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Biomedical subjects

L G Dawes

Publications and source records attributed to L G Dawes.

At least 19 recordsLinked to original sources
PubMed2001

Gallbladder cancer.

Gallbladder cancer often presents with advanced disease. When found early, surgery can be curative for this particular malignancy. Prognostic factors that influence the success of aggressive surgical therapy include depth of invasion, extent of hepatic infiltration, histologic grade, presence of venous, lymphatic or perineural invasion, and lymph node metastasis. Tumors with tumor limited to the subserosal layer, hepatic infiltration that is only 5 mm or less, papillary or well differentiated adenocarcinomas, tumors with no venous, lymphatic or perineural invasion and lymph node metastasis limited to the hepatoduodenal ligament have the best prognosis with surgery (15, 16, 36). Extended cholecystectomy with lymph node dissection has improved the results of treating T2 gallbladder cancers. More extensive resections should keep the above prognostic factors in mind. When surgical resection is not possible, endoscopic stenting of the biliary tree for palliation of obstructive jaundice is effective. Earlier detection or more effective chemotherapy will be needed to significantly improve the prognosis of this disease.

Chemotherapy, Adjuvant↗
PubMed1999

Altered gallbladder bile acidification with long-term total parenteral nutrition.

BACKGROUND: An important function of the gallbladder is to acidify and concentrate bile. Acidification helps protect against the precipitation of calcium salts, which promote gallstone formation. Altered acidification may result in pigment gallstones. We investigated gallbladder composition in a model of TPN-associated pigment gallstones to test whether changes in acidification may be important in this gallstone model. MATERIALS AND METHODS: Ten miniswine were intravenously fed for 21 to 27 days (mean 23 days). Ten fed pig chow with intravenous infusion of saline served as controls. Gallbladder and hepatic bile electrolytes, lipids, pH, and pCO2 were measured. RESULTS: All animals remained healthy and gained weight. Hepatic bile electrolytes and pH were similar among all animals. Pigs on TPN had a higher gallbladder pH and the [H+] was half the value of controls [8.1 +/- 1.6 x 10(-8) meq/liter (control) versus 3.9 +/- 0.7 x 10(-8) meq/liter (TPN)]. Gallbladder bile pCO2, sodium (Na), and potassium were higher in controls. Biliary lipids [bile salts (BS), phospholipids, and cholesterol] with TPN were decreased in both hepatic and gallbladder bile. CONCLUSIONS: Unlike short-term TPN where gallbladder pH and [BS] are similar, with long-term TPN pH is higher with lower [H+], [Na], and [BS]. Despite a presumed longer residence time in the gallbladder, intravenous feeding without oral intake results in gallbladder bile that is less concentrated and acidified. Enteral stimulation may be an important stimulus for gallbladder acidification and periods without feeding may promote gallstone formation by increasing the pH of gallbladder bile.

Animals↗
PubMed1999

Gangrenous cholecystitis: analysis of risk factors and experience with laparoscopic cholecystectomy.

BACKGROUND: Gangrenous cholecystitis occurs in up to 30% of patients admitted with acute cholecystitis. Factors predicting gangrenous disease in patients with acute cholecystitis remain poorly defined, making preoperative diagnosis difficult. Identification of these factors and early diagnosis of gangrenous cholecystitis will indicate more aggressive treatment, earlier operation, and a lower threshold for conversion of laparoscopic to open cholecystectomy. METHODS: We reviewed our experience with acute cholecystitis during the 2-year period of 1995 to 1996. Admitting history, physical examination, operative report, laboratory and radiology data, and pathology report were analyzed for each patient. Acute cholecystitis and its gangrenous complication were diagnosed by both gross and microscopic examination. RESULTS: One hundred fifty-four patients were admitted to the hospital with acute cholecystitis and underwent cholecystectomy; gallbladder gangrene was found in 27 (18%) of these patients. Four patients with gallbladder gangrene underwent open cholecystectomy and 23 patients underwent laparoscopic cholecystectomy, of which 15 (65%) were completed laparoscopically and 8 (35%) had open conversion as a result of severe inflammation. Risk factors for gallbladder gangrene included male gender, age older than 50 years, history of cardiovascular disease, and leukocytosis greater than 17,000 white blood cells/mL. CONCLUSIONS: Older male patients (age older than 50 years) with history of cardiovascular disease, leukocytosis greater than 17,000 white blood cells/mL, and acute cholecystitis have increased risk of gallbladder gangrene and conversion of laparoscopic cholecystectomy to open cholecystectomy. Urgent laparoscopic cholecystectomy with low threshold for conversion to open cholecystectomy should be considered in these patients at high risk for gallbladder gangrene.

Acute Disease↗
PubMed1999

Learning sentinel node biopsy: results of a prospective randomized trial of two techniques.

BACKGROUND: Evidence indicates that sentinel node (SN) biopsy can accurately predict axillary nodal status. Debate exists as to the optimal method of SN identification. METHODS: Patients with clinical T1 or T2 tumors and negative axillae were randomized to SN localization with blue dye (B) alone (n = 50) or blue dye plus radioactivity (B+R) (n = 42). Patients undergoing needle localization (n = 47) were assigned to blue dye. RESULTS: The SN was identified in 110 patients (79%) and contained metastases in 28. The SN predicted the axillary nodal status in 96% of cases. The SN identification rate did not differ between B (88%) or B+R (86%) but was significantly lower in patients requiring localization (64%). The time to SN identification also did not differ between B and B+R. The number of cases done by an individual surgeon was a significant predictor of SN identification. A stepwise logistic regression analysis of factors influencing the success of SN identification identified tumor location, needle localization, number of operations, and body mass index as significant predictors. CONCLUSIONS: Our study does not identify any advantage for the use of the more expensive and complex method of SN identification using B+R compared with B alone, even for surgeons learning the techniques.

Axilla↗
PubMed1998

Ductography for nipple discharge: no replacement for ductal excision.

BACKGROUND: Current management of nipple discharge depends on clinical history to distinguish pathologic from physiologic discharge. We investigated whether ductography supplied additional information in the decision for surgery and/or the localization of pathologic lesion. METHODS: A retrospective review of patients with a presenting complaint of nipple discharge seen at the Lynn Sage Breast Center was conducted from January 1995 to June 1996. Medical records, pathology, and ductograms were reviewed. RESULTS: Of 91 patients with nipple discharge, 49 met the criteria for physiologic discharge and 42 had pathologic discharge. Eleven with physiologic discharge had ductograms; none were abnormal. Four of 20 preoperative ductograms were normal but showed intraductal papillomas at the time of surgery; 6 of 20 (30%) had multiple lesions. Four lesions on ductograms did not demonstrate corresponding lesions in the surgical specimen. It is uncertain whether this is due to a missed lesion or a false-positive ductogram. CONCLUSIONS: Modern ductography does not reliably exclude intraductal pathology and is not a substitute for surgery in patients with pathologic discharge. Its utility is in identifying multiple lesions or those with lesions in the periphery of the breast.

Adult↗
PubMed1997

Cholecystokinin increases bile acid synthesis with total parenteral nutrition but does not prevent stone formation.

Total parenteral nutrition (TPN) is associated with cholestasis and gallstones. Gallbladder stasis may be important in the development of gallstones, and cholecystokinin (CCK) to stimulate gallbladder contraction has been proposed as a treatment to prevent this complication. We studied in vivo bile acid synthesis and bile acid output in miniswine on TPN to test whether daily CCK improves bile acid output and normalizes bile acid profiles with TPN. Nine miniswine were nutritionally maintained with TPN for 4 weeks; four pigs received CCK (0.1 mg/kg) iv daily. In vivo bile acid synthesis was measured with injection of 7 alpha-tritiated cholesterol. An increase in tritiated water reflects the activity of 7 alpha-hydroxylation, the rate-limiting step in bile acid synthesis. At the end of 4 weeks, bile was collected and bile acid output and bile salt profiles were determined. One of five animals on TPN developed gallstones while two of four receiving daily CCK developed stones. In vivo bile acid synthesis decreased with TPN (controls, 63 +/- 9 mg/24 hr versus TPN, 13 +/- 4 mg/24 hr) and increased in TPN animals with CCK treatment (TPN-CCK, 105 +/- 35 mg/24 hr). Bile acid profiles are changed with TPN with more secondary bile acids, this was not improved with CCK. CCK improved bile acid synthesis and bile acid output but failed to prevent gallstone formation or normalize bile salt profiles. In addition to promoting gallbladder contraction, CCK may have a stimulatory effect on bile acid synthesis. CCK alone did not prevent gallstone formation.

Animals↗
PubMed1993

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↗
PubMed1993

Reduced ileal taurocholate absorption with total parenteral nutrition.

Total parenteral nutrition is associated with decreased primary bile acid output. This may result from reduced synthesis or decreased absorption of primary bile acids in the enterohepatic circulation. Ileal atrophy occurs with total parenteral nutrition, and we postulated that absorption of primary bile acids is reduced. Ileal absorption of taurocholate was investigated in miniswine on total parenteral nutrition and this was compared to orally fed animals. Following cholecystectomy and bile duct cannulation, 20 cm, of ileum was perfused with taurocholate. Since miniswine have no significant endogenous taurocholate secretion, the measured taurocholate output reflected ileal absorption. To examine uptake and secretion of taurocholate by the liver, pigs on total parenteral nutrition and controls were infused with intravenous taurocholate (0.5 to 2.5 mumole/kg/min), and bile acid output was determined. Baseline bile acid output was decreased in animals on total parenteral nutrition, yet the response to intravenous taurocholate was similar to controls. When taurocholate was perfused in the ileum, taurocholate output was markedly different. Taurocholate output (pmole/cm ileum/min) at the taurocholate perfusate concentrations of 3 and 20 mM was, respectively, 65 +/- 14 and 183 +/- 63 for controls and 18 +/- 3 and 63 +/- 17 for miniswine on total parenteral nutrition. The latter group's output was significantly lower, at P < 0.05. Both groups of pigs had equal increases in bile acid output with intravenous infusion of taurocholate, suggesting normal hepatic uptake and secretion. Ileal perfusion with taurocholate, however, resulted in decreased taurocholate output with total parenteral nutrition due to decreased ileal absorption of bile acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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↗
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

Gastrointestinal lymphoma. A case for primary surgical resection.

The cases of 42 consecutive patients with primary gastrointestinal lymphoma were reviewed to compare the risks and outcomes of different primary treatment modalities. Among patients with localized disease (stages I and II), 12 underwent complete tumor resection and 6 underwent radiation therapy; 5-year survival was 82% and 50%, respectively. Among patients with disseminated disease (stages III and IV), 6 underwent resection of the primary tumor followed by chemotherapy and 18 were treated with radiation and chemotherapy; 5-year survival was 81% and 6%, respectively. Five patients who did not undergo surgical resection before radiation therapy or chemotherapy developed severe life-threatening complications from their primary tumor. Surgical resection before the administration of other therapy should be performed when the patient is considered to be a surgical candidate and resection of the primary tumor is deemed feasible.

Adolescent↗
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

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↗
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

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

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↗