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Biomedical subjects

R V Rege

Publications and source records attributed to R V Rege.

At least 55 records · Page 3Linked to original sources
PubMed1989

A foregut carcinoid tumor causing Zollinger-Ellison syndrome.

A patient had severe peptic ulcer disease complicated by gastric outlet obstruction and choledochoduodenal fistula. Serum gastrin levels were elevated preoperatively to 340 ng/L. A 1.5-cm histologically benign carcinoid tumor of the antrum of the stomach was found at surgery, and surgical resection of the tumor resulted in normalization of serum gastrin levels and amelioration of the peptic acid diathesis. The patient remains asymptomatic at one year. Immunohistochemical staining demonstrated that the carcinoid indeed contained gastrin along with chromogranin, cholecystokinin, and neuron-specific enolase. This is a case of Zollinger-Ellison syndrome caused by a benign foregut carcinoid (gastric carcinoid-gastrinoma).

Aged↗
PubMed1989

Reversal of pigment gallstone disease in a canine model.

Unlike dietary-induced cholesterol gallstones, which may disappear spontaneously when the lithogenic diet is withdrawn, little is known about the natural history of pigment gallstones. We examined whether pigment gallstone disease, which can be uniformly induced in the dog by six weeks of a methionine-deficient diet, can be reversed by return to normal diet. As previously reported, all dogs develop pigment gallstones as well as significant increases in biliary total calcium, free ionized calcium, and cholesterol concentrations after six weeks of a lithogenic diet. These changes are accompanied by a significant increase in the concentration of unconjugated bile salts in bile. In addition, histologic changes in the gallbladder wall occur that are consistent with a moderate degree of chronic cholecystitis. This study clearly demonstrates that return to a normal diet for six weeks allows bile composition to normalize, gallstones to disappear in 50% of dogs, and gallbladder histologic changes to return toward normal. Thus, it would appear that pigment gallstone disease in this model may be reversible, at least early during its course. Although the relevance of these findings to pigment gallstones in humans must be established, the potential for nonoperative treatment of pigment gallstones should not be discounted.

Animals↗
PubMed1989

Percutaneous cholecystostomy in the diagnosis and treatment of acute cholecystitis in the high-risk patient.

We performed percutaneous cholecystostomy in 22 critically ill patients with suspected acute cholecystitis. This procedure accurately diagnosed acute cholecystitis in 17 of these 22 patients and excluded the diagnosis in the other 5 patients. Moreover, percutaneous cholecystostomy stabilized the conditions of 16 of the 17 patients with acute cholecystitis, allowing elective surgery in 8 patients and effectively treating 8 patients who never became surgical candidates. Percutaneous cholecystostomy and bile cultures are useful in the diagnosis and treatment of acute cholecystitis and should be performed in critically ill patients with clinical, laboratory, and radiologic evidence of acute cholecystitis and an excessive risk for cholecystectomy.

Acute Disease↗
PubMed1989

Selection of patients for gallstone lithotripsy.

Although alternatives to cholecystectomy are now available to treat patients with gallstones, the primary treatment of gallstone disease remains surgical. It is therefore important to distinguish those patients who would benefit most from nonoperative therapy of gallstones from those who require cholecystectomy while ensuring patient safety. Current criteria for selection of patients for extracorporeal shock-wave lithotripsy (ESWL) are presented herein. In addition, preliminary results from recent in vitro experiments with human gallstones obtained at cholecystectomy are outlined. The current criteria for selection of patients for treatment with ESWL are similar to those used in the initial German experience. They appear to ensure patient safety, but the actual conditions that predict successful treatment of gallstones by ESWL are not yet known, since the clinical and in vitro studies which will define the patient and stone characteristics that predict a successful treatment outcome are still in progress. Thus, current criteria should be considered guidelines for treatment which will most certainly be modified as experience is gained with ESWL.

Cholecystography↗
PubMed1989

Supersaturation of canine gallbladder bile with calcium bilirubinate during formation of pigment gallstones.

Analogous to cholesterol gallstones forming in bile supersaturated with cholesterol, pigment gallstones may form in bile supersaturated with calcium bilirubinate. We tested this hypothesis in a dietary model of pigment gallstones. The concentration of ionized calcium (Ca++) and unconjugated bilirubin (UCB) was measured in 15 normal dogs and in 15 dogs with pigment gallstones induced by 6 weeks of a methionine-deficient diet. Although there was minimal change in the gallbladder's ability to acidify or concentrate bile, both [Ca++] and [UCB] markedly increased. These values were compared with equilibrium concentrations in model bile solutions. In all normal bile, the [UCB] was equal to or lower than the mean [UCB] concentration of model bile solutions with comparable [Ca++]. However, in all but one bile sample from dogs with pigment gallstones, the [UCB] exceeded this concentration and was therefore supersaturated with calcium bilirubinate. This supports the hypothesis that calcium bilirubinate precipitation is important in the formation and growth of pigment gallstones.

Animals↗
PubMed1989

Diverticular disease.

Although most often clinically silent, colonic diverticula are responsible for a large number of gastrointestinal illnesses in our society. Complications of diverticular disease, including perforation and hemorrhage, may occur in 15% to 20% of patients with diverticula during their lifetime, and although often mild and self-limiting diseases, they too frequently cause life-threatening problems that require prompt surgical intervention. Despite a cadre of sophisticated laboratory and radiologic tests that have been developed to aid in the diagnosis of complicated diverticular disease, the diagnosis and treatment of diverticulitis still relies heavily on patient history, physical examination, physician judgment, and the patient's clinical response to treatment. Thus it is important for the managing physician to fully understand the pathogenesis of diverticula, the clinical consequences and modes of presentation of complicated diverticular disease, and the array of interventions available for treatment of these problems. This monograph summarizes our knowledge of diverticular disease to date and tries to give specific guidelines for the treatment of patients with complicated diverticulitis. However, it must be understood that the presentation and severity of these complications vary widely from patient to patient. Thus one cannot take a single approach toward a patient who has diverticulitis or diverticular bleeding. Rather, successful outcomes depend on an individual approach to each patient while maintaining certain generally accepted principles of treatment.

Colonic Diseases↗
PubMed1989

Isolation of an acidic protein from cholesterol gallstones, which inhibits the precipitation of calcium carbonate in vitro.

In seeking to identify nucleating/antinucleating proteins involved in the pathogenesis of cholesterol gallstones, a major acidic protein was isolated from each of 13 samples of cholesterol gallstones. After the stones were extracted with methyl t-butyl ether to remove cholesterol, and methanol to remove bile salts and other lipids, they were demineralized with EDTA. The extracts were desalted with Sephadex-G25, and the proteins separated by PAGE. A protein was isolated, of molecular weight below 10 kD, which included firmly-bound diazo-positive yellow pigments and contained 24% acidic, but only 7% basic amino acid residues. The presence of N-acetyl glucosamine suggested that this was a glycoprotein. This protein at concentrations as low as 2 micrograms/ml, but neither human serum albumin nor its complex with bilirubin, inhibited calcium carbonate precipitation from a supersaturated solution in vitro. This protein could be precipitated from 0.15 M NaCl solution by the addition of 0.5 M calcium chloride. Considering that cholesterol gallstones contain calcium and pigment at their centers, and that small acidic proteins are important regulators in other biomineralization systems, this protein seems likely to play a role in the pathogenesis of cholesterol gallstones.

Amino Acids↗
PubMed1989

Canine common duct and gallbladder bile contain antinucleating factors that inhibit CaCO3 precipitation.

We performed studies involving large incremental additions of calcium to bile to examine the degree of CaCO3 supersaturation that can be achieved in bile, as compared with that in simple NaCl-NaHCO3 solutions. The addition of CaCl2 to bile increased total and free ionized calcium by from four to 12 times their original values and by from two to three times the highest concentrations encountered in bile in vivo. The increase in [Ca++] resulted in fourfold to 12-fold increases in the saturation indexes of bile, with the saturation index reaching as high as 73.4 in a common duct sample. Despite the markedly elevated CaCO3 saturation indexes, evidence of CaCO3 precipitation was not observed in either common duct or gallbladder bile over a 24-hour period. For comparison, calcium added to NaCl-NaHCO3 solutions resulted in the precipitation of CaCO3 within 4 hours if saturation indexes were greater than 12. These results indicate that native bile contains potent antinucleating factors that markedly inhibit CaCO3 precipitation, and they confirm our previous in vivo observations in canine common duct bile.

Animals↗
PubMed1988

Treatment of anastomotic leakage following low anterior colon resection.

Four hundred five consecutive cases of low anterior colon resection were studied to determine the best treatment of anastomotic leak. The triad of fever, leukocytosis, and pelvic pain was present in 15 of the 16 cases with leaks. Four (25%) of the 16 patients died. Eleven were managed by proximal decompression and drainage; four died (36%). Three patients underwent takedown of the anastomosis, end colostomy, and distal closure or exteriorization; none died. Neither of the two patients who had drainage alone died. Anastomotic leakage accounted for two thirds of the deaths in this series. Recognition of the clinical triad of fever, leukocytosis, and pelvic pain could lead to earlier diagnosis and improved outcome. Our data suggest that a procedure that includes takedown of the anastomosis, end colostomy, and closure of the rectum is the most efficacious treatment of anastomotic leakage after low anterior colon resection.

Anastomosis, Surgical↗
PubMed1988

Interactions of unconjugated bilirubin with bile salts.

The rate of peroxidation of unbound, unconjugated bilirubin (UCB) was used to assess the interactions of UCB with four taurine-conjugated bile salts at pH 8.2, 37 degrees C, and an ionic strength of 0.15. Each of the four structurally different bile salts markedly decreased the rate of peroxidation of UCB in the presence of horseradish peroxidase (HRP); 30% of UCB was bound even at low, premicellar bile salt concentrations (1 mM). At high bile salt concentrations (75 mM), taurocholate (TC) and tauro-3 alpha,7 alpha-dihydroxy-12-oxo-5 beta-cholan-24-oate (T12-OXO) exhibited the highest degree of inhibition of UCB peroxidation; only 0.6% and 1.1% of UCB were unbound, respectively. Taurochenodeoxycholate (TCDC) yielded somewhat less inhibition with 2.0% of UCB unbound. Taurodehydrocholate (TDHC), a bile salt that does not form micelles but does form dimers, was comparable to TC and T12-OXO with unbound UCB of 1.0%. With TC and T12-OXO, apparent affinity for UCB was at least four times greater above the published critical micellar concentration (CMC) than in the premicellar range. TCDC was only studied above its CMC value and only one region of UCB binding was noted. Interaction of UCB with TDHC was similar to premicellar interactions with TC and T12-OXO below 25 mM, but increased to values intermediate between monomer and micelle above 40 mM TDHC, compatible with formation of TDHC dimers above 20 mM. These data show that there are differences in the ability of bile salts to bind UCB. Thus, alterations in bile salt profile in bile might lead to higher concentrations of free UCB in bile predisposing to pigment gallstones.

Bile↗
PubMed1988

Increased total and free ionized calcium in a canine model of pigment gallstones.

It has been postulated that precipitation of calcium from bile is important in the formation and growth of pigment gallstones, since they contain large amounts of calcium. Therefore we studied biliary total calcium [( Ca]) and free ionized calcium [( Ca++]) concentrations in 12 dogs before and after 6 weeks of a methionine-deficient, high-cholesterol diet. In all dogs pigment gallstones and sludge formed while the animals were on the diet. Although gallbladder function--as assessed by biliary pH, total bile salt, and bile electrolyte concentrations--was minimally altered by the diet, both [Ca] and [Ca++] increased significantly, from 10.16 +/- 0.19 to 13.16 +/- 0.57 mmol/L and 3.02 +/- 0.07 to 3.76 +/- 0.17 mmol/L, respectively. The observed increases in calcium concentrations, and specifically in [Ca++], early during stone formation in this model would increase the likelihood that bile would become saturated with at least one calcium salt and support the hypothesis that calcium is important in pigment gallstone formation.

Animals↗
PubMed1987

One-stage resection and anastomosis in the management of colovesical fistula.

Thirty-four patients with colovesical fistulas seen over a recent 10 year period were reviewed. Diverticulitis was the most common cause of colovesical fistula, accounting for 71 percent of patients in our series. The majority of patients present electively, and most have urinary tract complaints. In those patients in our study who presented with systemic infection, urinary obstruction was present in 70 percent. Although proctosigmoidoscopy and barium enema examination are essential in the preoperative assessment, cystoscopy is the most useful test in suggesting or confirming the diagnosis of colovesical fistula. Intravenous urography is not necessary in the evaluation of these patients. The surgical treatment depends on the cause of the fistula. For patients with an inflammatory cause of the fistula, one-stage operative treatment is associated with low morbidity and decreased length of stay compared with operative treatment in more than one stage. In the presence of severe inflammation or inadequate bowel preparation, two-stage operative treatment is safe and effective. Operations in three stages for colovesical fistula are not indicated. The primary objectives in the management of colovesical fistulas due to unresectable malignancy are relief of intestinal and urinary obstruction and fecal diversion. Resection of the malignancy should be performed whenever possible.

Adult↗
PubMed1987

Evidence for H+ secretion by the in vivo canine gallbladder.

In humans and most other species, a decline in pH of gallbladder contents occurs during the concentration of bile. Recent in vitro studies in rabbit, guinea pig, and Necturus gallbladders have strongly suggested mucosal H+ secretion during sodium reabsorption, presumably representing a Na+/H+ exchange. The present in vivo studies are the first attempt to determine whether H+ secretion by the gallbladder can be demonstrated in the living animal. Gallbladder bile was obtained from 27 anesthetized dogs after 12-24-h fasts; 12 samples of common duct bile were also obtained in 3 dogs during variable taurocholate infusion. In common duct bile, observed ranges were as follows: pH, 7.37-7.85; CO2 partial pressure (PCO2), 21-32 mmHg; total CO2 concentration ([TCO2]), 16.4-41.4 mM; total bile salt concentration ([TBS]), 16-93 mM; and [Na], 153-192 mM. In gallbladder bile, respective ranges were as follows: pH, 5.72-7.29; PCO2, 36-101 mmHg; [TCO2], 1.21-15.5 mM; [TBS], 150-305 mM; and [Na], 199-266 mM. In all samples [Na] was linearly related to [TBS]. Carbon dioxide partial pressure increased from a mean of 27.3 mmHg in common duct bile to greater than 100 mmHg in gallbladder bile at [TBS] = 180 mM, then declined to approximately 36 mmHg as [TBS] increased to greater than 300 mM. Peak PCO2 occurred at pH approximately 6.4-6.6, then declined as pH decreased to approximately 5.7. Bile to plasma PCO2 ratios increased from a mean of 1.08 in common duct samples to greater than 2.0 in gallbladder samples at pH approximately 6.3, then declined to approximately 1.0 in fully concentrated bile. If the high PCO2 values in bile were solely due to tissue CO2 production, a sustained increase in PCO2 throughout Na+ reabsorption might be expected. The results strongly suggest H+ secretion (HCO3- neutralization), as peak PCO2 occurred when [TBS] was only about 180 mM, long before sodium absorption was complete. It is hypothesized that H+ secretion may have important favorable effects on calcium lithogenicity, reducing the likelihood of the formation of CaCO3- containing gallstones.

Animals↗
PubMed1987

Enzymatic oxidation of unconjugated bilirubin to assess its interactions with taurocholate.

The rate of peroxidation of unconjugated bilirubin (UCB), catalyzed by horseradish peroxidase (HRP), has been employed by Jacobsen (1969. FEBS Lett. 5: 112-114) to assess the fraction of unbound UCB in the presence of serum albumin. We used this method to examine the interactions of UCB with taurocholate (TC) at pH 8.2, assuming solubilization of UCB by TC is due to pigment binding and/or to partitioning into the micelle, thus rendering UCB unavailable for peroxidation. Inhibition of UCB peroxidation conformed with predictions based on these assumptions and demonstrated significant interaction of UCB with both monomeric and micellar TC. Although significant inhibition of UCB peroxidation was seen with TC monomer, inhibition was even greater with TC micelles. In contrast, pyrogallol, another substrate of HRP, acted very differently in the presence of TC. Inhibition of pyrogallol peroxidation by TC was much less than with UCB and occurred primarily with monomeric TC, with little further inhibition in the micellar range. The results of this study suggest that at taurocholate concentrations above 50 mM, similar to the physiologic bile salt concentrations in human bile, at least 99% of UCB is bound to bile salt, dramatically decreasing the concentration of unbound UCB. Since bile salts also bind Ca2+, they play a dual role in protection against the precipitation of calcium bilirubinate from bile. Therefore, bile salts are a major factor in the prevention of the formation and growth of pigment gallstones.

Bilirubin↗
PubMed1987

Absorption of biliary calcium from the canine gallbladder: protection against the formation of calcium-containing gallstones.

Calcium salts are the major components of pigment gallstones. The calcium species in bile that is critical for Ca++ precipitation is free ionized calcium, [Ca++]. Factors that regulate biliary [Ca++] in bile are therefore of great importance in the pathogenesis of pigment gallstones. The fate of biliary Ca++ on entry into the gallbladder has not previously been studied. We here report that a minimum of 51.3% +/- 8.8% (SEM) of Ca++ is absorbed from the canine gallbladder on concentration of bile during a 24-hour fast. In addition, there was absorption of least 70.9% +/- 6.2% of Na+, 56.5% +/- 8.6% of K+, and nearly all (greater than 98%) of Cl-. Absorption, neutralization, or both, of HCO3- was also nearly complete (greater than 98%). During concentration of bile by the gallbladder, the concentrations of all biliary cations increased as total bile salt concentration increased, whereas anion concentrations declined. These results are consistent with a Gibbs-Donnan effect induced by impermeable, negatively charged bile salt molecules. Comparison of bile/plasma [Ca++] ratios with those for [K+], a passively distributed ion, was also consistent with, although not proof of, the passive absorption and distribution of Ca++ across the gallbladder epithelium. The absorption of Ca++ by the gallbladder may be a factor in the prevention of pigment gallstones, because it limits free Ca++ ion in bile, and thus decreases the likelihood of precipitation of calcium.

Animals↗
PubMed1986

External duodenal fistula. Causes, complications, and treatment.

We reviewed records of 18 patients with external duodenal fistula. Fourteen patients developed duodenal fistulas following an operation, two following abdominal trauma, and two as a complication of other diseases. Copious drainage of intestinal juice from the abdomen was the most common presenting sign. Contrast fistulography, upper gastrointestinal tract roentgenography, and T-tube cholangiography were useful diagnostic studies. Nine patients were treated nonoperatively; nine patients required at least one operation. Complications occurred frequently; of special interest were three patients who developed postoperative acute cholecystitis. Six patients died (33% mortality). Factors associated with mortality were advanced age (greater than 65 years), uncontrolled infection and multiple organ failure, high-output fistula, malnutrition, delay in diagnosis (more than three days), and multiple reoperations to treat the fistula or complications. External duodenal fistula continues to be a life-threatening problem whether it is postoperative, posttraumatic, or secondary to a disease process.

Abdominal Injuries↗
PubMed1986

Pathogenesis of calcium-containing gallstones. Canine ductular bile, but not gallbladder bile, is supersaturated with calcium carbonate.

Calcium precipitation in bile is a requisite event in the initiation and growth of all pigment gallstones. Calcium solubility in bile is thus of great importance. This is the first attempt to define the ion-product of CaCO3 in bile in any species. If the ion-product: [Ca++] X [CO = 3] exceeds solubility product (K'sp), the sample is supersaturated and CaCO3 precipitation is thermodynamically possible. We have recently determined K'sp of calcite to be 3.76 X 10(-8) mol/liter at 37 degrees C and total ionic strength = 0.16 M. Gallbladder (GB) bile was obtained from 15 anesthetized dogs after 12-24-h fasts. Duct bile was obtained from three dogs (n = 12) during variable taurocholate infusion. Samples were assayed for pH, partial pressure of carbon dioxide (PCO2), total bile salt concentration ([TBS]), total calcium concentration ([Ca]), and free calcium ion concentration ([Ca++]). With increasing [TBS] in both GB and duct bile, there was a linear decline in pH, a curvilinear decline in [HCO-3] and [CO = 3], and linear increase in [Ca++] and [Ca]. All ductular samples were supersaturated with CaCO3, with saturation indices (SI) as high as 17.5 and a mean of 8.36 +/- 1.43 (SE). In sharp contrast, none of the GB samples were supersaturated, due to the marked decline in [CO = 3] upon concentration and acidification of bile. In GB bile, the SI ranged from 0.006 to 0.126, with a mean of 0.039 +/- 0.011. The gallbladder thus produced a change in the SI from a value as high as 17.5 to a value as low as 0.006 in concentrated GB bile, which is a nearly 3,000-fold change. The average change in the SI was approximately 215-fold. Since all duct samples were supersaturated, and since the dog does not normally form gallstones, the data support our previous hypotheses that: (a) in canine bile, as in canine pancreatic juice, a nucleating factor is necessary for CaCO3 precipitation; (b) bile salts are important buffers for Ca++ in bile; and (c) normal GB mucosal function (concentration and acidification of bile) plays an important role in reducing CaCO3 lithogenicity in GB bile.

Animals↗