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Biomedical subjects

R V Rege

Publications and source records attributed to R V Rege.

At least 19 recordsLinked to original sources
PubMed1992

Secretion of biliary calcium is increased in dogs with pigment gallstones.

We have previously demonstrated that gallbladder bile is supersaturated with calcium bilirubinate in a canine dietary model of pigment gallstones. Supersaturation resulted from combined increases in the concentrations of both biliary calcium and unconjugated bilirubin. The elevations in biliary calcium and unconjugated bilirubin concentrations remain unexplained but could possibly be due to increases in hepatic or ductular secretion, alterations in bile composition with respect to calcium-or bilirubin-binding affinity, decreases in absorption from the gallbladder lumen, or, in the case of unconjugated bilirubin, production within the lumen by hydrolysis of conjugated bilirubin. Here, we study a single possible cause for the observed increase in biliary calcium concentration during pigment gallstone formation in dogs. Secretion of calcium into bile in dogs with pigment gallstones before and after infusion of the bile salt, taurocholate, was compared to normal dogs. A significant increase in bile acid-independent bile flow and calcium output (CaO) was observed at any given bile acid output. Thus, plots of bile flow and CaO versus bile acid output yielded two separate functions in normal dogs and dogs with pigment gallstones. The slopes of these functions were similar, but intercepts extrapolated to zero bile acid output were markedly different, indicating that bile acid-independent, but not bile acid-dependent, bile flow and CaO was increased. The increase in CaO was not due to secretion of bile with increased concentrations of calcium but rather to the increases in the rate of bile flow. These findings might, in part, explain elevated calcium concentrations since increased amounts of calcium would be presented to the gallbladder in these animals during gallstone formation.

Animals↗
PubMed1992

Convective movement of Ca2+ across guinea pig gallbladder epithelium.

Recently, much interest has developed in biliary calcium because of its importance in the pathogenesis and composition of gallstones. While much progress has been made in understanding the thermodynamic factors that control biliary calcium concentrations, little is known about the kinetic factors that control the movement of calcium across the gallbladder epithelium. These studies measure guinea pig gallbladder epithelial permeability to Ca2+ during in vivo convective water movement across the membrane. Water movement, ranging from -15.2 (absorption) to 6.3 microliters.min-1.cm-2 (water entry), was induced by placing hypotonic, isotonic, and hypertonic solutions into the gallbladder lumen. Calcium movement was found to be directly and linearly related to water flow, indicating that Ca2+ moved with the convective water flow, presumably across paracellular channels. The slope of this relationship (0.602), representing the concentration of calcium in the fluid translocated across the gallbladder epithelium, was only about half that of plasma or luminal contents, indicating that calcium movement across the membrane was restricted. The mean sieving coefficient (1 - r) of guinea pig gallbladder, calculated from this slope, was approximately 0.5, indicating that the epithelium is only moderately permeable to Ca2+. The results suggest that intraluminal chelation of Ca2+ for the possible prevention and/or treatment of calcium-containing gallstones is a potentially feasible therapeutic modality.

Animals↗
PubMed1992

Treatment of peripancreatic fluid collections in patients with complicated acute pancreatitis.

We reviewed an experience with treatment of peripancreatic fluid collections in patients with complicated acute pancreatitis to identify clinical and computed tomography (CT) parameters that are helpful in the selection of patients for treatment and to assess treatment outcome. The extent of CT abnormalities determined a CT severity score (mild = 1, severe = 4). From 1985 to 1990, 650 patients were hospitalized with acute pancreatitis; a peripancreatic fluid collection was found in 36 patients (5.5 percent). Ten of 11 patients with successful outcome after no invasive treatment (group 1) had a low CT severity score of 1 or 2; mean serum albumin was 4.0 gram percent. Of 25 patients who had some form of drainage, 12 had a high CT severity score of 3 or 4 (p < 0.05) and a mean serum albumin of 3.4 grams percent (p < 0.05). Nine patients had only operative drainage (group 2) and 16 had CT-directed percutaneous catheter drainage (group 3). In group 3, percutaneous catheter drainage successfully drained the fluid collection in six patients, while ten patients needed an operation, in addition to percutaneous drainage, to effectively débride and drain the necrotizing pancreatic problem. As a result of the current review, we propose an algorithm for treatment of these patients.

Acute Disease↗
PubMed1991

Canine bile contains anticrystallization factors that inhibit precipitation of calcium carbonate.

Previous studies have strongly suggested that human bile contains a substance(s) that interferes with the precipitation of calcium phosphate and carbonate from solution. These studies, however, did not distinguish between calcium binding by biliary constituents resulting in decreased calcium carbonate saturation (alterations in solution thermodynamics) and true inhibition of calcium salt precipitation by kinetic factors. Because our recent studies have shown that canine common duct bile is always supersaturated with calcium carbonate (thermodynamically at risk for precipitation), we hypothesized that it must contain kinetic factors that inhibit formation and/or growth of calcium carbonate crystals. Effects of canine bile, bovine albumin and the bile salt taurocholate on calcium carbonate precipitation were studied in highly supersaturated solutions of calcium carbonate that spontaneously undergo rapid precipitation. Measured free ionized calcium concentrations, [Ca++], and calculated calcium carbonate saturation indices were compared in test solutions and controls to evaluate the thermodynamic effects of test solutions on the degree of saturation in the assay system. It is shown that addition of only 0.2 ml of normal canine gallbladder bile to the assay system (a 1:101 dilution of biliary components) abolished precipitation. A lesser inhibitory effect (a decrease in the rate of precipitation) was observed when gallbladder bile was diluted but was lost after 10-fold dilution. Canine common duct bile caused a decrease in the rate of precipitation similar to diluted gallbladder bile. In contrast, sodium taurocholate (250 mmol/L), the major bile salt in the dog, and albumin (1.5 gm/L), the most abundant protein in bile, had only a minimal inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Calcium and calcium binding in human gallstone disease.

Precipitation of calcium salts from bile is important in pigment gallstone formation and may serve as a nidus for cholesterol precipitation. We compared gallbladder bile from patients with symptomatic gallstone disease (40 with cholesterol gallstones and 12 with pigment gallstones) with bile from 10 patients undergoing surgery for non-biliary tract disease. Bile from patients with gallstone disease was less concentrated, with decreased sodium, bile salt, and phospholipid concentrations, but elevated biliary calcium concentrations were not observed. The relationship between free ionized calcium and total calcium was similar in all groups, indicating no difference in calcium binding by gallstone-containing bile. We cannot exclude elevated biliary calcium level as a factor in gallstone pathogenesis, as it could be a transient event. The importance of calcium precipitation was supported by our finding that more than half of the samples were saturated or supersaturated with at least one calcium salt, calcium carbonate.

Bile↗
PubMed1990

The effect of volume and number on fragmentation of gallstones by lithotripsy.

Several factors may affect the fragmentation of gallstones by lithotripsy. We hypothesized that stone volume is an important determinant of degree of fragmentation, while number of stones is less important. The volume of 30 single stones was measured in vitro by water immersion. Thirty sets of multiple stones were matched with single stones of similar volumes. The stones were subjected to 750 shock waves (18 kV) with the Dornier MPL 9000 lithotripter. Degree of fragmentation was assessed by passing fragments through sieves of 1, 2, and 4 mm and recording percentage of stone weight which passed through each sieve. The mean percentage of stone weight passing through sieves of 1, 2, and 4 mm for single stones was 38.2, 49.4, and 59.8. The corresponding values for multiple stones were 46.4, 61.3, and 75.4. These values were not significantly different at P less than or equal to 0.05. Thus, there was no significant difference in fragmentation between single and multiple stones when their volumes were similar. The mean volume of stones with 100% of fragments less than 4 mm (0.80 +/- 0.05 cc) was significantly less than that of stones with fragments greater than 4 mm (1.95 +/- 0.14 cc) (P less than 0.0001). There was a significant inverse linear correlation between stone volume and degree of fragmentation (r = -0.65). We conclude that stone volume is an important determinant of degree of fragmentation and may be the most important criterion in selecting patients for lithotripsy. In this in vitro setting, stone number alone had no effect on degree of stone fragmentation.

Calcinosis↗
PubMed1990

Biliary calcium secretion in the dog occurs primarily by passive convection and diffusion and is linked to bile flow.

Despite the importance of biliary calcium in the pathogenesis of gallstones, little is known about the sites or modes of entry of calcium into bile. We here examine the mechanisms of calcium entry into canine bile by comparing the entry of calcium, over a wide range of bile flows (2.4 to 38.0 microliters/kg per minute), with that of potassium, a small ion that is passively distributed throughout the biliary tract and that is also subject to alteration by Gibbs-Donnan forces. It is shown that (1) the concentrations of free ionized calcium, [Ca++], increases in an apparently linear fashion with increasing total bile salt concentration at low bile flow, whereas the rise in [Ca++] is strongly blunted at high rates of flow; (2) the entry of both calcium and potassium into bile is tightly linked to bile flow; and (3) calcium outputs are linearly related to potassium outputs with an intercept at the origin. These results indicate that the canaliculus is permeable to Ca++ ions, and that Ca++ enters bile primarily by passive convection and diffusion. Calcium entry is thus tightly linked to the water flux generated by bile salt secretion. Such passive entry and distribution indicate that calcium will always be present in bile and that possible therapeutic reduction of biliary [Ca++] for treatment, and possibly prevention of calcium-containing gallstones, will require sustained chelation of calcium within the lumen of the biliary tract.

Animals↗
PubMed1990

Rates of morbidity and mortality after closure of loop and end colostomy.

The purported ease and safety of closure of loop colostomy are cited as reasons for avoiding end colostomy, with or without resection. However, data comparing the complications of loop colostomy closure and end colostomy takedown and anastomosis are sparse. We analyzed data from 93 consecutive colostomy closures, of which 62 were loop and 31 were end colostomies. The two groups were comparable with respect to age, the underlying disease and risk factors, such as coronary artery disease, diabetes, hypertension, steroid dependence, hypoalbuminemia and smoking. Closure of end colostomies took longer and was associated with more loss of blood than closure of loop colostomies. However, the mortality rates for closure of loop (4.8 per cent) and end (3.2 per cent) colostomies were not significantly different. The complication rates were identical (16 per cent). Although none of the other risk factors were associated with increased rates of mortality or morbidity, the detrimental effects of steroid dependence and preoperative hypoalbuminemia were striking. All four of the deaths and 60 per cent of the complications occurred in patients with steroid dependence or hypoalbuminemia, or both. The rates of wound infection after primary or secondary closure of the stoma site were not significantly different. We concluded that loop colostomy closure is not associated with fewer complications than closure of end colostomy, even though the latter takes longer and is more difficult. Hypoalbuminemic and steroid-dependent patients should undergo colostomy closure with caution, if at all. Primary closure of the stomal site is safe and reduces the length of hospital stay.

Adrenal Cortex Hormones↗
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↗