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Biomedical subjects

A S Klein

Publications and source records attributed to A S Klein.

At least 55 records · Page 3Linked to original sources

Five major nuclear ribosomal repeats represent a large and variable fraction of the genomic DNA of Picea rubens and P. mariana.

The nuclear ribosomal repeats for the 18S, 5.8S, and 26S RNAs of two closely related Picea (spruce) species were characterized by restriction mapping and Southern blot hybridization. Restriction polymorphisms were identified in the IGS and ITS sequences; however, no polymorphism was species specific. As many as five different rDNA repeat units were observed in individual genomes. The repeat size for these gymnosperms ranged from a minimum of 32 kbp to greater than 40 kbp, two- to threefold larger than the typical angiosperm rDNA unit. Slot-blot hybridizations were used to determine the nuclear rDNA copy concentration. Among P. rubens individuals threefold variation was observed in the rDNA copy concentration, and among P. mariana individuals such variation was as much as sixfold. At a size greater than 32 kbp and at a concentration averaging 1.2-1.3 x 10(4) copies/pg, the rDNA constitutes approximately 4% of the total genome. Regression analysis revealed a significant relationship between copy concentration of the rDNA repeat unit in P. rubens and geographic origins. Differences in the rDNA content in Picea could contribute to the variation, in overall genome size, that has been observed within conifer species.

Base Sequence↗

Reduction of morbidity and mortality from biliary complications after liver transplantation.

Over a 4-yr period that began October 1, 1986, 103 orthotopic liver transplants were performed on 91 patients at the Johns Hopkins Hospital. Biliary reconstruction at the time of transplantation was performed in standard fashion by an appropriately trained member of the surgical team. Six (7%) patients developed biliary complications, which included three cases of common bile duct stricture and one case each of bile duct obstruction caused by biopsy-related hemobilia, biloma and a retained fragment of a T tube after removal. Five of the six patients were treated successfully by nonoperative interventional radiological procedures performed under local anesthesia with light intravenous sedation. Reoperative surgery (to remove the T-tube fragment from subcutaneous tissue) was required for only one patient, and no deaths (0 of 91) were attributable to biliary complications. All six patients are alive and well 6 to 33 mo after the operation with excellent liver function. Our findings would suggest that most biliary complications of orthotopic liver transplants are avoidable and that the few that do appear can usually be managed both safely and effectively by an interventional radiological approach.

Adult↗

Percutaneous intervention in portosystemic shunts in Budd-Chiari syndrome.

Budd-Chiari syndrome is a rare, often fatal illness resulting from hepatic venous outflow obstruction. Surgically created portosystemic shunts are frequently necessary in these patients for portal decompression. Over the past 15 years, 30 patients have been surgically treated for this condition at the Johns Hopkins Hospital. Of the 22 long-term survivors (range, 6 months to 13 years), five (23%) have required further surgical intervention and five (23%) have required percutaneous intervention for shunt complications. Percutaneous procedures included angioplasty (n = 10), atherectomy (n = 1), and urokinase therapy (n = 1). Of the five patients treated percutaneously, one has died of complications from her disease. The remaining four have been followed up for a mean of 16.2 months (range, 5-31 months) and all are in stable condition. None of the five treated with percutaneous interventional procedures have required additional surgical procedures or shunt revisions. Although this series is small, the findings indicate that percutaneous intervention may play a strong adjunctive role to surgery in the treatment of selected patients with portosystemic shunt complications.

Administration, Cutaneous↗

Suprarenal mesocaval shunt.

A new technique for performing a mesocaval shunt above the level of the renal veins is described. It should be considered an option for those patients with perirenal vena caval occlusion or obstruction who require surgical decompression of the portal venous system.

Adult↗

Excision and transposition of two Ds transposons from the bronze mutable 4 derivative 6856 allele of Zea mays L.

The regulatory mutation bronze mutable 4 Derivative 6856 (bz-m4 D6856) contains a complex 6.7 kb Dissociation (Ds) element tagged with a duplication of low copy bz 3' flanking sequences (Klein et al. 1988). This creates a unique opportunity to study the transposition of a single member of the repetitive family of Ds elements. Eighteen full purple revertants (Bz' alleles) of bz-m4 were characterized enzymatically and by genomic mapping. For 17 of the Bz' alleles, reversion to a wild-type phenotype was caused by excision of the 6.7 kb Ds transposon. Nine of these Bz' alleles retained the transposon somewhere in their genome. In this study we show that like Ac (Schwartz 1989; Dooner and Belachew 1989), the 6.7 kb Ds element can transpose within a short physical distance, both proximal and distal to its original position. Additional bz sequences have been mapped immediately distal to the mutant locus in bz-m4 D6856; genetic evidence suggests these are flanked by two additional Ds elements. The remaining Bz' revertant, Bz':107, arose from excision of a more complex 13 kb Ds element.

Alleles↗

Diagnosis and management of the Budd-Chiari syndrome.

Occlusion or obstruction of hepatic venous outflow results in the Budd-Chiari syndrome. The disorder should be suspected in any patient who suddenly develops massive ascites, and the diagnosis can be confirmed quickly and accurately by hepatic venography. In the absence of surgical intervention, survival is rare. Inferior venacavography and percutaneous liver biopsy can be performed safely in these patients, and both procedures provide useful information for the selection of appropriate surgical therapy. Most cases of the Budd-Chiari syndrome are amenable to mesocaval or mesoatrial shunting. Those patients with documented cirrhosis or fulminant hepatic failure are best managed by orthotopic liver transplantation.

Budd-Chiari Syndrome↗

Current management of the Budd-Chiari syndrome.

Twenty-six patients with the Budd-Chiari syndrome were treated surgically at the Johns Hopkins Hospital. Twenty-one of the patients were female and five were male, with a median age at diagnosis of 37 years. Nine patients had polycythemia vera, 6 were receiving estrogen therapy, 5 had a previous hepatitis A or B infection, and 4 had cirrhosis. There was one case each of hepatic malignancy, paroxysmal nocturnal hemoglobinuria, and idiopathic thrombocytopenic purpura. In five cases no etiologic factors or associated disorders were identified. Ascites was the most common presenting feature in this group of patients. Hepatic function at the time of diagnosis, as measured by standard serum chemistries, was only minimally abnormal. The diagnosis of the Budd-Chiari syndrome was confirmed in all 26 patients by hepatic vein catheterization. Inferior vena cavography was also performed and revealed caval occlusion in 4 patients, significant caval obstruction in 13 patients, and a normal vena cava in 9 patients. Interpretation of the vena cavogram was helpful in selecting the appropriate surgical procedure for each patient. Twenty-three of the twenty-six patients underwent percutaneous liver biopsy before operation, with no morbidity or mortality. Four patients had well-established cirrhosis noted on biopsy. Thirty mesenteric-systemic venous shunts were performed on the 26 patients. In 11 patients a mesocaval shunt was performed and in one instance conversion to a mesoatrial shunt was required as a second procedure. In 15 patients a mesoatrial shunt was performed as the initial procedure. Graft thrombosis occurring in 2 of these 15 patients prompted one revision in 1 patient and 2 revisions in the second patient. After mesenteric-systemic venous shunt, eight of the patients (31%) died before discharge from the hospital. The remaining 18 patients in this series were discharged from the hospital alive and well with patent shunts. Patients were followed for a median of 43 months (range, 9 months to 13 years). Five late deaths occurred between 5 and 84 months after the operation. Three- and five-year actuarial survival rates were 65% and 59%, respectively.

Adolescent↗

Superior mesenteric vein inflow for liver transplantation when the portal vein is occluded.

An alternative solution to the problem of liver transplantation in the patient with an occluded portal vein is described. It uses a bridge graft of donor iliac vein from the superior mesenteric vein at the base of the colonic mesentery. The graft is tunnelled over the pancreas and under the stomach to the region of the liver hilum to provide portal inflow. This procedure was employed successfully in four patients, with patency for more than 2 years in the patient with the longest follow-up. By this approach it is routinely possible to perform a transplant procedure in a recipient with an occluded portal vein.

Adult↗

Amanita poisoning: treatment and the role of liver transplantation.

Fatal mushroom poisoning has long been recognized as a major health problem in western Europe and more recently in the United States. The majority of deaths are attributable to the genus Amanita. Amanita phalloides (death cap) has been found with increasing frequency across the United States and presents a significant health hazard in this country to those who pick and consume wild mushrooms. This article discusses the pharmacologic basis and clinical manifestations of Amanita intoxication. It outlines the rationale of various treatment modalities and, from these, summarizes a protocol that the authors believe will be useful to the clinician. In addition, two patients are presented who underwent successful orthotopic liver transplantation for fulminant hepatic failure secondary to Amanita poisoning. The role of liver transplantation both acutely and as treatment for chronic active hepatitis secondary to severe intoxication is discussed.

Adult↗

Effect of a prior portasystemic shunt on subsequent liver transplantation.

Fifteen patients who had a prior portasystemic shunt underwent orthotopic liver transplantation. Shunt types were portacaval in six patients, H-graft mesocaval in six, distal splenorenal in two, and proximal splenorenal in one. Mean blood loss and hospital stay were highest in the portacaval group. Retransplants (two patients) and deaths (two patients) also were limited to this group. In this report, technical considerations, advantages, and disadvantages of the various shunt types are described. Management of patients with late stages of portal hypertension must include estimation of the effects of a portasystemic shunt on subsequent liver transplantation. It is concluded that portacaval shunts should be avoided in patients who may be considered for transplantation. Distal splenorenal shunts are best performed in younger patients with intractable variceal bleeding who are not expected to require transplantation in the near future. A mesocaval H-graft is the shunt of choice in patients who are current liver transplant candidates.

Adult↗

Randomized prospective trial of OKT3 for early prophylaxis of rejection after liver transplantation.

A group of 52 liver transplant patients was prospectively randomized to receive prophylactic immunosuppressive therapy consisting of either Orthoclone OKT3 for 14 days, azathioprine, and steroids (25 patients); or cyclosporine, azathioprine, and steroids (27 patients). The groups were similarly matched for age, diagnosis, and Child's classification. The patients were studied to determine the effect of these two regimens on the incidence of rejection, infection, renal dysfunction, and mortality. Seven rejection episodes, as determined by clinical and histological criteria, occurred in seven of 25 patients (28%) receiving OKT3 compared with 18 episodes in 27 patients (67%) receiving cyclosporine during the first 14 days after transplantation (P less than 0.02). In 20% of the OKT3 patients, CD3+ levels of greater than 10% developed during therapy, and 16% of the patients developed anti-OKT3 antibodies during OKT3 treatment. Five patients were retreated with OKT3 for steroid-resistant acute rejection episodes; all had resolution of the rejection episode. Infectious complications were similar in each group. Renal function, as measured by serum creatinine, was significantly better with OKT3 than with cyclosporine (P less than 0.003) at 14 days. We conclude that prophylactic OKT3 is effective in reducing the number of early rejection episodes after liver transplantation; after 14 days the incidence of rejection is similar; reuse of OKT3 has been successful in liver transplant patients; infectious complications are similar between OKT3 and cyclosporine; and OKT3 preserves renal function better than cyclosporine and is thus indicated in patients with compromised preoperative renal function.

Antibodies, Anti-Idiotypic↗

Use of epidural morphine for control of postoperative pain in selective dorsal rhizotomy for spasticity.

Postoperative pain control can be a major problem after selective dorsal rhizotomy for the treatment of spasticity. We report the use of epidural morphine delivered via a catheter placed at surgery for postoperative analgesia in 28 consecutive patients undergoing this procedure. Pain was well controlled using this technique, and no patients required concomitant parenteral analgesia. There were no instances of respiratory depression, wound infection, or central nervous system depression, and the patients were easily mobilized in the early postoperative period. Epidural morphine is concluded to be a safe and very efficacious method of analgesia after selective dorsal rhizotomy.

Adult↗