Patient satisfaction and results after evisceration with a split-sclera technique.

PURPOSE: A retrospective study of the postoperative results and patient satisfaction after evisceration with a split-sclera technique. MATERIAL AND METHODS: The medical records of 60 patients were reviewed. All patients were operated by evisceration with a split-sclera technique and placement of an orbital implant. The patients were operated by the same surgeon between 1995 and 2003. Multiple-choice questionnaires were sent to the patients, and the patients were also offered a clinical examination. RESULTS: Extrusion/exposure of the implant was seen in 3/62 (4.8%) orbits. Migration of the implant was seen in one patient. At the time of the study, 45/60 patients were still alive, 32 of these answered the questionnaire. In a question about the patient's psychological well-being after the operation, 9/32 (28%) answered that they had felt depressed; four of these had had a recent trauma to the eye resulting in the evisceration; 25/32 (78%) patients were pleased or very pleased with the operation. A clinical examination was performed in 31 patients. The motility of the prosthesis and implant was measured and found to be rather poor (mean between 2.5 to 4.1 mm in each direction); however, most patients judged their motility to be good or excellent. CONCLUSION: Evisceration with a scleral split modification has been used successfully in our clinic since 1995. The risk for exposure is low, 3/62 (4.8%). Postoperative depression was common (9/32). Recent trauma was a risk factor for postoperative depression.

Bile acids and lipoprotein metabolism: effects of cholestyramine and chenodeoxycholic acid on human hepatic mRNA expression.

Modulation of bile acid synthesis in human by cholestyramine or by chenodeoxycholic acid (CDCA) treatment affects lipoprotein metabolism leading to altered plasma lipid levels. The molecular changes caused by these treatments, which in turn influence lipoprotein metabolism, are still not entirely known in humans. In this study, mRNA levels were analyzed using real time RT-PCR in liver tissue from patients undergoing cholecystectomy due to gallstone disease. The patients were treated with either CDCA (n=6) or cholestyramine (n=5) for three weeks prior to surgery, six patients received no treatment and served as controls. Cholestyramine increased the expression of the LDL receptor (LDLR) by about 65% and that of proprotein convertase subtilisin kexin 9 (PCSK9) by 70%. After CDCA the levels of both LDLR and hydroxy-methyl-glutaryl coenzyme A reductase mRNA decreased approximately by 50%. The expression of PCSK9 was not changed. The mRNA levels of PCSK9, LDLR, and HMGCoAR were significantly correlated to those of sterol regulatory element binding protein 2 (SREBP2), indicating that SREBP2 is of importance in the regulation of the expression of these genes also in human liver.

Effects of combined treatment with pravastatin and ursodeoxycholic acid on hepatic cholesterol metabolism.

BACKGROUND: Treatment with ursodeoxycholic acid and also, to some degree, statins reduces cholesterol saturation of bile. The present study aimed [1] to study the effects of combined treatment with ursodeoxycholic acid and pravastatin on hepatic cholesterol metabolism and [2] to evaluate if the addition of pravastatin to ursodeoxycholic acid treatment has beneficial effects on the lipid composition of gallbladder bile in gallstone patients. MATERIALS AND METHODS: Nineteen patients with cholesterol gallstones were subjected to combined treatment with ursodeoxycholic acid (500 mg bid) and pravastatin (20 mg bid) for three weeks before cholecystectomy. Eleven patients received ursodeoxycholic acid only and 20 untreated gallstone patients served as controls. Gallbladder bile was collected, and for both the patients receiving combined treatment and the controls a liver biopsy was also obtained peroperatively. RESULTS: The cholesterol saturation of bile averaged 59% in the patients on combined treatment, 60% in the ursodeoxycholic acid-treated patients, and 130% in the untreated controls. In the patients receiving ursodeoxycholic acid, this bile salt constituted approximately 60% of all bile salts. The patients receiving combined treatment had reduced cholesterol synthesis, as reflected by a 45% reduction in serum lathosterol. The activity and the mRNA levels of cholesterol 7 alpha-hydroxylase and the mRNA levels for the low density lipoprotein-receptor were not significantly affected. CONCLUSIONS: Pravastatin does not further reduce the cholesterol saturation of bile in gallstone patients treated with ursodeoxycholic acid, although hepatic cholesterol synthesis is inhibited. The study supports the important concept that de novo synthesized cholesterol is not particularly important for biliary cholesterol secretion in humans.

DNA ploidy and S-phase fraction in carcinoma of the gallbladder related to histopathology, number of gallstones and survival.

Gallstones are a risk factor for the development of gallbladder cancer. We studied DNA ploidy and cell cycle composition by flow cytometry in archival specimens from 52 gall bladder carcinomas in relation to histopathological grade, tumour stage, gallstone number and survival. 69% of the gallbladder carcinomas showed aneuploidy. All tumours with single stones (N=11) were aneuploid while only 61% of tumours with multiple stones (N=41) were aneuploid (p=0.002). DNA aneuploidy was related to increase in T-category (p=0.01), grade (p=0.02), and nuclear pleomorphism (p=0.0005). The distribution of DNA ploidy shifted from tetraploid in low stage towards triploid positions in high stage tumours (p=0.02) combined with higher S-phase values in triploid tumours (p=0.05). S-phase fraction increased during development from normal tissue to dysplasia, cancer in situ and cancer in diploid cases (p=0.0002), and further at the change from diploid to aneuploid (p=0.004). At a median cancer specific survival time of four months patients with diploid tumours had a better survival than those with aneuploid tumours (p=0.02). In multivariate analysis of the tumour characteristic, only T-category and tumour grade were independent prognostic factors. The shift from diploid to aneuploid and the further shift of ploidy within aneuploid tumours are in agreement with the concept of a clonal development of gallbladder cancer. These changes are combined with a stepwise increase in the fraction of S-phase cells. Low frequency of symptoms in single stone patients may be the reason for detection of malignancy at a late stage of tumour development.

Panorama of orbital space-occupying lesions. The 24-year experience of a referral centre.

PURPOSE: The aim of this survey was to study the frequency and management of orbital lesions requiring incisional or excisional biopsy for diagnostic or therapeutic purposes. METHODS: A histopathological review of specimens from 300 consecutive patients with space-occupying orbital lesions managed over a period of 24 years at a tertiary referral centre. RESULTS: The lesions could be attributed to 73 different entities with low-grade, non-Hodgkin lymphoma being the most common. More than half (54.3%) of lesions were neoplastic and malignant disease was present in 29.0% of patients. The majority of lesions were biopsied using the anterior transseptal or transconjunctival approach. CONCLUSION: Most orbital space-occupying lesions requiring biopsy are benign and easily accessible. However, the diversity of these rare lesions and complexity of management suggest that patient care is best provided by a team of experienced subspecialists at a designated orbital centre.

The effect of vitamin C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of the nucleation time.

Vitamin C deficiency in guinea pigs leads to cholesterol supersaturation of bile and formation of cholesterol gallstones. It has been suggested that there may also exist an association between vitamin C and cholesterol gallstones in man, but such a relationship has not been studied in gallstone patients. In order to study the possible effects of vitamin C on gallstone disease in humans, plasma lipid levels, hepatic cholesterol metabolism, biliary lipid composition, cholesterol saturation and nucleation time of gallbladder bile were analysed in 16 consecutive gallstone patients, who were planned for laparoscopic cholecystectomy and were treated with vitamin C (500 mg, four times a day) for 2 weeks before surgery. The plasma concentration of vitamin C increased by 42% in the treatment group. The concentrations of plasma lipids did not differ before and after vitamin C treatment; nor did the plasma levels of lathosterol and 7 alpha-hydroxy-4-cholesten-3-one, reflecting cholesterol and bile acid synthesis respectively. The relative concentrations of cholesterol, bile acids and cholesterol concentration of bile did not differ significantly between the two groups, but the relative concentration of phospholipids was slightly higher in the treated group. The bile acid composition was changed; the percentage of cholic acid being lower and those of deoxycholic acid, ursodeoxycholic acid and lithocholic acid higher in the vitamin C-treated patients compared with the untreated group. The nucleation time was significantly longer in the treatment group (7 days) compared with the untreated group (2 days). Our findings indicate that vitamin C supplementation may also influence the conditions for cholesterol gallstone formation in humans.

Lysosomal enzyme activities in gallbladder mucosa of gallstone-free subjects and patients with gallstones.

BACKGROUND/AIMS: Gallstone patients have a reduced cellular lysosome content in the gallbladder mucosa cells compared with gallstone-free subjects. The purpose of the study was to further evaluate the possible role of lysosomes in the pathogenesis of cholesterol gallstone formation in humans. METHODS: Lysosomal enzyme activities were assayed in gallbladder mucosa and for comparison in liver specimens of 19 gallstone-free subjects and 24 gallstone patients undergoing cholecystectomy. RESULTS: Gallstone patients had 25-50% lower activities of the lysosomal proteases cathepsin B, D and L in their gallbladder mucosa compared with gallstone-free subjects. The activity of acid phosphatase also tended to be decreased in gallstone patients. The liver lysosomal enzyme activities were not significantly different between the two groups. CONCLUSIONS: The results show that gallstone patients have diminished lysosomal enzyme activities in the gallbladder mucosa, a finding which may be related to decreased intracellular degradation of proteins and/or mucin in the mucosal cells. This may lead to a higher concentration of mucin in gallbladder bile and thus an increased risk of precipitation of cholesterol crystals and gallstone formation.

Evaluation of the lacrimal drainage function by the drop test.

PURPOSE: To compare the fluorescein dye disappearance test with a new test for lacrimal drainage capacity, the drop test. METHODS: In the fluorescein dye disappearance test, 1 microliter of fluorescein solution was instilled into the conjunctival sac of normal subjects and of patients with epiphora. Fluorescence from the tear film was measured, and the rate of dye disappearance was calculated as a measure of tear drainage. In the drop test, drops of 10 microliters of lukewarm saline solution were repeatedly instilled into the conjunctival sac for 3 minutes. Excessive saline solution was then removed from the tear film and measured. The volume of saline solution drained by the lacrimal passage could thus be calculated. RESULTS: The fluorescein dye disappearance test showed, in normal subjects, a tear turnover rate of 10.9 +/- 3.1% (95% confidence interval) per minute, which was nor age dependent. The drop test showed a decreased lacrimal drainage capacity with increasing age in normal subjects, with a mean capacity of 150 +/- 38.5 microliters/3 min for those 41 to 80 years old. In patients with indoor epiphora, the fluorescein dye disappearance test values were significantly reduced. However, the fluorescein dye disappearance test could not differentiate among normal eyes, eyes with minor epiphora, or eyes with moderate epiphora. The drop test showed a significant decrease even in patients with minor epiphora and was further decreased with increasing severity of symptoms. CONCLUSION: The drop test provides a quantitative measurement for lacrimal drainage function and is more sensitive than the fluorescein dye disappearance test.

Total protein content of human gallbladder bile: relation to cholesterol gallstone disease and effects of treatment with bile acids and aspirin.

OBJECTIVE: To measure the total protein content of gallbladder bile, and assess how treatment with aspirin and the gallstone solvents chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) affects the biliary protein concentration. DESIGN: Prospective study. SETTING: Teaching hospital, Sweden. SUBJECTS: 102 Consecutive patients undergoing cholecystectomy for cholesterol gallstones (n = 73) or adenomyomas or cholesterolosis in the gallbladder wall (n = 29). Thirty of the patients with gallstones were treated with CDCA, UDCA or aspirin. INTERVENTIONS: Aspiration of bile from the gallbladder during operation. MAIN OUTCOME MEASURES: Protein content, and correlations between protein content and biliary lipids, cholesterol saturation and crystals, and concentrations of individual bile acids. RESULTS: There were no differences in total protein content among the groups except for the UDCA treated group, which had significantly less protein 2.1 (0.5) g/l compared with 6.1 (0.5) for untreated gallstones, 5.8 (0.9) for those treated with CDCA, 6.8 (1.2) for those treated with aspirin and 7.3 (0.7) for those with no gallstones). There were no differences between bile with and without crystals. There was a positive correlation between the protein content and biliary cholesterol concentration and saturation. Aspirin did not influence the total protein content in the bile. CONCLUSIONS: The total protein concentration in gallbladder bile was similar in patients with and without cholesterol crystals, which might indicate that the total protein content in bile does not influence formation of cholesterol crystals and consequently not the formation of gallstones. Patients treated with UDCA were the only group that had significantly less protein than the other groups, which indicates that the mode of action of UDCA is different from that of CDCA.

Rise and fall in the number of cholecystectomies: Stockholm 1932-1993.

OBJECTIVE: To assess the annual rates of cholecystectomy 1932-1993 in Stockholm and compare them with the rates for other common surgical procedures. DESIGN: Retrospective collection of data from annual hospital records. SETTING: Teaching hospital, Sweden. SUBJECTS: All subjects in Stockholm county who underwent cholecystectomy, herniorrhaphy, appendicectomy, colonic resection for cancer and mastectomy for cancer or who were admitted to hospital with acute cholecystitis and not operated on. MAIN OUTCOME MEASURES: Annual rates from 1932-1993. RESULTS: The rate of cholecystectomies/100000 inhabitants increased slowly from 1932 and peaked in 1957 at 315. It then decreased to 67 in 1990 after which the introduction of laparoscopic technique caused an increase to the present rate of 90. CONCLUSION: There has been a rise and a fall of the cholecystectomy rate during the last 60 years in Stockholm county which are probably explained by changes in the indications for the operation. There was no association with health care facilities or with changes in the rates of other operations.

Hepatic esterification rate of cholesterol and biliary lipids in human obesity.

Obesity is often associated with an increased hepatic secretion rate of cholesterol and saturated gallbladder bile. In order to evaluate the role of hepatic esterification of cholesterol in this phenomenon, we assayed the activity of acyl CoA:cholesterol acyl transferase (ACAT), which catalyzes the esterification of cholesterol, in liver microsomes obtained from 19 morbidly obese patients without gallstones undergoing vertical banded gastroplasty. Gallbladder bile was obtained and analyzed for lipid composition, cholesterol saturation, nucleation time, and occurrence of cholesterol crystals. Fourteen non-obese gallstone-free subjects undergoing cholecystectomy because of suspected polyp or adenomyoma in the gallbladder served as controls. The hepatic content of esterified cholesterol was increased by about 70% in the obese patients (P < 0.05). Still, the mean levels of the ACAT activity were equal in the obese and non-obese patient groups (11 +/- 1 and 11 +/- 2 pmol/min per mg protein, respectively). When exogenous cholesterol was added to the assay system, the activity was increased markedly in both groups. The ACAT activity was higher in obese patients with steatosis of the liver compared with those displaying normal liver morphology (12 +/- 1 vs 8 +/- 1 pmol/min per mg, P < 0.05). Obese patients did not have significantly more saturated gallbladder bile than the non-obese controls (84 +/- 7 and 77 +/- 8%, respectively). They had a normal nucleation time and their gallbladder bile did not contain any cholesterol crystals. We conclude that obese patients without gallstones usually have a normal esterification rate of cholesterol in the liver. Steatosis of the liver was associated with increased ACAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of desmopressin to prevent bleeding complications in patients treated with aspirin.

Aspirin induces a haemorrhagic diathesis that persists for at least 1 week after discontinuation of the drug. The effect of the vasopressin analogue desmopressin was studied in 12 patients treated with aspirin who were undergoing cholecystectomy. Desmopressin was given to six of these patients. There were five postoperative bleeding complications; all occurred in patients who had not received desmopressin (P < 0.05). The bleeding time was prolonged in aspirin-treated patients and normalized by desmopressin (P < 0.05). Desmopressin can be used safely to prevent bleeding induced by aspirin.

Monofilament versus multifilament absorbable sutures for abdominal closure.

This study compares monofilament continuous absorbable sutures with multifilament interrupted absorbable sutures for abdominal closure. Before closure of an abdominal incision, 988 patients were randomized to receive either a monofilament polyglyconate (Maxon) or a multifilament polyglactin 910 (Vicryl) suture. At 1 year after operation, 684 patients (69 per cent) were examined for the presence of incisional hernia, sinus and other wound-healing problems; 179 (18 per cent) had died and 125 (13 per cent) did not attend for follow-up. Incisional hernia occurred in 8 per cent of patients receiving monofilament continuous sutures compared with 6 per cent of those having multifilament interrupted closure (P not significant). Wound dehiscence occurred in 1 per cent of both groups. The mean time for suturing was 7.1 min for monofilament continuous and 8.7 min for multifilament interrupted sutures (P < 0.001). It is concluded that closure of an abdominal incision can be effected by a monofilament continuous absorbable suture more quickly than by multifilament interrupted absorbable sutures without an increased risk of wound dehiscence or incisional hernia.

Cholesterol metabolism in human gallbladder mucosa: relationship to cholesterol gallstone disease and effects of chenodeoxycholic acid and ursodeoxycholic acid treatment.

The objective of this study was to investigate cholesterol metabolism in human gallbladder mucosa, especially in relation to hepatic cholesterol metabolism, gallstone disease and treatment with bile acids. Gallbladder mucosa and liver tissue samples were collected in 44 patients undergoing cholecystectomy; 30 had cholesterol gallstones and the rest were stone free. Ten of the gallstone patients were treated with chenodeoxycholic acid and eight received ursodeoxycholic acid, with a daily dose of 15 mg/kg body wt, for 3 wk before surgery. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, governing cholesterol synthesis, was considerably lower in the gallbladder mucosa than in liver tissue (28 +/- 6 and 120 +/- 40 pmol/min/mg protein). The acyl coenzyme A:acyltransferase activity in the gallbladder mucosa catalyzing the esterification of cholesterol was, on the other hand, several times higher than corresponding activity in the liver (92 +/- 23 and 11 +/- 2 pmol/min/mg protein). In the presence of exogenous cholesterol, the acyl coenzyme A:acyltransferase activity increased about twofold in the gallbladder mucosa. The acyl coenzyme A:acyltransferase activity of the gallbladder mucosa from untreated gallstone patients was not stimulated further by the addition of exogenous cholesterol. Otherwise, there were no significant differences in acyl coenzyme A:acyltransferase and 3-hydroxy-3-methylglutaryl coenzyme A reductase activities in the gallbladder mucosa of gallstone patients compared with gallstone-free controls. Treatment with chenodeoxycholic and ursodeoxycholic acids did not affect the 3-hydroxy-3-methylglutaryl coenzyme A reductase activity of the gallbladder mucosa but reduced the acyl coenzyme A:acyltransferase activity by 60% to 65%.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in gallstone morbidity in a community with decreasing frequency of cholecystectomies. A statistical study of the county of Stockholm, Sweden, 1969-1982.

From 1969 to 1982 there has been a continuous decrease in the cholecystectomy rate in the county of Stockholm, Sweden, from 265 per 100.000 population to 105. The change is greatest among young females. During the same period there has been a two-fold increase in gallbladder cancer. Although the total number of cases with common bile duct stones have decreased, they have increased in relation to the number of cholecystectomies. A similar trend is true for cases with and operations for acute cholecystitis. From 1970 to 1982 there has been a fairly constant number of cholecystographies and ultra sound scans of the biliary tract indicating that the diagnostic efforts have been unchanged, at least quantitatively. However, cases with positive diagnosis have decreased especially among young females. It is concluded that the decreased cholecystectomy rate in the county of Stockholm can be explained by a simultaneous decrease of the prevalence of gallstones, at least among the young, and a decrease of operations among those who have gallstones.

Differentiation between attached and ingested immune complexes by a fluorescence quenching cytofluorometric assay.

Immune complexes attached to and ingested by human polymorphonuclear (PMN) cells were quantified by cytofluorometry using a fluorescence quenching assay which permits differentiation between attachment and ingestion. The fluorescence intensity decreased after ingestion as a result of the low pH in the phagolysosomes. When extracellular pH was lowered a slight decrease in phagolysosomal pH was detected in macrophages but not in PMN. When measuring total fluorescence, interaction at pH 5.8 for PMN and at pH 4.4 for macrophages is recommended, since the intensity of extra- and intracellular fluorescence are equal under these conditions. Thirty different dyes were tested for dye exclusion and fluorescence quenching of FITC-conjugated yeast particles, and FITC-conjugated IgG. Because of the lysosomotropic effect of basic dyes, acid and direct dyes are preferable as quenching agents. We could not find physical or chemical properties of the dyes that correlated with their quenching effect. Heat aggregated IgG was used as an immune complex analogue in the development of the assay. Trypan blue (0.2 mg/ml) at pH 4.4 was found to be the best quenching agent of extracellular fluorescence when using ingested aggregated IgG. The technique offers a simple method of quantifying ingested protein aggregates and of studying heterogeneity in phagocyte populations.