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M S Orloff

Publications and source records attributed to M S Orloff.

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

Long-term results of radical esophagogastrectomy for bleeding varices due to unshuntable extrahepatic portal hypertension.

This report describes the long-term results of one-stage total gastrectomy and distal two-thirds esophagectomy, with reconstruction by esophagojejunostomy (16 Roux-en-Y; 2 interposition), in 18 adult patients with recurrent variceal hemorrhage due to unshuntable extrahepatic portal hypertension (EHPH) from occlusion of all major tributaries of the portal venous system. The etiology of portal venous occlusion was unknown in 11 patients, abdominal trauma in 3, peritonitis in 3, and thrombotic coagulopathy in 1. Almost half of the patients had their first episode of bleeding in childhood, and 83% experienced bleeding before 40 years of age. The severity of the problem was reflected by frequent previous bleeding episodes (mean: 12.8, range: 4 to 21), a large cumulative requirement for blood transfusions (mean: 129 units, range: 28 to 247 units), repeated, costly hospital admissions (mean: 15, range: 4 to 24), and numerous previous unsuccessful operations (mean: 4.4, range: 1 to 14). Blood transfusions transmitted serum hepatitis to three patients and AIDS to one, for an incidence of 22%. Bleeding recurred after repetitive endoscopic sclerotherapy in 10 patients and after various operations in 16 (failed portal-systemic shunts in 9, splenectomy in 16, devascularization procedures in 13). All patients had large esophageal and gastric varices on endoscopy, normal liver function, and widespread portal venous occlusion on visceral angiography. Radical esophagogastrectomy was usually a long and arduous operation because of dense adhesions, extensive collateral veins, and a scarred, contracted bowel mesentery due to previous operations. All patients survived the operation and are currently alive. No patient has had recurrent bleeding during 1 to 26 years of follow-up (mean: 13.9 years, 7 or more years in 14 patients). Quality of life has been good. It is concluded that radical esophagogastrectomy is the only effective treatment of unshuntable EHPH and that the operation should be performed promptly when this disease, which is associated with high mortality, high morbidity, and high costs, is diagnosed.

Adult↗
PubMed1994

Treatment of bleeding esophagogastric varices due to extrahepatic portal hypertension: results of portal-systemic shunts during 35 years.

From 1958 to 1990, elective therapeutic portal-systemic shunt (PSS) procedures were performed for recurrent bleeding esophagogastric varices in 162 children and adults with extrahepatic portal hypertension (EHPH) resulting from portal vein thrombosis (PVT). The onset of EHPH was in childhood for at least 74% of patients. Of the 162 patients, 147 were eligible for and received 5 years of follow-up (100%), and 117 were eligible for and received 10 years of follow-up (100%). The longest follow-up was 35 years. The cause of PVT was unknown in 68%, neonatal omphalitis in 12%, umbilical vein catheterization in 8%, peritonitis in 6%, trauma in 4%, and thrombotic coagulopathy in 2%. The number of variceal bleeding episodes ranged from 2 to 18 (mean, 5.6). None of the patients had clinical, biochemical, or liver biopsy evidence of liver disease. Esophageal varices were demonstrated by endoscopy, and/or contrast x-rays, and/or angiography in all patients. Visceral angiography was always used to demonstrate the extent of portal obstruction and the veins available for shunting. Before referral, the following procedures had failed: endoscopic sclerotherapy (68 patients), splenectomy alone (32 patients), central splenorenal shunt with splenectomy (10 patients), transesophageal varix ligation (12 patients). Three types of PSS were used: (1) central side-to-side splenorenal without splenectomy (75 patients, 46%); (2) central end-to-side splenorenal with splenectomy (34 patients, 21%); and (3) mesocaval (end-to-side cavomesenteric) (53 patients, 33%). PSS reduced the mean corrected portal pressure from 292 to 28 mm saline. All patients survived the procedure and left the hospital (100%). The actuarial survival rate for 5 years is 99%, and for 10 years is 96%. Three of the 6 deaths were unrelated to EHPH or PSS. Shunt patency for up to 35 years was demonstrated in 98% of patients by angiography and/or ultrasonography. In four patients (2%), all of whom had end-to-side splenorenal shunts, shunt thrombosis and rebleeding developed 3, 4, 4, and 6 years (respectively) after PSS. There were the only patients who experienced rebleeding. A diligent and repeated effort was made to detect portal-systemic encephalopathy (PSE), and no instance of PSE was found during 3 to 35 years of follow-up. Liver function and morphology remained normal, and hypersplenism was corrected in all patients. Quality of life was good in 98% of patients, and 5 years after PSS 96% were gainfully employed, engaged in full-time homemaking, or attending school.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Nonheartbeating cadaveric organ donation.

OBJECTIVE: The authors evaluated the potential use of nonheartbeating (NHB) cadaver donors as an additional source to the current supply of brain-dead cadaver donors. SUMMARY BACKGROUND DATA: The numbers of cadaveric donors has not increased significantly during the last 5 years, despite a rising need for transplantable organs. Any improvement in cadaveric organ procurement will depend on the use of previously unrecognized potential donors. METHODS: During a 2-year period, 24 kidneys were retrieved from 12 NHB donors. Nineteen kidneys were transplanted. RESULTS: These kidneys sustained a mean warm ischemia time of 26 minutes (range 20-35 min). A mean lowest creatinine level of 2.0 mg/dL, (range 1.1-3.0 mg/dL), the rate of postoperative dialysis (22%), and a 1-year graft survival rate of 76% for kidneys from NHB-donated kidneys compare favorably to expected results achieved nationally from brain-dead cadaveric donors. CONCLUSIONS: Nonheartbeating donor kidneys can yield acceptable graft function and be of no disadvantage to recipients of cadaver transplants.

Adolescent↗
PubMed1994

Free jejunal autograft combined with extensive esophagogastrectomy for unshuntable extrahepatic portal hypertension.

This is the first report of the use of a free jejunal autograft vascularized by the internal thoracic (internal mammary) artery and vein to restore continuity of the digestive tract after total gastrectomy and distal 65% esophagectomy for recurrent bleeding esophagogastric varices caused by unshuntable extrahepatic portal hypertension. The procedure was used in two young adults who, because of numerous previous abdominal operations, had a severely scarred and contracted intestinal mesentery that precluded conventional use of the small or large intestine with an intact blood supply to bridge the gap between the upper thoracic esophagus and the abdominal jejunum. Before referral, the two patients had 21 and eight bouts of variceal hemorrhage, respectively, that necessitated a cumulative total of 108 and 74 units of blood transfusion, necessitated 17 and 12 admissions to the hospital, and failed to respond to four and five operations and 14 and 18 sessions of endoscopic sclerotherapy. After extensive esophagogastrectomy combined with a free jejunal autograft, both patients have done well during follow-up of 9 and 3 years, respectively. Both have been in good to excellent health with stable weight, freedom from digestive tract bleeding, normal liver function, and no encephalopathy. These results confirm our recently reported conclusions regarding the uniform long-term effectiveness of extensive esophagogastrectomy in the treatment of unshuntable extrahepatic portal hypertension and suggest that thoracic and general surgeons familiar with microvascular techniques may find the free jejunal autograft to be useful in various circumstances in which it is necessary to replace all or a substantial part of the thoracic esophagus.

Adult↗
PubMed1994

Induction of specific tolerance to small-bowel allografts.

BACKGROUND: The induction of specific tolerance would greatly improve survival and functional state of organ transplant recipients. One approach that has recently received attention is the creation of mixed hematopoietic chimerism through the transplantation of allogeneic and syngeneic T-cell-depleted (TCD) bone marrows. In these studies we examined whether tolerance to highly immunogenic small-bowel transplants could be induced by mixed allogeneic chimerism. Tolerance induction depends on the sharing of antigens between bone marrow cells and small-bowel tissue. METHODS: Adult Lewis rats were lethally irradiated and reconstituted with a mixture of 50 x 10(6) TCD bone marrow cells. Thirty days after reconstitution, animals were tested for chimerism by fluorescence-activated cell sorter analysis. Chimeric animals then received ACI heterotopic small-bowel allografts and were assessed daily for rejection. Small-bowel allograft survival was compared to three control groups: (1) untreated Lewis recipients, (2) irradiated TCD syngeneically reconstituted Lewis recipients, and (3) Lewis bone marrow recipients that did not develop chimerism. RESULTS: Median graft survival in control groups was 8 days. Graft survival in eight mixed chimeras ranged from more than 135 to more than 304 days (p < 0.0001), and no episode of rejection or graft-versus-host disease was observed. Mixed lymphocyte reactivity of chimeric lymphocytes confirmed in vivo observation of tolerance. CONCLUSIONS: Bone marrow cells share tissue-specific antigens with small-bowel cells to permit induction of tolerance.

Animals↗
PubMed1992

Long-term results of treatment of Budd-Chiari syndrome with portal decompression.

Thirty-three patients with Budd-Chiari syndrome were studied for 1 to 19 years following portal decompression. All had ascites, hepatomegaly, abnormal liver function, angiographic demonstration of inferior vena cava and/or hepatic vein occlusion, and biopsy specimens showing intense hepatic congestion and necrosis. When thrombosis was confined to hepatic veins (20 patients), side-to-side portacaval shunt resulted in 95% operative survival, 90% prolonged survival, permanent shunt patency, relief of ascites, reversal of liver dysfunction, and reversal or improvement of hepatic lesions. When thrombosis involved the inferior vena cava, mesoatrial shunt (eight patients) was unsatisfactory because of a 63% mortality rate from liver failure due to shunt thrombosis. In contrast, a new procedure consisting of combined portacaval and caval-atrial shunts (five patients) has been highly successful, with 100% survival, shunt patency, relief of ascites, and reversal of pathologic abnormalities.

Adult↗
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↗
PubMed1986

Partial purification of a novel stimulant of gastric acid secretion from canine non-antral mucosa.

A novel stimulant of gastric acid secretion was extracted and purified from the non-antral gastric mucosa of the canine stomach and some of its biological properties were examined. Tissue was boiled in water and extracted in 2% trifluoroacetic acid. The stimulatory activity was purified by a combination of reverse-phase high pressure liquid chromatography (HPLC) and gel filtration. Fractions were assayed for a stimulation of basal, pentagastrin- and histamine-stimulated gastric acid secretion in the anaesthetized rat. Stimulatory activity was eluted from reverse-phase HPLC columns with acetonitrile and its elution from Sephadex G-10 and G-50 columns suggested a molecular weight of 1,000 to 3,000. The highly purified extracts enhanced basal, pentagastrin- and histamine-stimulated acid secretion in the rat. A stimulatory fraction was purified which was devoid of immunoreactive gastrin and gastrin-releasing peptide and contained only small amounts of histamine. Its chromatographic properties differed from those of histamine and acetylcholine. On two occasions the stimulant was purified to homogeneity and found to contain amino acids. Insufficient pure material was obtained for full characterization. The stimulant has been tentatively called oxyntin.

Amino Acids↗
PubMed1986

Catabolism of substance P and neurotensin in the rat stomach wall is susceptible to inhibitors of angiotensin converting enzyme.

The purpose of this investigation was to examine the pathway of substance P (SP) and neurotensin (NT) catabolism in the gastric wall of the rat and identify some of the enzymes involved. Under anaesthesia an infusion catheter and a bundle of dialysis fibres were implanted into the stomach wall of the rat. Experiments commenced on conscious rats 2 days after surgery. In control experiments [3H]-SP(Pro-2,4) or [3H]-NT(Tyr-3,11) were injected into gastric tissues through the catheter and catabolites were collected in the dialysis fibres and separated by high pressure liquid chromatography. In other studies captopril, MK422 (inhibitors of angiotensin converting enzyme) or phosphoramidon (an inhibitor of endopeptidase-24.11, 'enkephalinase') were injected into gastric tissues before the peptide label. SP1-11 was degraded to mainly SP1-2, SP3-4 with some SP1-6, SP1-7 and SP1-8. Catabolism was partially but significantly (5% level) inhibited by MK422 and captopril, but not by phosphoramidon. NT1-13 was degraded to NT1-8, NT9-13, NT1-11 and NT1-12. NT catabolism was partially but significantly (5% level) inhibited by MK422. It is concluded that an enzyme resembling angiotensin converting enzyme is involved in the initial stages of SP and NT catabolism in the rat stomach. The involvement of other peptidases cannot be excluded because inhibition of breakdown was not complete.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Catabolism of substance P in the stomach wall of the rat.

The aim of this study was to examine the catabolism of substance P (SP) in the stomach wall of the rat. Catabolism in vitro was investigated by incubation of unlabelled and tritiated SP (prolyl 2,4-3,4(n)-3H SP) with membrane bound-peptidases prepared from the rat gastric corpus. Catabolism was studied in vivo by use of a catheter chronically implanted in the stomach wall to deliver tritiated SP to the gastric tissues and implanted dialysis fibers to collect the catabolic products. The products from both experiments were separated by high pressure liquid chromatography and identified by their retention times or amino acid analysis. Membrane-bound peptidases in vitro hydrolyzed both unlabelled and tritiated SP and the products of hydrolysis were consistent with the cleavage of three bonds: Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10. None of the peptide fragments would be expected to be biologically active. Only those fragments with tritiated Pro residues could be detected in vivo. The major identified products were SP(1-2) and SP(3-4), with smaller amounts of SP(1-4), SP(1-6), SP(1-7), SP(1-8) and SP(1-9). The enzymes that may be responsible for these cleavage patterns are discussed.

Amino Acids↗
PubMed1985

Dopamine and norepinephrine in the alimentary tract changes after chemical sympathectomy and surgical vagotomy.

The aim of this study was to examine the distribution of dopamine and norepinephrine in the proximal alimentary tract of the rat and to assess the contributions of sympathetic and vagal fibers to the tissue concentrations of both catecholamines. Tissues were extracted in perchloric acid and the catecholamines were separated by high pressure liquid chromatography and detected electrochemically. In untreated rats (controls) both catecholamines were concentrated in the gastric muscle but norepinephrine levels were 6-8 times higher (corpus, dopamine 35 +/- 7 ng . g-1, norepinephrine 265 +/- 50 ng . g-1, mean +/- SE, n = 6). In the mucosa norepinephrine concentrations were 10-12 times higher (corpus, dopamine 12 +/- 3 ng . g-1, norepinephrine 140 +/- 26 ng . g-1). Chemical sympathectomy (6 hydroxydopamine, 100 mg . kg-1 ip 3 days) significantly reduced dopamine concentrations in muscle and norepinephrine in muscle, mucosa, pylorus and duodenum. In all tissues the effects on norepinephrine were greater. Surgical vagotomy significantly reduced dopamine concentrations in the gastric muscle, but not the mucosa. Norepinephrine concentrations in the stomach of vagotomized rats were significantly reduced only in the pylorus. Differences in the relative concentrations of dopamine and norepinephrine in gastric tissues of the normal rat and differences in the effects of sympathectomy and vagotomy suggest that dopamine and norepinephrine exist, to an extent, in separate populations of cells and that dopamine is not merely a precursor of norepinephrine. Gastric mucosal dopamine, which was mainly unaffected by either treatment, may exist in APUD cells.

Animals↗
PubMed1985

Canine bombesin-like gastrin releasing peptides stimulate gastrin release and acid secretion in the dog.

The synthetic mammalian bombesin-like peptides, canine gastrin releasing peptide 27, 23 and 10, and porcine gastrin releasing peptide 27 were compared with amphibian bombesin 14 and 10 during intravenous infusions into six conscious dogs with chronic gastric cannulae. Gastrin and gastrin releasing peptide were measured in peripherally sampled venous blood by radioimmunoassay and gastric acid secretions were collected. All forms of gastrin releasing peptide stimulated gastrin release and gastric acid secretion in a dose-dependent manner. The larger canine and porcine peptides were more potent than the decapeptide. Bombesin 14 was more potent than bombesin 10. A rise in the venous concentration of immunoreactive gastrin releasing peptide of only 20 fmol ml-1 stimulated gastrin release to about 50% of maximal. Gastrin releasing peptide 10 was cleared from the circulation three times faster than the larger forms and this may account for the apparent differences in potency.

Animals↗
PubMed1984

Catabolism of neurotensin in interstitial fluid of the rat stomach.

The catabolism of neurotensin (NT) was studied in the gastric submucosa of the conscious rat using a novel technique to obtain a dialysate of interstitial fluid. A microdialysis fiber system was surgically implanted into the gastric submucosa, and 2 days later experiments were commenced on conscious animals. Isotope-labeled NT was administered to the tissue, and a dialysate of the submucosal interstitial fluid was collected. In the dialysate, NT and catabolites of NT formed in the interstitial fluid were identified and quantitated by high-pressure liquid chromatography. The catabolism of 125I-NT-(1-13) and [3H]NT-(1-13) was studied as was the further breakdown of the major catabolites. NT-(1-13) was, regardless of the type of label, catabolized mainly into NT-(1-8), NT-(9-13), NT-(1-11), and free tyrosine. None of the catabolites formed is known to possess significant biological activity. NT-(9-13) was rapidly cleared, whereas the amino-terminal fragments NT-(1-8) and NT-(1-11) were more resistant to degradation. The biological half-life of neurotensin in the gastric submucosa of the rat was between 9 and 15 min.

Animals↗
PubMedDate not supplied

Sonography: a useful tool to detect the mechanical causes of renal transplant dysfunction.

PURPOSE: The purpose of this study was to evaluate the utility of sonography in distinguishing between mechanical and nonmechanical causes for renal transplant dysfunction. METHODS: We reviewed all ultrasound examination reports (n = 286) for 63 consecutive patients who received 64 renal transplants. We assessed the sensitivity and specificity of different degrees of hydronephrosis (mild, moderate, or severe) in detecting urinary tract obstruction; different volumes of new or increasing peritransplant fluid in detecting urine leaks; different total volumes of peritransplant fluid in predicting significant compression of the transplant; and Doppler vascular criteria for predicting arterial and venous occlusion. RESULTS: All mechanical complications were detected (100% sensitivity) with specificities of 91.9% for ureteral obstruction (criterion, moderate hydronephrosis), 83.4% for urine leaks (criterion, any new fluid or any increase), 91.4% for fluid collections that compressed the transplant (criterion, > 100 ml), and 100% for vascular occlusion (criteria, no flow for arterial occlusion; no venous flow and reversal of arterial flow during diastole for venous occlusion). CONCLUSIONS: Sonography is very useful in distinguishing between mechanical and nonmechanical causes for renal transplant dysfunction. It has high sensitivity and acceptable specificity in this setting.

Adolescent↗
PubMedDate not supplied

Isolation and sequence analysis of human bombesin-like peptides.

The decapeptide form of human gastrin releasing peptide was isolated from acid extracts of liver tissue containing a metastatic human bronchial carcinoid tumor. A larger form also was isolated and partially characterized. During gel permeation chromatography the major immunoreactive peak eluted in the same region as synthetic gastrin releasing decapeptide while a second minor immunoreactive peak eluted near gastrin releasing peptide. Bombesin-like immunoreactivity (BLI) was purified by successive applications to reverse phase high pressure liquid chromatography (HPLC) columns. After four successive HPLC purifications a single peak of bombesin-like immunoreactivity was detected. Amino acid analysis, microsequence analysis and coelution with synthetic peptide indicated that the predominant form present in metastatic tumor tissue was identical to the decapeptide form of canine gastrin-releasing peptide. The less abundant form was purified by cation exchange chromatography followed by reverse phase high pressure liquid chromatography. Partial microsequence analysis of this peptide, through the first 11 residues, was Val-Pro-Leu-Pro-Ala-Gly-Gly-Gly-Thr-Val-Leu. This sequence differed from that of hog heptacosapeptide gastrin releasing peptide at positions 1,3,4 and 5 and from the canine peptide as positions 1,3,5, and 7.

Amino Acid Sequence↗
PubMedDate not supplied

Catabolism of gastrin releasing peptide and substance P by gastric membrane-bound peptidases.

The catabolism of two gastric neuropeptides, the C-terminal decapeptide of gastrin releasing peptide-27 (GRP10) and substance P (SP), by membrane-bound peptidases of the porcine gastric corpus and by porcine endopeptidase-24.11 ("enkephalinase") has been investigated. GRP10 was catabolized by gastric muscle peptidases (specific activity 1.8 nmol min-1 mg-1 protein) by hydrolysis of the His8-Leu9 bond and catabolism was inhibited by phosphoramidon (I50 approx. 10(-8) M), a specific inhibitor of endopeptidase-24.11. The same bond in GRP10 was cleaved by purified endopeptidase-24.11, and hydrolysis was equally sensitive to inhibition by phosphoramidon. SP was catabolized by gastric muscle peptidases (specific activity 1.7 nmol min-1 mg-1 protein) by hydrolysis of the Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10 bonds, which is identical to the cleavage of SP by purified endopeptidase-24.11. The C-terminal cleavage of GRP10 and SP would inactivate the peptides. It is concluded that a membrane-bound peptidase in the stomach wall catabolizes and inactivates GRP10 and SP and that, in its specificity and sensitivity to phosphoramidon, this peptidase resembles endopeptidase-24.11.

Animals↗