Biomedical subjects

K D Saunders

Publications and source records attributed to K D Saunders.

11 recordsLinked to original sources

PubMed1993

Lovastatin and gallstone dissolution: a preliminary study.

BACKGROUND: Lovastatin, an agent that reduces both serum and biliary cholesterol in humans, also inhibits cholesterol gallstone formation in an animal model. The present study was designed to assess the efficacy of lovastatin in gallstone dissolution. METHODS: All prairie dogs were fed a 1.2% cholesterol-enriched diet during the entire study. Gallbladders from five animals were examined at 3 weeks, and four of five gallbladders contained gallstones. Remaining animals were maintained on the 1.2% cholesterol-enriched diet and randomized to receive either water (n = 7); lovastatin, 8 mg (n = 7); ursodeoxycholic acid, 50 mg (UR, n = 7); or both drugs (lovastatin and UR, n = 7) twice daily by way of orogastric tube for 4 additional weeks. Response to therapy was determined by blinded examination of gallbladders. RESULTS: All three treatment groups had significant reductions in serum cholesterol, hepatic bile cholesterol, and hepatic cholesterol saturation index as compared to controls (water). Lovastatin induced a 28% response rate to dissolution therapy, which was equal to that achieved with UR, and the combination of lovastatin and UR produced a 56% response rate. CONCLUSIONS: This preliminary study suggests that lovastatin, alone or in combination with UR, may be useful in dissolving gallstones in humans.

Animals↗

PubMed1992

Altered Na+ and Cl- flux during diet-induced mixed gallstone formation in the prairie dog.

Recent studies suggest that altered gallbladder absorptive function may be an important and previously unrecognized factor in the pathogenesis of experimentally induced gallstones. The present study was designed to define the specific changes in gallbladder epithelial ion transport that occur during mixed gallstone formation. Fifteen prairie dogs were fed either control or corn-alfalfa chow for six months. No control animals developed gallstones or crystals. Three of eight corn-alfalfa-fed animals had large black stones, and the remaining five had crystals ("pregallstone" group). Corn-alfalfa-fed animals had significant increases in gallbladder bile cholesterol, phospholipids, and calcium as compared to controls. Gallbladders were removed and mounted in a Ussing chamber for electrophysiologic and ion flux studies. Gallbladders from animals fed corn-alfalfa demonstrated significant decreases in short-circuit current and potential difference as compared to controls (P less than 0.05). 22Na and 36Cl were used to determine unidirectional ion fluxes. While net ion fluxes were similar in pregallstone animals and controls, stone-forming animals exhibited a significant decrease in net Na+ flux and a significant reversal in the direction of net Cl- flux (from secretion to absorption) as compared to controls (P less than 0.05). These data indicate that mixed gallstone formation is associated with alterations in gallbladder ion transport. The role of these changes in the pathogenesis of mixed gallstones remains to be determined.

Animal Nutritional Physiological Phenomena↗

PubMed1992

The effects of extracellular calcium on prairie dog gallbladder ion transport.

Recent studies suggest that experimentally induced gallstone formation is associated with altered gallbladder absorptive function. Moreover, elevated biliary levels of calcium have been implicated in the pathogenesis of cholesterol gallstones. Nonetheless, the relationship between gallbladder ion transport and biliary calcium remains obscure. We tested the hypothesis that extracellular calcium modulates gallbladder ion transport. Prairie dog gallbladders were mounted in an Ussing chamber, and short-circuit current (Isc), transepithelial potential difference (Vms), and tissue resistance (Rt) were measured. Tissues were randomly exposed to physiologic salt solutions containing the following concentrations of calcium: 0.01, 1.3, 5, and 10 mmol/L. Exposure of gallbladder epithelium to increasing calcium concentrations resulted in concomitant increases in Isc and Vms (p < 0.001), without altering Rt. Regression analysis demonstrated a curvilinear correlation between calcium and Isc (Y = 167 + 22.5x - 1.4 x 26; p < 0.001). We conclude that extracellular calcium may be a modulator of gallbladder ion transport.

Animals↗

PubMed1992

The natural history of carcinoma of the bile duct in patients less than forty-five years of age.

Traditionally regarded as a disease of the elderly, the natural history of carcinoma of the bile duct in young patients has not been well defined. Of 186 patients (mean age of 62 years) treated at UCLA (1954 to 1988) for carcinoma of the bile duct, 26 were less than 45 years old. Younger patients had symptoms for an average of 4.5 +/- 0.8 months prior to diagnosis, as compared with 2.3 +/- 0.2 months for patients more than 45 years old (p less than 0.03). Of the younger patients, 96 per cent were managed surgically with either resection, surgical palliative bypass or laparotomy and tube drainage. Among the younger patients who underwent resections, 92 per cent were alive at one year, as compared with 60 per cent of patients who underwent palliative bypass procedures. Two patients who underwent tumor resections survived four years or longer. We conclude that carcinoma of the bile duct is not limited to the elderly and occurs in a significant number of young patients. In the younger population, carcinoma of the bile duct is characterized by delays in diagnosis. Early suspicion and aggressive management of young patients with obstructive jaundice are essential to ensure the best possible outcome for patients with this disease.

Adult↗

PubMed1991

Carcinoma of the ductus choledochus.

A retrospective review of patients treated for carcinoma of the common bile duct has demonstrated improvement in diagnostic capabilities, leading to earlier management by resectional therapy. The ability to resect these tumors is directly translatable to improved long-term survival. Efforts to obtain proof of malignancy prior to resection are often frustrated by the inability to obtain adequate representative tissue for frozen section. Choledochoscopic biopsies and incisional biopsies have given the highest yield of positive diagnoses. In experienced hands, a program of fewer preoperative tests with emphasis on early operation, diagnosis, and definitive treatment may be more cost-effective in the management of patients with common bile duct cancer.

Adenocarcinoma↗

PubMed1991

Intracellular calcium modulates gallbladder ion transport.

Although experimentally induced cholesterol gallstone formation has been associated with altered gallbladder (GB) absorption and increased biliary Ca2+, the relationship between these events remains unclear. Recent studies suggest that extracellular Ca2+ ([Ca2+]ec) influences GB ion transport. Whether the effects of [Ca2+]ec are mediated by changes in intracellular Ca2+ ([Ca2+]ic) has not been determined. This study was designed to define the effects of altered [Ca2+]ic on GB ion transport. Prairie dog GBs were mounted in a Ussing chamber and short-circuit current (Isc), potential difference (Vms), and resistance (Rt) were recorded. Mucosal surfaces were exposed to either Dantrolene (Dt) or nickel (Ni2+). Dt "traps" [Ca2+]ic within intracellular organelles, thereby lowering cytosolic Ca2+; and Ni2+ prevents influx of [Ca2+]ec, presumably by binding Ca2+ channels. Although Dt reduced both Isc and Vms (P less than 0.01), these effects were transient. Transport recovery was probably due to increased [Ca2+]ec influx with restoration of [Ca2+]ic. Ni2+ resulted in sustained decreases in Isc and Vms (P less than 0.05) despite subsequent addition of 10 mM Ca2+. These findings are consistent with the prevention of [Ca2+]ec influx by Ni2+. We conclude that: (1) [Ca2+]ic may be a modulator of GB ion transport and (2) previously reported [Ca2+]ec effects on ion transport may be mediated through [Ca2+]ic concentration changes.

Animals↗

PubMed1991

Uncoupled basal sodium absorption and chloride secretion in prairie dog (Cynomys ludovicianus) gallbladder.

1. Prairie dog gallbladders mounted in a Ussing-type chamber and bathed with symmetrical Ringer's solutions exhibited a transepithelial resistance (Rt) of 51 +/- 5 omega cm2, a lumen negative potential difference (Vms) of 11.5 +/- 0.7 mV and a short-circuit current (Isc) of 6.9 +/- 0.3 microEq/hr/cm2. 2. Radioisotopic ion flux experiments revealed that the basal Isc of 6.9 +/- 0.3 microEq/hr/cm2 was mostly accounted for by net Na+ absorption of 3.2 +/- 0.5 microEq/hr/cm2 and net Cl- secretion of 2.9 +/- 0.3 microEq/hr/cm2. 3. In HCO3- free Ringer's, net Na+ flux was virtually abolished, net Cl- flux decreased by 50% and Isc was reduced by 77%. 4. 10(-3) M mucosal amiloride and DIDS reduced Isc by 28 and 24%, respectively. 5. Mucosal NaCl diffusion potentials indicated that the paracellular pathway was cation selective. 6. Thin section electron micrographs showed a single cell population in this epithelium suggesting that net Na+ absorption and Cl- secretion may emerge from the same cells. 7. We conclude that prairie dog gallbladder epithelium is an electrogenic tissue and, in contrast to gallbladders of most other species, simultaneously but independently absorbs Na+ and secretes Cl-.

Animals↗

PubMed1991

Lovastatin inhibits gallstone formation in the cholesterol-fed prairie dog.

The efficacy of lovastatin, an inhibitor of hepatic cholesterol synthesis in the prevention of cholesterol gallstone formation, was evaluated in the prairie dog model. Two groups of animals were maintained on either nonlithogenic or 1.2% cholesterol-enriched chow for 21 days. Seven of the animals in each group received lovastatin, and the remaining six received only distilled water. All of the cholesterol-fed/water-treated animals had crystals and 83% had gallstones, but none of the cholesterol-fed/lovastatin-treated animals had gallstones and only three had microscopic crystals. These data indicate that lovastatin inhibits cholesterol gallstone formation in a diet-induced model of gallstone disease.

Animals↗

PubMed1990

Reoperative surgery for the morbidly obese. A university experience.

Patients who undergo surgery for morbid obesity are often subjected to reoperation for a wide array of indications. To evaluate outcome following revisional procedures, we reviewed the records of 32 such patients treated at UCLA between April 1986 and May 1989. Twenty-five women (78%) and 7 men (22%) with a mean age of 44 years underwent 76 reoperations (2.4 per patient) for complications of prior obesity surgery. Indications for initial surgical revision consisted primarily of metabolic derangements (12 patients) and weight-related problems (11 patients). In contrast, indications for the patients' final surgical procedure were commonly for bowel obstruction (41%), intra-abdominal sepsis (12%), and gastrointestinal bleeding (6%). Following initial revision, 23 patients (71.8%) required further surgery for major complications and four patients died (12.5%). While initial revisions are frequently indicated for metabolic problems, final reoperations are more frequently undertaken for urgent, life-threatening complications. Revisional procedures for morbid obesity should be carefully considered, and the potential for major complications and/or death should be weighted heavily against proposed benefits.

Adult↗

PubMed1990

Ca2+ channel blockade inhibits gallbladder ion transport.

Recent studies suggest that cholesterol gallstone (GS) formation is characterized by altered gallbladder epithelial ion transport and increased gallbladder (GB) luminal Ca2+. Moreover, intracellular Ca2+ has been reported to be an important modulator of intestinal ion transport. The aim of the present study was to determine the effects of Ca2+ channel inhibition on GB ion transport. Prairie dog GBs were mounted in a Ussing chamber and bathed in warm oxygenated Ringer's solution, and short-circuit current (Isc), transepithelial potential difference (Vms), and tissue resistance (Rt) were recorded. Following stabilization, the mucosal surfaces of the GBs were exposed to 1 or 0.1 mM verapamil (VER). Effects on Isc were apparent within 10 sec with nadir values reached in 5 +/- 1 min. Profound (76%) inhibition of Isc was seen with 1 mM verapamil exposure (26 +/- 6 microA.cm-2) as compared to baseline values (170 +/- 6 microA.cm-2) (P less than 0.001). Verapamil exposure (1 mM) also led to a marked inhibition of Vms (P less than 0.001, vs baseline) and a significant increase in Rt (P less than 0.05 vs baseline). Similar trends were seen using 0.1 mM verapamil (Isc nadir 133 +/- 13 microA.cm-2). Verapamil-induced effects on gallbladder electrophysiology were largely reversible (75-90% recovery of baseline Isc after tissue washing). These data suggest that (1) verapamil induces rapid but reversible inhibition of ion transport and (2) Ca2+ channel blockade inhibits ion transport in a dose-dependent fashion. We would propose that intracellular Ca2+ may be a regulator of GB ion transport.

Animals↗

PubMed1990

Pathogenesis of gallstones.

The many developments in nonoperative methods for the treatment of gallstone disease underscore the importance of understanding the pathogenesis of these stones. Elucidation of the factors responsible for nucleation of crystals and the mechanism by which it occurs would appear to be the challenge if we are to define the cascade of events that results in gallstone formation.

Cholelithiasis↗