Diagnosis and management of simple ovarian cysts.
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Adult↗
Biomedical subjects
A Barut
Publications and source records attributed to A Barut.
Evaluation of a local anaesthesia regimen using a subphrenic catheter after gynaecological laparoscopy.
BACKGROUND AND OBJECTIVE: The purpose of intraperitoneal local anaesthetic administration is to block visceral nociceptive conduction and to provide an additional route of analgesia. The present study evaluates the effects of sequential injections of bupivacaine on postoperative pain through a subphrenic catheter. METHODS: In this double-blinded controlled study, patients scheduled for gynaecological laparoscopy were randomly divided into two groups. One group received 20 mL of saline with 1:200000 epinephrine through a subphrenic catheter before the incision closure and at 4-hourly intervals for the first postoperative 20 h. The second group received 20 mL of bupivacaine 0.125% with 1:200000 epinephrine at the same injection times. Postoperative pain scores and consumption of analgesics were compared. RESULTS: There were no statistical differences in pain scores at rest or incidence of shoulder pain between the two groups, but the patients of the bupivacaine group reported lower pain scores on coughing only in the first hour postoperatively (P = 0.007). Although the patients consumed comparable amounts of metamizole and ondansetron, the number of patients requiring supplemental meperidine and flurbiprofen in the bupivacaine group were significantly lower than in the saline group (P < 0.05). CONCLUSIONS: This study demonstrates that intraperitoneal bupivacaine may reduce pain on coughing in the early postoperative period and the consumption of analgesics postoperatively. The subphrenic catheter technique had no impact upon pain at rest and shoulder-tip pain after gynaecological laparoscopy.
Analgesics, Opioid↗
Polymorphisms of the carcinogen detoxifying UDP-glucuronosyltransferase UGT1A7 in proximal digestive tract cancer.
Cancer of the proximal digestive tract is associated with tobacco smoke and ethanol exposure. The UDP-glucuronosyltransferase (UGT) 1A7 is a detoxifying enzyme capable of tobacco-borne carcinogen detoxification and cellular protection and has been implicated as a cancer risk gene. In this study, UGT1A7 expression is demonstrated in oral, esophageal, and gastric tissue, which are the principle sites of proximal digestive tract cancer. Genomic DNA from the blood of 76 patients with esophageal, orolaryngeal and gastric cancer as well as from 210 healthy blood donors was analysed for the presence of UGT1A7 polymorphisms by sequencing and temperature gradient gel electrophoresis. Wild type UGT1A7 alleles were equally distributed between controls (19 %) and cancer patients (22 %). However, the UGT1A7*3 allele combining W208R, N129K and R131K missense mutations and exhibiting substantially reduced carcinogen detoxification activity was significantly associated with proximal gastrointestinal cancer and identified as a risk allele present in 32 % of cancer patients and 19 % of controls (P = 0.0008, OR 2,02 (95 %-CI 1.33-3.07)). We identify the significant association of the UGT1A7*3 allele encoding a low catalytic activity protein as a risk gene in proximal digestive tract cancer and as a potential marker for cancer susceptibility.
Adult↗
Developmental aspects of human hepatic drug glucuronidation in young children and adults.
BACKGROUND AND AIMS: The liver represents one of the major sites of human glucuronidation. Many therapeutic drugs are substrates for UDP-glucuronosyltransferases (UGT) leading to the formation of usually inactive glucuronides. Hepatic glucuronidation undergoes significant changes during fetal and neonatal development requiring age adapted drug therapy. Regulation of individual UGT genes during hepatic development has not been defined. SUBJECTS AND METHODS: Expression of 13 UGT genes and glucuronidation activities were analysed in 16 paediatric liver samples (aged 7-24 months), two fetal samples, and 12 adult liver samples (aged 25-75 years) using duplex reverse transcription-polymerase chain reaction, western blot, and specific catalytic UGT activity assays. RESULTS: No UGT transcripts were detected in fetal liver at 20 weeks' gestation. In contrast, UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, and UGT2B15 transcripts were present without variation in all 28 hepatic samples after six months of age. Significantly lower expression of UGT1A9 and UGT2B4 mRNA was identified in paediatric liver. Hepatic glucuronidation activity in children aged 13-24 months was found to be lower than in adults for ibuprofen (24-fold), amitriptyline (16-fold), 4-tert-butylphenol (40-fold), estrone (15-fold), and buprenorphine (12-fold). CONCLUSIONS: An early phase characterised by the appearance of UGT gene transcripts and a later phase characterised by upregulation of UGT expression is demonstrated during human hepatic development. The differential regulation of UGT1A9 and UGT2B4 expression extends beyond two years of age and is capable of influencing hepatic glucuronidation of common therapeutic drugs in children. The development of hepatic UGT activities is significant for paediatric drug therapy and the prevention of adverse drug effects.
Adult↗
Identification of cyclosporine A and tacrolimus glucuronidation in human liver and the gastrointestinal tract by a differentially expressed UDP-glucuronosyltransferase: UGT2B7.
BACKGROUND/AIMS: The oral administration of the major transplant immunosuppressants cyclosporine A and tacrolimus leads to unpredictable drug levels requiring drug monitoring. Hepatic and extrahepatic metabolism of cyclosporine A and tacrolimus by cytochrome P450 proteins has been analyzed but metabolism and inactivation by glucuronidation has not been investigated. METHODS: Cyclosporine A and tacrolimus glucuronidation was measured in hepatic and gastrointestinal microsomal protein, and with 11 recombinant hepatic and extrahepatic family 1 and 2 UDP-glucuronosyltransferases. UDP-glucuronosyltransferase transcripts were determined by polymerase chain reaction. RESULTS: Significant cyclosporine and tacrolimus glucuronidation activity was present in endoplasmic reticulum from liver, duodenum, jejunum, ileum and colon, but was absent in stomach. Specific cyclosporine A glucuronidation activity was highest in liver and colon, tacrolimus glucuronidation was highest in liver. Analyses using recombinant UDPglucuronosyltransferases identified UGT2B7 as a human UDP-glucuronosyltransferase with specific activity toward cyclosporine A and tacrolimus. The hepato-gastrointestinal distribution of immunosuppressant glucuronidation activity corresponded to the differential expression pattern of UGT2B7 mRNA. CONCLUSIONS: This study provides conclusive evidence of hepatic and extrahepatic immunosuppressant glucuronidation by human UGT2B7 which was identified to be differentially expressed in the human hepatogastrointestinal tract. Hepatic and extrahepatic glucuronidation may influence the therapeutic efficacy of transplant immunosuppressants.
Administration, Oral↗
Hepatic autoantigens in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
BACKGROUND & AIMS: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations of both copies of the autoimmune regulator (AIRE) gene. It is characterized by susceptibility to mucocutaneous candidiasis and multiple autoimmune lesions. A serious disease component is hepatitis. To identify diagnostic autoantibodies for APECED hepatitis, sera from 64 patients with APECED were screened for autoantibodies established in the diagnosis of idiopathic autoimmune hepatitis, and for autoantibodies against 10 cytochrome P450s. METHODS: Screening methods were indirect immunofluorescence, Western blot, Ouchterlony gel diffusion, enzyme-linked immunosorbent assay, and immunoprecipitation. RESULTS: Anti-liver microsomal antibodies were detected in 50% of the patients with APECED hepatitis and 11% of those without hepatitis. Prevalences of antinuclear, smooth muscle, anti-liver cytosol, anti-soluble liver protein/liver pancreas, and anti-CYP2D6 autoantibodies were 9%, 6%, 3%, 0%, and 0%, respectively. CYP1A1, CYP2B6, CYP1A2, and CYP2A6 were identified as autoantigens. Thirty percent of patients with anti-CYP2A6 and 100% of patients with anti-CYP1A2 were affected by hepatitis. Despite the high specificity of anti-CYP1A2 for APECED hepatitis, its sensitivity was low (50%). Anti-CYP2A6 and anti-CYP1A2 were not detected in patients with autoimmune hepatitis (N = 68) or nonhepatitic controls (N = 81). CONCLUSIONS: Anti-CYP1A2 is a highly specific but insensitive marker for APECED hepatitis. No clinical correlation was observed for anti-CYP2A6. Autoimmune hepatitis and APECED hepatitis are characterized by different molecular targets of autoantibodies with no overlap.
Adolescent↗
Genetic link of hepatocellular carcinoma with polymorphisms of the UDP-glucuronosyltransferase UGT1A7 gene.
BACKGROUND & AIMS: Hepatocellular carcinoma is associated with risk factors including hepatitis C, hepatitis B, cirrhosis, genetic liver diseases, and environmental carcinogens. Uridine 5'-diphosphate-glucuronosyltransferases are a superfamily of detoxifying enzymes capable of tobacco-borne carcinogen detoxification and cellular protection. This study examines the association of UGT1A7 and UGT1A9 gene polymorphisms with hepatocellular carcinoma. METHODS: Genomic DNA from the blood of 59 patients with hepatocellular carcinoma and 70 control subjects without evidence of cancer was analyzed by UGT1A7- and UGT1A9-specific PCR, sequencing analysis, and temperature gradient gel electrophoresis. RESULTS: Three UGT1A7 missense mutations were detected defining the UGT1A7*2, UGT1A7*3, and UGT1A7*4 alleles. Wild-type UGT1A7 alleles were present in 41.4% of controls but only in 6.8% of cancer patients (P < 0.001; odds ratio [OR], 9.73; 95% confidence interval [CI], 3.17-29.83). UGT1A7 polymorphisms were present in 93.2% of hepatocellular cancer patients, 74.5% carried the UGT1A7*3 allele (P < 0.001; OR, 10.76; 95% CI, 4.75-24.38), which combines the W208R, N129K, and R131K mutations and encodes a protein with low carcinogen detoxification activity. No UGT1A9 polymorphisms were detected. CONCLUSIONS: The significant association of hepatocellular carcinoma with the UGT1A7*3 allele encoding a low detoxification activity protein is identified and implicates UGT1A7 as a risk gene of hepatocarcinogenesis in addition to a role as potential marker for cancer risk assessment in chronic liver disease.
Adolescent↗
Polymorphic gene regulation and interindividual variation of UDP-glucuronosyltransferase activity in human small intestine.
UDP-glucuronosyltransferases (UGTs) convert dietary constituents, drugs, and environmental mutagens to inactive hydrophilic glucuronides. Recent studies have shown that the expression of the UGT1 and UGT2 gene families is regulated in a tissue-specific fashion. Human small intestine represents a major site of resorption of dietary constituents and orally administered drugs and plays an important role in extrahepatic UGT directed metabolism. Expression of 13 UGT1A and UGT2B genes coupled with functional and catalytic analyses were studied using 18 small intestinal and 16 hepatic human tissue samples. Hepatic expression of UGT gene transcripts was without interindividual variation. In contrast, a polymorphic expression pattern of all the UGT genes was demonstrated in duodenal, jejunal, and ileal mucosa, with the exception of UGT1A10. To complement these studies, interindividual expression of UGT proteins and catalytic activities were also demonstrated. Hyodeoxycholic acid glucuronidation, catalyzed primarily by UGT2B4 and UGT2B7, showed a 7-fold interindividual variation in small intestinal duodenal samples, in contrast to limited variation in the presence of 4-methylumbelliferone, a substrate glucuronidated by most UGT1A and UGT2B gene products. Linkage of RNA expression patterns to protein abundance were also made with several mono-specific antibodies to the UGTs. These results are in contrast to a total absence of polymorphic variation in gene expression, protein abundance, and catalytic activity in liver. In addition, the small intestine exhibits considerable catalytic activity toward most of the different classes of substrates accepted for glucuronidation by the UGTs, which is supported by immunofluorescence analysis of UGT1A protein in the mucosal cell layer of the small intestine. Thus, tissue-specific and interindividual polymorphic regulation of UGT1A and UGT2B genes in small intestine is identified and implicated as molecular biological determinant contributing to interindividual prehepatic drug and xenobiotic metabolism in humans.
Blotting, Western↗
Epitope mapping of cytochrome P4502D6 autoantigen in patients with chronic hepatitis C during alpha-interferon treatment.
BACKGROUND/AIMS: Cytochrome P450 2D6 (CYP2D6) has been documented as the major target antigen of liver kidney microsomal autoantibodies type-1 (anti-LKM-1) in both autoimmune hepatitis type-2 (AIH-2) and hepatitis C (HCV). In HCV/anti-LKM-1-positive patients, the choice between alpha-interferon (alpha-IFN) or immunosuppression may be difficult. This study was conducted to evaluate the course and outcome of alpha-IFN therapy in HCV/anti-LKM-1-positive and -negative patients and the alterations in these autoantibody titers by the indirect immunofluorescence and a novel radioligand assay. Epitope mapping was also performed to screen for a potential shift in anti-LKM-1 binding towards small linear epitopes, which are more often detected in AIH-2 patients. METHODS: Twenty-one patients with HCV infection received alpha-IFN. Seven patients were anti-LKM-1 positive (study group) and 14 patients were anti-LKM-1 negative (disease control group). Anti-CYP2D6 detection was based on immunoprecipitation of [35S]-methionine-labeled CYP2D6 recombinant protein (rCYP2D6) produced by in vitro transcription/translation. RESULTS: Four out of seven (57%) patients in the study group and 5/14 (36%) in the disease control group initially responded, but subsequently relapsed. During follow-up, alanine aminotransferase significantly increased in the study group compared to the disease control group (p<0.01). A slight increase, followed by a plateau of autoantibody titers was recorded by the radioligand assay and by indirect immunofluorescence during therapy and follow-up in most cases. In one patient, however, gamma-globulins and anti-LKM-1 titers increased, reaching very high levels (1:40 960). alpha-IFN was interrupted and immunosuppression was started. HCV/anti-CYP2D6 positive sera recognized CYP2D6 expressed in E. coli and two truncated proteins (aa 250-494 and 321-494). Two out of seven sera, in addition reacted with a small linear epitope of aa 257-269 (one of which also reacted with a C-terminal domain of aa 350-494). CONCLUSIONS: A rather mild deterioration in liver disease was observed in only 1/7 HCV/anti-LKM-1-positive patients during alpha-IFN treatment. This patient showed high anti-CYP2D6 titers before the initiation of therapy, a sharp increase in anti-LKM-1 titers during treatment, and reactivities to a small linear epitope and an infrequently recognized C-terminal domain of CYP2D6. After switching to immunosuppressive treatment, a complete and sustained response was recorded. Further prospective studies from many centers are needed to define whether these features have general, clinical significance or not.
Adolescent↗
HLA DR, DQA, DQB and DP antigens in patients allergic to nickel.
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Adult↗
Detection of urinary interleukin-2, interleukin-2 receptor, and tumor necrosis factor levels in patients with superficial bladder tumors after intravesical BCG immunotherapy.
OBJECTIVES: To investigate the presence of urinary cytokines, after bacillus Calmette-Guérin (BCG) therapy, in order to provide further insight into the mechanisms of action of intravesical BCG therapy. METHOD: Urine levels of interleukin-2 (IL-2), interleukin-2 receptor (IL-2R), and tumor necrosis factor alpha (TNF alpha) levels were determined in 34 patients with superficial bladder tumors after a six-week course of intravesical BCG therapy. The urine samples were obtained at the fifth hour following the sixth course of therapy and the determinations were made by using an (enzyme-linked immunosorbent assay (ELISA)) technique. RESULTS: The pre-BCG levels of IL-2, IL-2R, and TNF (32.1 ng/L, 21.1 ng/L, 37.6 micrograms/L, respectively) were increased significantly after therapy (175.2 ng/L, 54.4 ng/L, 625.9 micrograms/L, respectively). These levels remained significantly increased after all patients were stratified according to tumor and patient characteristics. CONCLUSION: The results of this study provide further evidence for the immunologic basis of the mechanism of action of intravesical BCG therapy.
Administration, Intravesical↗
Urinary tumor necrosis factor levels in primary glomerulopathies.
In the present study, urinary tumor necrosis factor-alpha (TNF) levels in nonproliferative glomerulopathies [minimal change disease (n = 4), focal glomerulosclerosis (n = 4), membranous glomerulonephritis (GN) (n = 1), and in patients with chronic glomerulopathies (n = 4)] were compared to proliferative ones [a rapidly progressive GN patient and 8 patients with mesangial proliferative GN and membranoproliferative GN (MPGN) who had clinically active disease]. The mean urine TNF levels of the proliferative group were significantly higher than both the nonproliferative GN and 4 controls, whereas the mean value of the nonproliferative group was not significantly different than the controls. The urine TNF levels in 4 MPGN patients with chronic disease and in 2 who entered remission were also very low. In the patients with active renal disease and cellular proliferation there were significant correlations between the urinary TNF levels and both proteinuria and the clinical activity scores. We suggest that in human proliferative glomerulopathies TNF may be implicated in the glomerular inflammation.
Adolescent↗
[Relationship of histocompatibility groups to chronic HBV infections].
HLA-A, B, C and DR locus specificities studied in 168 patients (71 Chronic active Hepatitis, 97 Chronic Persistent Hepatitis) serologically and histopathologically proven Chronic Hepatitis B Virus infection. There were 113 men and 55 women with a mean age of 23.2 (21-52) years. Hundred and seventy four healthy subjects (107 men, 67 women) included in control group with a mean age of 26.4 (20-54) years. The frequency of HLA A3 (p < 0.01), HLA A11 (p < 0.01), HLA B35 (p < 0.05) and HLA B51 (p < 0.01) were significantly higher in patients than in healthy control subjects. Comparisons among the other HLA-A, B, C and DR locus were found to be statistically non-significant.
Adult↗
[Complement C3 and C4 levels in serum from acute viral hepatitis].
Serial measurements of C3 and C4 complement components were performed in 50 patients with acute, uncomplicated viral hepatitis, in the beginning of the symptoms and in the peaks of serum transaminases. There were 17 patients diagnosed as having Hepatitis A virus (HAV) infection and 33 patients diagnosed as having Hepatitis B virus (HBV) infection. There were 4 women and 46 men with a mean age of 22.1 years. In the sera of 50 healthy control subjects serum C3 and C4 complement components measured, this group was composed of 15 women and 35 men with a mean age of 26 years. The complement component levels were observed to be reduced in both viral infections, where the reduction in C3 serum concentration was found to be statistically significant but reduction in C4 serum concentration was not.
Acute Disease↗
[Incidence of hepatitis D virus infection in chronic hepatitis B virus carriers].
In carriers of HBsAg (Hepatitis B virus surface antigen) the incidence of Hepatitis D virus infection was studied in 72 (61.3%) males and 45 (38.5%) females, totally in 117 cases with a mean age of 34.8 years. There were 26 (22.2%) asymptomatic carriers of HBsAg where in other chronic carriers the diagnosis were as follows; 29 (24.7%) chronic persistent hepatitis, 20 (17.0%) chronic lobular hepatitis, 23 (19.6%) chronic active hepatitis and 19 (16.2%) posthepatic cirrhosis. The incidence of HDV serologic markers were found to be positive in 19 (16.2%) out of 117 cases.
Adult↗
[Comparison of PVRV and HDCV rabies vaccines as to immunity, reliability and protective value].
World Health Organization (WHO) recommends a new Inactivated Rabies Vaccine grown on Vero Cells, (PVRV: Purified Vero Rabies Vaccine) with the vaccine cultivated on Human Diploid Cells (HDCV: Human Diploid Cell Vaccine), for both pre and post-exposure prophylaxis. Following the widespread use of HDCV and PVRV, many comparative clinical trials have been conducted, studying the safety and predictive values of these two vaccines. In the present study, using the schedule recommended by the WHO for preexposure prophylaxis, days on 0, 7 and 21, we vaccinated 90 healthy male volunteers, age ranged between 18 and 24 (mean 20) and may expose to a risk of rabies. These 90 volunteers randomly divided into 3 different groups with 30 people in each. First group vaccinated by PVRV, 2nd by HDCV and the last group by placebo (PS) double blind. The neutralizing antibody titration was measured by Rapid Immunofluorescence Focus Inhibition Test (RFFIT) on days 0, 7, 21, 28 and 60 in Laboratories of Pasteur-Merieux, Lyon-France. On day 21, in both PVRV and HDCV group the neutralizing antibody titres have occurred and the difference was not statically significant (P less than 0.05). No serious side-effects occurred with either vaccine, although some vaccinees complained of redness, induration or local pain and exceptionally of fever, and lymphadenopathy. The geometric mean of antibody titres shows a higher titre in both PVRV and HDCV group on the 60th day of following 1st vaccination. Suggesting that a year-long protection could easily be provided with the both vaccines, till to the 1st booster dose administration.
Adult↗
[A new respiratory tract pathogen].
Chlamydia pneumoniae strain TWAR, a newly described Chlamydia organism is a common cause of pneumonia and other acute respiratory tract infections. Most TWAR infections are mild or asymptomatic, but occasionally severe pneumonia in elderly patients or with on going chronic diseases has been observed. Population antibody prevalence has shown that TWAR infection is world-wide infection and an important health problem since under-developing countries where the high rate of child death is predominant, TWAR infections cause acute respiratory tract infection in children who are less than 5 yrs of age. Re-infection during life-time emphasizes the importance of Chlamydia pneumoniae.
Antibodies, Bacterial↗