["Spontaneous" bacterial peritonitis].
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Adult↗
Biomedical subjects
J H Wilson
Publications and source records attributed to J H Wilson.
Characterization of a new mutation (R292G) and a deletion at the human uroporphyrinogen decarboxylase locus in two patients with hepatoerythropoietic porphyria.
A deficiency in the activity of uroporphyrinogen decarboxylase (UROD), the fifth enzyme of the haem biosynthetic pathway, is found in familial porphyria cutanea tarda (F-PCT) and hepatoerythropoietic porphyria (HEP). A new mutation (R292G) and a deletion have been found in a pedigree with two HEP patients (two sisters). The R292G mutation was not detected in 13 unrelated affected patients with F-PCT, so it appears to be uncommon. The possibility that the arginine 292 may participate at the active site of the enzyme is discussed. A summary of the 7 mutations/deletions found in the UROD gene with their frequency is presented.
Amino Acid Sequence↗
Forecasting hospital laboratory procedures.
Improved forecasts of hospital laboratory procedures can provide the basis for better resource planning and enhanced operating efficiency. The research reported here-in describes how multiple regression models can be both a source of insight into causal relationships and a tool for achieving accurate monthly forecasts. Past research in this area may have overstated the statistical significance of findings because of a failure to address the potential effect of serial correlation. The present study uses the Cochrane-Orcutt regression procedure, rather than OLS, to overcome this problem. A model using inpatient admissions, acuity days, length of stay, discharge days and seasonal dummy variables is shown to account for 87% of the variation in the number of billable laboratory procedures. A simpler multiple regression model and a Winters' exponential smoothing model were found to provide excellent forecasts for laboratory procedures. In a one year out of sample evaluation, the annual percent forecast error was 0.7% for the regression model. This compares favorably to a percentage forecast error of 11.6% using subjective forecasting methods.
Forecasting↗
Effects of long-acting somatostatin analog (SMS 201-995) on eicosanoid synthesis and survival in rats with acute necrotizing pancreatitis.
The effects of a long-acting somatostatin analog (SMS 201-995) were studied in an established model of acute necrotizing pancreatitis in rats. SMS 201-995, when given prior to induction of pancreatitis, decreased the mortality rate from 100% to 40% (P = 0.0001). When treatment was given after induction of pancreatitis, the mortality rate was 75% (P = 0.2). Administration of SMS 201-995 did not influence the serum concentrations of amylase markedly, but the lipase levels were significantly lowered (P less than 0.05). The low levels of serum insulin and the glucose level in whole blood were not influenced. The volume of ascitic fluid was reduced (P less than 0.01). Moreover, less peritoneal fat necrosis was seen, suggesting a reduction in toxic factors in the ascitic fluid. Treatment with SMS 201-995 prior to induction of pancreatitis caused a significant increase in the levels of circulating 6-keto-PGF1 alpha, the stable metabolite of prostaglandin I2 (P less than 0.01). The levels of thromboxane B2 and prostaglandin E2 did not change significantly. The present data support the hypothesis that SMS 201-995 is an activator of prostaglandin I2, thereby modifying the course of the disease.
6-Ketoprostaglandin F1 alpha↗
The role of iron in experimental porphyria and porphyria cutanea tarda.
Porphyria cutanea tarda (PCT) and experimental porphyria are characterized by a decreased activity of the enzyme uroporphyrinogen decarboxylase, and accumulation of uroporphyrins and heptacarboxylporphyrins in the liver. Iron (Fe) plays an important role in PCT and experimental porphyria. Biochemically and electron microscopically, we examined the relationship between Fe and porphyrins in liver tissue of C57BL/10 mice made porphyric by administration of iron dextran as Imferon (IMF), and in liver biopsies of patients with symptomatic PCT. Accumulation of uroporphyrins and heptacarboxylporphyrins, and an increased amount of Fe were observed in livers of mice treated with IMF and in liver biopsies of patients with PCT. In mice treated with IMF, the activity of uroporphyrinogen decarboxylase was decreased. Both in livers of mice treated with IMF and in livers of patients with PCT, needle-like structures, representing uroporphyrin crystals, were observed by electron microscopy. Uroporphyrin crystals and Fe (as ferritin) were observed in the same hepatocyte. Moreover, there was a striking morphological correlation between uroporphyrin crystals and ferritin-Fe, suggesting a role for (ferritin-)Fe in the pathogenesis of porphyria.
Animals↗
Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats.
The possibility of using the porphyrin precursor 5-aminolevulinic acid to cause selective porphyrin accumulation in tumors was examined. Syngeneic colon carcinomas CC531 were implanted in the livers of Wag/Rij rats. Groups of three to six animals each were given 2 mg/mL of 5-aminolevulinic acid in drinking water from the 8th, 14th, or 17th day after tumor implantation. Two other groups received either 2.5 or 5 mg/kg of Photofrin II (Photomedica Inc., Raritan, NJ) intravenously on day 17. On day 19 the livers were removed and porphyrin concentrations were measured in normal livers and tumors by solvent extraction and high-performance liquid chromatography. Protoporphyrin accumulated progressively in tumors with increasing duration of 5-aminolevulinic acid administration (P = 0.0001), whereas no increase was found in normal livers. After 11 days of 5-aminolevulinic acid administration the porphyrin concentration ratio between tumors and livers was 4:1. In contrast, after Photofrin II administration the concentration was higher in normal livers than in tumors (1:3 ratio, tumor to liver). Enzyme measurements showed a threefold decrease in ferrochelatase activity in tumors compared with livers (P less than 0.001). In conclusion, oral administration of 5-aminolevulinic acid results in progressive accumulation of protoporphyrin in a transplantable colon carcinoma without accumulation in the surrounding liver tissue. This selective accumulation of porphyrins appears to be caused by a relative ferrochelatase deficiency in malignant tissue. 5-Aminolevulinic acid administration may be a suitable approach to photosensitizing liver tumors for photodynamic therapy or to early detection of tumors by fluorescence in ultraviolet light.
Aminolevulinic Acid↗
Disseminated intravascular coagulation in liver cirrhosis.
UNLABELLED: We measured thrombin-antithrombin III complex (TAT), soluble fibrin (SF) and D-dimer levels in 51 patients with liver cirrhosis to determine whether these tests provide new evidence for the presence of disseminated intravascular coagulation (DIC) in liver cirrhosis. TAT levels (median, range) were increased in the patient group (4.2 micrograms/l, 1.8-60.0) compared to the reference group (2.0 micrograms/l, range 1.5-7.6 micrograms/l). SF levels (0 nmol/l, range 0-80 nmol/l) were also increased in the patients as compared to the controls (0 nmol/l, 0), but there was no correlation between TAT and SF levels (r = 0.23, p less than 0.98). TAT levels did not correlate with AT-III levels (r = -0.36, p less than 0.49), but there was an inverse correlation between SF and AT-III (r = 0.60, p less than 0.001). If AT-III levels were above 0.30 U/ml, SF levels remained low, whereas SF levels were increased in patients with AT-III levels below 0.30 U/ml. These findings suggest that if sufficient AT-III is present, thrombin formation is adequately controlled, whereas at low levels of AT-III, thrombin escapes inactivation by AT-III and may act upon fibrinogen, leading to the formation of SF and a low-grade DIC. SF levels correlated well with D-dimer levels (r = 0.55, p less than 0.001), which is consistent with DIC and secondary fibrinolysis. IN CONCLUSION: (1) thrombin formation is increased in liver cirrhosis, as indicated by increased TAT levels in 21 of 51 patients; (2) the plasma concentration of AT-III appears to be of major importance for the development of DIC. The present study provides evidence for DIC in severe liver cirrhosis when AT-III levels are less than 0.30 U/ml.
Adult↗
The validity of bioelectrical impedance analysis in estimating total body water in patients with cirrhosis.
This study assessed the validity of bioelectrical impedance analysis (BIA) to predict total body water (TBW) in patients with cirrhosis. TBW was estimated by deuterium oxide dilution (D2O) and compared with TBW predicted by BIA in 27 patients with cirrhosis with and without ascites or edema (Group A), in a subgroup of 18 'dry' cirrhotics without clinical signs of fluid overload (Group B) and in 27 healthy controls. Three different BIA regression equations were used. In all three groups of subjects high correlation coefficients were obtained between D2O-TBW and BIA-TBW (r > 0.88). In the cirrhotic Group A, BIA significantly underpredicted D2O-TBW by all 3 equations (2.9-3.8 l) and the regression lines were different from the lines of identity by two equations. Standard errors of estimate were high in Group A (3.04-3.97 l) in comparison with Group B (1.79-2.46 l) and the controls (1.03-1.41 l). In the 'dry' cirrhotics (Group B) and in the controls, TBW was correctly predicted by two of three BIA equations, and regression lines were not significantly different from lines of identity. Correlation coefficients in Group B were higher than in Group A (r = 0.96-0.97 vs. 0.89-0.92) and were comparable with controls (r = 0.98-0.99). We conclude that BIA is not a valid method of estimating TBW in cirrhotic patients with ascites and edema. In cirrhotic patients without clinical signs of fluid overload BIA can be used to predict TBW, although accuracy is slightly lower than in healthy controls.
Ascites↗
The art of physical diagnosis.
Preservation of the art of physical examination of food animals is warranted because veterinarians are still asked to assess sick valuable individuals as well as sick animals that may be representative of herd or flock problems. It is very important to establish a consistent, thorough routine for physical and rectal examination to ensure that no problems are overlooked. An example of a routine for examining dairy cattle is presented, as is a sample form for recording findings.
Animal Diseases↗
Endoscopic papillotomy in biliary tract pain and fluctuating cholestasis with common bile duct dilatation and small gallbladder stones.
In patients suspected of having functional disorders of the papilla it is often difficult to establish the indications whether or not to perform endoscopic papillotomy (EP). We report on thirty-two consecutive patients referred for endoscopic retrograde cholangiopancreatography who all had longstanding biliary tract pain and episodes of liver enzyme elevation indicating cholestasis. Further features were: 1) a dilated common bile duct (CBD) after cholecystectomy (n = 11) or 2) a dilated CBD without or with larger (greater than cystic duct diameter) gallbladder stones (n = 6) or 3) multiple small gallbladder stones, with a normal or dilated CBD, in patients with signs of acute gallstone pancreatitis or in whom elective cholecystectomy was not indicated (n = 15). No CBD stones, organic obstruction or other disorders were found in these patients. Without further diagnostic procedures, EP was routinely performed. The laboratory (up to 3 months) and clinical findings (2 to 4 years follow up) showed improvement in all patients undergoing EP. We conclude that immediate EP appears justified in these selected patients.
Aged↗
Whole-body and segmental bioelectrical-impedance analysis in patients with cirrhosis of the liver: changes after treatment of ascites.
Bioelectrical impedance analysis (BIA) is a simple technique for determining body water and calculating body composition. It has been validated in healthy control subjects but not in patients with liver disease. We examined the ability of BIA to detect changes in total body water (TBW) due to removal of ascites. In 12 cirrhotic patients, BIA of the whole body and of body segments was performed before and after treatment of ascites with paracentesis (n = 12) and diuretics (n = 2). TBW changes predicted by BIA, by using two prediction equations, were significantly less than body weight changes (51% and 45% of the weight loss). BIA of body segments showed highly significant changes in both the trunk and the leg and small changes in the arm. These data indicate that BIA of the whole body is not a suitable technique for monitoring fluid changes in cirrhotic patients with ascites. Changes in BIA of body segments may be due to mobilization of edema after the removal of ascites.
Adult↗
Body composition in growth hormone-deficient adults.
Body composition in a group of growth hormone (GH)-deficient adults was compared with a control group matched for age, sex, body height, body weight, and body mass index by using bioelectrical impedance and deuterium oxide-dilution methods and hydrodensitometry. The body-fat percentages of GH-deficient adults were higher despite comparable weight, height, age, and body mass index. Body impedance was higher in the GH-deficient adults after correction for differences in height and fat-free mass. As a consequence, prediction formulas for body composition from body impedance developed in normal subjects cannot be applied to GH-deficient subjects. The higher body impedance in the GH-deficient subjects can be ascribed to a smaller amount of extracellular water in these subjects than in control subjects.
Adipose Tissue↗
The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition.
OBJECTIVE: The effect on bone, protein, carbohydrate and lipid homeostasis as well as body composition of the administration of growth hormone to adult patients with growth hormone deficiency was studied. DESIGN: Growth hormone was administered at a dose of 25 micrograms/kg/day with a maximum of 1.48 mg (4 IU) a day, for 6 months in eight adults. Studies were done before the start and at 1, 3 and 6 months during therapy, as well as 3 months after treatment had been stopped. RESULTS: Subjective well-being as assessed by a short psychological tests showed an improvement in six and no change in two patients. Body composition, as assessed by body impedance assessment and D2O dilution, both showed an increase in lean body mass of 4 kg (5% of body weight), accompanied by a decrease in mean fat mass of 3 kg. Nitrogen turnover studies showed a transient increase in fed state nitrogen balance due to an increase in the rate of protein synthesis, which exceeded a smaller increase in the protein degradation rate. Growth hormone treatment did not affect the circulating levels of 25(OH)-vitD or PTH 1-84, while 1,25(OH)2-vitD had significantly increased after 6 months, as well as 3 months after treatment ended. Osteocalcin, procollagen I levels, as well as 24-hour urinary excretion of hydroxyproline and calcium rose during growth hormone administration but subsequently decreased rapidly after administration had been stopped, while the increase in alkaline phosphatase persisted. This increase in markers of both bone resorption and bone formation indicates an activation of bone remodelling, but this was not reflected by an increase in bone density. Glucose levels, measured before and during a normal breakfast, increased during growth hormone treatment, but serum insulin levels did not. Total cholesterol levels decreased by 0.5 mmol/l. Levels of T4 and free T4 as well as rT3 decreased, while T3 increased during growth hormone treatment. CONCLUSION: Therapy with growth hormone for 6 months in a dose varying between 6 and 25 micrograms/kg/day increased lean body mass and decreased fat mass. The sense of general well-being improved in most patients. Furthermore, growth hormone treatment increased bone turnover without a measurable increase in bone density, caused some minor changes in lipid and carbohydrate metabolism, and increased the metabolism of thyroxine to T3.
Adult↗
Hepatocellular carcinoma in porphyria cutanea tarda: frequency and factors related to its occurrence.
Thirty-eight patients with porphyria cutanea tarda (PCT) have been seen in the last 18 years. Five of these patients (13%) developed hepatocellular carcinoma (HCC) during follow-up. We analyzed the differences in clinical, laboratory and liver histology findings at presentation, between patients who developed HCC during follow-up (HCC-group, n = 5) and those who did not (PCT-group, n = 33). Of the clinical features the duration of skin-symptoms was longer in the HCC-group (mean: 10.4 +/- 1.1 years) than in the PCT-group (mean: 1.4 +/- 1 years) (p less than 0.001). No differences in routine laboratory findings were found. Although 11/38 (29%) patients had serologic evidence of a past hepatitis B virus infection and 7/38 (18%) patients had antibodies against hepatitis C virus, no differences in these parameters were found between the PCT-group and the HCC-group. In all 34 liver biopsies a variable degree of siderosis was found (PCT-group vs. HCC-group: NS). Only piecemeal necrosis (p less than 0.01) and advanced fibrosis or cirrhosis (p less than 0.001) were more common in liver biopsies in the HCC-group. In conclusion, factors related to an increased risk of HCC in PCT are: a) a long symptomatic period before start of treatment and b) the presence of chronic active hepatitis and/or advanced fibrosis or cirrhosis in liver biopsies.
Adult↗
Blood culture bottles are superior to lysis-centrifugation tubes for bacteriological diagnosis of spontaneous bacterial peritonitis.
The conventional method of ascitic fluid culturing was compared with the bedside inoculation of ascites into blood culture bottles and into lysis-centrifugation tubes. The conventional culture method was compared with the blood culture bottle method in 31 episodes of spontaneous bacterial peritonitis (SBP). Cultures were positive with the conventional culture method in 11 (35%) episodes and with the blood culture bottle method in 26 (84%) episodes (P less than 0.001). The lysis-centrifugation tube method was compared with the blood culture bottle method in 24 episodes of SBP. Cultures were positive with the lysis-centrifugation tube method in 11 (46%) episodes and with the blood culture bottle method in 19 (79%) episodes (P less than 0.05). Moreover, the blood culture bottle method also shortened the time needed for the detection of bacterial growth. In conclusion, bedside inoculation of ascites into blood culture bottles should be used routinely for patients with suspected SBP. Culturing of ascites in lysis-centrifugation tubes is more laborious than and inferior to that in blood culture bottles.
Ascites↗
Eicosanoid production by density-defined human peritoneal macrophages during inflammation.
Density-defined macrophages isolated from fluids of patients with liver cirrhosis mainly generated the 5-lipoxygenase products leukotriene B4 (LTB4, 16%) and 5-hydroxy-eicosatetraenoic acid (5-HETE, 24%) and the cyclooxygenase products 12-hydroxyheptadecatrienoic acid (HHT, 22%) and thromboxane B2 (TXB2, 18%). The synthesis of eicosanoids was linear with the maturity of the macrophage subpopulations, suggesting that eicosanoid production is increased in in-vivo activated macrophages.
Eicosanoids↗
15-HETE is the main eicosanoid formed by human colonic mucosa.
Eicosanoids were measured in colonic biopsies from eleven patients with active ulcerative colitis and from thirteen controls. Eicosanoid formation was measured after the addition of arachidonic acid and stimulation with calcium ionophore A23187. The 15-lipoxygenase derivative 15-hydroxy-eicosatetraenoic acid (15-HETE) was the predominant product formed in all biopsies. The amount of 15-HETE formed was dependent on the site of biopsy and decreased in the controls in biopsies taken in an aboral direction in the colon. The formation of 15-HETE and that of prostaglandin E2 (PGE2) and PGF2 alpha was proportional to the histologically obtained inflammation score. The role of 15-H(P)ETE as a mediator in ulcerative colitis should, therefore, be considered in addition to the effects of known modulators such as leukotriene B4 (LTB4) and PGE2.
Adult↗
Species differences in the pattern of eicosanoids produced by inflamed and non-inflamed tissue.
The synthesis of 14C labelled arachidonic acid metabolites was measured in colonic tissues obtained from mice, rats, guinea pigs, rabbits, piglets and in colonic biopsies from humans during colonoscopy. The main eicosanoids formed after stimulation with calcium ionophore A23187 were: in humans, 15-hydroxy-eicosatetraenoic acid (15-HETE); in mice, 12-HETE; in rats, 12-HETE, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 6-keto-prostaglandin F1 alpha (6kPGF1 alpha); in guinea pigs, PGD2; in rabbits, 6kPGF1 alpha, PGE2 and 15-HETE; and in pigs PGE2 and 12-HETE. In inflamed 15-HETE production was increased in man, HHT and 12-HETE production in rats and overall eicosanoid production in mice.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗