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Biomedical subjects

R V Rege

Publications and source records attributed to R V Rege.

At least 37 records · Page 2Linked to original sources

Interleukin-1 mediates guinea pig gallbladder inflammation in vivo.

Interleukin-1 (IL-1) is a cytokine with multiple immunologic and inflammatory properties. We previously demonstrated that lipopolysaccharide (LPS) stimulates release of IL-1, and IL-1 stimulates inflammation in guinea pig gallbladder in vivo. We hypothesized that IL-1 mediates LPS-induced guinea pig gallbladder inflammation in vivo. LPS and IL-1 were instilled into guinea pig gallbladder lumen alone (with cystic duct ligation) and with IL-1 ra and indomethacin, respectively (n = 4). Water transport across gallbladder mucosa, myeloperoxidase and IL-1 release from gallbladder tissue, and prostaglandin E2 (PGE2) in lumenal fluid were measured. Values for test agents and inhibitory agents were compared to saline controls using Student's t test (P < 0.05). Intralumenal LPS and IL-1 both stimulated gallbladder inflammation. LPS-induced and IL-1-induced inflammation were inhibited by both IL-1 ra and indomethacin. LPS stimulated IL-1 release and IL-1 itself caused gallbladder inflammation. LPS stimulated gallbladder inflammation as manifest by increased myeloperoxidase and PGE2 release, and water secretion into the gallbladder lumen. The inflammatory effects of LPS were inhibited by IL-1 ra. Taken together, these findings indicate that IL-1 is a mediator of LPS-induced guinea pig gallbladder inflammation in vivo.

Animals↗

Methionine, but not taurine, protects against formation of canine pigment gallstones.

Dogs fed a marginal protein, high carbohydrate diet containing borderline amounts of methionine consistently develop pigment gallstones, marked taurine deficiency, and abnormal secretion of unconjugated bile salts. Since taurine is essential for normal secretion of bile salts in the dog, a species that cannot use glycine for bile salt conjugation, we hypothesized that taurine deficiency plays an important role in the pathogenesis of canine pigment gallstones. The rates of formation of pigment gallstones at 6 weeks were compared in dogs fed normal dog chow, lithogenic diet alone, and lithogenic diet supplemented with either taurine or methionine (45-55 mg/kg/day). No dog fed normal dog chow, but 11 of 12 dogs fed lithogenic diet, formed pigment gallstones and sludge. Supplementation of the lithogenic diet with taurine did not protect against pigment gallstones; five of six dogs developed gallstones and sludge. However, supplementation with methionine was protective, only one of six dogs was found to have a few flecks of pigmented material in its gallbladder. Interestingly, neither taurine nor methionine protected against previously observed increases in the concentrations of biliary calcium and bile salt profile indicating that at least some of the abnormalities previously observed in this model are not related to methionine/taurine deficiency. These results disprove our initial hypothesis that taurine deficiency plays an important role in the pathogenesis of pigment gallstones, but did show that a lack of methionine is linked to the formation and growth of canine pigment gallstones. The mechanism(s) leading to the formation of gallstones in dogs that are methionine deficient are is not clear from these studies.

Animals↗

Hypercholeresis with cholate infusion in dogs with pigment gallstones.

We previously reported that dogs with pigment gallstones infused with taurocholate produce higher bile flow than normal dogs due to an increase in bile-acid independent bile flow. Since dogs with pigment gallstones are taurine-depleted and secrete large amounts of unconjugated bile salt, we hypothesized that the observed increased bile flow is secondary to the presence of unconjugated bile salts in the biliary tract, and cholate infusion was compared in normal and pigment gallstone dogs. Cholate increased bile flow significantly (P < 0.05) from 5.2 and 8.2 to 31 and 57 microliter/kg/min in normal and pigment gallstones dogs, respectively. Plots of bile flow versus bile acid output yielded separate linear relationships with a higher slope in gallstone dogs, but mannitol clearance indicated that excess flow originated in the canaliculus. Extended cholate infusion (570 min) severely taurine depleted normal dogs and increased cholate secretion, but bile flow remained significantly lower (P < 0.05) in normal dogs than in gallstone dogs. Choleretic activity of cholate in normal dogs was similar to that of taurocholate, but was nearly twice that of taurocholate in gallstone dogs. Choleretic activity increased in both groups with extended cholate infusion, suggesting adaptive changes in a biliary system bathed with unconjugated bile salts. These results are important since the increased bile flow in dogs with pigment gallstones would increase delivery of all biliary components to the gallbladder contributing to the high concentrations of gallbladder bile calcium previously observed in these dogs. It also has important physiological implications concerning the formation of bile in the proximal biliary tree. The data are most consistent with either direct hepatocyte stimulation to secrete another anion or with cholate/anion exchange at the canalicular, rather than ductal, level.

Animals↗

Inflammatory properties of bile from dogs with pigment gallstones.

BACKGROUND: Gallbladder inflammation and mucus hypersecretion are prominent features of cholesterol and pigment gallstones in humans and animals. The factors leading to inflammation and mucus hypersecretion are poorly understood. These studies examine the inflammatory potential of bile from dogs with pigment gallstones. METHODS: Dogs fed a methionine-deficient diet that produces pigment gallstones by 6 weeks were compared to normal dogs. Mucus layer thickness, myeloperoxidase activity, and interleukin-1-like activities were measured in canine gallbladder. The inflammatory potential of canine bile was determined by measuring mucus layer thickness, sodium absorption, myeloperoxidase activity and interleukin-1-like activity in guinea pig gallbladders exposed to normal and lithogenic canine bile for 4 hours. RESULTS: Mean mucus layer thickness, myeloperoxidase, and interleukin-1 activity were significantly greater in canine gallbladders containing pigment gallstones. Bile from dogs with pigment gallstones markedly increased mucus layer thickness, myeloperoxidase activity, and interleukin-1 activity and decreased sodium absorption in normal guinea pig gallbladder. These effects were not eliminated by centrifuging bile to remove crystals and gallstones. CONCLUSIONS: Canine bile from dogs with pigment gallstones contains soluble factors capable of causing inflammation in the gallbladder wall.

Animals↗

Laparoscopic splenectomy.

Dramatic decreases in length of hospital stay and time to complete recovery with laparoscopic cholecystectomy have led to the development of more advanced laparoscopic procedures. The rationale, technique, and early results with laparoscopic splenectomy are described in this article. Laparoscopic splenectomy is a complex procedure with a real potential for significant operative bleeding, but it can be accomplished successfully in greater than 80% of selected patients with minimal blood loss. If successful, length of stay is reduced in most patients to 1 to 3 days, but this benefit is not always seen in patients with complicated medical problems or with massive splenomegaly. The effects of increased blood loss in patients whose operations are converted to open operations are also not yet clear. Laparoscopic splenectomy is a procedure with great potential, but it is still in evolution.

Blood Loss, Surgical↗

Human polymorphonuclear leukocyte phagocytosis of crystalline cholesterol, bilirubin, and calcium hydroxyapatite in vitro.

We tested the hypothesis that human polymorphonuclear leukocytes (PMNs) phagocytize crystalline cholesterol, bilirubin, or calcium hydroxyapatite in vitro and in the process release oxygen metabolites and enzymes involved in the inflammatory process. Chemiluminescence (CL), elicited by the respiratory burst (release and activation of oxygen metabolites and enzymes) of PMNs during phagocytosis of a target particle, was used to quantitate PMN phagocytosis of each crystal. Significant CL (P < 0.05) was observed with cholesterol concentrations of 1.3-5.3 mg/ml and the dose-response was linear (r > or = 0.95). With bilirubin, significant CL was observed with concentrations of 0.07-0.33 mg/ml. The response to calcium hydroxyapatite was variable. Human PMNs phagocytize cholesterol, bilirubin, and to a lesser extent, calcium hydroxyapatite. PMN chemiluminescence was associated with phagocytosis, indicating that inflammatory substances are being released in the process. These results support the concept that crystals that occur in the gallbladder may initiate gallbladder inflammation.

Bilirubin↗

Adverse effects of biliary obstruction: implications for treatment of patients with obstructive jaundice.

The development of hypotensive complications, renal failure, and cholangitis in patients with jaundice [1-4] has particular implications for radiologists asked to perform diagnostic studies that require IV contrast material and for radiologists, gastroenterologists, and surgeons who do invasive procedures to relieve bile duct obstruction. Although systemic effects of obstruction eventually are eliminated by reestablishment of the free flow of bile, all invasive procedures are painful, require sedation or anesthesia, and can induce fluid shifts, electrolyte abnormalities, hemorrhage, bile peritonitis, and sepsis. A patient with jaundice is less able to respond to and easily decompensates after such stresses [4]. An awareness of the pathophysiologic effects of biliary obstruction is essential because proper preparation of patients with jaundice before invasive diagnostic and therapeutic procedures avoids complications and decreases morbidity and mortality [5-8]. An overview of the systemic effects of bile duct obstruction and their implications for patients who require invasive diagnostic and therapeutic procedures is provided in this article.

Anti-Bacterial Agents↗

Laparoscopic inguinal hernia repair. A preliminary experience.

OBJECTIVE: To evaluate the safety and efficacy of laparoscopic inguinal hernia repair. DESIGN: Nonrandomized trial. SETTING: Veterans Affairs hospital and a large university hospital. PATIENTS: The study included 38 patients (36 male and two female) who had an acceptable risk for general anesthesia, presented electively, and gave informed consent; patients were excluded for whom general anesthesia had a high risk or who had incarcerated or strangulated hernias. INTERVENTION: Laparoscopic inguinal hernia repair was performed with general anesthesia through bilateral, lower-abdominal, 12-mm lateral rectus sheath ports with an umbilical 30 degrees viewing laparoscope. After the peritoneum was incised and flaps were raised, an onlay patch of polypropylene mesh, secured with staples, covered both indirect and direct hernia regions in each patient. Small hernia sacs were usually reduced or excised. RESULTS: From December 1991 through October 1992, 40 inguinal hernias were repaired; two patients had bilateral hernias. There were 22 indirect and 17 direct inguinal hernias and one femoral hernia. Nine of the hernias repaired were recurrent, and five were sliding hernias. Complications occurred in nine patients, but there were no recurrences during a median follow-up of 26 weeks. All but one patient resumed preoperative activities by 7 days after the operation. CONCLUSIONS: Laparoscopic inguinal hernia repair is an effective operation with low morbidity. Long-term follow-up is needed to determine the durability of the repair.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗