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Biomedical subjects

W D Warren

Publications and source records attributed to W D Warren.

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

The Hermes transposable element from the house fly, Musca domestica, is a short inverted repeat-type element of the hobo, Ac, and Tam3 (hAT) element family.

The genome of the house fly, Musca domestica, contains an active transposable element system, called Hermes. Using PCR and inverse PCR we amplified and sequenced overlapping segments of several Hermes elements and from these data we have constructed a 2749 bp consensus Hermes DNA sequence. Hermes termini are composed of 17 bp imperfect inverted repeats that are almost identical to the inverted terminal repeats of the hobo element of Drosophila melanogaster. Full length Hermes elements contain a single long ORF capable of encoding a protein of 612 amino acids which is 55% identical to the amino acid sequence of the hobo transposase. Comparison of the ends of the Hermes and hobo elements to those of the Ac element of Zea mays, and the Tam3 element of Antirrhinum majus, as well as several other plant and insect elements, revealed a conserved terminal sequence motif. Thus Hermes is clearly a member of the hobo, Ac and Tam3 (hAT) transposable element family, other members of which include the Tag1 element from Arabidopsis thaliana and the Bg element from Zea mays. The evolution of this class of transposable elements and the potential utility of Hermes as a genetic tool in M. domestica and related species are discussed.

Amino Acid Sequence↗
PubMed1993

The hobo transposable element of Drosophila can be cross-mobilized in houseflies and excises like the Ac element of maize.

The hobo transposable element from Drosophila melanogaster was found to be capable of excision, resulting in donor sites unlike those reported for any other transposable element currently known in animals. These empty sites most closely resemble those left by the transposable elements Ac and Tam3 in Zea mays and Antirrhinum majus, respectively. Like Ac and Tam3, the hobo element was found to function in a distantly related species, in this case the housefly Musca domestica. Hobo excision in M. domestica was found not to require the expression of hobo-encoded transposase but instead appears to be driven by an endogenous hobo transposase-like activity. DNA sequences displaying high homology to the hobo transposase gene were isolated from the genome of M. domestica and appear to be part of a mobile-element system related to hobo, Ac, and Tam3.

Animals↗
PubMed1990

Endoscopic variceal sclerosis compared with distal splenorenal shunt to prevent recurrent variceal bleeding in cirrhosis. A prospective, randomized trial.

STUDY OBJECTIVE: To define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis. DESIGN: A prospective, randomized clinical trial with crossover for those failing therapy. The median follow-up was 61 months. SETTING: A private, tertiary-referral university hospital. PATIENTS: Seventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval. TREATMENTS: Endoscopic variceal sclerosis or distal splenorenal shunt. MEASUREMENTS AND MAIN RESULTS: Survival was significantly (P = 0.02) improved in patients randomly assigned to receive sclerotherapy: 13 of these 37 (35%) patients failed sclerotherapy and required surgical rescue. A survival advantage (P = 0.01) was seen in patients with alcoholic cirrhosis who had this combined therapy; however, in patients with nonalcoholic cirrhosis, survival for those receiving sclerotherapy and surgical rescue was not significantly (P = 0.36) different from that of patients receiving distal splenorenal shunt. Control of variceal bleeding was significantly (P less than 0.001) better in the distal splenorenal shunt group (34 of 35 [97%] compared with 15 of 37 [41%] in the sclerotherapy group). Using death, uncontrolled rebleeding, or shunt thrombosis as the endpoints resulted in no significant difference between treatment groups. Hepatocyte function and portal perfusion were significantly better maintained in patients with alcoholic cirrhosis who were managed by sclerotherapy rather than shunt (P = 0.01 and P = 0.001, respectively). CONCLUSIONS: Endoscopic sclerotherapy with surgical rescue for uncontrolled bleeding is the optimum therapy for patients with alcoholic cirrhosis and variceal bleeding. Survival is similar in nonalcoholic patients treated with either distal splenorenal shunt or endoscopic sclerotherapy, but shunting provides better control of variceal bleeding.

Endoscopy↗
PubMed1990

A hypercoagulable state follows orthotopic liver transplantation.

Orthotopic liver transplantation may be associated during the postoperative period with hepatic artery thrombosis, a catastrophic occurrence generally necessitating emergency retransplantation. To assess the contribution of the coagulation mechanism to this complication, the levels of procoagulant and anticoagulant proteins were followed in 41 liver transplant patients during the first 10 postoperative days. The mean activities of all procoagulant factors reach normal values on day 1 except for factors V and VII, which achieve normal activity by day 3. Supernormal levels of factor VIII activity and antigen are noted (peak values on day 5 of 334% +/- 113% and 481% +/- 260%, respectively). The anticoagulant proteins show delayed recovery, with deficient antithrombin III levels seen in 81% of patients on day 3 and 57% on day 5. Similarly, proteins C and S are subnormal in 24% and 21%, respectively on day 3, and 20% and 10%, respectively, on day 5. During this period, elevated levels of thrombin/antithrombin complexes are encountered, reflecting in vivo activation of the coagulation mechanism. Activated thrombin is, therefore, being generated at a time when a decrease in the major regulatory anticoagulant proteins exists. These data suggest an imbalance between the hemostatic and thrombotic mechanisms and indicate a sustained prothrombotic state that may contribute to the risk for hepatic artery thrombosis. Using a regimen of low-dose heparin and fresh frozen plasma infusion, no thromboses have been seen in 65 consecutive liver transplants.

Blood Coagulation Disorders↗
PubMed1990

Surgical options, hematologic evaluation, and pathologic changes in Budd-Chiari syndrome.

This article presents a scheme of management for Budd-Chiari syndrome based on experience with 33 patients. Therapy in acute Budd-Chiari syndrome is dictated by the liver biopsy, with hepatocyte necrosis indicating the need for placement of a decompressive shunt. The type of shunt was determined by intrahepatic vena cava obstruction; a higher morbidity rate was associated with the mesoatrial shunt in 11 patients than with a portacaval shunt in 10 patients. Successful shunt placement allowed stabilization of the liver biopsy and maintenance of good hepatocyte function [galactose elimination capacity (preoperative: 349 +/- 40 mg/minute; 20 months: 344 +/- 60 mg/minute)]. Severe fibrosis and reduced galactose elimination capacity (264 +/- 43 mg/minute) indicated advanced disease--chronic Budd-Chiari syndrome--and were indications for liver transplant. Hematologic evaluation documented a myeloproliferative disorder in 8 of the last 13 patients evaluated; perioperative and late anticoagulation and/or chemotherapy reduced recurrent thrombosis. We conclude that the Budd-Chiari syndrome requires different therapies depending on the stage of disease. If no hepatocyte injury is present on biopsy, therapy may not be needed. Acute, reversible injury can be managed by placement of a decompressive shunt. Irreversible damage requires transplantation. Selection of the right therapy requires a complete evaluation.

Budd-Chiari Syndrome↗
PubMed1990

The relative role of sclerotherapy vs. surgical procedures in portal hypertension.

This review is a discussion of the evolution of different modes of therapy to treat variceal bleeding. At the present time, endoscopic sclerosis represents the mainstay of therapy for most patients with chronic cirrhosis. In patients who fail sclerotherapy, selective shunt surgery is indicated in patients with good hepatic reserve, and liver transplantation for those who have chronic liver failure.

Humans↗
PubMed1989

Increased galactose clearance after liver transplantation: a measure of increased blood flow through the denervated liver?

This study measured the liver blood flow-dependent index of galactose clearance in patients after liver transplantation, to test the hypothesis that liver blood flow is increased in the denervated liver. Eight normal subjects and 16 patients 1 to 8 months after liver transplant were studied. All patients were stable with no evidence of severe rejection at the time of study. Galactose clearance was measured at steady state during continuous infusion of 75 mg per min of 5% galactose. The results show a statistically significant (p less than 0.01) higher average galactose clearance in the transplant patients (1,187 +/- 316 ml per min per m2) compared to the control group (709 +/- 121 ml per min per m2). The major limiting factor in galactose clearance at low concentrations is liver blood flow, and we interpret these data as evidence for increased blood flow in the transplanted liver. Possible mechanisms for the increased galactose clearance are (i) loss of normal vasomotor tone in the denervated liver, or (ii) persistence of abnormal systemic hemodynamics after transplantation. Elucidation of these mechanisms awaits further study.

Adult↗
PubMed1989

Change in hepatic function, hemodynamics, and morphology after liver transplant. Physiological effect of therapy.

Orthotopic liver transplantation (OLT) has become standard therapy for patients with acute hepatic necrosis and end-stage liver disease. This study measured change in hepatic function (galactose elimination capacity [GEC]), liver blood flow (low dose galactose clearance: flow), hepatic volume (CT scan; volume) and morphology after OLT. The aim was to measure the physiologic response after OLT and compare this response with that after selective shunt (SS) and sclerotherapy (ES) to determine which patients should receive specific therapy. Between January 1987 and November 1988, 37 patients underwent OLT. Operative mortality was 18%, which was similar to that of SS in Child's C cirrhotics. GEC and volume were less in transplant patients than in cirrhotics treated with SS or ES. GEC, flow, and volume normalized after OLT; GEC was preserved after ES and SS, but volume decreased. Three preoperative patterns were observed that can aid in selection of OLT candidates. Patients with chronic cirrhosis (chronic active hepatitis; cryptogenic) need OLT when GEC is less than or equal to 225 mg/min and volume is less than or equal to 50% normal. Patients with Budd-Chiari Syndrome require OLT if cirrhosis has evolved. Patients with sclerosing cholangitis and primary biliary cirrhosis qualify for transplants when complications of the portal hypertensive syndrome develop. The studies can also direct therapy for ES failures. Selective shunt is indicated in those patients with stable disease whose GEC is greater than or equal to 300 mg/min and liver volume is greater than 75% normal; OLT is indicated for cirrhotics with GEC that is less than 225 mg/min and liver volume that is less than 50% predicted normal.

Adult↗
PubMed1989

Distal splenorenal shunt with splenopancreatic disconnection. A 4-year assessment.

The aims of distal splenorenal shunt with splenopancreatic disconnection (DSRS-SPD) were to improve maintenance of portal flow and prevent siphoning of hepatotrophic factors from the pancreas, as occurs after standard DSRS. The main patient population targeted for improvement were alcoholic cirrhotics, who have poorer survival than nonalcoholic cirrhotics and greater loss of portal flow (60%) after standard DSRS. Seventy-eight patients had DSRS-SPD during the study period 1983 to 1987: thirty-two patients were Child's A, 25 were Child's B, and 21 were Child's C. The 35 patients with alcoholic cirrhosis were a significantly poorer risk group by Child's class and galactose elimination capacity (GEC) than the 39 patients with nonalcoholic cirrhosis. Four patients had portal vein thrombosis. At 4-year follow-up, portal perfusion is maintained in 84% alcoholic and 90% nonalcoholic patients, with hepatic and systemic hemodynamics showing identical patterns for both groups. Hepatic function measured by GEC was maintained in alcoholic patients (290 +/- 68 mg/min to 303 +/- 74 mg/min) and nonalcoholics patients (342 +/- 92 to 320 +/- 118 mg/min). Gastric variceal rebleeding occurred in 10 patients--4 early (less than 2 months) and 6 late (18 to 54 months), leading to operation in 4 and transhepatic embolization in 4 patients: 2 of these patients died from this complication. Survival data show an operative mortality rate of 6.4% and overall mortality rate of 30%, with no significant difference between alcoholic and nonalcoholic cirrhotics. DSRS-SPD has significantly improved maintenance of portal perfusion and survival in patients with alcoholic cirrhosis requiring selective shunt for variceal bleeding when compared to standard DSRS. In this population DSRS-SPD is the operation of choice. In patients with nonalcoholic cirrhosis, the current data have not shown DSRS-SPD to have advantage over standard DSRS.

Angiography↗
PubMed1989

Two-stage surgical management of Budd-Chiari syndrome with obstruction of the inferior vena cava.

A two-stage approach to the surgical management of acute Budd-Chiari syndrome complicated by inferior vena caval obstruction was advocated by our group in 1984. This entailed initial hepatic decompression by suprahepatic, mesoatrial shunt, with subsequent takedown of the mesoatrial shunt combined with conversion to a short infrahepatic, portacaval shunt. We report herein the late follow-up results for two patients managed in this manner. While both patients are alive and doing well, both of the courses have been complicated by stenosis of the inferior vena cava. The cause is unclear but probably relates to fibrosis at the hepatic venous orifices. Management was by percutaneous balloon dilation, which relieved the recurrent hepatic congestion. This cautions others considering this approach to provide careful longitudinal follow-up study for such patients.

Acute Disease↗
PubMed1988

Management of variceal bleeding in patients with noncirrhotic portal vein thrombosis.

Since 1971, 70 patients have been seen at Emory University Hospital with gastroesophageal varices secondary to extrahepatic portal vein thrombosis (PVT). Thirty-seven of these patients had had prior major operative therapy. In only three patients (8%) was shunt surgery successful, and there was a high incidence of rebleeding, other morbidity, and mortality. Of especial note are the serious consequences of simple splenectomy; splenomegaly and thrombycytopenia should rarely, if ever, be used as indication for splenectomy in portal hypertension. In 1977, the use of selective distal splenorenal shunt (DSRS) was begun at Emory in this population and a selective shunt has been possible in 24 of 29 patients (83%) who had had no prior operative therapy. Results have been excellent with a greater than 90% patency rate, long-term portal perfusion in all, no encephalopathy, and late rebleeding in one patient. Quantitative studies at 3-6 years show stability of liver function, significant decrease in spleen size, and rise in platelet count. However, long-term follow-up (greater than 15 years) is required in PVT patients before definitive assessment can be obtained. A specific problem of the PVT patient is late shunt stenosis which requires close observation; dilatation of the shunt was performed in six of the 24 patients with a patent shunt. Poor results with non-shunt operative procedures in PVT were again documented. The proper role of endoscopic variceal sclerotherapy is not yet clear, but appears to be an excellent addition to the therapeutic options. In conclusion, for patients with a patent splenic vein, initial therapy should be a selective shunt; for patients without a patent splenic venous system, endoscopic sclerotherapy is the procedure of choice.

Adult↗
PubMed1988

Bleeding due to portal hypertension: the role of surgery.

Several therapeutic options are available to stop acute variceal bleeding or prevent its recurrence. Sclerotherapy has emerged as the optimal method for stopping acute bleeding, and as primary therapy for preventing recurrence. Surgery is required for the 30% to 40% in whom sclerotherapy fails. Selective variceal decompression has emerged as the best surgical option to balance bleeding control and maintenance of liver function. Survival is significantly improved at five years in nonalcoholic (75%) compared with alcoholic (45%) cirrhotic patients. Recent advances have modified the operative technique to better maintain portal perfusion. Total shunts stop bleeding, and may be used in emergencies. Devascularization procedures have a 20% to 40% rebleeding rate, but do not accelerate liver failure. Liver transplantation, which is increasingly indicated for patients with end-stage liver disease and variceal bleeding, is dictated by the degree of hepatic failure. To provide optimal patient care, a center should be able to offer all of the treatment methods.

Esophageal and Gastric Varices↗
PubMed1988

1987 Gallie lecture. Quality control in surgical research: importance to the patient.

One of the deficiencies in surgical scholarship is the rarity of timely, well-controlled research to evaluate new operative procedures. The invasive aspect of surgery makes randomized studies more difficult to initiate, and in studies with large numbers of participating surgeons, the impact of unsatisfactory surgical expertise (craftsmanship) is a major variable. In an effort to improve surgical research, the use of quality control data for early assessment of the effectiveness of the operative procedure is strongly recommended. Early postoperative studies of stimulated gastric acid secretion have led to improved surgical performance during trials of operations using vagotomy for control of peptic ulcer disease. Similar, early, quality control studies have been effective when investigating selective shunts for control of variceal bleeding; necessary data include shunt patency, portal perfusion of the liver and obliteration of major portoazygous collaterals. Failure to incorporate objective tests for surgical quality control can lead to erroneous assessment of operations. Carefully planned prospective studies of well-performed operations are urgently needed.

Clinical Trials as Topic↗
PubMed1987

Evaluation and treatment of early hemorrhage of the alimentary tract after selective shunt procedures.

The cause and treatment of early variceal bleeding in 15 patients who had undergone distal splenorenal shunt were reviewed. Eight of these patients were taken from a group of 91 who underwent selective shunts from July 1983 through June 1985 and had extensive preoperative and postoperative evaluation of shunt patency and pressure gradient. Seven patients operated upon before July 1983 were reviewed because they illustrate the cause, diagnosis, successful and unsuccessful management of bleeding after selective shunt. Urgent selective arteriography combined with shunt catheterization is the key diagnostic and therapeutic maneuver. Thrombosis of the shunt can be successfully managed by revising the anastomosis. Stenosis of the shunt can be successfully treated with balloon dilation or operative revision of the anastomosis. When renal vein hypertension (RVH) occurs, there might be inadequate decompression of the varices. A gradient of 10 millimeters of mercury or greater from left renal vein to vena cava is diagnostic. Measurements of 30 patients who had no bleeding and one patient with documented RVH show the gradient decreases over time. Treatment should be supportive until this adaptation occurs. Hemorrhage can also occur in patients with a patient shunt but without a significant pressure gradient. Inadequate decompression of the varices through the short gastric veins leading to the spleen has been proposed as one cause. Termed short gastric hypertension, this syndrome could be expected to parallel RVH because the venous collaterals will enlarge and eventually decompress the varices. Treatment should be aimed toward supporting the patient until this adaptation occurs. A small number of patients continue to bleed despite these therapeutic interventions but can sometimes be salvaged with a total shunt.

Catheterization↗
PubMed1986

LeVeen vs Denver peritoneovenous shunts for intractable ascites of cirrhosis. A randomized, prospective trial.

Peritoneovenous shunts (PVSs) have provided salutary effects on medically recalcitrant ascites, functional renal impairment, nutritional derangements, ventilatory embarrassment, and locomotion potential in patients with cirrhosis. While the LeVeen (LPVS) and Denver (DPVS) PVSs are most frequently implanted in such patients, postoperative complications of bleeding gastroesophageal varices, sepsis, and shunt occlusion occur with notable frequency. Addressing primarily the complication of PVS occlusion, a randomized prospective trial of LPVSs and DPVSs was conducted in cirrhotic patients with refractory ascites. From July 1, 1982 to July 1, 1984, 26 initial PVSs were implanted for hepatic-related intractable ascites. Twenty-two patients were eligible for randomization (cirrhosis, sterile ascites, initial PVS, total bilirubin level less than or equal to 6.0 mg/dL, prothrombin time less than or equal to 5-s prolongation, serum creatinine level less than or equal to 2.0 mg/dL [creatinine clearance rate greater than or equal to 20 mL/min], absence of recent [less than 30 days] bleeding gastroesophageal varices, or absent spontaneous encephalopathy). Twelve LPVSs and ten DPVSs were implanted; however, one patient with a DPVS was found to have hepatic polycystic disease and was excluded from analysis. All patients were followed up until death or Jan 1, 1985. The PVS patency determinations included contrast shuntography, technetium Tc 99m albumin scintigraphy, sequential manual compression (DPVS), and operative or autopsy observation. Using the Kaplan-Meier actuarial analysis, the LPVS patency proved to be highly superior to that of the DPVS, while survival was not significantly different. As LPVS and DPVS complications other than patency are comparable, the LPVS is preferred for its superior patency in cirrhotic patients with intractable ascites.

Actuarial Analysis↗