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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

A learning curve for laparoscopic splenectomy at an academic institution.

BACKGROUND: Laparoscopic splenectomy is emerging as the standard for treatment of benign splenic disorders. Since splenectomy is indicated relatively infrequently, issues arise concerning training of surgeons to perform laparoscopic splenectomy. Our experience with 50 laparoscopic splenic procedures is reported with emphasis on the learning curve at an academic institution. MATERIALS AND METHODS: Data were prospectively collected on 50 consecutive patients undergoing attempted or successful laparoscopic surgical procedures on the spleen at Northwestern Memorial Hospital or The Chicago Health Care System, Lakeside Division, from April 1993 to April 1998, and on 5 patients undergoing open splenectomy from April 1993 to October 1995. Outcomes including conversion rate, operative time, day feedings were tolerated, and length of hospital stay was examined and correlated with the number of attempted cases. RESULTS: Laparoscopic splenectomy progressed from an operation requiring two advanced laparoscopic surgeons to one performed by carefully supervised senior residents. Success rates increased from 60% initially to greater than 95% recently. Likewise, operative time decreased significantly from 195 to 97 min, while length of stay declined from 2.5 to 1.5 days. High success rates, low operative times, and short length of stays were achieved during the last 20 patients while surgical residents were taught to perform the procedures. The reasons for improvement are multifactorial including use of the harmonic scalpel, a change to the lateral position, and increasing experience with the procedure. CONCLUSIONS: Laparoscopic splenectomy is a safe and effective procedure that reduces postoperative length of hospital stay. It can be performed successfully in most patients with operative times comparable to those of open splenectomy. Moreover, the procedure can (and should) be taught to residents once they master basic and advanced laparoscopic skills.

Adult

Inflammation and a thickened mucus layer in mice with cholesterol gallstones.

BACKGROUND: Based on previous work which suggested that biliary crystals may induce inflammation in the gallbladder wall and that inflammation is an early event during the formation of pigment gallstones in the dog, studies were performed examining mucus layer thickness, myeloperoxidase activity, and interleukin-1 (IL-1) activity in the wall of mouse gallbladder during formation and growth of cholesterol gallstones. METHODS AND MATERIALS: The inflammatory effects of cholesterol gallstones at 2 and 4 weeks were studied in BalB/C mice fed a crushed standard mouse chow with added cholesterol (1.0%) and cholic acid (0.5%). Results were compared to those of normal mice fed standard mouse chow. The presence or absence of crystals and stones was determined by gross and microscopic examination of bile. Myeloperoxidase and IL-1 activity in the gallbladder wall was measured using well-established bioassays. Mucus layer thickness was measured by darkfield microscopy. RESULTS: All mice fed a lithogenic, 1.0% cholesterol/0.5% cholic acid diet developed cholesterol crystals and gallstones at 2 and 6 weeks. No control mice developed either crystals or gallstones. Myeloperoxidase and IL-1 activities, markers of an inflammatory response, increased significantly in the gallbladder of mice with crystals at 2 weeks. Myeloperoxidase activity increased two- to three-fold, and IL-1 activity sevenfold, by 6 weeks. Mucus layer thickness also progressively increased during the 6-week period. CONCLUSIONS: It is concluded that inflammation is an early event associated with the appearance of crystals and gallstones in bile.

Animals

Bilateral adrenal cortical adenomas in primary hyperaldosteronism.

Bilateral adrenal cortical adenomas in the presence of primary hyperaldosteronism is an extremely rare condition. We present a case of primary hyperaldosteronism in which a unilateral hypersecreting aldosterone-producing adenoma coexisted with a large, contralateral adrenal mass ultimately found to be consistent with cortical adenoma. Management consisted of total adrenalectomy and enucleation of adenoma from the opposite adrenal. The patient is normotensive 3 years after surgery. Enucleation as a successful approach to hyperfunctioning cortical adenomas is proposed.

Adrenal Cortex Neoplasms

The inflammatory effects of crystalline cholesterol monohydrate in the guinea pig gallbladder in vivo.

BACKGROUND: The etiologic role of crystalline material in inflammatory arthritis is well established. The role of crystals in cholecystitis is unclear. We hypothesized that crystalline cholesterol monohydrate stimulates guinea pig gallbladder inflammation in vivo. METHODS: Crystalline cholesterol monohydrate, lipopolysaccharide (LPS), lysolecithin, polystyrene latex spheres (noninflammatory particles), and saline were instilled into guinea pig gallbladders for 24 to 72 hours after cystic duct ligation. Water transport across gallbladder mucosa was measured. Gallbladder tissue was analyzed for mucus layer thickness, myeloperoxidase, prostaglandin E2 (PGE2) prostaglandin F-1 alpha (PGF-1 alpha), and interleukin-1. Luminal fluid was also examined for PGE2 and PGF-1 alpha. Values for each test were compared with saline controls by using Student's test (p < 0.05). RESULTS: Crystalline cholesterol, LPS, and lysolecithin caused significant reduction in mucus layer thickness, reversed water absorption to secretion across the gallbladder mucosa, caused significant increases in myeloperoxidase and interleukin-1 in gallbladder tissue, and caused significant increases in PGE2 and PGF-1 alpha in luminal fluid. These effects were generally dose- but not time-dependent. Polystyrene latex particles caused no difference in outcomes compared with saline controls. CONCLUSIONS: Crystalline cholesterol monohydrate has dose-dependent inflammatory effects in the guinea pig gallbladder in vivo that are not simply-due to mechanical irritation of the gallbladder wall by crystalline particles. Crystals in the gallbladder may have an etiologic role in cholecystitis.

Animals

Neurogenic inflammation in cholecystitis.

Neurogenic inflammation implies stimulation of nerves with resultant inflammation in tissue surrounding the nerve terminals. We hypothesized that neurogenic inflammation has a role in cholecystitis. Capsaicin (stimulant of afferent, nociceptive neurons), 6-hydroxydopamine (stimulates release of peptides from sympathetic nerve terminals), bradykinin, lipopolysaccharide, and saline were instilled into guinea pig gallbladders for 24 hr (N = 5 in each group). In parallel, test agents were instilled with 1% Iidocaine. Water transport across gallbladder mucosa, myeloperoxidase and interluekin-1 release from gallbladder tissue, and prostaglandin E2 in luminal fluid were measured. Capsaicin caused water secretion and significant release of myeloperoxidase, interleukin-1, and prostaglandin-E2, effects that were blocked by Iidocaine. 6-Hydroxydopamine did not affect water transport or prostaglandin E2, but did cause myeloperoxidase and interleukin-1 release. Bradykinin- and lipopolysaccharide-induced inflammation were partially inhibited by lidocaine. Taken together, these results suggest that neurogenic inflammation has a role in the pathophysiology of cholecystitis.

Animals

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