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Biomedical subjects

M D Holzman

Publications and source records attributed to M D Holzman.

24 records · Page 2Linked to original sources

An alternative technique for laparoscopic cholangiography.

The current methods utilized for laparoscopic cholangiography involve cystic duct cannulation and present practical difficulties and potential hazards. An alternative method for intraoperative cholangiography is described which is easy, quick, and safe. The Kumar clamp (a gift from Sabi Kumar, M.D.) is placed across the infundibulum. A 23-gauge sclerotherapy needle is introduced through a side port in the clamp and directed into the infundibulum. The cholangiogram is obtained prior to any dissection in the triangle of Calot, thereby avoiding iatrogenic common bile duct injuries due to misidentification of the cystic duct or anomalous anatomy. To date no pathology has been missed and no complications have resulted from this technique.

Acute Disease↗

Development of a hybrid bioartificial liver.

OBJECTIVE: The authors developed an extracorporeal liver support system and tested its efficacy in experimental animals with liver failure. The first clinical use of this system to treat a patient with liver failure is reported. SUMMARY BACKGROUND DATA: Multiple attempts have been made, ranging from plasma exchange to use of charcoal columns, to develop liver support systems for treating patients with acute severe liver failure. None of these systems has achieved wide clinical use. There is a need for providing liver support as a "bridge" to transplantation and for treating patients with potentially reversible liver dysfunction. METHODS: A hybrid liver support system has been developed consisting of plasma perfusion through a charcoal column and a porous hollow fiber module inoculated with 5 x 10(9) matrix-attached hepatocytes. The system was tested in dogs with ischemic liver failure (n = 7) who underwent plasmapheresis; a control group (n = 6) underwent charcoal perfusion alone. A patient with liver failure was treated with this hybrid system. RESULTS: After 6 hours of hybrid liver support treatment, animals had significantly decreased serum ammonia and lactate levels, increased glucose level, normal prothrombin time, and increased systolic blood pressure compared with controls treated with charcoal perfusion alone. Use of the system to treat a patient was well tolerated with evidence of clinical improvement. CONCLUSIONS: Plasma perfusion through a system consisting of a charcoal column and matrix-attached porcine hepatocytes had significant beneficial effects in animals with liver failure and was well tolerated by a patient with liver failure.

Animals↗

Selective intraportal hepatocyte transplantation in analbuminemic and Gunn rats.

Although significant progress has been achieved in isolated hepatocyte transplantation, the optimal site of cell implantation has not yet been determined. We have developed a novel experimental method of intraportal hepatocyte transplantation that allows easy assessment of the morphology and function of transplanted hepatocytes. Donor hepatocytes were harvested from Sprague-Dawley rats by in situ EDTA/collagenase perfusion. Fifteen recipient Nagase analbuminemic rats (NAR) underwent cannulation of the gastroduodenal vein under ether anesthesia. Either the posterior or anterior liver lobes were selectively infused with cells by occluding the portal venous supply of the nontransplanted liver lobes. Normal donor hepatocytes (2 x 10(7)) suspended in normal saline were infused over 1 min (4 ml). Recipients were treated with cyclosporine for the duration of the experiment. Plasma albumin levels were determined by ELISA, before and at various intervals after transplantation. In NAR rats transplanted with normal hepatocytes, there was a significant (P < 0.003) and sustained (12 weeks) increase in plasma albumin levels. Control NAR rats transplanted with NAR hepatocytes (n = 8) showed no significant changes in plasma albumin levels. Similarly, normal Wistar hepatocytes were infused intraportally into the posterior lobes of Gunn rats (n = 4), which lack the ability to conjugate bilirubin. Pre- and posttransplantation bile was collected following bile duct cannulation. Bile analysis by HPLC, demonstrated a significant (P = 0.04) increase in the level of bilirubin conjugates following transplantation and a corresponding decrease in total serum bilirubin (P = 0.04). Our experimental data demonstrate that direct selective intraportal infusion of hepatocytes is an effective technique of hepatocyte transplantation in the rat.

Animals↗

Coronary vasoconstrictor effects of atriopeptin II.

Atrial natriuretic peptides lower arterial pressure, cardiac filling pressure, and cardiac output. In isolated, Langendorff-perfused guinea pig hearts, atriopeptin II, the 23-amino acid atrial natriuretic peptide, is also a potent coronary vasoconstrictor. The median effective dose for atriopeptin II in guinea pig hearts is 26 nanomoles, the threshold constrictor dose is 5 nanomoles, and flow nearly ceases at a dose of 100 nanomoles in perfused hearts at constant pressure. Similar concentrations of atriopeptin II also cause coronary vasoconstriction in rat and dog heart preparations. The disulfide bridge is necessary for vasoconstrictor activity; reduction of this bridge abolishes the activity, as it does the other biological activities of atrial natriuretic peptides.

Adenosine↗

The role of laparoscopy in the management of suspected pancreatic and periampullary malignancies.

Laparoscopic evaluation of patients with suspected periampullary malignancies has been utilized more frequently in recent years. Its exact role with regard to staging and surgical bypass for palliation have yet to be clearly defined. To better define the role of laparoscopy in the evaluation and palliation of periampullary malignancy, a retrospective review of the Duke experience was carried out. Fifty-three patients with suspected pancreatic or periampullary malignancies were referred for surgical evaluation at Duke University Medical Center between 1993 and 1995. All patients underwent CT scanning and lesions were classified as resectable or unresectable based on previously established criteria. Patients either underwent laparoscopic evaluation (n = 30; 11 with laparoscopic palliation) or proceeded directly to celiotomy (n = 23). Charts were reviewed for postoperative course including complications, length of stay, and hospital costs. Although laparoscopy had a sensitivity of 93.3% for metastatic disease, CT scans accurately staged 86.8% of patients missing only one patient with peritoneal/hepatic disease. Based on these results, laparoscopy may not be beneficial for every patient with a suspected pancreatic malignancy. Retrospectively an attempt was made to determine which patients benefited from laparoscopy and which patients are best served by proceeding directly to open exploration. From these data we devised an algorithm that outlines an efficient and cost-effective approach for this patient population.

Adult↗