Refrigerated storage of Ham's F10 culture medium in assisted reproduction programs.
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Biomedical subjects
Publications and source records attributed to H Bell.
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We investigated a group of 111 amenorrhoeic females with associated liver disease. These comprised alcoholic cirrhotics (N = 38), non-alcoholic cirrhotics (N = 12), non-cirrhotic alcoholics (N = 21) and those suffering from other chronic liver diseases (N = 40) admitted to our medical department from 1986 to 1991. The serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), oestradiol, testosterone, sex hormone binding globulin (SHBG) and prolactin were measured. Serum LH was decreased below the normal range in 50% of patients with alcoholic cirrhosis and in 42% of patients with non-alcoholic cirrhosis. One third of non-cirrhotic alcoholics also had decreased LH, in contrast to only 8% of patients with other chronic liver diseases (p < 0.01). A close correlation was found between LH and FSH when all patients were pooled (r = 0.91, p < 0.001). A gonadotrophin-releasing hormone (GnRH) injection elicited a clear LH and FSH response in 11 out of 14 patients with cirrhosis, indicating that the hypothalamus rather than the pituitary is the site of disturbance in gonadotrophin secretion. Serum SHBG was within normal limits and similar in all four groups. In nine females with alcoholic cirrhosis who abstained for 3 months, serum SHBG increased significantly from 39 +/- 18 to 70 +/- 25 nmol/l (p < 0.001), while LH increased in five of nine females and was unchanged in four. In conclusion, half of the amenorrhoeic females with alcoholic as well as non-alcoholic cirrhosis had inappropriately low serum LH and FSH levels, indicating dysfunction of the hypothalamo-pituitary axis.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: We recently reported that the contact and kallikrein-kinin systems are activated in malignancy-related ascites. We have now studied the fibrinolytic system in ascites and plasma from patients with gastrointestinal cancer(n = 14) and non-malignant liver disease (n = 18). METHODS AND RESULTS: Enzyme immunoassays (EIAs) showed that urokinase and tissue plasminogen activators (uPA, tPA) and PA inhibitors (PAI-1, PAI-2) were present in ascites from both patient groups and that tPA was the predominant PA. uPA, tPA, and PAI-1, were detected in plasma from patients and controls. These EIA findings were supported by zymography studies. Functional assays showed considerable generation of plasmin-like activity and low plasminogen and antiplasmin values in malignancy-related ascites. The plasmin/antiplasmin and tPA/PAI-1 ratios were particularly high in malignancy-related ascites as compared with non-malignant ascites. Plasma from the liver disease patients showed a higher tPA/PAI-1 ratio and, thus a higher potential for plasminogen activation than plasma from cancer patients and controls. Patient plasma showed low values of plasmin-like activity, antiplasmin, and plasminogen. CONCLUSION: Our findings show that the fibrinolytic system is activated in malignancy-related ascites.
BACKGROUND: Recombinant interferon remains the cornerstone of treatment of chronic hepatitis C virus (HCV) infection. Still, evaluation of treatment on the basis of response indicators and long-term effect of the treatment raises several questions. METHODS: Seventy-four patients with chronic HCV infection were randomized to a high (3 MIU, 3/7 days) or low (1 MIU, 3/7 days) dose of recombinant interferon-alpha-2b for 48 weeks after a 4-week course of 3 MIU, 3/7 days. Response to treatment was assessed by means of liver enzymes (transaminases), HCV RNA, and liver histology. RESULTS: The higher maintenance dose was associated with a significantly higher rate of sustained alanine aminotransferase (ALAT) response (45% versus 19%) and with a significantly better chance of becoming HCV RNA-negative during therapy (47% versus 23%). In the high maintenance dose group 14 of the 29 (48%) patients with available HCV RNA data were negative at the 3-month follow-up, compared with 4 of 27 (15%) in the low maintenance dose group. Significantly more patients had improved liver biopsy findings after interferon in the high maintenance dose group (79%) than in the low maintenance dose group (36%). There was a close correlation between ALAT response and HCV RNA response. Of 17 patients who were HCV RNA-negative 3 months after the end of treatment, 10 remained HCV RNA-negative 2-4 years later. CONCLUSION: The study demonstrates a higher response rate as assessed by biochemistry, HCV RNA, and liver histology in the higher dose group.
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Computed tomography (CT) was performed to estimate the density of the hepatic and splenic parenchyma in 18 patients with hemochromatosis. The mean CT density was 79 +/- 21 Hounsfield units compared with 61 +/- 9 (p < 0.01) in 31 controls without hepatic disease. Increased density above 79 Hounsfield units was found in eight patients out of 18 (44%). The highest density (125 Hounsfield units) was found in a patient with a serum ferritin of 6500 micrograms/l. There was an association between CT density and serum ferritin (r = 0.72, p < 0.01). The difference in density between liver and spleen gave better discrimination between patients and controls: 12 of 18 (67%) showed an increased difference in density between liver and spleen. We conclude that CT represents a non-invasive alternative to liver biopsy in cases where the latter is contraindicated. However, CT is not sensitive when serum ferritin is below 1,000 micrograms/l.
During the period 1986-93 22 patients were diagnosed as having primary hemochromatosis. Only 11 of them had elevated aminotransferases. Transferrin saturation was higher > 63% in 17 (77%) and serum-ferritin was higher in all the patients. (257 mumol/l to 6,500 mumol/l). A percutaneous liver biopsy was performed in 20 patients, all of whom showed a characteristic grading from 2 + to 4+ using Perls' stain. Two males had cirrhosis with simultaneous hepatocellular carcinoma, and another two had cirrhosis. One patient had diabetes mellitus type I. We conclude that fasting serum-iron and transferrin should be determined in all subjects over 40 years of age and in patients with chronic elevation of liver enzymes. If transferrin saturation is higher than 50% in females and 60% in males, serum ferritin should be determined. A percutaneous liver biopsy should be performed if both values are higher than normal. Screening of siblings is important because of the autosomal recessive pattern of inheritance.
OBJECTIVES: To compare serum ferritin concentration and transferrin saturation in patients with alcoholic and non-alcoholic chronic liver diseases. DESIGN: Consecutive patients with liver diseases. SETTING: The department of internal medicine in a teaching hospital. SUBJECTS: Three hundred and twelve patients with different liver diseases consecutively admitted between 1987 and 1992. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Fasting serum iron, transferrin and ferritin. RESULTS: Serum ferritin was increased above 200 micrograms L-1 in all 18 patients with haemochromatosis (range 310-6500 micrograms L-1), in 64 of 111 alcoholics (58%) and in 30 of 137 (22%) with chronic non-alcoholic liver diseases (P < 0.01). Twelve of 111 alcoholics (11%) had serum ferritin above 1000 micrograms L-1 compared with one of 137 (0.7%) with chronic non-alcoholic liver diseases. In 13 alcoholics who abstained after admission, serum ferritin decreased from 1483 micrograms L1 +/- 1134 to 388 micrograms L-1 +/- 237 (P < 0.001) after 1 1/2 to 6 weeks. The transferrin saturation was increased above 62% in 13 of 18 patients (72%) with haemochromatosis, in 16 of 105 alcoholics (15.2%) and in three of 132 (2.3%) with chronic non-alcoholic liver disease (P < 0.01). CONCLUSION: Serum ferritin is more frequently elevated in abusing patients with alcoholic liver disease than in patients with other chronic liver diseases such as autoimmune liver diseases and hepatitis C. Because serum ferritin decreases rapidly during abstinence, the measurement of ferritin for the detection of haemochromatosis in patients abusing alcohol should be postponed until the patients are abstaining. Most of the patients with increased serum ferritin have normal transferrin saturation values which can be used to separate them from haemochromatosis.
An isoform of transferrin, carbohydrate-deficient transferrin (CDT) is increased in a high percentage of abusing alcoholics and has been found superior in its specificity compared with other biological markers. We used serum CDT as a screening parameter in 502 patients consecutively admitted to our medical department during a 4-week period. The intake of ethanol during the last 4 weeks was registrated by personal interviews and the mean daily consumption calculated. Serum CDT was measured at admission (CDTect) and compared with gamma-glutamyltranspeptidase (GGT), AST, ALT, and mean corpuscular volume (MCV). Serum CDT detected 18 of 26 (69%) patients who consumed > 50 g ethanol daily. The clinical sensitivity of CDT of detection ethanol consumption > 50 g daily was 69%, compared with 73%, 50%, 35%, and 52% for increased values of GGT, AST, ALT, and MCV, respectively. Altogether, 38 of 476 patients (8%) with a daily ethanol consumption < 50 g also had increased serum CDT levels. The specificity of CDT was 92%, compared with 75%, 82%, 86%, and 85% for GGT, AST, ALT, and MCV, respectively. In the 60 patients who consumed > 10 g ethanol daily, we found a significantly positive correlation between CDT and ethanol consumption (r = 0.52, p < 0.001). A positive correlation was also found between serum transferrin and CDT (r = 0.51, p < 0.001). In conclusion, the specificity of CDT is much higher compared with GGT in detecting alcohol abuse. Some acute and chronic illnesses may increase the serum level of CDT. False-positive CDT levels may be caused by changes in serum transferrin concentration.
The performance of CDTect (Kabi-Pharmacia, Uppsala, Sweden) and two versions of AXIS % CDT (AXIS Biochemicals, Oslo, Norway) for determining carbohydrate deficient transferrin (CDT) was examined in 502 consecutive patients admitted to the Department of Medicine, Aker University Hospital. The sensitivity for detecting an alcohol consumption > or = 50 g/day for the last 4 weeks was 69% for CDTect, 65% for AXIS % CDT, version 1 (AX CDT 1) and 50% for AXIS % CDT, version 2 (AX CDT 2). The specificity at the same level of alcohol consumption, markedly differed between the two methods: 92%, 76% and 90% for CDTect, AX CDT 1 and AX CDT 2, respectively. The variation coefficient (day-to-day) was 10%, 22% and 10% for CDTect, AX CDT 1 and AX CDT 2, respectively.
During the period from 1985 to 1993 primary sclerosing cholangitis was diagnosed in 16 patients, five females and 11 males, mean age 43 years. 12 of the patients (75%) had inflammatory bowel disease. Among 262 patients with ulcerative colitis, cholangitis was found in ten, whereas the disease was diagnosed in only two (1.9%) of the 108 patients with Crohn's disease. In eight patients (50%) no progression of the cholangitis was observed. However, six patients (38%) died during the observation period, three 19% due to cholangiocarcinoma and one due to liver failure. Cholangiocarcinoma is frequently found in patients with primary sclerosing cholangitis. A mortality of 38% indicates a serious clinical course in many patients.
The concentrations of thiamin and thiamin monophosphate and diphosphate in plasma and whole blood samples were assessed in six healthy subjects for 12 h and in urine for 24 h following an IV and PO bolus dose of 50 mg thiamin HCl. Unphosphorylated thiamin increased rapidly in plasma after IV administration and then decreased to its initial value within 12 h in all but one subject; the half-life was 96 min. Thiamin mono and -diphosphate increased moderately (56%), and decreased slowly; the half-life of diphosphate was 664 min. Within 24 h, 53% of the administered dose was recovered in the urine, indicating a restricted distribution. After oral administration, the peak thiamin concentration in plasma was reached after 53 min and the concentration then had increased to 179% of its initial value. The elimination half-life was 154 min, and only 2.5% of the given dose was recovered in the urine. The relative bioavailability of thiamin was 5.3%. A moderate amount of the administered thiamin was stored in blood. Other body tissues must play an important part, therefore, in the distribution of thiamin.
We measured serum levels of carbohydrate deficient transferrin (CDT) in 420 subjects: 100 healthy blood donors, 82 healthy employees, 70 abstaining patients with different chronic nonalcoholic liver disease, 16 abstaining patients with alcoholic fatty liver, 50 abstaining patients with alcoholic liver cirrhosis, 25 abusing patients with alcoholic fatty liver, 41 abusing patients with alcoholic liver cirrhosis, and 36 patients with alcohol dependence syndrome with a daily ethanol consumption of 173 +/- 120 g the last 4 weeks before blood was drawn. In controls the serum level of CDT was significantly higher in females compared with males (17.7 +/- 5.1 and 13.7 +/- 3.8 units/liter, respectively), and the upper normal limit was defined as 27 and 20 units/liter. Sixty-two of 102 (60.8%) abusing patients with alcoholic liver disease had increased levels of CDT compared with 1 of 66 abstaining (1.5%) patients with alcoholic liver disease, and 10 of 70 (14.3%) abstaining patients with nonalcoholic liver disease among them 3 with primary biliary cirrhosis and 2 with chronic autoimmune hepatitis. No correlation was found between serum CDT and gamma-glutamyltranspeptidase (GGT), AST, ALT, and mean red cell volume (MCV). The sensitivity and specificity for serum CDT was 61 and 92%, respectively, compared with 85 and 18% for GGT and 70 and 66% for MCV. No advantage was gained by using the CDT/transferrin ratio. Our study confirms that CDT is a specific marker for chronic alcohol abuse, except in few patients with other chronic liver diseases. Serum CDT seems to be a better indicator of abstention than GGT; AST and MCV in patients with alcoholic liver disease. However, in our hands CDT is not so sensitive for alcohol abuse in patients with liver disease as reported earlier in unselected alcoholics.
The concentrations of thiamin and thiamin phosphate esters were determined by high performance liquid chromatography in four patients with clinical Wernicke encephalopathy. Three were alcohol abusers, and one had prolonged vomiting and anorexia. Thiamin and thiamin monophosphate were assessed in plasma and whole blood (four patients) and in cerebrospinal fluid (two patients) before and during thiamin treatment. Thiamin diphosphate was also assessed in whole blood in the four patients. Before treatment, thiamin monophosphate was significantly decreased in all patients, and thiamin diphosphate in three. A poor increase in thiamin mono- and diphosphate was paralleled by a slow clinical improvement in one patient, while an increase in all thiamin compounds was observed in two patients with a rapid recovery. Thiamin monophosphate was a more sensitive marker of deficiency than thiamin diphosphate and unphosphorylated thiamin.
In the present study the prophylactic effect of concentrated wheat fibre on duodenal ulcer recurrence was evaluated. Eleven grams of fibre (Fiberform) or placebo was added to an ordinary Norwegian diet for 1 year after endoscopic healing of duodenal ulcer. The ulcer recurrence rates were 84% (31 of 37 patients) in the fibre-supplemented group and 85% (30 of 36 patients) in the placebo group (NS). The effect on ulcer symptoms was similar in both groups. Side effects were infrequently seen. A concentrated wheat fibre supplement seems to have no preventive effect when given to duodenal ulcer patients living on a traditional Norwegian diet.