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Biomedical subjects

J J Roslyn

Publications and source records attributed to J J Roslyn.

At least 19 recordsLinked to original sources
PubMed1996

Apical and basolateral Ca(2) channels modulate cytosolic Ca(2)+ in gallbladder epithelia.

Gallstone formation is associated with altered gallbladder (GB) ion transport and increased concentration of GB bile Ca2+. Recent studies show that increased cytosolic Ca2+ ([Ca2+]i) stimulates GB Cl- secretion. However, the mechanism by which extracellular Ca2+ ([Ca2+]e) enters the cytosol remains unclear. We tested the hypothesis that entry of [Ca2+] into cytosol occurs via apical and basolateral membrane Ca2+ channels. Prairie dog GBs were mounted in Ussing chambers, standard electrophysiologic parameters were recorded, and unidirectional Cl- fluxes (J, microEq x cm(-2) x hr(-1) were measured using 36Cl at various mucosal Ca2+ in the absence or presence of mucosal lanthanum (La3+), a non-diffusible Ca2+ channel blocker. Serosal [Ca2+]e was maintained at trace levels. In the absence of mucosal La3+, short circuit current (Isc) showed a positive correlation with mucosal [Ca2+]e as represented by a second order polynomial equation (y = 4.1 + 2.5x - 0.73x(2), r = 0.68, P < 0.001). In contrast, unidirectional mucosa to serosa Cl flux (JCl/ms) was inversely correlated with [Ca2+] (y = 47.9 - 8.7x + 0.9x(2), r = 0.51, P <.05) Addition of 1 mM mucosal La3+ blunted the effects of [Ca2+]e on electrophysiologic parameters and JCl/ms. However, basolateral repletion with 5 mM Ca2+ reverses the blocking effects of La3+ on JCl/ms. These data suggest that [Ca2+]e enters the cytosol via apical and basolateral Ca2+ channels. We conclude that GB apical Ca2+ channels may represent a pathway for biliary Ca2+ entry into the cell and therefore may represent an important regulatory pathway for GB ion transport during gallstone formation.

Analysis of Variance↗
PubMed1996

Converting gallbladder absorption to secretion: the role of intracellular calcium.

BACKGROUND: Experimental cholelithiasis is associated with elevated biliary calcium concentration and altered gallbladder absorption. Recent studies showed that extracellular calcium ([Ca2+]ec) plays a role in regulating gallbladder ion transport. The extent to which intracellular calcium ([Ca2+]ic) mediates the changes in gallbladder ion transport is not clear. We hypothesize that [Ca2+]ic is an important regulator of gallbladder ion transport. METHODS: Prairie dog gallbladders were mounted in Ussing chambers, standard electrophysiologic parameters were recorded, and unidirectional Na+, Cl- and H2O fluxes were measured before and after mucosal exposure of 10-5 mol/L calcium ionophore A23187 was performed. RESULTS: A23187 caused an increase in transepithelial short-circuit current and potential difference and a decrease in transepithelial resistance. A23187 inhibited mucosa to serosa Cl- flux and stimulated serosa to mucosa Na+ flux, resulting in increased net Cl- secretion and decreased net Na+ absorption. A23187 converted H2O from absorption to secretion. Transepithelial short-circuit current effect of A23187 was delayed by indomethacin pretreatment and was completely blunted by low bathing Ca2+. CONCLUSIONS: This is the first demonstration that increased [Ca2+]ic converts the gallbladder from its normal absorptive state to a secretory one. Furthermore [Ca2+]ic appears to regulate ion transport through mechanisms that are partially prostaglandin-dependent. Studies are necessitated to define possible links between gallbladder secretion of Cl- and H2O and mucus hypersecretion, a well-described phenomenon associated with cholesterol gallstone formation.

Animals↗
PubMed1996

Surgical management and treatment of sepsis associated with gastrointestinal fistulas.

The development of sepsis associated with a GI fistula can be a catastrophic complication of any surgical procedure in the vicinity of the abdominal cavity. The predominant sites of infection directly associated with GI fistulas are in the surgical wound and within the abdominal cavity. Some patients present with florid signs of sepsis, whereas others may have minimal signs of infection. CT scanning is the main diagnostic method for intra-abdominal collections. Often, it also provides a means of treatment by percutaneous placement of catheters. Patients who develop extensive cellulitis or necrotizing fasciitis, intra-abdominal collections incompletely drained by percutaneously placed catheters, multiple intra-abdominal collections not amenable to percutaneous drainage, dissociation of the ends of an anastomosis with flow of enteric contents into the peritoneal cavity, large intra-abdominal hematoma, or a septic course without identifiable source should be taken to the operating room on an urgent basis. The operative approach varies with the particular situation and extends from incision and drainage of the wound, extraperitoneal drainage of an abscess, and formal exploratory laparotomies, to the placement of tube enterostomies for decompression and drainage. The overall mortality of fistulas has decreased owing to better fluid and electrolyte replacement and the proper use of parenteral nutrition. However, patients continue to die from fistulas, and the cause of death is nearly always infection. The burden is on the surgeon to expeditiously diagnose and treat sepsis associated with GI fistulas.

Drainage↗
PubMed1996

Treatment of gallstones in the 1990s.

Gallstone disease continues to be one of the more common abdominal problems that prompts medical evaluation, particularly in the elderly population. The presentation is diverse, and the treatment options varied. Primary care physicians need to be familiar with the differential diagnosis, evaluation, and therapeutic options available. LC has emerged as the preferred treatment for patients with symptomatic gallstone disease.

Cholangitis↗
PubMed1995

Octreotide promotes gallbladder absorption in prairie dogs: a potential cause of gallstones.

BACKGROUND/AIMS: Gallstone formation during octreotide administration has been causally linked to increased biliary concentrations of calcium, protein, and total lipids, all purported prolithogenic factors. These changes may be caused by octreotide-induced gallbladder stasis or a direct effect of octreotide on gallbladder absorption. We tested the hypothesis that octreotide stimulates gallbladder ion and water transport. METHODS: Prairie dog gallbladders were mounted in Ussing chambers and bathed in oxygenated Ringer's solution. Electrophysiological parameters were recorded, and unidirectional Na+, Cl-, and H2O fluxes were measured before and after serosal exposure to 50 nmol/L octreotide. RESULTS: Octreotide exposure caused a significant decrease in transepithelial short-circuit current and potential difference and an increase in tissue resistance compared with baseline. These alterations in electrophysiological parameters coincided with changes in ion transport. Octreotide stimulated net Na+ and H2O absorption and converted the gallbladder from a state of Cl- secretion to one of Cl- absorption by increasing mucosal to serosal fluxes. Octreotide effects on ion transport were blocked by 4,4'-diisothiocynostilbene-2,2'-disulfonic acid and amiloride and reversed by theophylline. CONCLUSIONS: Octreotide may promote gallstone formation by inducing gallbladder stasis and by directly increasing gallbladder absorption, which may act synergistically to increase the concentration of prolithogenic factors in bile and to facilitate nucleation and stone growth.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Protein kinase C regulates prairie dog gallbladder ion transport.

BACKGROUND: Gallstone formation is characterized by increased biliary calcium (Ca2+) level and altered gallbladder absorption. Recent studies suggest that luminal Ca2+ regulates gallbladder ion transport via intracellular calcium ([Ca2+]ic). Ca2+-calmodulin and protein kinase C (PKC) are two major systems through which [Ca2+]ic carries out second-messenger functions in many cell types. We have previously shown that Ca2+-calmodulin regulates basal gallbladder ion transport in prairie dog. The present study tests the hypothesis that PKC is also essential in regulation of gallbladder ion transport in this model. METHODS: The role of PKC in regulation of gallbladder ion transport was determined by studying the effects of phorbol esters, synthetic analogues of diacylglycerol, which directly activates PKC. Gallbladders were mounted in Ussing chambers, and standard electrophysiologic parameters were recorded after exposing tissues to either 10(-5) mol/L of 4-alpha-phorbol 12,13-didecanoate (PDD), 4-beta-phorbol 12-myristate 13-acetate, 4-beta-phorbol 12,13-dibutyrate (PDB), or 10(-4) mol/L serotonin. Unidirectional Na+, Cl-, and H2O fluxes were measured before and after treatment with only inactive PDD and most active PDB. RESULTS: Mucosal and serosal exposure of tissues to either 4-beta-phorbol 12-myristate 13-acetate or PDB resulted in a decrease in short-circuit current and transepithelial potential difference without any change in tissue resistance. Serotonin induced similar changes in gallbladder electrical properties. PDB caused an inhibition of mucosal to serosal fluxes of Na+, Cl-, and H2O, with a decrease in net Na+ absorption, an increase in net Cl- secretion, and a conversion of net H2O absorption to net H2O secretion. Serosal-to-mucosal fluxes of Na+, Cl-, and H2O did not change. Inactive PDD had no effect on either electrophysiologic parameters or ion and water fluxes. Pretreatment of tissues with PKC antagonist 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine blocked the phorbol ester-induced inhibition of ion transport. CONCLUSION: PKC regulates gallbladder ion transport in the prairie dog by inhibiting Na+ absorption and stimulating Cl- secretion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Variability in the clinical skills of residents entering training programs in surgery.

BACKGROUND: Residents may have significant differences in clinical skills at the start of their surgical training. The purpose of this study was to investigate the variability in these skills by using an objective structured clinical examination. METHODS: A needs assessment was performed, and an objective structured clinical examination composed of 10, two-part stations was developed. Standardized patients (SPs) were trained, validated, and used as both simulated patients and evaluators to assess history taking, physical examination, and interpersonal skills of 10 first-year surgical residents. Structured patient notes (PNs) written by residents after the SP encounters were used to assess history and physical examination documentation skills. Data from one station were not used because more than 25% of the SP ratings were missing. RESULTS: The alpha-reliability was 0.78 for SP ratings, 0.91 for PN scores, and 0.91 for the combined scores. ANOVA revealed significant variation in individual residents' clinical skills as assessed by SPs (F = 4.56, p < 0.01), PNs (F = 11.09, p < 0.001), or both (F = 10.9, p < 0.001). Paired t tests showed that residents scored significantly higher on history taking than on physical examination and attained significantly lower scores on documentation as compared with performance of both history and physical examination (p < 0.001 for each comparison). CONCLUSIONS: The results showed significant variability in clinical skills of the group of residents and yielded detailed information on the performance of each resident. The data were shared with individual residents and are being used to make changes in the educational activities of the program.

Clinical Competence↗
PubMed1994

Increased biliary protein precedes gallstone formation.

Although nucleation is critical to the pathogenesis of cholesterol gallstones, the factors responsible for this process are poorly defined. Numerous potential nucleating agents have been identified in the bile of humans and animals with cholelithiasis, including mucus, calcium, and bilirubin. Recent studies have shown that patients with cholesterol crystals and gallstones have increased biliary total protein, suggesting that protein may be a previously unrecognized nucleating factor. We tested the hypothesis that biliary total protein is increased prior to cholesterol gallstone formation. Prairie dogs were maintained on either control (N = 22) or 0.4% cholesterol-enriched chow (N = 18) for up to 18 weeks. Cholesterol-fed animals were classified as pregallstone (N = 12) or gallstone (N = 6) based on gross examination of the gallbladder bile. Both hepatic and gallbladder biles were then analyzed for lipid, bile acid, calcium, and protein content. Cholesterol feeding was associated with increased gallbladder concentrations of cholesterol, phospholipids, and calcium in the pregallstone and gallstone groups. Biliary total protein was significantly elevated in the pregallstone (5.8 +/- 0.4 mg/ml, P < 0.001) and gallstone animals (6.0 +/- 0.6 mg/ml, P < 0.001) as computed to controls (3.8 +/- 0.3 mg/ml). Regression analysis showed positive correlations between gallbladder bile total protein and the gallbladder bile cholesterol saturation index (CSI) (P < 0.001), as well as between gallbladder total protein and calcium (P < 0.001). Although the hepatic bile CSI was elevated in cholesterol-fed animals, total protein remained unchanged, suggesting that the alteration in biliary protein is a gallbladder phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Surgical treatment of inflammatory bowel disease.

Surgery continues to play an important role in the overall treatment strategy for patients with Crohn's disease and ulcerative colitis. Innovative techniques have greatly facilitated the operative approach in patients with both disorders.

Humans↗
PubMed1994

Pancreatitis associated with adult choledochal cysts.

We reviewed the records of 32 adult patients with choledochal cysts (CDC) to determine the characteristics of the associated pancreatic disease. Eighteen patients (56%) had 30 documented episodes of pancreatitis with epigastric pain and elevated serum amylase levels. Three patients developed a prolonged course with a pancreatic phlegmon and one patient died secondary to a pancreatic abscess after endoscopic retrograde cholangiopancreatography (ERCP). Pancreatitis occurred in all types of CDC and was not related to the age, gender or race of the patient. There was an association with the size of the CDC: 90% of patients with CDC > or = 5 cm developed pancreatitis compared with only 9% of patients with CDC < 5 cm (p < 0.0004). In addition, ERCP was performed in 14 patients and demonstrated an abnormal pancreaticobiliary duct junction in eight (57%). All eight patients with an abnormal pancreaticobiliary junction developed pancreatitis compared with only 2 out of 6 patients with normal pancreatic duct anatomy (p < 0.006). Patients undergoing surgical bypass rather than resection also tended to have higher rates of pancreatitis (80 vs. 50%). One patient with a Type I CDC and chronic pancreatitis was treated with surgical resection of the CDC and pancreatic head; this combined procedure relieved the pain. Microscopic examination of the CDC and the abnormal "common channel" within the pancreas revealed identical fibrous thickening of the duct walls with focal chronic inflammation and loss of surface epithelium. In conclusion, these data stress the previously unrecognized high incidence of symptomatic pancreatic inflammatory disease that accompanies adult CDC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Surgical issues for the elderly patient with hepatobiliary disease.

Hepatobiliary disease is the most common reason for abdominal surgery in the elderly population. Therefore, familiarity with these diseases as they occur in geriatric patients has become increasingly important. This article reviews hepatobiliary disease with a specific emphasis on issues that affect the treatment of the elderly. Although the focus of this review is primarily clinical, pertinent experimental findings have been included.

Aged↗
PubMed1993

The realities of idealism.

I started out asking the question can we achieve our goals and are our goals realistic in the 1990s? I believe that we can achieve anything that we set our minds to. Our goals of providing quality care to our patients, performing research, teaching the next generation, and having an impact on our local environment are worth pursuing. However, the rules have changed and the status quo is simply not good enough. If we are to survive, we must be prepared for the future. You have the ability to change and the power to control the future. You are the future. Seize the opportunity and get involved. Become knowledgeable about health care economics, become involved with the political process, and position yourselves so that you can be a part of the solution to our health care system's woes. Don't allow the moment to pass. Don't be afraid of the realities of today, and don't forget your ideals and principles. Confront today's challenges with the same determination that academic surgeons through the years have confronted the unknown mysteries of disease. Let me conclude by trying to synthesize my remarks in five generic recommendations: 1. We need to go forward in the research area by developing multidisciplinary programs that involve basic science. These programs can be used to highlight our clinical areas and expertise. In this manner, both areas will be benefitted. 2. We need to educate the public and the government about the virtues of research and the importance of maintaining academic surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Canada↗
PubMed1993

Prostaglandin E2 stimulates ion transport in prairie dog gallbladder.

The effects of prostaglandins, and specifically prostaglandin E2, on gallbladder ion transport were examined in the prairie dog. Gallbladders were mounted in an Ussing chamber and baseline short-circuit current, potential difference, and tissue resistance were measured. Addition of arachidonic acid (10(-4) M, mucosal surface) produced sustained elevations in short-circuit current and potential difference (P < 0.05), with mild reductions in resistance. In a second set of tissues, indomethacin exposure (10(-6) M) resulted in a significant (P < 0.02) decrease in short-circuit current and potential difference, with an increase in resistance. Subsequent addition of prostaglandin E2 (10(-7) M, serosal surface) fully reversed these changes and led to a significant increase in short-circuit current and potential difference (P < 0.001) with a return of resistance to baseline values. These findings suggest that endogenous prostaglandins mediate gallbladder ion transport.

Animals↗
PubMed1993

Incisional hernia.

Incisional hernias are a relatively common occurrence after abdominal operations, having been reported to occur in 2% to 11% of all patients undergoing such procedures. Although many hernias become manifest early, others may not be noted until many years after the index procedure. Predisposing factors for incisional hernia have been well described, and several of these can be altered by the surgeon, including the technique employed for repair. For many years, the repair of incisional hernia was associated with a high recurrence rate. In more recent years, the introduction of synthetic prosthetic materials has provided the opportunity to perform a tension-free repair, thereby reducing the rate of recurrence.

Abdominal Muscles↗
PubMed1993

Early and long-term effects of colectomy and endorectal pullthrough on bile acid profile.

OBJECTIVE: Although total colectomy with mucosal proctectomy and endorectal pullthrough affects two sites critical to the enterohepatic circulation of bile acids, little information is available regarding the manner in which normal digestive physiology is altered by these procedures. This study defines the early and long-term effects of colectomy and endorectal pullthrough on bile acid profile and the long-term effects on biliary lipid metabolism. SUMMARY BACKGROUND DATA: Specific changes in bile acid absorption have been reported in patients after ileal resection. Recent studies from our laboratory indicate that in the early postoperative period, colectomy with endorectal pullthrough causes a significant decrease in gallbladder bile concentrations of total bile acids, cholesterol, phospholipids, and calcium. The observation by several authors that the pouch undergoes morphologic and perhaps functional adaptation suggest that these changes may be transient and perhaps reversible. METHODS: These studies were done in an awake, unanesthetized canine model that allows periodic sampling of gallbladder bile without creation of an external biliary fistula and its associated sequelae. Animals were ultimately randomly assigned to either laparotomy and gallbladder cannulation (N = 6), or gallbladder cannulation with total colectomy and ileorectal anastomosis (N = 7), or biliary cannulation, colectomy, mucosal proctectomy and endorectal pullthrough with ileal reservoir (N = 5). RESULTS: Six weeks after operation, colectomy and ileorectal anastomosis were associated with a significant alteration in the relative composition of bile acids in gallbladder bile. These early changes were manifested by a significant (p < 0.05) increase in taurocholic acid and a concomitant decrease in taurodeoxycholic acid. These changes became even more pronounced in the ileorectal anastomosis group 12 weeks after colectomy and ileorectostomy. Although similar changes in the relative concentrations of individual bile acids occurred in the 6-week endorectal animals, bile acid profile was restored to normal by 12 weeks. CONCLUSIONS: Colectomy with ileorectal anastomosis leads to early and significant changes in bile acid profile, which persist and become even more pronounced with time. In contrast, the construction of an ileal reservoir after colectomy facilitates restoration of a normal bile acid profile. We propose that these alterations in bile acid metabolism result from adaptation of the ileal reservoir as its mucosa assumes functional characteristics of normal colon.

Adaptation, Physiological↗