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Biomedical subjects

D Kahn

Publications and source records attributed to D Kahn.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1994

Immunoscintigraphy with 111In-satumomab pendetide in patients with colorectal adenocarcinoma: performance and impact on clinical management.

PURPOSE: The role of immunoscintigraphy with 111In-satumomab pendetide in the medical and/or surgical management of colorectal cancer patients was evaluated in a multicenter trial. METHODS: This 103 patient study population included 46 individuals with rising serum carcinoembryonic antigen levels and otherwise negative diagnostic evaluation, 29 patients with known recurrence, presumed to be isolated and resectable, and 28 patients for whom standard diagnostic tests provided equivocal information. RESULTS: No adverse reactions were noted following intravenous administration of 1 mg of satumomab pendetide radiolabeled with approximately 5 mCi of 111In. Thirty percent of patients developed human anti-mouse antibodies postinfusion. In the 84 patients for whom correlation with histopathologic, diagnostic, and/or clinical findings was available, antibody imaging demonstrated a sensitivity of 73 percent in patients with confirmed tumor (36/49) and negative results for all 35 patients with no evidence of malignancy. Occult disease was detected in 18 patients. CONCLUSION: 111In-satumomab pendetide immunoscintigraphy was helpful in the medical and/or surgical management of 45 (44 percent) patients and provided information unavailable from other diagnostic modalities.

Adenocarcinoma↗
PubMed1994

Intrapartum fetal subcutaneous tissue/femur length ratio: an ultrasonographic clue to fetal macrosomia.

OBJECTIVE: Our purpose was to compare the accuracy of ultrasonographic intrapartum measurement of fetal abdominal circumference, estimated fetal weight, and fetal subcutaneous tissue/femur length ratio in predicting large-for-gestational-age fetuses. STUDY DESIGN: A cross-sectional analysis of 173 normal patients delivered of normal, appropriate-for-gestational-age infants (group 1) was performed to determine the normal changes of standard fetal biometric parameters and subcutaneous tissue throughout pregnancy. Measurements of fetal subcutaneous tissue were made at the level of the femoral diaphysis. A second group of 101 well-dated patients had these measurements obtained within 24 hours of delivery (group 2). Large for gestational age was defined as a birth weight > 90th percentile for gestational age. The sensitivity and specificity for prediction of large for gestational age of an intrapartum measurement of an abdominal circumference > 90th percentile, estimated fetal weight > 90th percentile, and fetal subcutaneous tissue/femur length ratio > 2 deviations of the mean was calculated. RESULTS: In group 1 the mean gestational age was 31.4 +/- 5.4 weeks (range 17 to 41 weeks). The femur length, abdominal circumference, and fetal subcutaneous tissue correlated well with gestational age (p < 0.0001). The fetal subcutaneous tissue/femur length ratio was stable throughout pregnancy, with a mean of 0.05 +/- 0.014 (range 0.02 to 0.09, R2 0.09). In group 2 mean gestational age was 38 +/- 2.5 weeks (range 30 to 42 weeks). Mean birth weight was 3280 +/- 740 gm (range 1513 to 4801 gm). Nineteen (19%) fetuses were large for gestational age. Significant differences were found between the appropriate- and large-for-gestational-age fetuses for birth weight, abdominal circumference, estimated fetal weight, and fetal subcutaneous tissue/femur length ratio (p < 0.0001). The sensitivity and specificity of the fetal abdominal circumference, estimated fetal weight, and fetal subcutaneous tissue/femur length ratio were 44% and 98%, 68% and 85%, and 82% and 96%, respectively. CONCLUSION: The fetal subcutaneous tissue/femur length ratio is a gestational age-independent parameter that has a greater sensitivity than the fetal abdominal circumference or estimated fetal weight formula for the intrapartum identification of large-for-gestational-age fetuses.

Abdomen↗
PubMed1994

Radioimmunoscintigraphy with 111indium labeled CYT-356 for the detection of occult prostate cancer recurrence.

We assessed the safety and ability of the 111indium labeled immunoconjugate 7E11-C5.3-glycyl-tyrosyl-(N,e-diethylenetriaminepentaacetic acid)-lysine (CYT-356) to detect sites of occult prostate cancer in 27 subjects who had undergone radical prostatectomy and whose only evidence of recurrent disease was an increasing (0.8 ng./ml. or greater) serum prostate specific antigen (PSA). All subjects underwent whole body scintigraphy between 2 and 4 days following the radiopharmaceutical injection. Routine blood work and human anti-mouse antibody titers were monitored. Scintigraphic findings were compared with clinical parameters, prostatic fossa biopsy results and conventional imaging techniques. Except for transient hypotension in 1 subject following the second infusion, no side effects or human anti-mouse antibody titers were detected. In 22 subjects 1 or more lesions were detected, of which 11 (50%) were confirmed by biopsy, computerized tomography or magnetic resonance imaging. Of 14 subjects with lesions in the prostatic fossa 13 had biopsies performed, 8 (62%) of which were positive. Magnetic resonance imaging confirmed tumor in the spine and chest computerized tomography findings were compatible with lesions seen in the mediastinum in 1 subject each. There was a statistically significant relationship between detecting a scan abnormality and the initial pathological stage of disease but not with the serum PSA. These data provide preliminary evidence that 111indium labeled CYT-356 can be safely administered and readministered, and it detects sites of occult prostate cancer recurrence in subjects whose PSA is increasing following radical prostatectomy.

Humans↗
PubMed1994

A 15-year experience of injection sclerotherapy in adult patients with extrahepatic portal venous obstruction.

OBJECTIVE: The authors report a 15-year experience with injection sclerotherapy in the management of adult and teenage patients with esophageal varices due to extrahepatic portal venous obstruction (EHPVO). SUMMARY BACKGROUND DATA: Extrahepatic portal venous obstruction is an uncommon cause of esophageal varices and is associated with normal liver function. Effective control of variceal bleeding is the major factor influencing survival. The results of surgery have been unsatisfactory, and therefore, more conservative management policies have been adopted. METHODS: Fifty-five patients with proven EHPVO underwent repeated injection sclerotherapy via either a modified rigid esophagoscope under general anaesthesia or a fiber-optic endoscope under light sedation, using ethanolamine oleate as the sclerosant. RESULTS: Esophageal varices were eradicated in 44 patients after a median number 6 injections (range 1-17) over a mean of 12.5 months (range 1-48). The mean follow-up was 6.8 years (range 1.1-14.6 years). Eleven patients were admitted on eighteen occasions with bleeding from esophageal varices before eradication and there were seven bleeding episodes in six patients from recurrent varices after initial eradication. Complications related to sclerotherapy included injection site leak (6), stenosis (11) and mucosal ulceration (32) during 362 injection sclerotherapy episodes. Four patients died during the study period. CONCLUSIONS: Injection scelotherapy is the treatment of choice in most patients with EHPVO.

Adult↗
PubMed1994

Detection of recurrent colorectal carcinoma with In-111 CYT-103 scintigraphy in a patient with nondiagnostic MRI and CT.

Detection of recurrent colorectal carcinoma can be a diagnostic challenge. The authors report a case of a patient who, after resection of his primary colorectal carcinoma, had a recurrence that was not detected by MRI or serial CT examination, but was clearly demonstrated by In-111 labeled CYT-103 scintigraphy. This case demonstrates the use of CYT-103 scintigraphy in detecting recurrent colorectal cancer in a patient, despite results of nondiagnostic MRI or serial CT examinations.

Adenocarcinoma↗