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Biomedical subjects

D Kahn

Publications and source records attributed to D Kahn.

At least 145 records · Page 8Linked to original sources
PubMed1995

Detectability of simulated brain activation using dual radioisotope SPECT based on size and intensity of the focal hyperactivity.

RATIONALE AND OBJECTIVES: Simultaneous single-photon emission computed tomography (SPECT) neuroimaging with both technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and iodine-123 (123I) N-isopropyl-iodoamphetamine is a recently introduced method with potential for assessing activation phenomena in the brain. However, there is limited information on the accuracy of the technique for detecting focal cortical sites of neuroactivation. We determined, in vitro, what levels of activation could be detected as a function of the size of the activated region. METHODS: A Lucite brain phantom was filled with both 123I and 99mTc so as to simulate both a nonactivated state (123I) along with focal sites of activation (99mTc). Simulated activations ranged from 0 to 18% in volumes of 7, 14, 20, and 27 cm3. Imaging was performed with a triple-detector gamma camera using a 10% symmetric window at 140 keV and 10% asymmetric window around 159 keV. No correction was made for gamma cross-talk. To determine whether a simulated activation was "detected," the 99mTc: 123I count ratios in the activated regions were compared by t test with ratios in nonactivated regions of similar volume. Detection sensitivities also were calculated as the fraction of the activated 99mTc: 123I ratios that were greater than the mean + 2 standard deviations of the corresponding nonactivated ratios. RESULTS: All sites of simulated activations of 10% or greater were detected. The detection sensitivity was 100% (95% confidence interval, 90-100%) for the two largest chambers with simulated activations of 13-18%. Activations in the 3-6% range, in the same-sized chambers, were detected with a limited sensitivity (67% with a confidence interval of 45-84%). In the 14-cm3 chamber, simulated activations in the 13-18% range were detected with 90% sensitivity (confidence interval, 74-98%). In general, the detection sensitivity was greater for larger chambers and higher levels of simulated activation. CONCLUSION: We conclude that the dual-radioisotope technique using triple-detector SPECT systems and low-energy all-purpose (LEAP) collimators should be highly reliable for identifying focal brain activations above 13% that cover at least 14 cm3 of brain cortex. Smaller, less intense sites of activation will be detected with reduced frequency. These conclusions are based on our assessment of only the physical parameters involved in this methodology and other factors (e.g., the possibility that the relation between cerebral radiotracer concentration and regional cerebral blood flow) may affect the results obtained with patients.

Brain↗
PubMed1995

Emphysematous pyelonephritis in diabetic patients.

OBJECTIVE: To determine the clinico-pathological profile of patients with emphysematous pyelonephritis (EPN). PATIENTS AND METHODS: The records of 22 diabetic patients who presented with EPN were reviewed. RESULTS: EPN occurred predominantly in female diabetic patients without evidence of ureteric obstruction. The ages of the patients and the duration of the diabetes were variable. EPN occurred in insulin-dependent as well as non-insulin-dependent patients. The patients presented following a prodromal illness of urinary sepsis, with an acute severe illness with symptoms and signs on the affected side. Dehydration and ketoacidosis were common. The diagnosis was made by recognizing gas in the kidney on an X-ray or ultrasound. Eighteen patients were subjected to emergency nephrectomy. CONCLUSIONS: EPN is an uncommon, life-threatening condition characterized by the production of intraparenchymal gas. We believe that vigorous resuscitation and emergency nephrectomy is the treatment of choice.

Adult↗
PubMed1995

Haemostatic and immunological sequelae of portacaval shunt in rats.

We have evaluated the link between haemostatic abnormalities and immune dysfunction in liver disease by evaluating parameters of cellular and humoral immunity in conjunction with coagulation profiles in rats following portacaval anastomosis, induction of portal hypertension by portal vein stenosis or by sham surgical procedures. Twelve weeks following surgery, portacaval shunted rats were markedly anaemic (8.9 +/- 0.6 g/dl; controls 12.3 +/- 1.4 g/dl, p < 0.05), had low plasma fibrinogen levels (0.6 +/- 0.3 g/l, controls 2.5 +/- 0.2 g/l p < 0.05) and markedly elevated fibrin(ogen) degradation products (FDP) titres (1/40-1/80; controls < 1/10. p < 0.05). Portal vein stenosed rats were less anaemic (11.5 +/- 0.8 g/dl), had near normal fibrinogen levels (2.1 +/- 0.3 g/l) but elevated FDP levels (1/40-1/80). Both portacaval shunted and portal vein stenosed rats had elevated serum IgG levels (35.1 +/- 14.1 g/l; 29.2 +/- 13.9 g/l respectively; control values 20 +/- 5.9 g/l p < 0.05 for comparison with both experimental groups). Intrinsic lymphocyte proliferation to T and B cell mitogens was markedly depressed in the portacaval anastamosed rats when compared to controls. Serum factors inhibitory to control lymphocyte proliferation were noted in the shunted rats. Phagocytosis of complement and immunoglobulin sensitised sheep RBC by Kupffer cells purified from rats that had undergone portacaval shunting was markedly reduced (p < 0.05). The increased degree of phagocytosis following exposure to LPS-endotoxin (50 micrograms/ml) was proportionate in degree to the control group. Spontaneous release of bioactive lymphocyte activating factors (IL-1 and IL-6) by purified rat sinusoidal cell populations was decreased in the portacaval shunted group, and decreased still further following stimulation with LPS (50 micrograms/ml) in vitro. The observation that many of the haemostatic and immunological abnormalities associated with chronic liver disease are present in rats with surgically created portacaval shunts or with induced portal hypertension, lends credence to the hypothesis that shunting of portal blood is, at least in part, responsible for many of the systemic manifestations associated with chronic liver disease.

Animals↗
PubMed1995

Serotonin syndrome.

We describe a patient treated with trazodone, isocarboxazid, and methylphenidate hydrochloride who developed confusion, agitation, poor concentration, rigidity, myoclonus, involuntary movements, orthostatic hypotension, and hyperreflexia. CK was normal, and the syndrome resolved spontaneously over 12 hours. The serotonin syndrome occurs following the use of serotomimetic agents (serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, tryptophan, 3,4-methylenedioxy-methamphetamine, dextromethorphan, meperidine, S-adenosylmethionine) alone or in combination with monoamine oxidase inhibitors. It is characterized by various combinations of myoclonus, rigidity, hyperreflexia, shivering, confusion, agitation, restlessness, coma, autonomic instability, low-grade fever, nausea, diarrhea, diaphoresis, flushing, and rarely, rhabdomyolysis and death.

Depressive Disorder↗
PubMed1995

Patients with multiple sclerosis presenting to psychiatric hospitals.

BACKGROUND: Although many neuropsychiatric syndromes are associated with multiple sclerosis, few recent studies have examined the clinical features of psychiatric illness in inpatients with multiple sclerosis. Florid psychopathology can obscure neurologic symptoms in multiple sclerosis. It is therefore important to consider the range of severe psychiatric states that can occur in multiple sclerosis and the frequency with which multiple sclerosis patients are seen in inpatient facilities. METHOD: We examined records for 2720 consecutive admissions to three psychiatric units and conducted a chart review comparing the DSM-III psychiatric diagnoses of patients with multiple sclerosis with those of the inpatient population as a whole. RESULTS: The 10 patients with multiple sclerosis were significantly more likely to present with histories of mania and manic psychosis than the inpatient population as a whole. Further, 7 of the 10 patients had psychiatric hospitalizations before the multiple sclerosis diagnosis. In 4 of these 7 patients, a review of the medical record documented neurologic symptoms that were not recognized as typical of multiple sclerosis. Three of these 4 patients were psychotic and the fourth was catatonic at the time of their admissions. CONCLUSION: While multiple sclerosis patients account for a small proportion of all psychiatric admissions, clinicians should consider the diagnosis of multiple sclerosis in patients exhibiting manic symptoms in tandem with unexplained neurologic findings.

Adult↗
PubMed1995

Repair of a massive ventral hernia in a morbidly obese patient.

Aggressive perioperative management, with progressive preoperative pneumoperitoneum, is a worthy method of repairing massive ventral hernias with associated loss of domain in morbidly obese patients. The authors present a case and its successful outcome.

Adult↗
PubMed1995

A cost-to-benefit analysis of blood products used during the initiation of an orthotopic liver transplantation programme.

Orthotopic transplantation is the treatment of choice for selected patients with end-stage post-necrotic and cholestatic liver diseases. These individuals typically have disturbed haemostasis, which reflects both impaired hepatic synthesis of clotting factors and disseminated intravascular coagulation compounded by large-volume transfusions of blood products occasionally required during surgery. The latter contribute significantly to the cost of this procedure, but may approximate the cumulative consumption of that required for the support of patients in liver failure. Perspective is provided by prospective analysis of data from the first 10 patients in the current programme. There were striking, if transient, intra-operative changes in standard laboratory parameters of coagulation and fibrinolysis; all patients were readily controlled with replacement therapy administered according to serial haemostatic measurements combined with clinical judgement. In most patients these values had stabilised within 24 hours of surgery. Those with post-necrotic liver cirrhosis had the most marked degrees of hepatic dysfunction, reflected in more profound haemostatic disturbances; these patients required the largest amounts of blood products. Inclusive median costs for the first year were estimated at R35,000 and for the first 5 years at R60,000, with 80% of the patients expected to be alive between 5 and 10 years later and enjoying an excellent quality of life. These figures contrast with those estimated for optimal medical and non-transplant surgical management following variceal bleeding as a major complication of liver disease (R30,000 for the first year and R70,000 at 3 years). In addition, the latter patients would usually be unable to work and have a poor quality of life with minimal likelihood of survival beyond this point. We conclude that with a multidisciplinary approach in an academic centre, surgical replacement of the irreversibly damaged liver in properly selected patients is no more expensive and has a better outcome than acceptable alternative approaches.

Adult↗
PubMed1995

Omentopexy for the difficult perigraft lymphocele after renal transplantation.

Between January 1977 and October 1992, 6 patients who had undergone renal transplantation presented with a symptomatic lymphocele that failed to resolve after conventional therapy and eventually required surgical intervention. This complication developed between 7 and 36 months postoperatively. Patients presented with local discomfort combined with deteriorating graft function caused by ureteric obstruction. The lymphoceles recurred after aspiration or external drainage and resolved after omentopexy. We conclude that omentopexy is a satisfactory procedure for the treatment of lymphoceles which fail to resolve after aspiration or external drainage.

Adult↗
PubMed1994

Phosphorylation of the Rhizobium meliloti FixJ protein induces its binding to a compound regulatory region at the fixK promoter.

The FixJ protein is a member of the regulator class of two-component systems involved in the transcriptional activation of nitrogen fixation genes in Rhizobium meliloti. Phosphorylation of FixJ was previously demonstrated to dramatically enhance its transcriptional activity at the nifA and fixK promoters. Here we show that the isolated carboxyl-terminal domain of FixJ, FixJC, binds the fixK promoter, whereas binding of the full-length FixJ protein requires its phosphorylation. By analyzing the DNase I and Exonuclease III protection patterns of the wild-type and a mutant fixK promoter, we have identified two overlapping binding regions for both phosphorylated FixJ and FixJC. A higher affinity region is located between positions -69 and -44 relative to the transcription start site, and a lower affinity region, between positions -57 and -31, overlaps the -35 region of the promoter.

Bacterial Proteins↗
PubMed1994

Intramolecular signal transduction within the FixJ transcriptional activator: in vitro evidence for the inhibitory effect of the phosphorylatable regulatory domain.

FixJ is a phosphorylatable 'response regulator' controlling the transcription of the key nitrogen fixation genes nifA and fixK in Rhizobium meliloti. Sequence and genetic analyses indicated that FixJ comprises an N-terminal phosphorylatable regulatory domain, FixJN, and a C-terminal transcriptional activator domain, FixJC. We have now overexpressed and purified the FixJC protein and show that it is fully active in an in vitro transcription system with purified RNA polymerase. FixJC appeared to act synergistically with RNA polymerase at the nifA promoter. Furthermore FixJC was more active in vitro than the full-length dephosphorylated FixJ protein. Therefore activity of FixJC is inhibited by FixJN within the FixJ protein. This inhibition is relieved by phosphorylation of FixJN. Such a negative mode of intramolecular signal transduction may be generalizable to other response regulators.

Bacterial Proteins↗
PubMed1994

The effect of administration of FK506 on delayed regeneration in flushed partially hepatectomized livers.

It has been shown previously that liver regeneration after partial hepatectomy in rats is delayed if the liver is subjected to either concurrent ischaemia, flushing with cold solution, or grafting. We have shown recently that treatment with CsA preoperatively overcomes the suppressive effect of flushing and returns the regenerative response to a normal time scale. The present study was designed to investigate whether administration of FK506 would also return the observed delayed regenerative response to normal. Long-Evans rats weighing 250-350 g were subjected to standard 68% partial hepatectomy. Group 1 had no further treatment; in group 2, the liver remnant was flushed with 10 ml cold (4 degrees C) Ringers lactate solution, and in group 3, FK506 (1 mg/kg/day) was administered by intramuscular injection for 3 days before the partial hepatectomy and flushing as in group 2; a final dose was given after completion of the procedures. Animals were killed in sets of 6 per group at 4, 24, 48, 72, and 96 hr after surgery and blood samples were taken for measurement of plasma aspartate amino-transferase. Liver biopsies were analyzed for measurement of thymidine kinase and ornithine decarboxylase activity and for counting of mitotic figures. While the highest recorded thymidine kinase activity occurred in group 1 at 24 hr, this was delayed to 48 hr in both group 2 and 3 and counts remained high up to 96 hr in group 3. Mitotic indices were only significantly elevated (compared with group 1 at 96 hr), while ornithine decarboxylase activity did not correlate with these changes being significantly lower than in groups 2 and 3 at 4 hr and in group 3 also at 24 hr. Plasma aspartate aminotransferase was also significantly higher in group 3. It is concluded that the administration of FK506 preoperatively to rats subjected to partial hepatectomy and flushing did not restore the delayed regenerative response to normal but enhanced the response (as measured by thymidine kinase but not by mitotic indices) which commenced at 48 hr and was still present at 96 hr.

Animals↗
PubMed1994

Positron emission tomographic measurement of bone marrow blood flow to the pelvis and lumbar vertebrae in young normal adults.

Ten young normal adults had pelvic and lumbar vertebral body bone marrow blood flow examined using [15O]water and positron emission tomography (PET) in a study designed to assess the feasibility and reproducibility of the PET technique for measuring marrow blood flow to various marrow regions. The procedure was well tolerated. Repeated blood flow measurements obtained from two consecutive [15O]water exams on each individual subject were highly reproducible. In addition, there was minimal variation in marrow blood flow from individual to individual and no gender differences were noted. In contrast, mean +/- SD bone marrow blood flows (expressed as milliliters per minute per 100 g) at selected anatomical sites were significantly different and were as follows: lower lumbar vertebral bodies, 17.6 +/- 3.1; most posterior and superior pelvis (conventional site of percutaneous bone marrow biopsy), 14.3 +/- 3.1; and total superior pelvis, 11.1 +/- 2.0. We conclude that PET is a relatively noninvasive, simple, and reproducible technique for measuring bone marrow blood flow. Marrow blood flow is consistent between normal young subjects, but varies significantly between different anatomic regions of the marrow.

Adult↗
PubMed1994

Primary sclerosing cholangitis. Requiem for biliary drainage operations?

OBJECTIVE: To review the outcome of a consecutive number of patients with primary sclerosing cholangitis (PSC) treated at one institution to define prognostic variables and determine the influence of surgery on outcome. DESIGN: Case series of patients with PSC seen in Cape Town, South Africa, between 1981 and 1991. SETTING: Tertiary referral center. PATIENTS: Thirty-six patients with PSC were studied. Diagnosis was based on cholangiographic findings of multiple strictures of the bile ducts together with compatible clinical and biochemical features. Thirty-two patients were followed up prospectively for up to 9 years. MAIN OUTCOME MEASURES: Patient outcome was defined as good (stable or slowly progressive disease) or poor (death or liver transplantation). RESULTS: During the follow-up period, seven patients with PSC died and two underwent liver transplantation. Actuarial survival at 5 years was 52%. An increased serum bilirubin concentration was the only variable at presentation that independently predicted a poor outcome. Cholangiography was unhelpful in predicting patient outcome. Six patients who developed obstructive jaundice associated with advanced liver disease underwent biliary drainage operations for surgically correctable strictures, but this did not seem to prevent progression of the disease. Two patients who progressed to end-stage liver disease went on to have liver transplantation and were alive with functioning grafts at 7 and 14 months, respectively. CONCLUSIONS: Symptomatic PSC is a progressive disorder with a poor prognosis. Our experience suggests that patients with advanced liver disease caused by PSC should be considered directly for liver transplantation rather than biliary bypass operations.

Adolescent↗
PubMed1994

Perioperative administration of a single dose of conjugated oestrogen to uraemic patients is ineffective in improving haemostasis.

The excessive bleeding that occurs in uraemic patients undergoing surgery is reported to be reversed by at least one schedule of prior oestrogen administration. To assess this possibility a single intravenous injection of 25 mg of the conjugated hormone was given to ten uraemic patients undergoing regular haemodialysis and randomly compared to eight matched patients who received only the diluent. Two hours later there was no reduction in bleeding time, improvement in platelet aggregation, nor an increase in plasma levels of factor VIII (VIII:C), von Willebrand factor (VWF:Ag), or the factor VIII-related ristocetin cofactor state. Furthermore, there was no reduction in intraoperative blood loss, being a median of 558 +/- 154 (range 225-1,260) mL in the test group and 412 +/- 55 (range 270-555) mL in the control and additional median postoperative portovac drainage was 123 +/- 27 (range 0-170) mL and 153 +/- 41 (range 45-240) mL, respectively. These findings differ from the shortening in bleeding time achieved by others with repeated administration of the same agent, and emphasize the importance of dose and duration of oestrogen therapy when used for this indication.

Adolescent↗
PubMed1994

Modular arrangement of proteins as inferred from analysis of homology.

The structure of many proteins consists of a combination of discrete modules that have been shuffled during evolution. Such modules can frequently be recognized from the analysis of homology. Here we present a systematic analysis of the modular organization of all sequenced proteins. To achieve this we have developed an automatic method to identify protein domains from sequence comparisons. Homologous domains can then be clustered into consistent families. The method was applied to all 21,098 nonfragment protein sequences in SWISS-PROT 21.0, which was automatically reorganized into a comprehensive protein domain database, ProDom. We have constructed multiple sequence alignments for each domain family in ProDom, from which consensus sequences were generated. These nonreduntant domain consensuses are useful for fast homology searches. Domain organization in ProDom is exemplified for proteins of the phosphoenolpyruvate:sugar phosphotransferase system (PEP:PTS) and for bacterial 2-component regulators. We provide 2 examples of previously unrecognized domain arrangements discovered with the help of ProDom.

Amino Acid Sequence↗