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M L Shiffman

Publications and source records attributed to M L Shiffman.

88 records · Page 5Linked to original sources
PubMed1992

In vivo studies of biliary ceftriaxone excretion and solubility in guinea pig hepatic bile.

Ceftriaxone (CFTX), a third-generation cephalosporin, has occasionally been reported to produce biliary sludge composed of its calcium salt. We performed studies in guinea pigs to (1) investigate the hepatic route of CFTX excretion, (2) determine ceftriaione's effects on bile flow and composition, and (3) quantify the solubility and metastability of the calcium salt as a function of administered dose. Our results show that even at high doses ceftriaxone has only minimal effects on bile flow and biliary electrolyte secretion, either alone or in combination with bile salt (taurocholate) infusion. A significant increase in total calcium concentration was observed without change in free Ca2+ concentration, this is compatible with formation of a soluble calcium salt of ceftriaxone, as previously demonstrated in vitro. Ion products of Ca2+ and ceftriaxone as high as 3.5 times the solubility product constant without crystal formation were observed, confirming the presence of a metastable state for the calcium salt of ceftriaxone in the living animal. Biliary excretion of ceftriaxone inhibited excretion of indocyanine green, suggesting that ceftriaxone and indocyanine green share a common anionic excretory pathway in this species.

Animals↗
PubMed1992

Calcium in human gallbladder bile.

Biliary calcium is believed to be of great importance in gallstone pathogenesis. These studies were therefore performed to determine if quantitative and/or qualitative differences in calcium are present in gallbladder bile from patients with and without gallstones. Bile was obtained by direct gallbladder aspiration from 68 obese patients undergoing elective gastric bypass surgery. Forty-five patients had no evidence of gallstones or sludge, 18 had cholesterol gallstones, and five had black pigment stones. Gallbladder bile was also obtained from 27 nonobese patients undergoing elective cholecystectomy (19 cholesterol; eight black pigment gallstones). For all patients, total calcium ranged from 1.50 to 16.44 mmol/L (mean: 6.05 +/- 0.31 mmol/L); free Ca++ ion ranged from 0.53 to 2.83 mmol/L (mean: 1.28 +/- 0.05 mmol/L). Considerable overlap was observed between obese and nonobese subjects and between patients with and without gallstones. For all patient groups, calcium, Ca++, and bound calcium increased linearly with increasing concentrations of bile salt. No significant differences in the slopes of these relationships were observed with obesity or gallstones. In contrast, free Ca++ ion was greater in gallbladder bile from gallstone patient groups throughout the entire range of bile salt. We hypothesize that this observed increase in Ca++ resulted from increased Gibbs-Donnan forces and excess gallbladder mucin present within the gallbladder bile of patients with gallstones.

Adolescent↗
PubMed1991

Recovery of bile secretion following orthotopic liver transplantation.

Recovery of hepatic function following orthotopic liver transplantation includes the ability to produce 'adequate' bile. What constitutes adequate bile flow, however, has not previously been defined. The present study was undertaken to characterize biliary water and electrolyte secretion following hepatic transplantation. Bile was sampled from nine liver transplant recipients for 15-25 consecutive days during chronic t-tube biliary drainage. Liver biopsies and t-tube cholangiograms were unremarkable in all patients. During the first post-operative day mean bile flow, bile salt concentration, [BS], and bile salt output (BSO) were 60.0 microliters/min, 6.8 mM and 0.41 mumol/min, respectively. [BS] increased over days 1-5 and then plateaued at 12.2 mM over days 6-25 post-transplant. BSO and bile flow increased over days 1-12 before achieving steady-state values of 4.52 mumol/min and 334.7 microliters/min, respectively. In each patient bile flow increased linearly with increasing BSO. Choleretic index (CI), varied from 36.9-77.1 microliters/mumol (mean: 50.7 +/- 8.8). The y-intercept for this relationship ranged from 52.4-156.9 microliters/min (mean: 95.9 +/- 81.8). Only primary bile salts (82% cholate and 17% chenodeoxycholate), were observed in the bile of each patient. Biliary electrolyte concentrations were similar to that observed in plasma. Each was relatively unaffected by changes in bile flow and BSO. Electrolyte outputs increased linearly with respect to both BSO and bile flow. We conclude that recovery of bile secretion following orthotopic liver transplantation occurs gradually over a 10-12 day period and is strongly dependent upon bile salt secretion.

Adolescent↗
PubMed1991

Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity.

The present study evaluated the incidence of gallstone formation in 105 morbidly obese patients undergoing rapid weight loss after proximal gastric bypass surgery. Intraoperative ultrasonography demonstrated gallstones in 20 (19%) and gallbladder sludge in four (4%) patients. Eighty-one patients had a normal gallbladder ultrasound. After bariatric surgery, these patients were followed prospectively with periodic gallbladder ultrasound examinations. At 6 months, gallstones had developed in 36% and gallbladder sludge in 13% of patients. These percentages remained relatively constant at 12 and 18 months. Body weight declined rapidly after surgery from a mean of 132.3 kg to 95.5, 87.0, and 84.0 kg at 6, 12, and 18 months, respectively. Gallstones developed significantly more often in the white race, and in women. No significant differences in age, body weight, percent ideal body weight, percent weight loss, or percent of excess body weight lost existed between patients who developed gallstones or sludge and those who did not. Patients who developed gallbladder sludge had less cholesterol and lower cholesterol saturation (1.25 +/- 0.42) in their gallbladder bile than persons who developed gallstones (2.00 +/- 0.79). Forty percent (13/32) of patients who developed gallstones became symptomatic; nine (28%) underwent elective cholecystectomy. An attempt to prevent gallstone formation during rapid weight loss appears warranted.

Adult↗
PubMed1990

Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility.

Ceftriaxone, a semisynthetic third-generation cephalosporin, has recently been associated with biliary sludge formation. Analysis of the biliary concretions induced by this agent shows a calcium salt of ceftriaxone. The present in vitro studies were undertaken to provide insight into the pathogenesis of ceftriaxone-associated biliary sludge formation by evaluating possible interactions that may exist between calcium, bile salts, and ceftriaxone. Ceftriaxone possessed high calcium-binding affinity. The formation constant for the calcium ceftriaxone salt at 37 degrees C was about 157.3 L/mol; stoichiometry of the salt was 1:1, i.e., calcium ceftriaxone. The calcium-binding property of ceftriaxone was observed to be additive to that of taurocholate in mixed taurocholate-ceftriaxone solutions. Although the solubility product constant for calcium ceftriaxone was only 1.62 x 10(-6) mol/L2, marked metastability was observed; neither visible nor microscopic precipitates developed until the [Ca2+] x [ceftriaxone] ion product exceeded the solubility product constant by a factor of 10.4. Metastability of the calcium ceftriaxone salt was also observed in human gallbladder bile in vitro. Estimates of human biliary calcium ceftriaxone solubility in vivo were than calculated from previously-reported values for biliary [Ca2+], [ceftriaxone], and from the solubility product constant as defined in this study. Calculated saturation indices for calcium-ceftriaxone in human bile generally increased (corresponding to a decrease in solubility) with increasing ceftriaxone dose. At doses less than or equal to 1 g, saturation index was well within the metastable range of this calcium-salt. However, at doses greater than or equal to 2 g, the saturation index surpassed the metastable limit. Under these conditions, precipitation of ceftriaxone could occur. It was concluded that the development of ceftriaxone-induced biliary sludge is a solubility problem that occurs in patients receiving high-dose treatment (greater than or equal to 2 g). This study proposes that the risk of developing ceftriaxone-associated biliary "pseudolithiasis" increases with increasing ceftriaxone dose and in patients with impaired gallbladder emptying.

Bile↗
PubMed1990

Human gallbladder mucosal function. Effect of concentration and acidification of bile on cholesterol and calcium solubility.

The most recognized function of the human gallbladder is to store bile. However, this organ is not a static reservoir. It actively modifies bile by two processes: concentration and acidification. This study was designed to simultaneously evaluate the relationship between these two physiological processes in the normal human gallbladder and to define their effects on biliary cholesterol and calcium solubility. Bile was sampled directly from the gallbladder of 78 morbidly obese patients undergoing elective gastric bypass procedures. All had negative results of intra-operative ultrasound examinations for sludge and gallstones, normal liver function tests, and no history of hepatobiliary disease. Bile salt concentrations, an indirect index of concentration by the gallbladder, ranged from 15.1-272.8 mmol/L. As [bile salt] increased, [Na+], [K+], free [Ca2+], [cholesterol], [phospholipid], and [total lipid] increased linearly; [Cl-1] decreased linearly. Molar percent cholesterol decreased from 17.2% in dilute bile to 10.1% in fully concentrated bile, suggesting that cholesterol was absorbed by the gallbladder. As bile was concentrated, cholesterol saturation index decreased curvilinearly from a maximum of 3.7 in dilute bile to 1.0-1.5 in concentrated bile. Concentration of gallbladder bile was accompanied by progressive acidification. Bile pH decreased linearly with increasing [bile salt]; [CO3(2-)] decreased curvilinearly. Despite increasing [Ca2+], CaCO3 saturation index decreased curvilinearly with increasing [bile salt] from a maximum of 3.62 in dilute bile to a minimum of 0.12 in concentrated and acidified bile. CaCO3 saturation index also decreased exponentially with decreasing pH. This study concludes that concentration of bile enhances cholesterol solubility while acidification enhances calcium salt solubility. By increasing the solubilities of these two species, gallbladder mucosal function may play a key role in preventing gallstone formation.

Analysis of Variance↗
PubMed1990

Liver transplantation in Virginia.

Survival rates ranging from 70-80% have been documented over the past three years in liver transplant patients at the Medical College of Virginia. Survival declined in patients with numerous complications of chronic liver disease and with significant deterioration in hepatic synthetic function. Early referral was a major factor contributing to survival.

Adult↗
PubMed1989

Breast-milk composition in women with cystic fibrosis: report of two cases and a review of the literature.

Breast milk was collected from two women with cystic fibrosis (CF) and data from the literature was reviewed. The sodium concentration was within normal limits, 11-24 mmol/L in colostrum and 7-8 mmol/L in mature milk. Normal physiologic changes in milk composition after parturition (decreases in Na and increases in lactose) and during individual feeding periods (increases in fat and decreases in protein) were observed. Concentrations of milk protein, fat, and sugars were normal when the pulmonary disease of these patients was mild. During exacerbations of pulmonary disease, the concentrations of milk macronutrients were reduced. Milk secreted by women with CF appears to be physiologically normal, safe for the infant, and breast-feeding by mothers with CF should no longer be discouraged. Variations in the macronutrient content of CF milk warrants routine monitoring of the mother with CF and the breast-fed infant, especially during exacerbations in the pulmonary aspects of this disease.

Adult↗
PubMed1982

Pancreatic function in the reserpinized rabbit--a model for cystic fibrosis. I. Effect of secretin.

Pancreatic juice was collected from rabbits treated with reserpine and from untreated controls. The volume of pancreatic juice secreted, flow rate and the bicarbonate output were all significantly reduced in the treated animals during both spontaneous flow and during secretin-stimulated flow. On the other hand, the total protein concentration, the amylase activity and the calcium concentration of the pancreatic juice were all significantly elevated in the treated animals. The elevation in the total protein concentration appeared to be due to both increased amounts of protein and decreased amounts of water. Of particular interest was that secretin stimulation caused the same % increase in the flow rate and output of pancreatic juice in both control and reserpine treated rabbits. The method by which fluid is secreted by the treated animal, therefore, appeared to be depressed at all times and under all conditions. Decreased volumes of pancreatic juice, a decreased bicarbonate output and increased concentrations of protein and calcium are found in this model and are consistent with clinical findings present in the pancreatic secretions obtained from individuals with cystic fibrosis. Therefore, the similarities between secretions of the reserpine treated rabbit and those observed in the cystic fibrosis patient support its use as an experimental model for investigating the abnormal pancreatic secretions in this disease.

Amylases↗
PubMed1978

Protein dissociation from DNA in model systems and chromatin.

Salt induced dissociation of protamine, poly(L-lysine) and poly(L-arginine) from DNA was measured by relative light scattering at theta = 90 degrees and/or centrifugation. Dissociation of histones from DNA was studied using relative light scattering and intrinsic tyrosine fluorescence. Protamine was dissociated from DNA at 0.15 M MgCl2 (ionic strength mu = 0.45) or 0.53 M NaCl (mu = 0.53) based on light scattering data and at approximately 0.2 M MgCl2 (mu = 0.6) or 0.6 M NaCl based on centrifugation data. NaCl induced dissociation of poly(Lys) or poly(Arg) from natural DNAs measured by light scattering did not depend on the guanine plus cytosine content. To dissociate poly(Arg) from DNA higher ionic strength using NaCl, MgCl2, or CaCl2, similar ionic strength using NaClo4, and lower ionic strength using Na2SO4 was needed then to dissociated poly(Lys). Both the decrease in light scattering and the enhancement of tyrosine fluorescence of chromatin occurred between 0.5 and 1.5 M NaCl when histones were dissociated.

Anions↗
PubMedDate not supplied

Risk of bleeding after endoscopic biopsy or polypectomy in patients taking aspirin or other NSAIDS.

The present study was performed to determine if the risk of bleeding after endoscopic biopsy or polypectomy was increased in patients taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Of 694 patients who underwent either upper gastrointestinal endoscopy with biopsy or colonoscopy with biopsy or polypectomy, 320 (46%) had recently consumed NSAIDs. Postprocedure bleeding was assessed by both written questionnaire and telephone follow-up. A total of 32 patients (4.6%) reported bleeding. Minor, self-limited, clinically insignificant bleeding occurred in 20/320 (6.3%) patients taking NSAIDs and 8/374 (2.1%) control patients (p = .009). Major bleeding requiring hospitalization or treatment occurred in only 4 patients (0.58%) (2 from the control group and two from the drug group), each of whom had undergone colonic polypectomy. The risk of bleeding increased with polyp size, but this did not seem to be affected by NSAID use. We conclude that the risk of significant gastrointestinal bleeding after endoscopic biopsy or poly removal is small (< 1%). Although use of NSAIDs did increase the incidence of minor self-limited bleeding, an increase in the rate of major bleeding was not observed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Transjugular intrahepatic portosystemic shunt: a medical perspective.

The transjugular intrahepatic portosystemic shunt (TIPS) is an exciting new addition to the therapeutic armamentarium against portal hypertension. It is currently indicated for salvage of patients with active variceal hemorrhage despite sclerotherapy or where sclerotherapy is not feasible. Its use for recurrent episodes of bleeding despite chronic sclerotherapy and for ascites and hepatorenal syndrome remains experimental. It is contraindicated in patients with right-heart failure and portal vein thrombosis. TIPS is not indicated for primary prophylaxis of variceal hemorrhage or portal decompression prior to liver transplantation. TIPS is associated with its unique spectrum of complications which can occasionally be life-threatening. Although initial experience with this procedure is encouraging, a great amount of work remains to be done to fully define its role in clinical practice.

Contraindications↗