major morphological changes, indicating a difference in mode of action for nimbolide and epoxyazadiradione. and epoxyazadiradione.

Animals↗
PubMed1996

Prenatal naltrexone facilitates male sexual behavior in the rat.

The involvement of endogenous opiates in the differentiation of sexual behavior was tested by exposing rat fetuses to continuous naltrexone during the last 9 days of gestation. Time-mated female rats received oral naltrexone, 40 mg/kg/day, via their drinking water, from gestational day 13 until parturition. Early motor development, measured by swimming ability in 7-, 9-, and 11-day-old offspring of the treated dams, was unaffected by prenatal naltrexone. Adult male offspring were given three tests of male sexual behavior, then castrated, primed with ovarian hormones, and given two tests of feminine receptivity (lordosis quotient). Prenatal naltrexone facilitated masculine behavior and suppressed feminine receptivity: latencies to first mount and to ejaculation were shorter, mount rate was higher, and lordosis quotient was lower in naltrexone-treated rats, compared with control animals. These findings implicate endogenous opiates in prenatal organization of sex-specific behavioral dispositions.

Animals↗
PubMed1996

Prenatal exposure to morphine alters analgesic responses and preference for sweet solutions in adult rats.

In the present study, we examined long-term effects of prenatal morphine on pain response and on preference for sweet solutions. Pregnant Fischer 344 rats were given increasing doses of morphine (0.75-12.0 mg/day) in slow-release emulsion, during gestational days 12-18. Control rats were injected with vehicle and were either pair-fed to morphine rats, or ad libitum fed. At birth, all litters were culled to 8-10 pups (half males and half females) and cross-fostered to naive, surrogate dams. Testing began when rats were 10-12 week old. Rats prenatally exposed to morphine exhibited higher analgesia in response to a morphine challenge, and a greater preference for saccharin solution as compared with both control groups. These findings indicate that prenatal morphine induces long-lasting alterations of systems involved in reward processes and in opiate analgesia, perhaps by modulating endogenous opiate systems.

Analgesics, Opioid↗
PubMed1996

Positive end-expiratory pressure during one-lung ventilation improves oxygenation in patients with low arterial oxygen tensions.

OBJECTIVE: The application of 10 cm H2O of positive end-expiratory pressure (PEEP10) to the ventilated lung during one-lung ventilation (OLV) has an unpredictable effect on PaO2. It was hypothesized that patients with a low PaO2 (< 80 mmHg) during OLV may benefit from application of PEEP. DESIGN: Prospective, open. SETTING: A university medical center. PARTICIPANTS: Eighteen patients were studied who were undergoing OLV for pulmonary resection. All were anesthetized with thiamylal, N2O/O2 (50%/50%), isoflurane, and pancuronium. INTERVENTIONS: Application of PEEP10 during one-lung ventilation. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and oxygenation were measured during two-lung ventilation in the lateral position, OLV, and OLV plus application of PEEP10. Overall, PEEP10 during OLV failed to produce significant changes in PaO2, Qs/Qt%, cardiac output (CO), SvO2, or mean arterial pressure. However, in 11 patients whose PaO2 was less than 80 mmHg during OLV, application of PEEP10 significantly increased PaO2, decreased Qs/Qt%, and decreased CO (p < 0.05). In the 7 patients whose PaO2 was greater than 80 mmHg on OLV, the authors did not find a significant effect of PEEP10 on the hemodynamic or oxygenation parameters measured. CONCLUSIONS: In patients with a low PaO2 (< 80 mmHg) during OLV with F1O2 = 0.5, PaO2 is increased by the application of PEEP10. This maneuver may be useful in situations in which application of continuous positive airway pressure (CPAP) to the nonventilated lung is not possible.

Anesthesia↗
PubMed1996

The human immunodeficiency virus type 1 5' packaging signal structure affects translation but does not function as an internal ribosome entry site structure.

The role of the RNA secondary structure in the 5' packaging signal region of human immunodeficiency virus type 1 (HIV-1) in initiating translation of gag mRNA has been investigated both in vitro and in the presence of cellular cofactors in vivo. Heat denaturation of the structure and mutagenic deletion both lead to an increase in levels of translated products, indicating that the structure is a significant inhibitor of translation. The proximity of the gag AUG to the packaging signal structure suggested that it might function as an internal ribosome entry site. However, in both a cell-free system and eukaryotic cells, translation will initiate at a novel upstream initiation codon introduced within the 5' noncoding region. This codon is utilized exclusively, resulting in gag protein products with an extra 11 amino acids at the amino terminus, which, when expressed in T lymphocytes, are confined intracellularly, probably because of the lack of an N-terminal glycine myristoylation signal. Deletion of the secondary structure abolishes gag production even in the presence of tat and rev in trans. Using dicistronic constructs containing the HIV-1 5' leader cloned between two heterologous open reading frames, we were unable to detect any significant expression of the second open reading frame that would have been supportive of an internal ribosome entry site mechanism. Using mutant proviruses either lacking the entire packaging signal structure region or containing the introduced upstream initiation codon in long-term replication studies, we were unable to detect reverse transcriptase activity in culture supernatants. The 5' packaging signal structure of HIV-1 does not serve as an internal ribosome entry site. The translation of gag is consistent with ribosomal scanning. However, the packaging signal structure causes significant translational inhibition.

Amino Acid Sequence↗
PubMed1996

Outcome of children born to epileptic mothers treated with carbamazepine during pregnancy.

AIM: The purpose of the study was to assess whether there was an increased rate of congenital anomalies or significant developmental delay in infants of women with epilepsy who had been treated with carbamazepine during pregnancy. METHODS: 47 children were studied, aged 6 months-6 years, who were born to 37 epileptic mothers on carbamazepine monotherapy (group A). All children had a complete physical and neurodevelopmental assessment by a developmental paediatrician, and 41 a complete psychological evaluation. They were compared with 47 children of similar socioeconomic status (group B). RESULTS: Six of the 47 children in group A had typical facial features of 'carbamazepine syndrome'. The average cognitive score of children in group A was significantly lower than in group B. This was mainly because all six children with carbamazepine syndrome had a development quotient or intelligence quotient below 90. There were no differences between the two groups in physical growth or in the rate of major anomalies. Two children in group A had cleft palate but in each case this was found in a parent as well. CONCLUSIONS: In utero exposure to carbamazepine may result in 'carbamazepine syndrome' characterised by facial dysmorphic features and mild mental retardation. Prevalence of carbamazepine syndrome does not seem to be related to the dose of carbamazepine or the presence of maternal convulsions. It may depend upon heredofamilial factors that have yet to be defined. One possible factor is decreased activity of the enzyme epoxide hydrolase with resulting increased concentrations of carbamazepine epoxide which may be teratogenic.

Anticonvulsants↗
PubMed1995

Interleukin-1 inhibits sexual behavior in female but not in male rats.

The cytokine interleukin-1 (IL-1) is released by a variety of cells in response to infection or injury. IL-1 produces several neuroendocrine and behavioral effects, including a suppression of reproductive functions and goal-directed behaviors. The present study examined the effect of IL-1 on sexual behavior in male and female rats. The following behavioral tests were employed: preference for a sexually appropriate partner, proceptive (soliciting) behavior, the lordosis quotient (sexual receptivity), and mating performance. Peripheral (ip) IL-1 beta, 2 or 10 micrograms/kg, injected 2 h before testing, significantly suppressed proceptive behavior and sexual receptivity in intact, normally cycling females. In ovariectomized rats treated with ovarian hormones, IL-1 beta (2 or 10 micrograms/kg) significantly decreased the preference for a sexually active male partner and suppressed proceptive behavior and sexual receptivity. These effects were evident 2, but not 4 or 6, h after IL-1 beta administration. Intracerebroventricular administration of IL-1 beta (10 ng/rat) also suppressed the preference for a male partner and proceptive behavior in normally cycling females. Similar doses of IL-1 beta had no suppressive effect on any aspect of male sexual behavior, and the highest dose even increased the preference for a receptive female partner. In contrast to the gender-specific effects on sexual behavior, the suppressive effects of IL-1 beta on activity in the open-field test were comparable in male and female rats. The inhibition of female sexual behavior by IL-1 may be adaptive, in that it prevents conception while the animal is sick, thus reducing the risk of spontaneous abortion or abnormal development.

Animals↗