Cryoglobulinemia and chronic liver diseases]

Taxotere, a promising anticancer agent, is metabolized almost exclusively in liver and excreted from bile in all species. To determine which cytochrome P450 is involved in taxotere biotransformation, 11 cDNA-expressed human cytochrome P450s were examined for their activity in the metabolism of taxotere and its derivatives. Of all P450s, cytochrome P450 3A4 and 3A5 were the most active for the oxidation of taxotere to the primary metabolite RPR104952 and for subsequent oxidation of RPR104952 to RPR111059 and RPR111026. RP70617, an epimer of taxotere was also metabolized by both P450 3A enzymes to form metabolite XII. The activity of 3A4/5 enzymes for these substrates was 4-50-fold greater than the other P450s examined. The Kms of 3A4 and 3A5 for taxotere were 0.91 and 9.28 microM, and Vmax for the formation of RPR104952 were 1.17 and 1.36 m(-1), respectively. The contribution of the 3A enzyme complex to the metabolism of taxotere in human livers from 21 individuals was assessed with the inhibitory monoclonal antibody and ranged from 64-93%. The primary oxidative metabolism of taxotere by human liver microsomes was well correlated with 3A4-dependent reactions for testosterone 6beta-hydroxylation (r2 = 0.84), taxol aromatic hydroxylation (r2 = 0.67) and aflatoxin B1 3alpha-hydroxylation (r2 = 0.63); whereas a poor correlation was found for reactions specifically catalysed by other P450s (all r2 < or =O.17). The extent of taxotere metabolism also closely correlated with levels of 3A4 enzyme in human livers quantified with immunoblot monoclonal antibody (r2 = 0.61). These results demonstrate that the P450 3A4 and 3A5 enzymes are major determinants in taxotere oxidation and suggest that care must be taken when administering this drug with other drugs that are also substrates for these enzymes.     

Endoscopic cholangiography in biliary tract diseases in HIV+ patients]

We report a case of soft tissue infection with Kluyvera cryocrescens and a critical review of Kluyvera infections. A 31-year-old diabetic man used a new chemical for stripping the floor with his bare hands. Two days later he developed a blister on a finger which progressed to tenosynovitis in spite of intravenous nafcillin therapy. After 11 days culture and sensitivity results dictated treatment with intravenous ticarcillin/clavulanic acid. The wound was debrided twice, and later a skin flap was done. Wound cultures became sterile after 7 days of treatment with ticarcillin/clavulanic acid, and he recovered. This case represents the fourth clinical infection with K. cryocrescens and the eighteenth of Kluyvera to be reported. Four others were K. ascorbata, and the remaining ten Kluyvera infections in humans were not identified beyond genus. Our case and review of the 17 previous cases emphasize that while Kluyvera rarely cause disease, these opportunistic Gram-negative bacilli may be virulent in a variety of sites under as yet poorly defined host conditions. Sites of infection varied, but the brain and meninges were not among them. Two patients had diabetes mellitus, none had AIDS, and four died. Once shown clinically to be the cause of an infection, Kluyvera deserve aggressive treatment which acknowledges their ampicillin resistance.     

Humoral immune reaction in chronic liver diseases

In 60 patients with a morphologically ascertained chronic liver disease and 40 hepatologically examined patients with a healthy liver of a control group the quantitative determination of the immunoglobulin and the immunofluorescence-serological determination of antibodies against nuclei, smooth musculature and mitochondria were carried out. Only in one female patient with a chronic active hepatitis out of 51 patients with morphologically ascertained liver cirrhosis or chronic active hepatitis antibodies against nuclei and smooth musculature in a level of the titre of more than 1 : 40 and only in 2 female patients with a primary biliary cirrhosis antibodies against mitochondria could be proved in a level of the titre of more than 160. Titres of antibodies lying below were found in the group of patients with liver diseases and the control group in the same frequency, so that an autoimmune form of the cryptogenic cirrhosis could not be differentiated. The proof of antibodies against nuclei and smooth musculature of a high titre in connection with an isolated increase of the IgG is of special diagnostic importance for the autoimmune form of the chronic active hepatitis; the same is the case in the proof of antibodies against mitochondria of a high titre in connection with an isolated increase of IgM.     

Mixed cryoglobulinemia in chronic virus diseases of the liver

OBJECTIVE: To establish the tolerance of breast irradiation by women aged 65 and older. DESIGN: Retrospective chart review. PATIENTS AND SETTING: Women undergoing partial mastectomy and postoperative radiation therapy at the H. Lee Moffitt Cancer Center and Research Institute between 1986 and 1990. Of 163 women eligible for the study, 100 were under age 65, and 63 were aged 65-78. MEASUREMENTS: Comparison of total treatment dose, treatment duration, number of treatment interruptions, incidence of cutaneous, mucosal, and hematological toxicity between women aged 65 and older and women younger than age 65. MAIN RESULTS: All study measurements were comparable among younger and older women: total radiation dose (P = 0.5); treatment interruptions (P = 0.063); treatment duration (P = 0.78); cutaneous toxicity (P = 0.37); anemia (P = 0.83); leukopenia (P = 0.07), and thrombocytopenia (P = 0.94). There was no mucosal toxicity, nor higher than grade 2 hematological or cutaneous toxicity. The incidence and severity of toxicity was not higher for women aged 70 and older. CONCLUSIONS: Postoperative breast irradiation is well tolerated by older women. Age is not a contraindication to breast preservation.     

Thyroid gland and thyroid status in patients with chronic liver diseases

We have conducted a prospective study aimed to analyse contraceptive use among women seeking for legal abortion in the State University Hospital "Ma?chin dom"--Sofia. Our date demonstrate that the patients were well informed about the existing contraceptive methods. On the contrary the percentage of women-using contraception and especially those, using highly effective ones is relatively low. The patients claim the possible side effects of the high effective contraception as a reason against use.     

Role of chlamydia in chronic renal and urogenital diseases in man]

Specimens of the joint surfaces of the tibia from patients with OA and RA were exposed were examined for bone mineralization, bone formation, osteoid tissue and bone resorption. Judging from the appearance of the osteoblasts in OA the sclerotic changes are mainly focal with relatively little osteogenesis. No osteoclasia was seen in the sclerotic areas. Breakdown of the mineralized cartilage is followed by the development of cysts with highly cellular connective tissue with high osteoblastic activity and osteoclasia. Osteoid tissue is relatively sparse. The changes in RA are more diffuse with a more active osteoblastic activity and widespread zones of osteoid tissue as well as resorption by osteoclasts. It appears as if the increased uptake of 85Sr in OA is more dependent on the occurrence of relatively inert osteosclerosis than on a rapid turnover of the bone tissue.     

The hydro-MRT of chronic inflammatory bowel diseases]

OBJECTIVE: This study examined the effects of an interpersonal stressor on subsequent calorie intake in females with (N = 20) and without (N = 20) significant bulimic symptomatology. METHOD: Subjects participated in two laboratory sessions that differed according to experimental condition (stress versus no stress), completed self-report measures of mood and anxiety before and after the experimental task, and were provided with an array of snack foods after each session. RESULTS: Counter to the hypothesis, women with bulimic symptoms did not differentially increase their intake when exposed to stress. However, results for the intake of each macronutrient indicated that both bulimic and control women increased their consumption of carbohydrates following the stressor. Thus, stress was related to increased carbohydrate consumption by all subjects but did not differentially affect the consumption of women with bulimic symptoms. CONCLUSIONS: It may be that women with bulimic symptoms are not differentially vulnerable to eating in response to stress or that current laboratory paradigms are unable to detect differences in eating following a stressor.     

Diagnostic value of the study of caffeine elimination in chronic liver diseases

Data from the past few years have shown that as caffeine metabolizes solely in the liver, caffeine elimination can serve as a liver function test. We have collected data by monitoring 40 persons with liver diseases (11 chronic alcoholic hepatitis, 24 liver cirrhosis, 5 non-cirrhotic liver disease). Eight subjects served as controls. The patients with liver cirrhosis were classified according to the Child--Pugh scoring system. To determine caffeine elimination blood samples were collected before and at 3, 6, 9 and 12 hours after oral administration of 0.2 g caffeine. Fasting serum caffeine concentration and concentration 12 hours after administration, serum clearance, half life, peak concentration and volume of distribution have been compared. The respective values measured in patients with non-cirrhotic liver diseases did not differ significantly from the controls. The disappearance of caffeine was significantly decreased in cirrhotics. Our results demonstrated a good correlation between impairment of caffeine elimination and assessment of severity of liver disease by the Child--Pugh classification. Measuring serum levels in samples taken 12 hours after caffeine administration is a simple and useful method in the diagnosis of liver diseases at cirrhotic stage.     

Cell mediated immune response in chronic liver diseases: schistosomal, viral and neoplastic

Cell mediated immune response (CMIR) was studies in 120 patients having chronic liver diseases. Patients were divided into 6 groups, (20 each). (1) Early hepatosplenic Schistosomiasis. (EHSS), (2) Late hepatosplenic Schistosomiasis. (LHSS), (3) Hepatosplenic Schistosomiasis with hepatitis B and/or C infections, (4) Hepatitis B virus cases. (HBV), (5) Hepatitis C virus cases (HCV), (6) Hepatocellular carcinoma cases. (HCC). Twenty within normal subjects taken as controls. Laboratory investigations revealed significant esinophilia in patients of group (1), haemoglobin level was significantly reduced in patients of group (1, 2, 3, & 6), serum albumin was significantly reduced in group (2). The percentage of positivity of skin testing using purified protein derivative, ranged between 10% of patients with LHSS, HBV, HCC and HSS with HBV and/or HCV, 20% of patients with HCV and 25% of patients with EHSS. Percentage of positivity in control group was 100%. The mean diameter of delayed intradermal reaction (2.2 +/- 0.5-6.1 +/- 2.1 mms.) was significantly lower in patients than controls. The response of lymphocyte transformation test to phytohaemmagglutinin was significantly lower in patients when compared to controls. The association of HBV and/or HCV with hepatosplenomegaly was accompanied with a marked depression in cell mediated immune response. Anaemia, hypoalbuminemia and nutritional status of the patients with chronic liver diseases play a major role in the suppression of cell mediated immune response.