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Biomedical subjects

D Kahn

Publications and source records attributed to D Kahn.

At least 235 records · Page 13Linked to original sources

Hepatic artery thrombosis after pediatric liver transplantation--a medical or surgical event?

Hepatic artery thrombosis (HAT) is one of the most serious complications after orthotopic liver transplantation, and is associated with a high morbidity and mortality. This study retrospectively reviewed 66 liver transplants in children under the age of 10 years during a year-long period at a single institution. A total of 28 perioperative variables were analyzed to identify responsible factors of HAT. Of the 66 children, 18 (26%) developed HAT within 15 days after the transplant (HAT group); 29 (42%) had an uneventful postoperative course (control group). To avoid the possible influence of other complications 19 patients were excluded. Of the variables compared between the 2 study groups, three surgical factors (diameter of the hepatic artery--greater or less than 3 mm; type of arterial anastomosis--end-to-end versus the use of an iliac graft or aortic conduit; and number of times the anastomosis was redone--one versus more than one), were found to be significantly different (P less than .05) between HAT and control groups. Two medical factors also were significantly different: the use of intraoperative transfusion of fresh frozen plasma (FFP) and the administration of postoperative prophylactic anticoagulant treatment. A heparin and dextran-40 protocol appeared to be effective in preventing HAT (P less than .02). Moreover, after multivariate analysis, anticoagulation therapy was demonstrated to be the major independent variable influencing HAT. A better definition of factors responsible for the occurrence of HAT is required. This study should help in formulating effective methods to decrease the incidence of this dreaded complication after liver transplantation.

Anastomosis, Surgical↗

Rhizobium meliloti fixGHI sequence predicts involvement of a specific cation pump in symbiotic nitrogen fixation.

We present genetic and structural analyses of a fix operon conserved among rhizobia, fixGHI from Rhizobium meliloti. The nucleotide sequence of the operon suggests it may contain a fourth gene, fixS. Adjacent open reading frames of this operon showed an overlap between TGA stop codons and ATG start codons in the form of an ATGA motif suggestive of translational coupling. All four predicted gene products contained probable transmembrane sequences. FixG contained two cysteine clusters typical of iron-sulfur centers and is predicted to be involved in a redox process. FixI was found to be homologous with P-type ATPases, particularly with K+ pumps from Escherichia coli and Streptococcus faecalis but also with eucaryotic Ca2+, Na+/K+, H+/K+, and H+ pumps, which implies that FixI is a pump of a specific cation involved in symbiotic nitrogen fixation. Since prototrophic growth of fixI mutants appeared to be unimpaired, the predicted FixI cation pump probably has a specifically symbiotic function. We suggest that the four proteins FixG, FixH, FixI, and FixS may participate in a membrane-bound complex coupling the FixI cation pump with a redox process catalyzed by FixG.

Adenosine Triphosphatases↗

Rhizobium meliloti regulatory gene fixJ activates transcription of R. meliloti nifA and fixK genes in Escherichia coli.

When present in Escherichia coli on the multicopy expression vector pUC19, a Rhizobium meliloti regulatory gene, fixJ, belonging to a two-component regulatory system, activated the expression of two R. meliloti symbiotic genes, nifA and fixK. Primer extension by reverse transcription showed that FixJ stimulates nifA expression in E. coli by activating pnifA.

Escherichia coli↗

A 10-year prospective evaluation of balloon tube tamponade and emergency injection sclerotherapy for actively bleeding oesophageal varices.

During a 10 year study period 234 patients were admitted on 371 occasions with a total of 566 acute variceal bleeding episodes. Of these, 173 patients had 343 variceal bleeds which required balloon tamponade to achieve initial control of bleeding during 229 admissions and were then referred for emergency injection sclerotherapy. Sixty-eight percent of these patients had alcoholic cirrhosis and 42% were poor risk Grade C patients. Injection sclerotherapy was performed initially using the rigid Negus oesophagoscope under general anaesthesia and later using the fibreoptic endoscope under light sedation. Definitive control of variceal bleeding was achieved with sclerotherapy during 197 hospital admissions (92%). Of the 17 failures of emergency sclerotherapy, 4 patients died from uncontrolled bleeding and 13 patients underwent major surgical intervention. Definitive control of variceal bleeding was achieved with a single injection treatment in 138 hospital admissions (70%). Complications were mostly of a minor nature and occurred at a rate of 6% per injection treatment. The overall hospital admission mortality was 36%. The majority of patients died due to liver failure. The mortality in patients who required 4 injection treatments to control variceal bleeding was 71%. Injection sclerotherapy is proposed as the emergency treatment of choice for patients whose variceal bleeding continues or recurs after initial conservative management. Patients whose variceal bleeding is not controlled by 2 injection treatments require more major emergency surgery.

Adolescent↗

Use of verapamil with conventional immunosuppression after porcine renal transplantation.

It has recently been suggested that the use of calcium channel-blocking agents may improve the results of renal transplantation either by enhancing the immunosuppressive effects of ciclosporin, or by improving posttransplant acute renal failure. In the present study, unlike others, verapamil was administered to the animals for 10 days posttransplant, alone or in conjunction with ciclosporin and/or solumedrol. In the group in which all three agents were given together, there were minimal changes in plasma urea or creatinine for the 10 days after transplantation. However, survival and the histological appearances of the kidneys at autopsy showed no improvement as compared with those in animals treated with cicloporin and steroids. There is thus no evidence from this study to suggest that verapamil could advantageously be added to a clinical immunosuppressive regime.

Animals↗

The effect of different types of hepatic injury on the estrogen and androgen receptor activity of liver.

Mammalian liver contains receptors for both estrogens and androgens. Hepatic regeneration after partial hepatectomy in male rats is associated with a loss of certain male-specific hepatic characteristics. In this study we investigated the effects of lesser forms of hepatic injury on the levels of estrogen and androgen receptor activity in the liver. Adult male rats were subjected to portacaval shunt, partial portal vein ligation, hepatic artery ligation, or two-thirds partial hepatectomy. Another group of animals was treated with cyclosporine. At the time of sacrifice the livers were removed and used to determine the estrogen and androgen receptor activity in the hepatic cytosol. A significant reduction (p less than 0.05) in the hepatic cytosolic androgen receptor activity and a slight increase in the estrogen receptor activity occurred following total portosystemic shunting. Partial ligation of the portal vein, which produces a lesser degree of portosystemic shunting, had no effect on the levels of the estrogen and androgen receptor activity present within hepatic cytosol. Cyclosporine-treated animals had significantly greater (p less than 0.01) levels of estrogen receptor activity in the hepatic cytosol compared to vehicle-treated control animals. Levels of estrogen and androgen receptor activity within the hepatic cytosol remained unchanged after ligation of the hepatic artery. The reduction in the cytosolic estrogen and androgen receptor activity in the liver after partial hepatectomy was confirmed. In summary, certain types of hepatic injury are associated with profound changes in the estrogen and androgen receptor content within the liver.

Animals↗

A modified technique of orthotopic transplant of the kidney in rabbits.

In this study kidneys were harvested from bred-for-research cats weighing 4 to 5 kg. General principles of donor bilateral nephrectomy en bloc with aorta, vena cava, renal vessels, and ureters were followed. After the harvest the grafts were placed in lactated Ringer slush. A cuff was prepared on the renal vein over a 10 French plastic tube. The aorta was divided and left in connection with the renal artery at each side. Twenty female checkered Flemish giant rabbits weighing 4.0-6.0 kg served as recipients. After premedication with 40 mg/kg of ketamine, anesthesia was maintained with repeated doses (every 10-15 min) of a 0.1-mL mixture of 5 parts ketamine and 1 part acepromazine diluted 50% in a normal saline. Arterial pressure, CVP, blood gases, and temperature were monitored. Through a limited midline incision a native left nephrectomy was performed. The venous anastomosis was performed with a cuff technique without clamping the vena cava (which causes severe hemodynamic instability); the anastomotic time was 2-3 min. The arterial anastomosis was performed with an end-to-side aorta-to-aorta anastomosis; the anastomotic time was 5 to 7 min. There were no episodes of venous or arterial thrombosis. The donor procedure took approximately 40 min, and the backtable preparation of the graft an additional 45 to 60 min. Preparation of the recipient for the anastomosis took 15 min and the anastomotic time (warm ischemia) was 13 +/- 5 min. In this model suitable for xenograft research the duration of the surgery in the recipient has been greatly reduced because of (1) the previous backtable preparation of the graft, and (2) the cuff technique used for venous anastomosis. The present anesthesia regimen and careful hemodynamic monitoring were also important in the success of this model.

Anesthesia, General↗

The safety of switching rapidly from tricyclic antidepressants to monoamine oxidase inhibitors.

Monoamine oxidase inhibitors (MAOIs) are increasingly used for patients who do not respond to an initial trial of tricyclic antidepressants (TCAs). Although there are insufficient data documenting the optimal manner for switching a patient from a TCA to an MAOI, standard references advise a drug-free interval of at least 1 week. In clinical practice, however, such a delay may be difficult to observe. In order to explore the safety of a more rapid switch from TCA to MAOI therapy, we survey members of our department (Columbia University) as to their experience with different methods of switching patients from TCAs to MAOIs. Thirty-three respondents reported having switched an estimated 432 patients over the course of 3 years, with 178 patients switched within 4 days of discontinuing TCA therapy, including 63 who had the MAOI added while still being tapered from the TCA. More experienced psychiatrists tended to be less conservative, some using time intervals of 4 days or less. No adverse reactions were reported, including hypertensive and hyperpyrexic crises. This retrospective survey and an accompanying review of the literature suggest that the recommended drug-free interval of a week or more when switching patients from TCAs to MAOIs may be overly conservative.

Antidepressive Agents, Tricyclic↗

Incidence and management of complications after injection sclerotherapy: a ten-year prospective evaluation.

The incidence and management of complications of injection sclerotherapy are reviewed in 304 consecutive patients with esophageal varices followed up prospectively for a 10-year period. The 304 patients were injected on 1336 occasions. Three hundred eleven local esophageal complications occurred in 140 patients (complication rate, 23% per injection and 46% per patient). Esophageal mucosal slough, which was diagnosed by endoscopy, occurred on 250 occasions in 126 patients but did not require specific treatment. An injection site leak occurred in 25 patients, was managed conservatively, and was associated with a mortality rate of 28%. Stenosis of the esophagus was found in 32 patients, but only five patients required dilatation for relief of symptoms. Rupture of the esophagus occurred in four patients, three of whom had surgical treatment, and was associated with a mortality rate of 50%. Serious complications were more frequent with the rigid esophagoscope. An injection site leak occurred more frequently after acute sclerotherapy via the rigid esophagoscope. All four patients with rupture of the esophagus were injected electively via the rigid esophagoscope. Although the incidence of serious complications after injection sclerotherapy in this series appears acceptable, complications have been noted to be cumulative with time.

Adolescent↗

Clinical outcome of patients with a 'low probability' of pulmonary embolism on ventilation-perfusion lung scan.

Lung ventilation and perfusion (V/Q) scintigraphy is usually indicated when pulmonary embolism (PE) is a suspected diagnosis. Typically, V/Q scintigraphic interpretation is reported as a "normal," "low," "intermediate," or "high probability" of PE. Although a "low probability" interpretation does not exclude the diagnosis of PE, it significantly reduces the likelihood. We retrospectively analyzed up to one year of follow-up in 90 patients who were clinically suspected of having PE, but in whom V/Q scintigraphy implied a low probability of PE. None of the 90 patients demonstrated clinical evidence of PE subsequent to the V/Q scan. Our findings suggest that significant pulmonary embolism is uncommon and that the clinical course appears to be predictable in patients with a low probability V/Q scan.

Follow-Up Studies↗

Cascade regulation of nif gene expression in Rhizobium meliloti.

We report the discovery of two genes from Rhizobium meliloti, fixL and fixJ, which are positive regulators of symbiotic expression of diverse nitrogen fixation (nif and fix) genes. nif gene regulation is shown to consist of a cascade: the fixLJ genes activate nifA, which in turn activates nifHDK and fixABCX. Like nifA, fixN can be induced in free-living microaerobic cultures of R. meliloti, indicating a major physiological role for oxygen in nif and fix gene regulation. Microaerobic expression of fixN and nifA depends on fixL and fixJ. The FixL and FixJ proteins belong to a family of two-component regulatory systems widely spread among prokaryotes and responsive to the cell environment. We propose that FixL, which has features of a transmembrane protein, senses an environmental signal and transduces it to FixJ, a transcriptional activator of nif and fix genes.

Amino Acid Sequence↗

Partial hepatectomy and liver regeneration in pigs--the response to different resection sizes.

Liver regeneration has been extensively studied in the rat and dog models but pigs have seldom been used. They resemble man closely in their omnivorous diet and their gastroenterological and endocrinological responses. This paper describes techniques of 15, 50, 65, and 70% partial hepatectomy in the pig. Thymidine kinase activity and mitotic index were used as indices of liver regeneration. The timing and events of the regenerative response in the pig compared favorably with other animal models and the maximum regenerative response occurred on the third postoperative day, irrespective of the size of the partial hepatectomy. The 15% partial hepatectomy, which shows a minimal response to resection, provides a suitable "primed" model for the study of stimulatory substances.

Animals↗

Temporal factors influence recovery of function after embryonic brain tissue transplants in adult rats with frontal cortex lesions.

Adult rats with lesions of the medial frontal cortex received implants of frontal cortex taken from embryos on the 19th day of gestation and placed directly into the zone of injury at 7, 14, 30, or 60 days after initial surgery. Another group was given bilateral frontal lesions, followed 20 days later by a second small lesion to enhance the release of putative neurotrophic factors. They then received transplants 7 days after this second operation. All rats began postoperative training on a spatial alternation learning task within 4 days after the implants of fetal tissue. The brain-damaged rats with transplants at 7 or 14 days after surgery significantly improved postoperative acquisition of spatial alternation. Transplants made 30 or 60 days postoperatively had no effect; these groups were as impaired as those with lesions alone. The animals given a second, "priming" lesion after a 20-day delay, followed by implants of fetal brain tissue, performed as poorly as the group with frontal cortex lesions alone.

Animals↗

Rigid versus fiberoptic endoscopic injection sclerotherapy. A prospective randomized controlled trial in patients with bleeding esophageal varices.

During a 3-year period (June 1981-July 1984), 70 patients who presented with an endoscopically proven variceal bleed were randomized to receive either fiberoptic injection sclerotherapy (FIS, 36 patients) or a rigid scope technique (RIS, 34 patients), using ethanolamine oleate as the sclerosing agent. After discharge, patients entered into a chronic injection sclerotherapy program. Control of the acute bleeding episode (FIS, 91%, RIS, 95%) and the first hospital admission mortality (FIS, 34%, RIS, 44%) were similar. Eradication of varices was achieved in 16/19 and 13/16 cases in the two respective groups of patients who survived longer than 3 months, and only 2 of these patients (both of whom were in the RIS group) had a further major variceal bleed. The overall complication rate per injection was significantly lower in the FIS group (p less than 0.005). Twenty-six patients (14 FIS, 12 RIS) were alive at the end of the 4-year trial period. Of the total of 44 deaths, only 3 were not associated with a bleeding episode. Only five of the 29 patients who had their varices eradicated died during the trial period (median follow-up of 16 months). FIS has become the preferred method of treatment at the Groote Shuur Hospital, particularly in the long-term management of these patients. The procedure is safe, does not require a general anesthetic, and in long-term management, most patients can be treated on an outpatient basis. RIS should be reserved for the difficult recurrent acute bleeder, where the more controlled situation with a rigid scope under general anesthesia may provide safer and more effective sclerotherapy. The study stresses the importance of achieving eradication of all varices to prevent rebleeding and its attendant high mortality.

Esophageal and Gastric Varices↗

Hepatic stimulator substance in extracts from regenerating porcine liver. Basic physiochemical properties.

Previous studies in rats and dogs have implicated the liver as the source of some of the factors which are responsible for its regeneration. In the present study extracts from regenerating and normal livers were infused into the portal vein of pigs after a 15% partial hepatectomy. Thymidine kinase activity was measured on the 3rd and 4th days as an index of liver regeneration. An intraportal infusion of extracts from regenerating, but not normal, livers resulted in an increased regenerative response. The response was dose-related. The stimulator substance was stable when stored at -20 degrees C and could be precipitated by absolute ethanol.

Animals↗