Postcholestatic alkaline phosphatase activity after relief of bile duct obstruction in the rat

The effects of obstructive cholestasis on the activity of alkaline phosphatase have been extensively studied in serum and liver tissue. However, very little is known about the activity of this enzyme in the postcholestatic condition after relief of the biliary obstruction. The purpose of this study has been to characterize alkaline phosphatase activity in serum, liver and bile in the postcholestatic period and to relate it to changes in bile acid secretory rate. Serum activity and biliary secretory rates of alkaline phosphatase were markedly increased in rats subjected to a reversible obstructive cholestasis for 24 hr or 48 hr and progressively declined along the postcholestatic period to values not significantly different from those of control rats within 48 hr. A significant direct linear relationship between the biliary secretory rates of enzyme activity and bile salts was apparent both in cholestatic groups and in the control groups. The slope of the regression line (units of alkaline phosphatase secreted per micromole of bile salts) was 1.5-fold to 3-fold higher in cholestatic animals. Remarkably, a positive y-intercept of regression lines suggested that a significant fraction of the enzyme was secreted independently of bile salts; this fraction was 18-fold and 34-fold greater in 24-hr and 48 hr cholestatic rats, respectively, compared with that in controls. Sodium taurocholate administered intravenously, either as a bolus or as an infusion at increasing submaximal rates, resulted in parallel increases of bile salt and alkaline phosphatase secretory rates into bile. The enzyme activity secreted per micromole of taurocholate was significantly greater in cholestatic than in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

"Significance of serum gamma glutamyl transpeptidase in cholestatic jaundice"

In conclusion, our study showed that serum G.G.T rises in cholestasis, and the rise is significantly higher in extraphepatic cholestasis as compared to intrahepatic cholestasis. Serum G.G.T has not shown any superiority over alkaline phosphatase in the evaluation of cholestatic liver disease. However, two considerations must caution against the use of serum G.G.T. alone for evaluation of hepatobiliary disease. The first of these is the lack of specificity for hepatobiliary disease. Serum G.G.T. activity can be elevated in some non-hepatic disorders such as acute pancreatitis, congestive cardiac failure, myocardial infarction, diabetes mellitus and alcoholism. Determination of serum G.G.T. in these patients is of no value. Second, the possibility that changes in serum G.G.T. activity results from drug administration in man.     

Wound botulism associated with black tar heroin

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is thought to play an important role in cellular immunological reactions. Expression can be induced by inflammatory cytokines in a wide variety of cells, including hepatocytes. OBJECTIVE: To compare the behaviour of ICAM-1 in liver diseases. PATIENTS AND METHODS: We assayed serum ICAM-1 (sICAM-1) in patients with hepatocellular carcinoma-associated liver cirrhosis, and compared them with a group of cirrhotic patients and controls. sICAM-1 values were also correlated with some biochemical parameters of liver function. Moreover, immunohistochemical localization of ICAM-1 was performed on liver tissue sections of patients with hepatocellular carcinoma, liver cirrhosis and a sample of normal liver. RESULTS: sICAM-1 levels were significantly higher in the hepatocellular carcinoma patients than in controls (P < 0.0001) and the cirrhosis group (P < 0.001). sICAM-1 values directly correlated with alanine aminotransferase, total bilirubin, alkaline phosphatase and gamma-glutamyltranspeptidase serum values (P < 0.05), with an inverse correlation with albuminaemia values (P < 0.05). There was no correlation with alpha-fetoprotein values, but sICAM-1 values were higher in hepatocellular carcinoma patients with large tumours (> 3 cm) than in those with small tumours (< 3 cm) (P < 0.04). Immunohistochemical localization of ICAM-1 was negative in normal liver tissue; positive staining for endothelial cells was found in chronic liver disease, while in hepatocellular carcinoma tissues, positive membrane staining was observed in hepatocytes and, to a lesser extent, at the cytoplasmic level. CONCLUSION: These results suggest that high serum levels of sICAM-1 are associated with severe liver disease, such as liver cirrhosis and hepatocellular carcinoma, and that they tend to increase with deteriorating hepatic function and tumour size.     

Paraneoplastic elevation of serum alkaline phosphatase in renal cell carcinoma: incidence and implication on prognosis

PURPOSE: We investigated the incidence and prognostic significance of paraneoplastic elevation of serum alkaline phosphatase in patients with renal cell carcinoma. MATERIALS AND METHODS: Clinical data of 365 pathologically proved renal cell carcinoma cases were reviewed. Serum alkaline phosphatase level greater than 100 units per 1., but without obvious conditions that may cause phosphatase elevation, including metastasis to or disease of liver or bone and pregnancy, was regarded as paraneoplastic serum alkaline phosphatase elevation. Survival was evaluated using the Kaplan-Meier method. RESULTS: Of 365 patients 77 (21.1%) had paraneoplastic serum alkaline phosphatase elevation. The respective incidence from stage I to IV cases was 9.9% (16 of 161), 31.9% (15 of 47), 34.3% (23 of 67) and 25.6% (23 of 90). Patients with stage I disease had the lowest incidence but there were no statistically significant differences among stages II, III and IV disease. Of 77 patients with elevated serum alkaline phosphatase 48 had additional paraneoplastic manifestations. The disease specific 5-year survival rate in patients with normal serum alkaline phosphatase was significantly better than in patients with isolated phosphatase elevation, which in turn was better than in patients with multiple paraneoplastic syndromes (70.7 versus 50.5 versus 30.8%). Patients with persistent or recurrent elevation of serum alkaline phosphatase after radical nephrectomy had metastatic lesion or local recurrence. In some patients serum alkaline phosphatase returned to normal after nephrectomy but metastasis developed later without recurrent phosphatase elevation. CONCLUSIONS: Paraneoplastic serum alkaline phosphatase elevation in renal cell carcinoma patients implies an unfavorable prognosis, and additional paraneoplastic syndromes further worsen the prognosis. Recurrent or persistent serum alkaline phosphatase elevation after radical nephrectomy suggests distant metastasis or residual tumor. However, the return of serum alkaline phosphatase to normal does not guarantee cure of the disease. Identification of paraneoplastic serum alkaline phosphatase elevation is valuable in the prediction of outcome and postoperative followup of renal cell carcinoma patients.     

Synthesis and QSAR of some 3-amino-2-(substituted)aminomethyl-5,6-disubstituted thieno[2,3-d]pyrimidin-4(3H)-ones as novel H1-receptor antagonists

The plasma concentrations of two bone matrix proteins (osteocalcin, osteonectin) were monitored in 56 samples from 14 patients receiving renal transplants and the values compared with serum bone alkaline phosphatase mass concentrations and osteotropic hormone levels (parathyroid hormone, calcitriol). There were no significant changes in the concentrations of plasma osteonectin at any time after transplantation, as compared with the values before transplantation (P > 0.1). None of the plasma samples showed osteonectin levels above the reference interval. There was a weak but significant relationship between platelet counts and plasma osteonectin levels (r = +0.322; P < 0.05). Osteocalcin showed a marked decrease of the values 1 week following transplantation as compared with the values before transplantation without further change of the values 1 and 3 months after transplantation (P > 0.5) whereas 3 months after transplantation bone alkaline phosphatase levels were higher than before transplantation (P < 0.05). Multiple regression analysis (performed with data from 42 samples obtained after transplantation) revealed serum creatinine as an independent predictor of plasma osteocalcin whereas serum calcitriol was an independent predictor of serum bone alkaline phosphatase (P < 0.05). No correlation was observed between serum calcitriol/plasma parathyroid hormone on the one hand and plasma osteocalcin on the other (P > 0.05). After transplantation there was a lack of correlation between serum bone alkaline phosphatase mass concentrations and plasma osteocalcin values (P > 0.05). In conclusion, serum bone alkaline phosphatase should be preferred to bone matrix proteins for the assessment of bone metabolism in patients receiving renal transplants: (a) bone alkaline phosphatase-but not osteocalcin-is significantly correlated with calcitriol and adequately reflects increased bone formation after renal transplantation; (b) interpretation of osteocalcin values is severely hampered by their strong correlation with serum creatinine concentrations; (c) plasma osteonectin determinations are not useful for monitoring bone formation.     

Pruritus as a presenting symptom of chronic hepatitis C

Pruritus is a common symptom in cholestatic liver disease but is rare in chronic hepatitis C. Eight patients with chronic hepatitis C and severe pruritus were compared with regard to biochemical, serological, and histological features to eight disease controls with primary biliary cirrhosis and seven with cirrhosis due to hepatitis C. Among those with severe pruritus associated with chronic hepatitis C, serum aminotransferases were raised in all, alkaline phosphatase in four, and gamma-glutamyl-transpeptidase levels in all except one. Serum cholylglycine levels were elevated in seven of eight patients. Liver biopsies showed moderate to severe fibrosis in all patients and cirrhosis in five. Compared to control subjects with cirrhosis due to hepatitis C but no pruritus, ductopenia, and cholestatic changes were prominent, although less so than in controls with primary biliary cirrhosis. Chronic hepatitis C with moderate to severe fibrosis may result in low-grade cholestasis with pruritus, possibly in association with bile duct disappearance.     

Selective vestibular neurectomy: a comparison of techniques

Viral chronic hepatitis often occurs in heart transplant recipients receiving cyclosporin. This essential immunosuppressive drug may induce cholestasis. We investigated the effect of treatment with cyclosporin on serum conjugated bile acids in patients with chronic hepatitis developing after heart transplantation. Fifty-nine patients were studied: 17 with chronic hepatitis, 15 heart transplant patients with normal alanine aminotransferase activity, and 27 heart transplant patients with chronic hepatitis, the last two groups receiving cyclosporin. Hepatic biochemical tests and total bile acid concentration were determined on fasting blood samples. The individual glyco- and tauroconjugated bile acids were quantified by high-performance liquid chromatography and direct spectrometry. In patients taking cyclosporin the bilirubin concentration and the alkaline phosphatase activity were increased only when hepatitis was present, in association with a slight increase in cholic acid level (5.13 microM vs. 0.68 microM; P < 0.01). Conjugated lithocholate concentration was dramatically higher when hepatitis and immunosuppression with cyclosporin were associated (1.17 microM vs. 0.03 and 0.04 microM; P < 0.01). Chenodeoxycholate was the main circulating bile acid only in the heart transplant patients treated with cyclosporin but without hepatitis. These results suggest that the mechanisms which explain the cyclosporin-associated modifications of the bile acid pool are different according to the presence or absence of hepatitis. The occurrence of hepatitis in patients on cyclosporin led to an increase in serum lithocholate and primary bile acid concentrations. Further studies are required to assess the effect of ursodeoxycholic acid for this cholestasis.     

Evidence for a luteinizing hormone surge center in the hypothalamus of the pig

Lipoprotein-X (Lp-X) is an abnormal low-density lipoprotein frequently found in liver disease. It is regarded as the most sensitive and specific biochemical parameter for the diagnosis of intra- and extrahepatic cholestasis. Moreover, Lp-X is supposed to contribute to the development of hypercholesterolemia in cholestatic liver disease, because it fails to inhibit de novo cholesterol synthesis. This investigation will focus on the relationship between the presence of Lp-X and serum lipid concentrations in cirrhosis. The significance of Lp-X in the diagnosis of cholestasis, compared with alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), and bilirubin levels, will be assessed as well. The present cross-sectional study includes 212 patients with histopathologically proven cirrhosis. The detection of Lp-X and the quantification of -, beta-, and pre-beta-cholesterol was based on agar gel electrophoresis and polyanion precipitation. For the characterization of liver function, the concentrations of albumin and bilirubin, the activities of liver enzymes, and coagulation times were assessed. In a subgroup of 40 individuals, liver biopsies were re-evaluated to confirm or exclude intrahepatic cholestasis. As a result, there was no association between the appearance of Lp-X and total cholesterol concentrations. While all patients with Lp-X showed intrahepatic cholestasis (predictive value of the positive test = 1), only 16 of 28 patients with cholestasis formed Lp-X (sensitivity = 0.57). The activities of AP and of GGT, as well as the concentrations of bilirubin, were strongly elevated in most patients, with and without cholestasis. The predictive values of AP, GGT, and bilirubin were 0.77, 0.69, and 0.74 for the positive test and 0.5, 0, and 0.6 for the negative test, respectively. We conclude that Lp-X is not related to hypercholesterolemia in cirrhosis. The positive, but not the negative, Lp-X test has high predictive value for the diagnosis of cholestasis in cirrhosis. The biochemical parameters traditionally used for the assessment of extrahepatic cholestasis, AP, GGT, and bilirubin, do not support the diagnosis of intrahepatic cholestasis caused by cirrhosis.     

Bone density and skeletal metabolism in patients with orthotopic ileal neobladder

The interposition of a bowel segment as a bladder substitute into the urinary tract may result in impaired calcium metabolism. We studied 25 male patients (aged 45 to 77 yr) who had undergone a Vescica Ileale Padovana (VIP) reconstruction following cystectomy 29 to 75 mo before. Bone mineral density of the spine and femur was measured by dual x-ray absorptiometry. Blood and 24-h urine samples were analyzed for the main parameters of bone metabolism. Sixteen healthy men were enrolled as a control group. Although blood pH did not differ between patients and control subjects, VIP subjects showed lower levels of plasma HCO3- (P < 0.005) and higher serum chloride (P < 0.001). Bone alkaline phosphatase was higher (P < 0.001), and urine calcium, phosphate, and creatinine levels were lower in VIP patients (P < 0.01, P < 0.01, and P < 0.05, respectively). Bone mineral density at the femoral neck (P < 0.03) and Ward's triangle (P < 0.05) was decreased in VIP patients. When subdivided according to time since operation, patients who had the ileal neobladder implanted for a shorter period of time showed lower blood pH (P < 0.03) and urine calcium (P < 0.05) levels and higher urinary hydroxyproline (P < 0.02). Duration of the ileal neobladder was positively correlated with PTH (r = 0.46, P < 0.03) and blood pH (r = 0.47, P < 0.02). Furthermore, pH values were positively correlated with urine calcium (r = 0.48, P < 0.02). In conclusion, in patients with ileal neobladder, a mild metabolic acidosis is responsible for an increased bone turnover and lower bone mass. Moreover, a decrease over time in the absorption capacity of the ileal pouch might result in calcium malabsorption, which represents an additional risk factor for reduced bone mass in these patients.     

Effects of cyclosporin A on various indices of cholestasis in kidney transplant recipients

A cholestatic syndrome has been reported as one of the main side effects of CyA therapy. The aim of the present study was to evaluate frequency and degree of severity of the cholestatic syndrome in a group of patients with renal transplant treated with CyA. In 55 patients we evaluated both clinical: jaundice, pruritus, presence of biliary lithiasis and biochemical parameters: total serum biliary salts (TBS), total bilirubin (TB), alkaline phosphatase (AP), gammaglutamyl transpeptidase (GGT), transaminase (AST, ALT), cholesterol (CT), triglycerides (TG), HDL-cholesterol (HDL-C) and compared them with a control group matched for sex and age. In the transplant patients significantly higher values of TBS, TB, AP (p < 0.05) were found; 55% of the patients had above mean values of at least one of the classical parameters of liver function and an higher frequency of biliary lithiasis was also found, in the absence of the classical risk factors. However, none of the patients presented severe signs of hepatic disease and to date it has never been necessary to stop treatment. In conclusion, our study shows that the dosage of CyA used at present is quite safe; however, it is necessary to monitor in these patients some parameters of liver function to prevent the minor side effects we observed from progressing into more serious damage.     

Serum bile acids in cholestasis of pregnancy

Using routine liver function tests, cholestasis of pregnancy was diagnosed in 86 pregnant women with pruritus. Serum aminotransferase levels were elevated in all cases, ASAT in 99%, and ALAT in 100%. In these patients serum concentrations of cholic, chenodeoxycholic, and deoxycholic acid were determined using a gas chromatographic method and were compared with those in a group of 40 uncomplicated pregnancies. Of these bile acids, cholic acid levels were most frequently elevated, ie, in 92% of the patients. The frequency of elevation of serum levels of alkaline phosphatase, and total and conjugated bilirubin was lower. Thus, it appears that in addition to serum aminotransferase levels the serum cholic acid concentration is a sensitive indicator of cholestasis of pregnancy. The cholestasis series was divided into 3 subgroups of increasing severity of cholestasis as assessed by maternal serum cholic acid levels, and the occurrence of signs of fetal distress was compared between these subgroups. The only intrauterine fetal loss in the series belonged to the severe cholestasis group. The incidence of meconium-stained amniotic fluid also increased significantly in this group, and 21 of the 24 cases with other signs of fetal distress were in the groups of moderate and severe cholestasis.     

Terbinafine-induced prolonged cholestasis with reduction of interlobular bile ducts

The antifungal drug terbinafine has infrequently been incriminated in the occurrence of acute liver injury. We report a case of prolonged cholestasis that occurred in a 75-year-old woman, following terbinafine administration. Jaundice followed by pruritus appeared after four weeks of therapy and was associated with mixed hepatocellular and cholestatic liver tests abnormalities. Following drug withdrawal, serum bilirubin returned to normal values within three months, but anicteric cholestasis persisted for over six months. A liver biopsy performed after six months showed centrilobular cholestasis, discrete portal fibrosis, and a reduction in the number of interlobular biliary ducts. Terbinafine should be added to the list of drugs that can cause reduction in interlobular bile ducts.     

Early-response cytokine expression in adult middle ear effusions

We determined the diseases associated with extremely high levels of alkaline phosphatase in hospitalized patients. Computerized laboratory records of the Hospital of Saint Raphael identified all inpatients who had elevations of alkaline phosphatase above 1,000 U/l from April 1994 to September 1995. Thirty-seven inpatients with alkaline phosphatase levels above 1,000 U/l were identified. Six had bone involvement from malignancy or Paget's disease and were eliminated from further analysis, and 31 patients were included in the study. Levels of alkaline phosphatase ranged from 1,014 to 3,360 U/l. Ten patients had sepsis as the cause of the elevated alkaline phosphatase. These included gram-negative organisms, gram-positive organisms, and two patients with fungal sepsis. Seven of 10 patients with sepsis had an extremely high alkaline phosphatase level and a normal bilirubin, 3 of 10 patients with sepsis also had acquired immunodeficiency syndrome (AIDS). Eight patients had biliary obstruction, 7 with malignant obstruction and 1 with a common bile duct stone. Nine patients had AIDS. The cause of the elevated alkaline phosphatase in these included three with sepsis, three with mycobacterium avium intracellulare (MAI) infection, two with cytomegalovirus infection, and one with Dilantin toxicity. Three patients had diffuse liver metastases. Finally, four patients had benign intrahepatic disease, including one patient with liver hemangiomas, one patient with sarcoid hepatitis, one patient with lead toxicity, and one patient with drug-induced cholestasis. Extremely high elevations of alkaline phosphatase are most frequently seen in patients with sepsis, malignant obstruction, and AIDS. Patients with sepsis can have an extremely high alkaline phosphatase level and a normal bilirubin. A variety of other causes were also noted.     

Intermittent calcitriol therapy in secondary hyperparathyroidism: a comparison between oral and intraperitoneal administration

BACKGROUND: Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism (secondary HPT). This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis (CCPD). METHODS: Forty-six patients aged 12.5+/-4.8 years on CCPD for 22+/-25 months were randomly assigned to treatment with oral (p.o.) or i.p. calcitriol for 12 months; 17 subjects given p.o. calcitriol and 16 subjects given i.p. calcitriol completed the study. Bone biopsies were performed at the beginning and at the end of the study, while determinations of serum and total ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and calcitriol levels were done monthly. RESULTS: Serum total and ionized calcium levels were higher in subjects treated with i.p. calcitriol, P < 0.0001, whereas serum phosphorus levels were higher in those given p.o. calcitriol, P < 0.0001. For the i.p. group, serum PTH levels decreased from pre-treatment values of 648+/-125 pg/ml to a nadir of 169+/-57 pg/ml after nine months. In contrast, serum PTH levels did not change from baseline values of 670+/-97 pg/ml in subjects given p.o. calcitriol, P < 0.0001 by multiple regression analysis. Serum alkaline phosphatase levels were also lower in patients treated with i.p. calcitriol, P < 0.0001, but there was no difference between groups in the average dose of calcitriol given thrice weekly. The skeletal lesions of secondary HPT improved in both groups, 33% of patients developed adynamic bone lesion. CONCLUSION: Differences in the bioavailability of calcitriol and/or in phosphorus metabolism may account for the divergent biochemical response to p.o. and i.p. calcitriol.     

Serum interleukin-6 levels in metastatic renal cell carcinoma before treatment with interleukin-2 correlates with paraneoplastic syndromes but not patient survival

PURPOSE: We sought to determine the frequency of interleukin-6 (IL-6) expression in renal cancer cell lines, the frequency of the detection of IL-6 in the serum of patients with metastatic renal cell carcinoma, whether serum IL-6 level correlates with the development of paraneoplastic syndromes and whether serum IL-6 level in patients with metastatic renal cancer correlates with response to treatment with interleukin-2 (IL-2) or patient survival. MATERIALS AND METHODS: Conditioned media from 21 cell lines from 20 patients were examined for IL-6. We identified 2 matched groups of patients with metastatic renal cancer (30 responders and 29 nonresponders) to IL-2 based immunotherapy. Stored pretreatment serum specimens were evaluated for IL-6. Medical records were reviewed to determine the presence of paraneoplastic syndromes. RESULTS: IL-6 was detected in 19 of 21 renal cancer cell lines (90%) obtained from 20 patients with metastatic renal cancer as well as in the serum of 33 of 59 patients (56%) with metastatic renal cell carcinoma. A significant association between serum IL-6 level and anemia (p = 0.0032), elevated platelet count (p = 0.01), decreased albumin (p = 0.034) and elevated alkaline phosphatase (p = 0.04) was found. A trend was noted of the association of increased serum IL-6 level and fever (p = 0.051). No correlation was found between pretreatment serum IL-6 level and survival or response to IL-2. CONCLUSIONS: IL-6 was frequently secreted by renal cancer cell lines but it was only present in the serum of approximately half of the patients with metastatic renal cancer. Elevations of serum IL-6 were associated with paraneoplastic manifestations frequently seen in patients with renal cancer, including anemia, thrombocytosis, decreased albumin and elevations of alkaline phosphatase (Stauffer's syndrome). A weak relationship was noted between serum IL-6 level and fever but none was noted between that and survival or response to IL-2.     

Effects of nitric oxide synthase gene knockout on neurotransmitter release in vivo

Previous studies suggest that low bone mass is a complication of alcoholic liver disease. Nevertheless, little is known about bone mass and bone metabolism in viral cirrhosis. To evaluate the prevalence and magnitude of hepatic osteopenia in these patients, bone remodeling status, and its relationship with the severity of liver disease and serum levels of insulin-like growth factor I (IGF-I), we studied 32 consecutive patients with viral cirrhosis and no history of alcohol intake. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN), and the values were expressed as the z score. Bone metabolism markers and hormone profiles were measured. Patients with viral cirrhosis showed reduced BMD in all sites (LS: -1.27 +/- 1.06, P < .001; FN: -0.48 +/- 0.96; P < .01). Of the 32 patients, 53% met the diagnostic criteria for osteoporosis. In patients, urine deoxypyridinoline (D-Pyr) as a marker of bone resorption and serum bone alkaline phosphatase (b-AP) as a marker of bone formation were significantly higher than in control subjects (P < .001 and P < .01, respectively). Serum IGF-I was lower than in control subjects (P < .001), and significant differences were also found between patients with and without osteoporosis (P < .05). BMD in LS correlated with severity of the disease, with serum levels of IGF-I, and with urine D-Pyr. Our findings show that viral cirrhosis is a major cause of osteoporosis in men, and that low serum IGF-I levels seem to play a role in the bone mass loss in these patients. The biochemical markers of bone remodeling suggest high-turnover osteoporosis in patients with viral cirrhosis.     

Hepatic concentrations of proenkephalin-derived opioids are increased in a rat model of cholestasis

The liver of adult rats with cholestasis secondary to bile duct resection has been shown to express the proenkephalin gene and, by immunohistochemical stains, to contain met-enkephalin. To further study hepatic opioids in cholestasis, concentrations of proenkephalin-derived endogenous opioids were measured in a rat model of cholestasis by the use of radioimmunoassays. The specificity of the immunoreactivity detected by the assays was confirmed by high performance liquid chromatography (HPLC). In adult male rats with cholestasis due to BDR, the concentrations of three proenkephalin-derived opioid peptides were increased. Specifically, the mean hepatic concentrations of met-enkephalin, Met-Enk-Arg6-Phe7 and leu-enkephalin were 2.5 (p < 0.005), 2.1 (p < 0.005) and 2.5 (p < 0.01) fold higher than the corresponding mean for controls. These findings provide further independent evidence that opioid peptides accumulate in the liver in a model of cholestasis and are consistent with de novo synthesis of opioid peptides occurring in the cholestatic liver. This phenomenon may have relevance to the altered function of the opioid system in cholestasis and to the role of the liver as a neuroendocrine organ.     

Serum calcium, phosphate and alkaline phosphate levels in epileptic children treated with phenobarbitone

A longitudinal study to estimate the serum calcium, phosphate and alkaline phosphatase levels of 89 ambulatory epileptic children, aged between 3 years and 12 years, and having generalised tonic-clonic seizures, was carried out. None was on any form of medication for the treatment of seizures prior to presentation. Each patient received only phenobarbitone during the period of study. Serum levels of the biochemical parameters were determined at presentation, 6 months and 12 months, while serum phenobarbitone levels were estimated at 6 months and 12 months. Mean serum calcium, phosphate and alkaline phosphatase of the patients remained within the normal range. Using the paired 't' test, the differences in the levels of the parameters at the three measurements were not statistically significant (P > 0.05). Serum phenobarbitone levels remained within the therapeutic range during the period of study. Our results show that over a 12-month period, serum levels of calcium, phosphate, and alkaline phosphatase, remain normal in ambulant epileptic children treated with phenobarbitone.     

Pharmacotherapy in outpatient psychiatric practice

Calcium metabolism was studied in 47 patients with borderline or lepromatous leprosy. Total and ionized calcium, phosphorus, creatinine, total alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxy vitamin D [25(OH)D], and 1,25-dihydroxy vitamin D [1,25(OH)2D] were measured in serum; calcium and total hydroxyproline were determined in urine. Total subperiosteal diameter and medullar cavity diameter were measured on an X-ray of the hand of all patients. Average values were within normal ranges for all of the biochemical determinations. Total serum calcium was moderately below the normal range in eight patients but ionized calcium levels were within the normal ranges in all of the patients. Four patients, all of them with lepromatous leprosy, had levels of 1,25(OH)2D higher than normal but none of them was hypercalcemic and PTH levels were within normal range. Although all values were within the normal ranges, lepromatous leprosy patients had lower total calcium, higher alkaline phosphatase, and higher urinary hydroxyproline than borderline leprosy patients (9.1 +/- 0.4 vs 9.4 +/- 0.3 mg%, p < 0.001; 10.3 +/- 2.9 vs 7.4 +/- 2.3 King-Armstrong units, p < 0.02 and 27.2 +/- 12 vs 19.4 +/- 5.6 mg/24 hr, p < 0.02, respectively). No differences were found between patients and controls in the average micrometric measurements of the second metacarpal bone but significant osteopenia was found in 19% of the patients. The main finding of the present study in a representative sample of leprosy patients is that the average total serum calcium was in the lowest limit of the normal range, but the ionized serum calcium was in the middle of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Triggering of acute myocardial infarction onset by episodes of anger. Determinants of Myocardial Infarction Onset Study Investigators

PURPOSE: We performed this study to identify prognostic factors in a subgroup of patients with carcinoma of unknown primary site treated with cisplatin combination chemotherapy. PATIENTS AND METHODS: Seventy-nine patients with poorly differentiated adenocarcinoma or undifferentiated carcinoma of unknown primary site were treated on two consecutive phase II chemotherapy protocols. The first protocol consisted of treatment with 3-week courses of cisplatin, etoposide, and bleomycin (BEP). In the second protocol, cisplatin was administered weekly combined with oral administration of etoposide (DDP/VP). To identify prognostic factors, univariate and multivariate analyses were conducted. RESULTS: In the univariate analysis, performance status, histology, liver or bone metastases, and serum levels of alkaline phosphatase and AST were significant variables to predict survival. In the multivariate analysis, performance status and alkaline phosphatase were the most important prognostic factors. CONCLUSION: Good-prognosis patients had a performance score of 0 (World Health Organization [WHO]) and an alkaline phosphatase serum level less than 1.25 times the upper limit of normal (N). These patients had a median survival duration greater than 4 years. Intermediate-prognosis patients were characterized by either a WHO performance status < or = 1 or an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of 10 months and a 4-year survival rate of only 15%. The poor-prognosis group had both a WHO performance status > or = 1 and an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of only 4 months and none survived beyond 14 months. Treatment strategies for these three groups are discussed. It is suggested that this prognostic model be validated in other patients series.