Reversal of antidepressant activity of fluoxetine by cyproheptadine in three patients

Three male patients are described in whom anorgasmia developed during treatment with fluoxetine for depression. During attempts to treat the anorgasmia with cyproheptadine, all three patients suffered a relapse of depressive symptoms. The possible mechanism of this effect is discussed in relation to serotonergic systems.     

Transneuronal degeneration of thalamic neurons following deafferentation: quantitative studies using [3H]thymidine autoradiography.

Transneuronal degeneration of thalamic neurons following partial deafferentation was studied using [3H]thymidine autoradiography. Timed-pregnant female Sprague-Dawley rats received systemic injections of [3H]thymidine on embryonic day (E) 13, 14 and/or 15. On the day of birth, pups were anesthetized by hypothermia and subjected to unilateral enucleation, unilateral removal of the inferior colliculus or sham lesion. Animals were sacrificed on postnatal day 10 or 30 and the brains processed for autoradiography. Material from sham-lesioned animals demonstrates that neurons destined for the dorsal lateral geniculate nucleus (LGd) undergo final mitoses on E13, 14 and 15. Neurons in the ventral medial geniculate nucleus (MGv) undergo final mitoses on E13 and 14. Thirty days following neonatal unilateral eye removal, the contralateral LGd displays a loss of approximately 30-35% of [3H]thymidine labeled neurons. Neonatal unilateral removal of the inferior colliculus results in a loss of approximately 30-40% of labeled neurons in MGv. For both LGd and MGv, shorter survival times reveal less severe cell loss. Late generated (E15) LGd neurons show less severe loss following enucleation than do earlier generated neurons. These results document the degree of cell loss in sensory thalamic nuclei following deafferentation and demonstrate that [3H]thymidine autoradiography provides a useful quantitative method for assessing anterograde transneuronal cell loss in targeted populations of neurons in the developing central nervous system.     

An in vivo study of the ontogeny of long-term potentiation (LTP) in the CA1 region and in the dentate gyrus of the rat hippocampal formation.

The influences of stimulus intensity, intratrain frequency, and number of trains were studied for their effects on the development of long-term potentiation (LTP) in the hippocampal formation. LTP was analyzed with full input-output curves for population spike (PS) amplitudes (PS-LTP) calculated from responses elicited in the CA1 region and in the dentate gyrus by monosynaptic activation. A standardized protocol employing a sequence of stimuli was devised to systematically compare LTP in the dentate gyrus to that in the CA1 region in rats of various ages ranging from postnatal day (PN) 6 to adults (PN 60). In adult animals, the degrees of LTP were comparable in the dentate gyrus and CA1 region for the 3 stimulus strengths studied (intensity just subthreshold for PS, intensity giving 1/4 maximal PS, and intensity giving 1/2 maximal PS). LTP developed at different rates in the two regions, reaching adult values about two weeks after birth in CA1 but about 3 weeks after birth in the dentate gyrus. We postulate that differences in the rate of development in CA1 and in the dentate gyrus are related to the later neurogenesis of dentate granule cells and also possibly to a later functional maturation of N-methyl-D-aspartate (NMDA) receptor-channel complexes on these cells.     

Surgical treatment of gastric cancer: retrospective survey of 1,704 operated cases with special reference to total gastrectomy as the operation of choice.

Total gastrectomy is discussed as the operation of choice among different surgical approaches for gastric carcinoma. We prefer the performance of an elective total gastrectomy with systematic lymphadenectomy (compartments I and II) and obligatory splenectomy. A retrospective study of 1,704 consecutive cases of gastric carcinomas showed a better outcome following total gastrectomy in relationship to distal subtotal gastrectomy, but these results cannot be used as evidence because of the lack of a prospective study. Nevertheless, a precise analysis of our cases in regard to tumor site and tumor type could show a frequency of only 6% to maximally 30%, in which elective total gastrectomy may represent a procedure too extensive to justify for an oncological course.     

X chromosome instability associated with familial Turner syndrome

A family with two members (two generations) exhibiting Turner syndrome is described. Cytogenetic studies on these individuals showed the presence of multiple X chromosome changes. Evidence is presented to show that the maternally inherited X chromosome is the chromosome involved in the structural alterations observed. The effect of a tendency of the maternal X chromosome to break at specific sites on the development of the Turner phenotype and abnormal karyology is discussed.     

Modulation of mild bleeding disorder during remissions and exacerbations of Graves' disease

A patient with Graves' disease had a symptomatic thrombocytopathy during periods of remission. When euthyroid, she noticed bruising, petechiae, and epistaxis. Hemostatic abnormalities included prolongation of the bleeding time by aspirin, reduced platelet retention (a second-phase defect), and abnormal thrombin-induced aggregation and serotonin release. When hyperthyroid, bleeding symptoms resolved, and platelet function returned to normal. These observations suggest that mild bleeding disorders may be influenced either directly or indirectly by thyroid hormone levels.     

Plasma tumor necrosis factor and mortality in critically ill septic patients

Tumor necrosis factor (TNF) cachectin has been implicated as an important host mediator responsible for shock and multiple organ failure (MOF) observed during sepsis. Using a sensitive enzyme-linked immunosorbent assay, we measured plasma TNF levels in 43 septic patients suffering from a broad range of diseases. Measurements were taken on the day that sepsis was diagnosed. Eleven patients had detectable TNF plasma levels ranging from 10 to 100 pg/ml (TNF-positive group); in 32 patients circulating TNF could not be detected (TNF-negative group). The groups did not differ significantly as to age, underlying disease, percentage positive bacteremia and bacteriologic profile, sepsis score, and extent of MOF. Eight (73%) of 11 TNF-positive patients died from sepsis during ICU stay, vs. 11 (34%) of 32 TNF-negative patients (p less than .05). This study demonstrates that sepsis is accompanied by detectable circulating TNF in 25% of the cases, and for these patients mortality is twice that for comparable TNF-negative patients.     

Medical and financial implications of discontinuing a statewide free insulin program involving 3,720 people

In 1981 a statewide program supplying free insulin to 3,720 patients of state health clinics was discontinued. We attempted to assess whether this action had an adverse effect medically and financially on those concerned. A computer randomized sample of 351 patients (9%) was studied by personal interview and questionnaire. Information obtained focused on certain events that occurred 18 months before and after the program ceased. Measurements used to determine medical impact were number of hospitalizations, emergency room and physician visits, changes in weight and glucose levels, and episodes of ketoacidosis. Financial impact was measured by cost of hospitalization and physician visits. Our results revealed no significant changes in any of the medical parameters studied except for fasting serum glucose levels above 300 mg/dl, which occurred less frequently after the free insulin program was discontinued. There were fewer hospitalizations, more visits to physicians, and no change in number of emergency room visits after discontinuance of the free program. The overall cost saving was estimated to be +883,558 for the 18-month study period, in addition to the +550,000 the plan had been costing the state.