Voltage-gated calcium channels in adult hippocampal neurons.
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Biomedical subjects
Publications and source records attributed to R Fisher.
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As a part of an ongoing prospective controlled trial, the Southwest Oncology Group compared the results of treatment of advanced non-Hodgkin's lymphoma with two CHOP regimens (cyclophosphamide, adriamycin, vincristine and prednisone with either low-dose bleomycin or BCG by scarification) to a COP regimen (cyclophosphamide, vincristine and prednisone) with low-dose bleomycin (COP-Bleo). The study design emphasized histopathology review and systematic restaging to define complete remission (CR). Confirmed rates of CR for 443 evaluable patients were 59% for 286 patients receiving the CHOP regimens and 59% for 157 patients receiving COP-Bleo. Rates of CR were higher for patients with nodular lymphoma (69%) compared to those with diffuse lymphoma (54%) (p = 0.005). For patients with nodular lymphoma there was no difference in CR rates according to treatment. For patients with diffuse lymphomas the CR rate was higher with the CHOP programs (58%) than with COP-Bleo (44%) (p = 0.10). Overall duration of CR and survival was significantly longer for patients with nodular lymphoma compared to diffuse lymphoma (p less than 0.01). At this time, remission duration and survival were similar regardless of induction regimen used in patients with nodular lymphoma. However, in patients with diffuse lymphoma, the duration of CR and overall survival were improved by treatment with the CHOP regimens compared to COP-Bleo (p = 0.02). Thus, in this controlled study we have demonstrated that initial combination chemotherapy employing the CHOP regimen was a superior remission induction therapy for patients with diffuse lymphoma.
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The effect of severe T-cell depletion on mucosal mast cells of the small intestine and on connective tissue mast cells has been studied in adult thymectomized, irradiated, bone marrow reconstituted (B) rats. Under normal conditions, intestinal mucosal mast cell numbers do not differ significantly between B rats, normal age matched rats and non-thymectomized irradiated controls. Connective tissue mast cells are significantly fewer in the tongues of B rats than in normal rats, but the difference is atributable to an effect of irradiation. Infestation with Nippostrongylus brasiliensis produced approximately equal increases in mucosal mast cells in non-thymectomized irradiation controls and in normal rats. In B rats there was no increase in mucosal mast cells following infestation. B rats failed to expel the parasites normally. Failure of mast cell proliferation was not due to the effects of the persisting worm burden. Antihelminthic treatment at the time of worm expulsion by normal rats did not reveal a hitherto masked mast cell response in B rats. Nippostrongylus infestation did not reveal evidence of thymus-dependency of connective tissue mast cells. As in athymic nude mice, mucosal mast cells in the rat have been shown to be T-cell dependent during the proliferation that follows infestation with an intestinal nematode parasite.
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Of 760 direct admissions to a specialized trauma center, 173 (22.7%) victims of motor vehicle accidents died. Excluding patients dead on arrival, the mortality rate was 14.5%. Autopsy reports were reviewed and showed that the major cause of death was head injury (49.7%). Uncontrollable hemorrhage from massive trauma was the next most common problem and usually proved fatal in the first 24 hours after admission. The incidence of sepsis and renal failure increased with prolongation of CCRU stay. Following admission, respiratory failure was not a common cause of death (3%). Because of direct helicopter rather than ambulance transport from the scene of the motor vehicle accident, earlier attention was paid to diagnosis of trauma and treatment of respiratory insufficiency with mechanical ventilation. Because of the early initiation of therapy, there was rapid restoration of circulating volume and tissue perfusion. This may account for the low mortality.
Between 1972 and 1977, the Southwest Oncology Group studied the following three chemotherapy programs for the treatment of patients with advanced forms of mycosis fungoides: (a) cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) (seven patients); (b) adriamycin, vincristine, and prednisone (HOP) (five patients); and (c) cyclophosphamide, vincristine, prednisone, and bleomycin (COP plus bleomycin) (12 patients). Among the 24 evaluable patients there was an overall objective response rate of 95% with seven (29%) achieving a complete remission. With the adriamycin-containing chemotherapy, five (42%) of 12 patients achieved a complete remission compared to two (17%) of 12 patients treated with COP plus bleomycin. The median duration of remission (partial plus complete) was longer with the COP plus bleomycin combination (median, 47 weeks) than with the adriamycin-containing combinations (median, 22 weeks; P = 0.03). The median survival for all 24 evaluable patients was 95 weeks and was similar regardless of remission-induction therapy. In summary, combination chemotherapy proved to be effective palliative therapy for advanced mycosis fungoides.
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The relation between clinical and biochemical changes in thyrotoxicosis were studied in 12 patients with Graves's disease who were being treated with carbimazole. Clinical assessment (using the Crooks-Wayne index) was combined with the measurement of free thyroxine and triiodothyronine indices (FT4I and FT3I) and the assessment of two tissue markers of thyroid hormone action--sex-hormone-binding globulin (SHBG) levels and the thyrotrophin responses to TRH. In general the FT4I and FT3I fell rapidly once treatment was started, and returned to normal in one to four weeks, followed shortly by SHBG levels. The thyrotrophin response returned at this time in two patients, who still had borderline high levels of FT3I and SHBG. The clinical score fell more slowly and variably and was less closely related to any of the biochemical indices than these were to each other. During the early phase of treatment with antithyroid drug the clinical evaluation may be an unreliable indicator of persisting thyroid hormone excess, and when the patient seems clinically but not biochemically thyrotoxic the symptoms should be treated on their own merits with beta-blocking drugs and not with increased doses of antithyroid drugs.
Thirty-six institutionalized geriatric patients with particularly severe and longstanding dementia were selected by chart review and were studied neurologically. Criteria for clinical diagnosis are derived, and it is shown that arteriosclerosis had caused or contributed to their dementias in 33 patients (91.7%) and probably did so in two others (97.2%). Arteriosclerotic dementia may not be rare and may be much more prevalent than may now be considered the case. As 23 patients (63.9%) showed evidence of carotid and/or vertebrobasilar involvement, large-vessel disease also may be more prevalent in geriatric dementia than is now thought and should be considered in all such patients. The results further confirm that careful review of ward records without reference to psychiatric diagnoses of etiology is a simple, rapid, and reliable method of screening a large institutionalized population for possible arteriosclerotic dementia. The selectees should then be surveyed appropriately to confirm the presence of the disease. Since a careful review of the complete hospital records and a thorough neurologic examination proved sufficient, more definitive but more dangerous invasive diagnostic procedures may not be necessary for clinical pharmacologic and similar investigations.
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Sarcomas of the kidney are highly malignant neoplasms. Abnormal vascularity can be detected in almost all types of sarcomas, but arteriovenous shunting, pooling of contrast material, and tumor staining are seldom present. Extension to renal vein and inferior vena cava may occur. While angiographic findings in our seven cases of renal sarcomas were nonspecific, this diagnosis should be considered in a relatively hypovascular neoplasm especially when the capsular arteries contribute considerably to the vascular supply. Nevertheless, statistically the most likely diagnosis of a hypovascular mass is renal cell carcinoma. Angiographic studies do not alter the management of the patient but merely suggest the diagnostic possibility of sarcoma. Angiographic diagnosis of different histologic types of sarcomas is not possible.
Sixty-three percent of victims of the sudden infant death syndrome had a subnormal volume and 23 percent an enlarged volume of glomic cells in their carotid bodies. Evidences of antecedent chronic alveolar hypoxia and hypoxemia were found in both groups but were more severe in the victims with enlarged glomic tissue.
Hypothalamic-pituitary-gonadal function was studied in 37 cirrhotic males, 25 of whom were alcoholic. Irrespective of aetiology, cirrhotic patients had significantly reduced free testosterone concentrations. Despite low free testosterone concentrations and reduced or absent spermatogenesis, basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were normal in nearly all patients, suggesting impaired function of the hypothalamic-pituitary-gonadal axis. In 14 cirrhotic men, seven of whom had gynaecomastia, the ability of the pituitary to secrete LH and FSH in response to exogenous gonadotrophin releasing-hormone (LH/FSH-RH) was asssessed. A normal LH response to LH/FSH-RH was obtained in patients without gynaecomastia. An exaggerated LH response was found in four of seven with gynaecomastia, suggesting Leydig cell failure. The Leydig cell response to exogenous gonadotrophin in eight consecutive cirrhotic patients was probably abnormal but difficult to interpret as all but one were within conventionally accepted limits of normality. The patients without gynaecomastia gave a normal or minimally exaggerated FSH response to LH/FSH-RH. Six of seven with gynaecomastia gave a markedly exaggerated response suggesting failure of spermatogenesis, and all tested were either azoospermic of oligospermic. The single patient with a normal FSH response had a normal sperm count. The pituitary cells can therefore respond to LH/RSH-RH and the Leydig cells of the testes show some response to exogenous gonadotrophin. Similar abnormalities in hypothalamic-pituitary-gonadal function have recently been described in patients with normal liver function on chronic oestrogen therapy.
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The meaning of the human movement response (M) to inkblot stimuli was explored in terms of correlations between children's M productions and the attributes of their parents in 119 familes. M scores were available for the family members; and for each parent there were also measures of personality, values, and childrearing attitudes. A number of the parent-child correlational patterns were congruent with Rorschach's theories concerning the significance of M.
The reactivity of the lymphocytes from 40 carcinoma patients and 19 patients without detectable malignancies was tested by means of the macrophage-electrophoresis-mobility (MEM) test exposing lymphocytes from one individual to a large spectrum of antigenic preparations. Besides the encephalitogenic protein (EP) and the carcino-embryonic antigen (CEA) hypertonic KCl-extracts from human cancer and normal tissues were used as antigens to be tested. When performed in such a complex manner, the MEM-test resulted in characteristic reaction patterns allowing one not only to discriminate between cancer and noncancer, but also to draw a conclusion in which organ a carcinoma has arisen. The characteristic "immunological tumor profiles", thus obtained, are obviously due to the existance of common antigens in carcinomas of the same tissue origin. The CEA seems to be another antigen of high diagnostic value in that system, since the lymphocyte response to CEA was restricted to patients with tumors of the colon, rectum and stomach. The results show for the first time that lymphocytes of the tumor patients mentioned are able to react to CEA. The human lymphocyte response to CEA seems to be far more cancer- and (or embryo-specific than the reactions obtained with xenogenic hyperimmune sera) which areused for the detection of CEA in human sera or plasma samples. The "immunological tumor profile" opens a new step of quality among the attempts to develop immunological tumor tests.