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Biomedical subjects

D E Goldman

Publications and source records attributed to D E Goldman.

At least 19 recordsLinked to original sources

Morbidity and mortality of recurrent hepatitis C infection after orthotopic liver transplantation.

Through molecular virological testing it is now clear that HCV reinfection of the allograft is virtually universal in liver transplant recipients. Although histopathological recurrence of hepatitis C occurs in the majority of patients, it is absent in a substantial minority. To date, no prognostic factors, other than genotype 1b, have been identified that accurately predict these dissimilar outcomes. The natural history of recurrent hepatitis C varies. Historically, it has been regarded as generally benign. However, with increasing numbers of patients transplanted for hepatitis C it is now clear that a subgroup of patients develops severe progressive cholestatic hepatitis associated with allograft failure and death without retransplantation. Within 5 years following OLT, approximately 15-20% of patients progress to chronic active hepatitis and another 15-20% become cirrhotic. A minority of patients develop glomerulopathy or vasculitis, which are often associated with cryoglobulinaemia. The impact of immunosuppressive medications and rejection episodes on histopathological recurrence of progressive hepatitis C remains controversial and requires further studies. Although actuarial survival rates of patients transplanted for hepatitis C differ among transplantation centres, it appears that histopathological recurrence of hepatitis C does have an adverse impact on actuarial survival compared to the survival of patients transplanted for autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis and metabolic liver diseases. When allograft failure develops in patients with recurrent hepatitis C, retransplantation is indicated, even though recent reports indicate that mortality may be increased, especially with concurrent renal insufficiency.

Hepatitis C↗

Choledocholithiasis in patients with normal serum liver enzymes.

Retrospective chart review of 330 patients undergoing ERCP over a two-year period yielded five patients with choledocholithiasis whose serum liver enzyme and total bilirubin levels were repeatedly normal. All were female, three were elderly, and the gallbladder was in situ in three of the five, one of whom had a large gallbladder remnant. In four patients, the common bile duct was dilated (> 10 mm), whereas none had intrahepatic duct dilatation. Four patients had a prominent ampulla, and stone size varied widely. Each patient was managed with endoscopic sphincterotomy and stone extraction followed by cholecystectomy for the four patients with the gallbladder or its remnant in situ. This small series proves that common duct stones may exist in patients with repeatedly normal serum liver enzyme and total bilirubin levels. We hypothesize that marked dilatation of the common bile duct or gallbladder may serve as a pressure sump and blunt liver enzyme elevation. Normal liver enzymes should not dissuade one from performing cholangiography in patients with suspected choledocholithiasis.

Adult↗

Diagnostic considerations in evaluation of patients presenting with melena and nondiagnostic esophagogastroduodenoscopy.

Proper evaluation of patients with melena and nondiagnostic esophagogastroduodenoscopy is comparatively undefined. We sought to determine the percentage of patients with melena and nondiagnostic upper endoscopy and assess the yield of further evaluation. Of 209 patients presenting with melena, 180 underwent esophagogastroduodenoscopy as the initial study, which was nondiagnostic in 43 cases (24%). Further evaluation was pursued in 30. A presumed source of melena was found in 11 patients (37%), identified by colonoscopy in seven, bleeding scan in three, and barium enema plus flexible sigmoidoscopy in one. Nearly all such defined cases originated from the right colon. Small bowel contrast studies, flexible sigmoidoscopy of barium enema alone, and angiography failed to reveal a source. Our findings suggest that many (24%) patients presenting with melena will have nondiagnostic upper endoscopy; further evaluation reveals a potential source in 37% of this group, with the right colon being the most likely location of pathology; and colonoscopy is the test of choice in this cohort.

Adolescent↗

Wilderness emergency medical services: the experiences at Sequoia and Kings Canyon National Parks.

This article describes the National Park Service wilderness emergency medical services (EMS) system, as implemented at Sequoia-Kings Canyon National Park. EMS records on all 434 patients in the period from August 1, 1986, to July 31, 1987, were reviewed. Most patients had minor problems. Overall, 77% of patients contacting the EMS system were released at the scene, and base hospital contact was made in only 28% of cases. However, there were three deaths, 44 (10%) patients who received advanced life support, and 292 (67%) patients who received basic life support. Seven patients who received advanced life support were released without transport. Decisions regarding scope of practice in a low-volume, wilderness EMS system are complicated by long transport times and problems with skills maintenance. Differences between the times and problems with skills maintenance. Differences between the patients treated by a wilderness system and those seen in most urban systems may make it appropriate to release a greater portion of patients without ambulance transport. In a system with long response and transport times, use of personnel with different training than in the urban setting becomes necessary.

Adolescent↗

The polypeptide and the phospholipid components of axon plasma membranes.

The axon plasma membrane fraction isolated from garfish olfactory nerve was analyzed for its polypeptide composition by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. There were present over 20 well-resolved polypeptide components in this membrane, and eleven of them, with an apparent molecular weight range of 22,000-130,000, accounted for most of the membrane proteins. None of the major polypeptide species present in the membrane appeared to be glycoprotein. Based on electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel, eight of the major polypeptides found in garfish nerve membrane appeared to be also present in the axon plasma membrane isolated from lobster walking leg nerve. Both garfish and lobster nerve membranes contained high concentration of lipids (66-76%) which were essentially cholesterol and phospholipids. The classes of phospholipids present were phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol and sphingomyelin. Lobster nerve membrane also contained about 3% phosphatidic acid. Assays for acetylcholinesterase in axon plasma membrane fractions isolated from different nerve sources showed a wide variation, ranging from a specific activity of 2.4 for garfish nerve to 312.5 for lobster nerve membrane.

Acetylcholinesterase↗

Isolation and characterization of plasma membrane fractions from garfish Lepisosteus osseus olfactory nerve.

Garfish Lepisosteus osseus olfactory nerve, because of its large size and the unusually high concentration of axonal membrane, is an excellent source of axonal membrane. A procedure is described for the isolation of two types of plasma membranes from the nerve which are obtained in yields of about 20 mg (fraction I) and 1.5 mg (fraction II) per g of wet nerve. Both membrane fractions consist mostly of rounded membrane vesicles, with a unit membrane thickness of approximately 7.5 nm. The two membrane fractions are different in their lipid to protein ratios, Na-K ATPase activities, polypeptide patterns on sodium dodecyl sulfate (SDS) gel electrophoresis, and fatty acid compositions. They have similar phospholipid composition. On the basis of the relative concentration of axonal and Schwann cell plasma membranes in the nerve, the Na-K ATPase activities of the two membrane fractions and a comparison of the properties of the membrane fractions to those of squid and lobster nerve membrane preparations, fraction I seems to be the axonal membrane and fraction II the Schwann cell plasma membrane. Fraction I has a low protein to lipid ratio. Its polypeptide pattern on SDS gel appears to be much more complex as compared to that of fraction II membrane.

Adenosine Triphosphatases↗

The action of certain polyvalent cations on the voltage-clamped lobster axon.

Calcium appears to be an essential participant in axon excitation processes. Many other polyvalent metal ions have calcium-like actions on axons. We have used the voltage-clamped lobster giant axon to test the effect of several of these cations on the position of the peak initial (sodium) and steady-state (potassium) conductance vs. voltage curves on the voltage axis as well as on the rate parameters for excitation processes. Among the alkaline earth metals, Mg(+2) is a very poor substitute for Ca(+2), while Ba(+2) behaves like "high calcium" when substituted for Ca(+2) on a mole-for-mole basis. The transition metal ions, Ni(+2), Co(+2), and Cd(+2) also act like high calcium when substituted mole-for-mole. Among the trivalent ions, La(+3) is a very effective Ca(+2) replacement. Al(+3) and Fe(+3) are extremely active and seem to have some similar effects. Al(+3) is effective at concentrations as low as 10(-5)M. The data suggest that many of these ions may interact with the same cation-binding sites on the axon membrane, and that the relative effects on the membrane conductance and rate parameters depend on the relative binding constants of the ions. The total amount of Na(+) transferred during a large depolarizing transient is nearly independent of the kind or amount of polyvalent ion applied.

Action Potentials↗

Action of anionic and cationic nerve-blocking agents: experiment and interpretation.

Barbiturates and anesthetics similar to procaine bind to phospholipids in vitro. The former increase the binding of calciumn to the phospholipids; the latter decrease it. The data can be correlated with the effects of these drugs Otl peripheral nerve. The nonpolar portion of the narcotic agents may lie between the lipid chains of the membrane, with the charged region in close approximation to the polar heads of the phospholipids.

Anesthetics, Local↗

Competitive action of calcium and procaine on lobster axon. A study of the mechanism of action of certain local anesthetics.

Voltage clamp studies with the squid giant axon have shown that changes in the external calcium concentration (Frankenhaeuser and Hodgkin, 1957) shift the sodium and potassium conductance versus membrane potential curves along the potential axis. Taylor (1959) found that procaine acts primarily by reducing the sodium and, to a lesser extent, the potassium conductances. Both procaine and increased calcium also delay the turning on of the sodium conductance mechanism. Calcium and procaine have similar effects on lobster giant axon. In addition, we have observed that the magnitude of the response to procaine is influenced by the external calcium concentration. Increasing external calcium tends to reduce the effectiveness of procaine in decreasing sodium conductance. Conversely, procaine is more effective in reducing the membrane conductance if external calcium is decreased. The amplitude of the nerve action potential reflects these conductance changes in that, for example, reductions in amplitude resulting from the addition of procaine to the medium are partially restored by increasing external calcium, as was first noted by Aceves and Machne (1963). These phenomena suggest that calcium and procaine compete with one another with respect to their actions on the membrane conductance mechanism. The fact that procaine and its analogues compete with calcium for binding to phospholipids in vitro (Feinstein, 1964) suggests that the concept of competitive binding to phospholipids may provide a useful model for interpreting these data.

Animals↗