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Biomedical subjects

L Podesta

Publications and source records attributed to L Podesta.

36 records · Page 2Linked to original sources

Extended preservation of human liver grafts with UW solution.

The fate of 185 cadaveric liver homografts preserved for four to 24 hours with University of Wisconsin (UW) solution was compared with that of 180 grafts preserved for three to 9 1/2 hours with conventional Euro-Collins solution. Although the average preservation time of the UW-preserved livers was almost twice as long as that of the Euro-Collins-preserved livers, the UW-preserved grafts survived at a higher rate; permitted equal patient survival; and had a lower rate of primary nonfunction, a reduced need for retransplantation, and a lower rate of hepatic artery thrombosis. There was no correlation between the time of preservation of UW-preserved grafts up to 24 hours and liver function abnormalities in the first postoperative week. In contrast, livers preserved with Euro-Collins solution for more than five hours had significantly increased perturbations of hepatic function tests. The potential revolutionary effect of the UW solution on liver transplantation is described herein.

Cause of Death↗

Effect of tamoxifen on hepatic regeneration in male rats.

A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.1 mg/rat/day or 1.0 mg/rat/day) or vehicle for three days prior to and after partial hepatectomy, and the anatomic and biochemical process of hepatic regeneration was assessed. Tamoxifen administration caused a dose-dependent decrease in the hepatic cytosolic estrogen receptor activity and, conversely, a dose-dependent increase in cytosolic androgen receptor activity. Despite these changes in baseline hepatic sex steroid receptor status, all receptor activities were comparable between the three groups within 24 hr of partial hepatectomy. Moreover, no differences in any of the parameters assessing hepatic regeneration following partial hepatectomy were evident: liver-body ratio, ornithine decarboxylase activity, and thymidine kinase activity. This lack of effect of tamoxifen treatment on hepatic regeneration suggests either that estrogens do not play a role in the modulation of liver growth after partial hepatectomy or that, once initiated, the regenerative process per se determines a series of events that regulate hepatocellular sex hormone receptor status independent of extrahepatic stimuli.

Animals↗

Effect of antiandrogen flutamide on measures of hepatic regeneration in rats.

Male rat liver undergoes a process of demasculinization during hepatic regeneration following partial hepatectomy. The possibility that antiandrogens might potentiate this demasculinization process and in so doing augment the hepatic regenerative response was investigated. Adult male Wistar rats were treated with the antiandrogen flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for three days prior to and daily after a 70% partial hepatectomy. At various times after hepatectomy, the liver remnants were removed and weighed. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. Hepatic estrogen receptor status and the activity of alcohol dehydrogenase, an androgen-sensitive protein, were measured. Prior to surgery, the administration of 5 mg/day flutamide reduced the hepatic cytosolic androgen receptor activity by 98% and hepatic cytosolic estrogen receptor content by 92% compared to that present in vehicle-treated controls. After hepatectomy, however, all differences in sex hormone receptor activity between the treatment groups were abolished. The rate of liver growth after partial hepatectomy in the three groups was identical. Moreover, hepatectomy-induced increases in ornithine decarboxylase activity and thymidine kinase activity were comparable. These data demonstrate that, although flutamide administration initially alters the sex hormone receptor status of the liver, these affects have no effect on the hepatic regenerative response following a partial hepatectomy.

Alcohol Dehydrogenase↗

Abdominal organ cluster transplantation for the treatment of upper abdominal malignancies.

Ten patients with primary malignant tumors of the biliary tract, duodenum, or stomach and with secondary involvement of the liver underwent removal of most or all of the stomach, liver, pancreas, spleen, duodenum, proximal jejunum, terminal ileum, and ascending and transverse colon. The void in the upper abdomen was filled with an organ cluster graft consisting of the liver, pancreas, duodenum, and variable segments of proximal jejunum. Eight of the ten patients are alive after 3 to 9 months, all with good liver and pancreas function, and most with satisfactory function of the gastrointestinal tract. One of the surviving patients was in the hospital for 4 months because of multiple enteric fistulas and infections; the other seven survivors were discharged after an average of 43 +/- 17.61 (SD) days. Recurrent tumor has not been proved in any of the surviving recipients and is suspected in only one. The study of such cases should provide insight and guidelines applicable to other visceral transplantation procedures that may be attempted in the future.

Abdominal Neoplasms↗

Liver transplantation: an unfinished product.

Liver transplantation has become an extraordinarily valuable and useful operation, but one that is not perfect and that has not been exploited to anything like its full potential. Better immunosuppression may become available soon as exemplified by developments with the Japanese drug, FK506. Improved preservation with the UW solution is already here. With these advantages, liver transplantation is certain to become far more widely used than at any time in the past. Examples were cited of innovative approaches using liver transplantation for the treatment of hepatic malignancies.

Animals↗

Liver regeneration in rats treated with the antiandrogen flutamide.

Previous studies have shown that male rat liver undergoes demasculinization during hepatic regeneration after partial hepatectomy. In the present study the effect of the antiandrogen flutamide on liver regeneration was assessed. Adult male Wistar rats were treated with flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for 3 days prior to and daily after partial hepatectomy. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. The rate of liver growth after partial hepatectomy in the three groups was similar at all time points examined. The increases in thymidine kinase activity and ornithine decarboxylase activity after partial hepatectomy were comparable throughout the study. Thus, administration of flutamide did not influence the regenerative response after partial hepatectomy.

Animals↗

Effect of FK506 in experimental organ transplantation.

FK506 is the most potent immunosuppressive agent known. Its toxicity is substantial in dogs, minor in rats, and unknown in subhuman primates. In small doses that are nontoxic even in dogs, it can be used in synergistic combination with cyclosporine, steroids, and presumably in other drugs.

Animals↗

Knee bracing.

Bracing the knee is a controversial, complex, and often confusing subject. Knee braces are categorized as either prophylactic, rehabilitative, or functional. Bracing goals are to prevent, assist, restrict, align, or simulate function of the knee. A working knowledge of the capabilities and limitations of specific braces in these different categories is required of the physician to properly prescribe these orthotics.

Braces↗

Amelioration of normothermic canine liver ischemia with prostacyclin.

A model of hepatic ischemia was developed in dogs using a pump-driven splanchnic-to-jugular vein bypass during crossclamping of the portal triad. An LD50 was established with three hours of ischemia. PGI2 given for one hour before the ischemic insult ameliorated the ischemic injury and increased survival.

Animals↗

Effect of an antiandrogenic H2 receptor antagonist on hepatic regeneration in rats.

Because biochemical "feminization" of the liver in males is observed with hepatic regeneration and because the hepatic regenerative response in females is greater than that in males, the possibility that antiandrogens might potentiate liver regeneration was investigated. Before 70% hepatectomy, adult male Wistar rats were treated with cimetidine, an antiandrogenic H2 antagonist, at doses up to 10 times greater than those used clinically. Control animals received either the saline vehicle or ranitidine, an H2 antagonist without antiandrogenic properties. Treatment with cimetidine reduced the hepatic cytosolic androgen receptor content compared with ranitidine treatment. Hepatectomy caused a further reduction in androgen receptor activity in all groups. Hepatic cytosolic estrogen receptor activity was comparable in all groups throughout the study. Moreover, the rate of liver growth and the levels of ornithine decarboxylase and thymidine kinase activity induced as part of the regenerative response were similar in all groups. Thus, cimetidine, despite its ability to bind to androgen receptors, and ranitidine, an H2 receptor antagonist without antiandrogen action, do not modulate the hepatic regenerative response to a 70% partial hepatectomy.

Animals↗

Prolongation of pig-to-dog renal xenograft survival by modification of the inflammatory mediator response.

The pathogenesis of hyperacute renal rejection consists of a nonspecific effector cascade that invokes most of the components of a typical acute inflammatory response. Platelet-activating factor (PAF) represents the most recent and perhaps the most significant mediator and promoting agent of this phenomenon. These studies evaluated SRI 63-441, a novel, synthetic, and the most potent PAF receptor antagonist available, alone and in combination with other prostanoids, for their ability to influence this response and to prolong renal xenograft survival and function in a model of pig-to-dog heterotransplantation. Inhibition of PAF by SRI 63-441 alone, at the dosage and schedule used in these experiments, did not significantly prolong xenograft survival or function. However, the combination of SRI 63-441 with either prostacyclin (PGI2) or prostaglandin E1 (PGE1) infusion demonstrated significant synergism, and resulted in a 6-9-fold increase in kidney survival and a 3-20-fold increase in urine output. Neither PGI2 nor PGE1 infusions alone significantly influenced this xenograft model. Electromagnetic flow studies demonstrated significantly delayed diminution in renal artery blood flow in the combination-treated animals. Serial and end-stage histologic examination of kidneys receiving combination therapy demonstrated a delayed onset of the pathologic deterioration and an overall amelioration of the entire process. These studies demonstrate that significant abrogation of a rapid and violent form of hyperacute rejection can be achieved solely by the pharmacologic manipulation of the inflammatory mediator response.

Alprostadil↗

Orthotopic liver transplantation in dogs receiving FK-506.

Ten dogs that survived the perioperative events of liver transplantation were treated with 1 mg/kg/d oral FK. Eight of the recipients lived for at least 1 month postoperatively, and seven are still alive with normal hepatic function after 35 to 65 days. The consistency and good quality of results with this difficult transplant preparation using FK, in spite of its rumored great toxicity in dogs, have highlighted the importance of further developing the drug.

Animals↗

Survey results of transplant patients' attitudes on xenografting.

For centuries, many cultures have described mythical creatures with bodies that combined human and animal features, often the result of violating taboos. This study attempted to investigate the beliefs of transplant patients about xenografting. A survey was given to 100 patients ranging in age from 17 to 74 years old, with 65 men and 35 women, including 72 whites, 18 Hispanics, 5 African Americans, and 4 Asian Americans. The subjects included liver, heart, kidney, lung, and multi-organ transplant patients. The patients were not aware of plans for xenografting at the center under study. Eighty patients agreed with xenografting in an emergency situation. Ten subjects replied, "under no circumstances." Ninety percent believed animal research has advanced medical science. In descending order, the patients preferred human (96%), monkey (44%), mechanical (43%), pig (42%), or dog (34%) organs. Twenty-four patients thought a xenograft would change their appearance, personality, or eating or sexual habits. Twenty patients believed animals have souls. The patients also documented any ethical concerns about xenografting.

Adolescent↗

The long-term followup of primary anterior cruciate ligament repair. Defining a rationale for augmentation.

Fifty primary ACL repairs using the Marshall multiple suture technique were analyzed. The average age at surgery was 23 years (range, 15 to 56), with 76% under the age of 30. The average followup was 61.3 months (range, 48 to 86). The average time from injury to surgery was 7 days (range, 1 to 18). Eighty percent of the injuries were sports-related with football and skiing predominating. Thirty-eight percent were "isolated" ACL tears, and 62% had associated injuries. There was a 46% incidence of meniscal tear with 59% of the meniscal tears being repaired. The postoperative evaluation included a multifactorial analysis correlating 43 variables including subjective, objective, radiographic, and KT-1000 data. The Hospital for Special Surgery Knee Diagnostic Score, a clinical objective score based on the postoperative Lachman and pivot shift examination, a KT-1000 arthrometer data score, and an overall combined assessment score were determined. The results showed 59% excellent, 18% good, 14% fair, and 8% poor. The Lachman test was diagnostic in all cases. The quality of ACL tissue at repair was rated excellent or good in 62% of the cases. Four patterns of ACL tears were distinguished by the location of the tear. Football injury, younger age, increased peroperative pivot shift, midsubstance Type IV tear, and return of full motion correlated with poor postoperative results. Increasing age, tight jointedness, Type I tears, and a 5 degrees flexion contracture correlated with good postoperative results.

Adolescent↗

Bilateral simultaneous rupture of the infrapatellar tendon in a recreational athlete. A case report.

Bilateral rupture of the infrapatellar tendons is a rare event in an otherwise healthy athletic individual. The event is usually quite severe and diagnosis can be readily made on a clinical examination. In the case presented here, predisposing factors consisted of an underlying patella alta and a long history of repetitive trauma to the knee. Prompt diagnosis and surgical repair will lead to a good functional result.

Adult↗