Biomedical subjects
D Kahn
Publications and source records attributed to D Kahn.
Ascites and serum bilirubin value predict survival in acute variceal bleeding.
Factors affecting the outcome of acute variceal haemorrhage treated by injection sclerotherapy were analysed. The data on 82 patients undergoing their first admission for acute variceal bleeding were collected prospectively. Using multiple logistic regression analysis and multiway contingency table analysis only the presence of ascites and an elevated serum bilirubin value contributed independently to survival out of a total of 26 discontinuous and 12 continuous variables. A derived regression equation was constructed to predict survival using the data from the 82 patients and this was tested against the observed outcome in a different group of 113 patients also undergoing their first variceal haemorrhage treated by injection sclerotherapy, the data from whom were also collected prospectively. Using a cut-off point of P = 0,71, the equation accurately predicted death for 91% of patients who died and accurately predicted survival for 65% of patients who survived. Overall accuracy of prediction was 73%.
Arteriovenous fistula in the presence of subclavian vein thrombosis: a serious complication.
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Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy.
Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P less than 0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P less than 0.01) and thymidine kinase activity (P less than 0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P less than 0.05) in the rats treated with cyclosporine as compared to the vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
Cyclosporine augments hepatic regenerative response in rats.
A number of mechanisms participate in the hepatic injury that occurs during and following liver transplantation. A normal allograft regenerative response is probably essential for a successful transplant outcome. In this study, the effect of cyclosporine, a potent immunosuppressant used routinely after liver transplantation, on the regenerative response of the liver after partial hepatectomy was investigated. Male Wistar rats were pretreated for one week with either cyclosporine or the olive oil vehicle and were subjected to either a two-thirds partial hepatectomy or a sham operation. Animals were sacrificed at various times postoperatively and the remnant livers were weighed to determine the liver weight to body weight ratio, two biochemical measures of a regenerative response (cytosolic ornithine decarboxylase activity and thymidine kinase activity), and the hepatic content of estrogen and androgen receptors, as the content of these receptors has been shown to modulate, at least in part, the subsequent hepatic regenerative response. The preoperative hepatic cytosol content of ornithine decarboxylase, thymidine kinase, and estrogen receptor was significantly greater (P less than 0.05) in rats pretreated with cyclosporine than in those treated with the vehicle alone. A significant increase in ornithine decarboxylase and thymidine kinase activities occurred after partial hepatectomy in both the cyclosporine-pretreated and vehicle-pretreated animals. The absolute levels for each parameter were also greater in the cyclosporine-treated animals than in the vehicle-treated controls at 24 hr after partial hepatectomy (P less than 0.05). The pattern of change in the hepatic cytosolic content of estrogen and androgen receptors in both groups of animals was comparable with those described previously for regenerating liver.(ABSTRACT TRUNCATED AT 250 WORDS)
The dichotomy of drugs and psychotherapy.
Psychiatrists increasingly combine medication with psychotherapy when treating depression and other disorders. Among the public and practitioners, however, there remains controversy about the compatibility of these treatments. The roots of the controversy can be traced to the ubiquity of dualistic beliefs about mind and body and the historical development of mental health professions. Confusion has also been generated by deriving notions of etiology from observations of phenomenology and treatment response. Understanding these issues will help the practitioner to more successfully combine treatment modalities when both are indicated.
The psychotherapy of mania.
The manic or hypomanic patient paradoxically lives on the edge of loss and lowered self-esteem. This is due to present realities of the impact of the illness upon life and the prospect of cycling into depression and earlier developmental problems to which bipolar patients may be especially prone. Furthermore, manic behavior itself engages others in arguments and countertransference problems that may actually worsen the course of the illness. A psychotherapeutic approach taking these factors into account can have a favorable impact on the acute episode and the long-term course of the illness, provided the patient and psychiatrist are able to form a trusting relationship that survives any recurrences. Justification for these views derives from small series of patients and anecdotal impressions of experienced clinicians. Empirical research is needed on the efficacy of psychotherapy, independent of medication effects.
The incidence of serious hemodynamic changes in physically-limited patients following oral dipyridamole challenge before thallium-201 scintigraphy.
Dipyridamole has liberalized referrals for stress TI-201 chloride (thallium) studies at the Iowa City Veterans Administration Medical Center. Seventy-five percent of referrals now receive dipyridamole and, unlike patients who tolerate conventional exercise testing, these patients are often quite debilitated. Therefore, the hemodynamic consequences of dipyridamole were reviewed in 120 consecutive, physically-limited patients referred for thallium scintigraphy following an average oral dose of 5.4 mg/kg. Each patient's blood pressure was measured every 5 minutes for 1 hour after dipyridamole and compared with several clinical factors to determine if blood pressure change was predictable. In all patients, blood pressure changed from 136 +/- 21/83 +/- 15 (mean +/- 1 SD) to 117 +/- 25/72 +/- 15 following dipyridamole administration. One hundred nine of the 120 patients had a blood pressure decline from 137 +/- 21/82 +/- 12 to 113 +/- 21/70 +/- 13. Of the 109, 43% (N = 47) had a systolic blood pressure decline greater than 20 mmHg, 16% (n = 18) greater than 40 mmHg, and 13% (n = 14) greater than 50 mmHg. Thirteen percent (n = 14) required emergent reversal of the dipyridamole with aminophylline. Significant hypotension is relatively common but generally unpredictable after oral dipyridamole. Therefore, patient eligibility criteria should be carefully considered; strict hemodynamic monitoring must be routine in the usual patient undergoing thallium scintigraphy after oral dipyridamole challenge.
Selective response to carbamazepine in a case of organic mood disorder.
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Ileocolectomy enhances the regenerative response after partial hepatectomy in the pig.
Although portal blood has been shown to be more hepatotrophic than peripheral venous blood, the origin and nature of the factors responsible remain obscure. In this study the effect of partial ileocolectomy (IC) or partial ileal resection (I) on the regenerative response after 50% partial hepatectomy (PH) in the pig was investigated using thymidine kinase activity and mitotic figures as indices of regeneration. IC with 50% partial hepatectomy resulted in a significantly greater regenerative response on the 3rd day than hepatectomy alone or hepatectomy plus partial I. Levels of plasma insulin were elevated after PH and I but not after IC, although there were no significant differences in levels of plasma glucagon or plasma glucose. Levels of aspartate amino-transferase were similar in all groups. These results extend previous data and suggest that the proximal colon may be the source of a regeneration inhibitory factor.
Indium-111-leukocyte/technetium-99m-MDP bone and magnetic resonance imaging: difficulty of diagnosing osteomyelitis in patients with neuropathic osteoarthropathy.
Fourteen patients (16 sites) with clinical and/or radiographic evidence of neuropathic osteoarthropathy (Charcot joints) were evaluated with combined indium-111-leukocyte (111In-WBC) and technetium-99m-methylene diphosphonate (99mTc-MDP) bone imaging for suspected osteomyelitis. Magnetic resonance (MR) images were obtained in seven patients. Using a positive bone culture as the criterion for the presence of osteomyelitis, there were four true-positive studies, six true-negative sites, and one false-negative 111In-WBC study. Five of 16 sites (31%) had false-positive 111In-WBC uptake at noninfected sites. There were four true-positive and three false-positive MR studies. All false-positives showed at least moderately abnormal findings by both techniques at sites of rapidly progressing osteoarthropathy of recent onset. In this preliminary study, both techniques appear to be sensitive for detection of osteomyelitis, and a negative study makes osteomyelitis unlikely. However, the findings of 111In-WBC/99mTc-MDP and MR images at sites of rapidly progressing, noninfected neuropathic osteoarthropathy may be indistinguishable from those of osteomyelitis.
Dismayed by response on incontinent pads.
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Orthotopic liver transplantation and the cytosolic estrogen-androgen receptor status of the liver: the influence of the sex of the donor.
Mammalian liver is known to contain cytosolic receptors for both estrogens and androgens. Furthermore, certain mammalian hepatic functions are known to display a sexual dimorphism. However, in clinical liver transplantation, the sex of the donor is not taken into consideration in selection of the donor. In this study, the effect of liver transplantation on the estrogen and androgen receptor content of the liver was determined. Adult male and female rats were subjected to orthotopic liver transplantation, using donors from both the same and the opposite sex as the recipient. The animals were killed on the tenth postoperative day, and the livers were assayed to determine their cytosolic estrogen and androgen receptor content. Transplantation of a liver from a male donor into a male recipient, from a male donor into female recipient and from a female donor into a male recipient produced similar changes in the number of cytosolic estrogen and androgen receptors in hepatic cytosol. In all three situations, the estrogen receptor content in the cytosol of the transplanted liver was the same as that found in an unoperated male liver, and the cytosolic content of the androgen receptor was the same as that of an unoperated female liver. After transplantation of the liver from a female donor into a female recipient, the estrogen and androgen receptor content in the cytosol of the transplanted liver was the same as that of an unoperated female.(ABSTRACT TRUNCATED AT 250 WORDS)
fixK, a gene homologous with fnr and crp from Escherichia coli, regulates nitrogen fixation genes both positively and negatively in Rhizobium meliloti.
Nitrogen fixation genes are shown to undergo a complex positive and negative regulation in Rhizobium meliloti. Activation of fixN by fixLJ is shown to require a third regulatory gene, fixK. As fixK is activated by fixLJ, we propose a cascade model for fixN regulation such that fixLJ activates fixN via fixK. In addition fixK negatively regulates expression of the nif-specific activator nifA as well as its own expression by autoregulation. Thus nifA and fixK are subject to a mixed regulation, positive (by fixLJ) and negative (by fixK). The sequence of fixK shows homology with the Escherichia coli regulators fnr and crp, which makes fixK the third characterized member of this family of prokaryotic regulators.
Model-building of Fnr and FixK DNA-binding domains suggests a basis for specific DNA recognition.
The DNA-binding C-terminal domains of the regulatory proteins Fnr from Escherichia coli and FixK from Rhizobium meliloti have been modelled on the basis of their homologies to the CAP protein from E. coli. Residues Glu181, Thr182 and Arg185 of CAP, which are exposed residues of the DNA-recognition helix alpha F, are conserved in Fnr and FixK. However, Arg180 and Gly184 are substituted by Val and Ser respectively in Fnr. We propose that this valine makes a Van der Waals' contact with the first thymine in the Fnr consensus TTGA-N6-TCAA, and that the serine contributes to the binding by displacing a thymine-bound water molecule. The corresponding residues in FixK, Ile and Ser allow the same interactions with a thymine. Therefore we predict that FixK may recognize the same sites as Fnr. This is supported experimentally by showing that Fnr can substitute for FixK in activating the fixN gene in E. coli.
Effect of tamoxifen on hepatic regeneration in male rats.
A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.1 mg/rat/day or 1.0 mg/rat/day) or vehicle for three days prior to and after partial hepatectomy, and the anatomic and biochemical process of hepatic regeneration was assessed. Tamoxifen administration caused a dose-dependent decrease in the hepatic cytosolic estrogen receptor activity and, conversely, a dose-dependent increase in cytosolic androgen receptor activity. Despite these changes in baseline hepatic sex steroid receptor status, all receptor activities were comparable between the three groups within 24 hr of partial hepatectomy. Moreover, no differences in any of the parameters assessing hepatic regeneration following partial hepatectomy were evident: liver-body ratio, ornithine decarboxylase activity, and thymidine kinase activity. This lack of effect of tamoxifen treatment on hepatic regeneration suggests either that estrogens do not play a role in the modulation of liver growth after partial hepatectomy or that, once initiated, the regenerative process per se determines a series of events that regulate hepatocellular sex hormone receptor status independent of extrahepatic stimuli.
Effect of antiandrogen flutamide on measures of hepatic regeneration in rats.
Male rat liver undergoes a process of demasculinization during hepatic regeneration following partial hepatectomy. The possibility that antiandrogens might potentiate this demasculinization process and in so doing augment the hepatic regenerative response was investigated. Adult male Wistar rats were treated with the antiandrogen flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for three days prior to and daily after a 70% partial hepatectomy. At various times after hepatectomy, the liver remnants were removed and weighed. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. Hepatic estrogen receptor status and the activity of alcohol dehydrogenase, an androgen-sensitive protein, were measured. Prior to surgery, the administration of 5 mg/day flutamide reduced the hepatic cytosolic androgen receptor activity by 98% and hepatic cytosolic estrogen receptor content by 92% compared to that present in vehicle-treated controls. After hepatectomy, however, all differences in sex hormone receptor activity between the treatment groups were abolished. The rate of liver growth after partial hepatectomy in the three groups was identical. Moreover, hepatectomy-induced increases in ornithine decarboxylase activity and thymidine kinase activity were comparable. These data demonstrate that, although flutamide administration initially alters the sex hormone receptor status of the liver, these affects have no effect on the hepatic regenerative response following a partial hepatectomy.