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Biomedical subjects

M J Orloff

Publications and source records attributed to M J Orloff.

At least 37 records · Page 2Linked to original sources
PubMed1992

Is portal-systemic shunt worthwhile in Child's class C cirrhosis? Long-term results of emergency shunt in 94 patients with bleeding varices.

A prospective evaluation was conducted of 94 unselected patients ("all comers") with biopsy-proven Child's class C cirrhosis (93% alcoholic) and endoscopically proven acutely bleeding esophageal varices who underwent emergency portacaval shunt (EPCS) (85% side-to-side, 15% end-to-side) within 8 hours of initial contact (mean, 6.1 hours) during the past 12 years. Follow-up has been 100% and includes all patients for at least 1 year, and 61 patients (65%) for 5 to 12 years. Incidence of serious risk factors on initial contact was: ascites, 97%; jaundice, 86%; portal-systemic encephalopathy including past history, 71%; severe muscle wasting, 96%; alcohol ingestion within 7 days, 66%; delirium tremens, 16%; serum albumin, less than or equal to 2.5 g/dL 76%; indocyanine green dye retention greater than or equal to 50% in 45 minutes, 66%; serum glutamic-oxaloacetic transaminase greater than or equal to 100 units/L, 60%; hyperdynamic cardiac output greater than or equal to 6 L/minute, 98%. Mean Child's point score was 13.7 out of a maximum of 15. EPCS reduced mean corrected free portal pressure from 286 to 23 mm saline, and permanently controlled variceal bleeding in every patient. Of the 94 patients, 74 (80%) left the hospital alive and 68 (72%) survived 1 year. Five-year actuarial survival rate is 64%. Hepatic failure was the main cause of death during initial hospitalization as well as during follow-up, when it was related to continued alcoholism. Portal-systemic encephalopathy, which was present on initial contact in 55% of patients, occurred at some time during follow-up in 18.7%, but was recurrent and required dietary protein restriction in only 9%, all of whom had resumed alcoholism. The low incidence of portal-systemic encephalopathy was attributable to the lifelong program of follow-up with regular dietary counseling and continued emphasis on both protein restriction to 60 g/day and abstinence from alcohol. Abstinence was sustained in 69%, liver function improved in 82%, general health was judged excellent or good in 73%, and Child's risk class converted to class B in 73% and class A in 21%. Excluding retirees because of age, 42% were gainfully employed or engaged in full-time housekeeping. Long-term shunt patency was documented in 100% of survivors by yearly angiography or Doppler ultrasonography. It is concluded that EPCS within 8 hours of initial contact permanently controls variceal hemorrhage and results in prolonged survival and a life of acceptable quality in many alcoholic cirrhotic patients in Child's class C.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Reversal of diabetic somatic neuropathy by whole-pancreas transplantation.

To answer the crucial question regarding reversibility of diabetic somatic neuropathy by whole-pancreas transplantation, metabolic studies and electron microscopic morphometry of the sciatic and testicular nerves were performed monthly for 2 years in three groups of highly inbred rats: (1) NC, 47 nondiabetic controls; (2) DC, 90 untreated alloxan-induced diabetic controls; and (3) DT, 230 diabetic rats given syngeneic pancreaticoduodenal transplants 6, 9, 12, 15, 18, and 21 months after induction of diabetes mellitus (DM). Six diabetic nerve lesions were quantitated by a "blind" protocol: (1) loss of myelinated axons, (2) intraaxonal glycogen deposits, (3) axons with glycogen deposits, (4) demyelinated axons, (5) degenerating axons, and (6) loss of intact axoglial junctions in paranodal terminal myelin loops. In the DT group, testicular nerve specimens were obtained just before transplantation and at death so that each animal served as its own control. As we have observed previously in untreated diabetic controls, all six nerve lesions progressed relentlessly for 2 years, in contrast to nondiabetic controls (p less than 0.01). Whole-pancreas transplants produced complete metabolic control of DM for life and reversed all six lesions in both sciatic and testicular nerves, even when done late in the course of DM. There was complete reversal of the nerve lesions when pancreatic transplantation was done within 15 months of the onset of DM. These results provide the first demonstration of reversal of diabetic somatic neuropathy by any form of DM therapy and extend our previous work in which whole-pancreas transplants were found to prevent both diabetic neuropathy and nephropathy and reverse mesangial enlargement in the kidney.

Animals↗
PubMed1989

Long term results of treatment of Budd-Chiari syndrome by side to side portacaval shunt.

This is a report of a long term prospective study of 13 seriously ill patients with Budd-Chiari syndrome as a result of occlusion of the hepatic veins who were treated by side to side portacaval shunt from four to 78 weeks after the onset of symptoms and who were under observation for three to 16 years. The patient population was young, ranging in age from 19 to 45 years; seven were men and six were women. The presumed cause was the use of oral contraceptives in three, polycythemia rubra vera in two, Behcet disease in one patient and unknown in seven patients. All of the 13 patients had abdominal pain, marked ascites, hepatosplenomegaly, wasting and disturbed liver function. Diagnosis was based on the symptoms and signs: angiographic demonstration of hepatic vein occlusion and a patent inferior vena cava; pressure measurements that showed an inferior vena caval pressure that was normal or within the usual range for patients with massive ascites and an elevated wedged hepatic vein pressure that was much higher than the inferior vena caval pressure, and the results of biopsy of the liver showing centrilobular congestion and necrosis. Side to side portacaval shunt was very effective in decompressing the liver, reducing the mean corrected portal pressure from 240 millimeters of saline solution before to 7 millimeters of saline solution after the shunt. Operative survival rate was 92 per cent, and the long term survival rate for three to 16 years is 85 per cent. All of the survivors are free of ascites without requiring diuretic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Hyperparathyroidism, cirrhosis, and portacaval shunt. A new clinical syndrome.

This is a report of six patients with cirrhosis of the liver in whom primary hyperparathyroidism occurred due to a solitary parathyroid adenoma 3 months to 9 years after undergoing emergency portacaval shunt for hemorrhage from esophageal varices. The presenting symptoms in all six patients were weakness and bone pain. Three patients had a bone fracture after insignificant trauma, one and probably two passed kidney stones, and a duodenal ulcer developed in two. Bone x-ray films showed generalized osteoporosis in all patients. Renal function and arterial blood pH were within normal limits in every patient. The diagnosis of primary hyperparathyroidism in each patient was based on repeated demonstrations of hypercalcemia, hypophosphatemia, and markedly elevated serum immunoreactive parathyroid hormone concentrations. In all six patients, removal of the parathyroid adenoma resulted in disappearance of symptoms; normalization of serum calcium, phosphorus, and immunoreactive parathyroid hormone levels; and in four of the six, improvement in radiographic evidence of osteoporosis during follow-up of from 1 to 6 years. The association of cirrhosis, portacaval shunt, and primary hyperparathyroidism has not been documented previously. Our six patients with primary hyperparathyroidism constitute 3.4 percent of 174 survivors of emergency portacaval shunt in a series of 264 unselected, consecutive patients with cirrhosis and bleeding esophageal varices. Hepatic osteodystrophy is known to have occurred in only 11 of these 174 survivors. Primary hyperparathyroidism may be a more common cause of hepatic osteodystrophy than has been previously recognized, and should be considered in patients with cirrhosis in whom weakness, bone pain, and bone demineralization develop, particularly if they have a portacaval anastomosis.

Adenoma↗
PubMed1988

Comparison of the metabolic control of diabetes achieved by whole pancreas transplantation and pancreatic islet transplantation in rats.

To compare the long-term effectiveness of whole pancreas transplantation and pancreatic islet transplantation in controlling the metabolic disorders of alloxan diabetes, metabolic studies were performed monthly for 2 years in 4 groups of highly inbred rats: (1) NC-116 nondiabetic controls; (2) DC-273 untreated alloxan-diabetic controls; (3) PDT-182 rats that received syngeneic pancreaticoduodenal transplants shortly after induction of diabetes with alloxan; and (4) IT-92 rats that received an intraportal injection of at least 1500, but usually 2000, syngeneic pancreatic islets shortly after induction of diabetes with alloxan. Whole pancreas transplantation maintained strict metabolic control throughout the 2 years of study. In group PDT, hyperglycemia was abolished; plasma glucose concentration was maintained tightly within the normal range; markedly depressed plasma insulin levels were raised to above normal; glucose tolerance tests had insulin levels above normal and glucose levels that increased less and declined more rapidly than normal; and body weight gain and growth approached normal. In contrast, pancreatic islet transplantation failed to maintain precise metabolic control. In group IT, plasma glucose concentration initially fell to normal but then was elevated significantly above normal beginning with the 3rd posttransplant month; plasma insulin level declined progressively after the 6th posttransplant month; glucose tolerance tests had a diabetic glucose tolerance curve as a result of a markedly deficient plasma insulin response; and body weight gain and growth were significantly less than in group PDT. The results of these long-term metabolic studies may explain the effectiveness of whole pancreas transplantation and the ineffectiveness of pancreatic islet transplantation in preventing diabetic nephropathy.

Animals↗
PubMed1988

Effect of pancreas transplantation on diabetic somatic neuropathy.

To determine whether pancreas transplantation is capable of preventing diabetic somatic neuropathy, metabolic studies and electron microscopic morphometry of the sciatic nerve were performed monthly for 2 years in four groups of highly inbred rats: (1) NC-28 nondiabetic controls; (2) DC-82 untreated alloxan-diabetic controls; (3) WPT-122 diabetic rats that received a syngeneic whole-pancreas transplant; and (4) IT-90 diabetic rats that received intraportal injections of 1500 to 2000 syngeneic pancreatic islets. Five diabetic nerve lesions were quantitated by a "blind" protocol: intra-axonal glycogen deposits, axons with glycogen deposits, demyelinated axons, intact axoglial junctions in paranodal terminal myelin loops, and basal lamina thickness of vasa nervorum. Untreated diabetic control animals had significant and progressive increases in all five nerve lesions compared to nondiabetic controls (p less than 0.01). Whole pancreas transplants produced precise metabolic control of diabetes and prevented development and progression of all five diabetic nerve lesions throughout the 2-year study period. Pancreatic islet transplantation produced strict metabolic control and prevented diabetic neuropathy for the first 6 months, but then diabetes recurred and nerve lesions that were similar in severity to those in untreated diabetic rats developed. The finding that whole pancreas transplantation prevents diabetic somatic neuropathy adds to and extends our previous studies showing that whole-pancreas transplants prevent diabetic nephropathy.

Animals↗
PubMed1987

Comparison of whole pancreas and pancreatic islet transplantation in controlling nephropathy and metabolic disorders of diabetes.

To compare the long-term effectiveness of whole pancreas transplantation and pancreatic islet transplantation in controlling the metabolic disorders and preventing the kidney lesions of alloxan diabetes, metabolic and morphologic studies were performed in four groups of rats: (1) NC-116 nondiabetic controls; (2) DC-273 untreated alloxan-diabetic controls; (3) PDT-182 rats that received syngeneic pancreaticoduodenal transplants not long after induction of diabetes with alloxan; and (4) IT-92 rats that received an intraportal injection of at least 1500 and usually 2000 syngeneic pancreatic islets soon after induction of diabetes with alloxan. Each month for 24 months after diabetes was well established, body weight and plasma concentrations of glucose and insulin were measured, and five lesions were scored by light microscopy in 50 glomeruli and related tubules in each kidney by a "blind" protocol: glomerular basement membrane thickening, mesangial enlargement, Bowman's capsule thickening, Armanni-Ebstein lesions of the tubules, and tubular protein casts. There were progressive and highly significant increases in the incidence and severity of all five kidney lesions in the diabetic control rats compared with the nondiabetic control rats. No significant differences were found between the kidneys of Group PDT and those of Group NC, demonstrating that whole pancreas transplantation prevented all of the diabetic kidney lesions throughout the 2-year study period. In contrast, within 3-9 months after pancreatic islet transplantation and thereafter, the incidence and severity of the five diabetic kidney lesions were similar in Group IT and Group DC. Whole pancreas transplantation produced precise metabolic control of diabetes throughout the 24 months of study, whereas pancreatic islet transplantation did not accomplish complete metabolic control, particularly beyond the first several months after transplantation. The difference in the completeness of metabolic control achieved by the two types of transplants is the most likely explanation for their sharp difference in effectiveness in preventing diabetic nephropathy.

Animals↗
PubMed1986

Long-term survival after emergency portacaval shunting for bleeding varices in patients with alcoholic cirrhosis.

Since 1963, a prospective evaluation of the emergency portacaval shunt procedure has been conducted in 264 unselected patients with cirrhosis and bleeding varices who underwent operation within 8 hours of admission to the emergency department. Of 153 patients who underwent operation 10 or more years ago, 45 (29 percent) have survived from 10 to 22 years and their current status is known. On admission, 40 percent of the long-term survivors had jaundice, 44 percent had ascites, 13 percent had encephalopathy (with an additional 9 percent with a history of encephalopathy), 29 percent had severe muscle wasting, and 82 percent had a hyperdynamic state. There were 9 Child's class A patients, 33 Child's class B patients, and 3 Child's class C patients. At operation, all patients had portal hypertension which was reduced by the shunt to a mean corrected free portal pressure of 18 mm saline solution. The emergency portacaval shunt procedure permanently controlled variceal bleeding. None of the patients bled again from varices, and the shunt remained patent throughout life in every patient. Encephalopathy did not affect 91 percent of the patients, but was a recurrent problem in 9 percent, usually related to the use of alcohol. Lifelong abstinence from alcohol occurred in 58 percent of the long-term survivors, but 11 percent resumed regular drinking and 31 percent consumed alcohol occasionally. Liver function declined compared with preoperative function in only 18 percent of the patients, almost always because of alcohol use. Ten years after operation, 73 percent of the patients were in excellent or good condition, and 68 percent were gainfully employed or engaged in full-time housework. Comparison of the 10 to 22 year survivors with our early group of 180 patients reported previously and our recent group of 84 patients showed no significant differences in preoperative or operative data. The single factor that appeared to influence long-term survival was resumption of regular use of alcohol. We conclude that the emergency portacaval shunt procedure, by preventing hemorrhage from varices, results in prolonged survival and an acceptable quality of life for a substantial number of patients with advanced alcoholic cirrhosis.

Adult↗
PubMed1986

Lifelong reversal of the metabolic abnormalities of advanced diabetes in rats by whole-pancreas transplantation.

Evidence suggests that metabolic abnormalities are responsible for the widespread microvascular complications of insulin-dependent diabetes mellitus (IDDM). Interest in endocrine pancreas replacement therapy, including pancreas transplantation, is based on the hope that such treatment will reverse the complications of IDDM by providing more precise metabolic control than conventional therapy. To determine if whole pancreas transplantation is capable of reversing well-established metabolic abnormalities of diabetes mellitus (DM) and maintaining strict metabolic control for life, we performed monthly metabolic studies for 2 years in 141 nondiabetic control rats, 273 diabetic control rats with alloxan-induced DM, and 267 diabetic rats that received syngeneic whole pancreaticoduodenal transplants 6, 9, 12, 15, 18, and 21 months after induction of DM with alloxan. Whole-pancreas transplantation in rats with long-standing DM permanently reversed the metabolic disorders. Elevated plasma glucose concentrations were permanently reduced to normal, depressed plasma insulin levels were permanently increased to normal, elevations of BUN and serum creatinine were permanently normalized, and there was a striking gain in body weight. Hyperglycemia during glucose tolerance tests was of lesser magnitude and shorter duration than normal, as a result of greater-than-normal plasma insulin levels. The only abnormality that persisted was hyperglucagonemia, but it did not interfere with control of hyperglycemia and is of unknown significance. These results indicate that whole-pancreas transplantation produces the most complete and sustained correction of the metabolic abnormalities of experimental DM of any available therapeutic modality.

Animals↗
PubMed1986

Reversal of mesangial enlargement in rats with long-standing diabetes by whole pancreas transplantation.

An important unanswered question about clinical use of pancreas transplantation is: can pancreas transplants reverse or, at least, stabilize well-established lesions of insulin-dependent diabetes mellitus (IDDM)? To answer this question, we performed whole pancreas transplantations in 190 highly inbred rats 6, 9, 12, 15, 18, and 21 mo after induction of diabetes mellitus (DM) with alloxan. We then studied the effect on renal mesangial enlargement (ME) for 24 mo after onset of DM by a quantitative morphologic technique in which camera lucida tracings of the mesangium were made at X 1250 and were analyzed using an electronic planimeter connected to a calculator/computer. A pretransplant kidney biopsy was obtained so that the rats served as their own controls. In addition, studies were performed for 28 mo in 57 untreated diabetic controls and in 55 nondiabetic controls. Monthly metabolic studies showed that whole pancreas transplantation maintained very tight, lifelong metabolic control of diabetes. Kidney sections obtained for 2 yr from diabetic controls and for 21 mo from diabetic rats before transplantation showed highly significant increases in total mesangial area, nuclear-free mesangial area, and percentage of glomerular area occupied by nuclear-free mesangial area. Pancreas transplantation consistently produced a highly significant reversal of well-established ME, regardless of when it was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Outcome in cirrhotic patients with acute alcoholic hepatitis after emergency portacaval shunt for bleeding esophageal varices.

Operative liver biopsy findings were reviewed in 164 consecutive, unselected patients with alcoholic cirrhosis who had bleeding from esophageal varices and underwent emergency portacaval shunt. The survival rate up to 10 years in 49 patients with acute alcoholic hepatitis and alcoholic cirrhosis was not significantly different from that of patients with alcoholic cirrhosis alone. The two groups of patients were compared with respect to 35 other preoperative clinical and laboratory variables, and no other difference between the groups was found that obscured an adverse effect of acute alcoholic hepatitis on survival. We have concluded that acute alcoholic hepatitis and the presence of Mallory bodies in the liver are not a contraindication to portacaval shunt and that there is currently no demonstrated role for preoperative liver biopsy in the evaluation of patients with alcoholic cirrhosis and bleeding esophageal varices.

Acute Disease↗
PubMed1982

Vasovasostomy in the rat. Improved technique using absorbable microsuture (polyglycolic acid).

An improved technique for vasovasostomy in the rat is presented. To eliminate the suture crowds that could cause obstruction of the vasal lumen, one deep raw suture technique had been employed using polyglycolic acid (Dexon) microsuture. A total of 62 vasal anastomoses in 48 male Lewis rats was performed, and follow-up to twelve months found no disruption or constriction at the anastomoses. Despite occasional sperm granuloma formation at the anastomotic sites, all anastomoses demonstrated patency. Dexon appears to be suitable for genitourinary tract surgery, at least, in the rat.

Animals↗
PubMed1982

A simplified model for heterotopic rat heart transplantation.

A technique for simplified heterotopic rat heart transplantation having only aorto-aortic anastomosis is presented. The heterotopic rt heart survives and functions well when one lung lobe is attached t the transplantation and functions as a reservoir. Iso- and allotransplants are compared by electrocardiogram (ECG) determination and histological examination. Isotransplants exhibited normal heart and lung throughout the 6-month observation period. allotransplants ceased to function by the 16th postoperative day, with the cessation of palpable heart beat over the abdominal wall by the 10th postoperative day. This simplified heterotopic rat heart transplantation model can be operated by nonsurgeons in an unhurried manner with minimal training in microvascular surgery, and can be applied to various transplantation immunological studies.

Animals↗
PubMed1982

Correlation of hepatic and portal wedged venography and manometry with histology in alcoholic cirrhosis and periportal fibrosis.

Histologic, manometric, and direct magnification venographic studies of four patients with portal fibrosis and 10 patients with alcoholic cirrhosis were compared before and for variable periods after portacaval shunt procedures. Unique to this investigation was the availability of postoperative wedged portal vein manometry and venography. In periportal fibrosis (presinusoidal obstruction), portal studies demonstrated portal venular atrophy and occlusions, with egress of contrast material from hepatic sinusoids via hepatic veins; hepatic studies were near normal. The reverse was observed in patients with cirrhosis (postsinusoidal obstruction). The degree of elevation of portal vein pressures did not enable clear discrimination of pre- and postsinusoidal obstruction. Results support classical concepts of pre-and postsinusoidal obstructive disease and confirm the utility of wedge hepatic and portal venography in differentiating these two entities.

Blood Pressure↗
PubMed1982

Clonidine and lidamidine to inhibit watery diarrhea in a patient with lung cancer.

A patient with watery diarrhea syndrome secondary to bronchogenic carcinoma responded to treatment with clonidine and lidamidine. Stool weight decreased to 43% and 53% of control on two separate trials of clonidine. Stool weight decreased to 35% of control during a trial of lidamidine. Both clonidine and lidamidine increased sodium and chloride absorption in vitro in human intestine. Clonidine, lidamidine, or drugs that are structurally similar may become therapeutic choices for secretory diarrhea.

Aged↗