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Biomedical subjects

A Rane

Publications and source records attributed to A Rane.

At least 55 records · Page 3Linked to original sources
PubMed2000

Survey of unlicensed and off label drug use in paediatric wards in European countries. European Network for Drug Investigation in Children.

OBJECTIVE: To determine the extent of use of unlicensed and off label drugs in children in hospital in five European countries. DESIGN: Prospective study of drugs administered to children in general paediatric medical wards over four weeks. SETTING: Children's wards in five hospitals (one each in the United Kingdom, Sweden, Germany, Italy, and the Netherlands). SUBJECTS: Children aged 4 days to 16 years admitted to general paediatric medical wards. MAIN OUTCOME MEASURE: Proportion of drugs that were used in an unlicensed or off label manner. RESULTS: 2262 drug prescriptions were administered to 624 children in the five hospitals. Almost half of all drug prescriptions (1036; 46%) were either unlicensed or off label. Of these 1036, 872 were off label and 164 were unlicensed. Over half of the patients (421; 67%) received an unlicensed or off label drug prescription. CONCLUSIONS: Use of off label or unlicensed drugs to treat children is widespread. This problem is likely to affect children throughout Europe and requires European action.

Adolescent↗
PubMed2000

Cytochrome P450 2D6 and glutathione S-transferase M1 genotypes and migraine.

BACKGROUND: Migraine is thought to be a disease of the brain and trigeminovascular system. Migraine patients often claim that stress, food, and beverages trigger their attacks. Chemical substances in these foodstuffs with the property of triggering migraine attacks have not yet been characterised. Cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase M1 (GSTM1) are thought to be present in the brain. They metabolise numerous environmental compounds. The genes exhibit genetic polymorphism that is associated with altered enzyme activity. The aim of this study was to determine if the genotypes of these two enzymes are associated with migraine. MATERIALS AND METHODS: The study included 100 female patients and 245 female controls from the general population. Genomic DNA was isolated from whole blood. Allele specific PCR methods were used to identify the normal CYP2D6*1 allele and the mutated CYP2D6*3 and CYP2D6*4 alleles. Initially all samples were genotyped only for GSTM1 plus (+) and GSTM1 null (-) variants. All samples positive for GSTM1 were further analysed for the presence of allelic variants GSTM1*A and GSTM1*B. RESULTS: None of the CYP2D6 and GSTM1 genotypes was associated with migraine. We observed an odds ratio (OR) for the poor metaboliser genotype of CYP2D6 of 1.4 (95% CI = 0.5-3.6) and for the GSTM1 null genotype of 1.0 (95% CI = 0.6-1.5). CONCLUSION: The results of this study indicate that deficient metabolism because of mutated CYP2D6 alleles or GSTM1 allele variants is not important in the aetiology of migraine.

Adolescent↗
PubMed2000

Does conventional HRT protect from urogenital atrophy? A prospective study.

Urogenital atrophy is a poorly defined entity. This prospective study looked at the effect of conventional HRT on urogenital atrophy. One hundred and sixty-three women were studied in a 12-month period. The incidence of urinary symptoms and clinical evidence of urogenital atrophy was found to be similar in both the 'HRT group' and the 'no HRT group'. This can be explained by the new oestrogen receptor theory. Conventional HRT does not seem to protect women from urogenital atrophy and receptor specific oestrogen therapy may be required to address the problem of urogenital atrophy and postmenopausal urinary symptoms.

Journal Article↗
PubMed2000

To stent or not to stent? That is still the question.

BACKGROUND AND PURPOSE: Most patients are stented after ureteroscopy for stone extraction. This practice necessitates a second procedure to remove the stent, with its inherent morbidity. The aim of our study was to determine whether routine stenting of the ureter is really necessary after ureteroscopy. PATIENTS AND METHODS: This prospective study evaluated 26 men and 18 women admitted for elective distal ureteral stone fragmentation. The stones ranged in size from 6 mm to 1 cm. Of the series, 16 patients (10 men) had been stented prior to ureteroscopy. A 9F semirigid ureteroscope was used in 31 cases, and a 7.5F semirigid ureteroscope was used in the other 11 cases; there was no need for ureteral orifice dilatation with either ureteroscope. Ballistic intracorporeal lithotripsy was performed in all cases with the Swiss Lithoclast; all stone fragments were retrieved with a 3F helical basket. The patients were followed up as inpatients for 24 hours and reviewed in the clinic 1 week later with a request to report if they felt significant discomfort or loin pain or became feverish. RESULTS: Only one patient (male) had to be readmitted with loin pain. Two others (both women) complained when they attended for follow-up of having had dull lower abdominal pain and some frequency. CONCLUSIONS: The low incidence of complications in this preliminary study suggests that routine stenting is not necessary after ureteroscopy. The chief exception to this statement is patients who had a difficult and prolonged stone fragmentation.

Abdominal Pain↗
PubMed2000

Polymorphisms of NAT2 in relation to sulphasalazine-induced agranulocytosis.

Agranulocytosis is a rare, but serious adverse reaction to sulphasalazine. The polymorphic enzyme N-acetyltransferase 2 (NAT2) plays an important role in the metabolism of sulphasalazine. This study was conducted to analyse whether the risk of sulphasalazine-induced agranulocytosis is increased in slow acetylators. Patients were treated for inflammatory disease, mostly joint disease, with a mean dose of 2 g sulphasalazine daily. Thirty-nine patients reacted with agranulocytosis, while 75 patients had been treated for a minimum of 3 months without haematological side-effects. A population-based control panel of 448 individuals was used for comparison. All subjects were genotyped for NAT2 by polymerase chain reaction followed by restriction enzyme digestion. The six most common allelic variants were analysed: NAT2*4, NAT2*5A, NAT2*5B, NAT2*5C, NAT2*6 and NAT2*7. The proportion of slow acetylators was significantly higher in patients with sulphasalazine-induced agranulocytosis (69%) and population-based controls (64%) compared to patients who tolerated sulphasalazine (45%); odds ratio 2.71 [95% confidence interval (CI) 1.20; 6.15], P = 0.015, and odds ratio 2.17 (95% CI 1.32; 3.56), P = 0.002, respectively. Patients who developed agranulocytosis did not differ from population-based control subjects in the frequency of slow acetylators; odds ratio 1.25 (95% CI 0.62; 2.53), P = 0.535. The risk of agranulocytosis did not appear to be increased in slow acetylators, provided that the difference compared with sulphasalazine-treated control subjects was not due to a predominance of fast acetylators among patients with inflammatory joint disease. Instead, selection bias was suspected since more slow acetylators may have discontinued sulphasalazine therapy because of drug-intolerance.

Acetylation↗
PubMed2000

Comparative assessment of pelvic floor strength using a perineometer and digital examination.

OBJECTIVE: To determine whether digital assessment of pelvic floor contraction strength is as reliable as vaginal perineometry and to assess the practice of pelvic floor exercises by women. DESIGN: A blinded, two-assessor protocol, prospectively testing a volunteer sample of women. POPULATION: Two hundred and sixty-three women (from a total of 278), aged 16-75 years, attending a general gynaecological clinic with nonurinary symptoms. METHODS: Participants answered a questionnaire regarding urinary symptoms and practice of pelvic floor exercises. History and examination was carried out by the clinician, and pelvic floor strength scored digitally using the Oxford Scale. Pelvic floor strength was then assessed by the physiotherapist, using a PFX perineometer. The physiotherapist was blinded to the woman's history, examination findings and digital assessment score. Both the clinician and physiotherapist were blinded to the questionnaire responses. MAIN OUTCOME MEASURES: Digital pelvic floor contraction assessment, according to the Oxford Scale, was compared with perineometric assessment as the gold standard - examined against the background of the questionnaire findings. RESULTS: Of 263 patients, 53 were nulliparous (20%), and 210 parous (80%). Only 49 women carried out regular pelvic floor exercises (19%), and all were parous and admitted to troublesome urinary symptoms. Stress urinary incontinence was reported by 28% of all women (38.1% of parous women and 10.5% of nulliparous women). For both methods, there was no difference in the range of results when parity was taken into account. Concordance studies showed good agreement between digital and perineometric assessment of pelvic floor strength. The kappa value of 0.73 (95% confidence interval 0.67-0.79) indicated substantial agreement between the two methods. CONCLUSION: There is good agreement between digital assessment of pelvic floor contraction strength and vaginal perineometry. Assessment during gynaecological examination may help to identify women with fascial defects of the pelvic floor, as well as those at risk of genital prolapse or urinary symptoms.

Adolescent↗
PubMed1999

Quantitation of cytochrome P450 mRNAs in patients with suspected liver diseases as assessed by reverse transcriptase-polymerase chain reaction.

The cytochrome P450 system (CYP) is vital for the oxidation and detoxification of numerous drugs and other xenobiotics in the liver. Many of the CYP enzymes are polymorphically expressed and may be induced or inhibited by xenobiotics including drugs and alcohol. The measurement of gene expression is thus important in studies of the mechanisms of interaction with and function of the CYP system. We have developed a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method for the study of the mRNA expression of three CYP enzymes--2E1, 1A2, and 3A4--in snap-frozen percutaneous liver biopsy samples. The method was made quantitative by the introduction of a recombinant RNA internal standard that contains a transcript of the beta-globin gene and sequences specific for the studied CYP enzymes. The method allows the analysis of mRNA expression of several enzymes in as little as 5 mg of liver tissue. Liver tissue specimens from 19 patients with suspected liver disease were analyzed for CYP-specific mRNA expression. The mean mRNA concentrations for CYP1A2, 2E1, and 3A4 were 0.16, 0.74, and 0.32 amol of specific mRNA per nanogram of poly (A+) mRNA, respectively, but a large interindividual variation was observed. CYP3A7 primers were included in the internal standard. However, because of low expression it was not possible to quantitate the enzyme. This quantitative RT-PCR method is of value for studies of the mechanisms of variation and interactions with the members of the CYP enzyme family in healthy and diseased liver and other organs.

Cytochrome P-450 Enzyme System↗
PubMed1999

Dietary caffeine as a probe agent for assessment of cytochrome P4501A2 activity in random urine samples.

AIMS: To validate the use of randomly collected urine samples for assessment of cytochrome P4501A2 (CYP1A2) activity based on dietary caffeine (caffeine metabolic ratio, MRcaff ), and to relate the MRcaff to caffeine intake and smoking habits in a larger group of individuals. METHODS: Nineteen healthy volunteers were included in the validation study. Caffeine (100 mg) was ingested and a urine sample was collected after 6 h. Within the following week a random urine sample was collected in the individuals without a preceding test dose of caffeine. Urine samples were analysed for caffeine and its metabolites by h.p.l.c. and the (AFMU+1U+1X)/1,7U metabolic ratio was used to reflect CYP1A2 activity. In an extended investigation of 522 healthy pregnant women the MRcaff was related to intake of caffeine from various sources, and to smoking. RESULTS: The results from the random and standardised sampling methods correlate with each other (correlation coefficient of MRcaff was 0. 91). The MRcaff as assessed by the random sampling method in a larger population was not affected by source or amount of caffeine ingested. Significantly higher MRcaff was found in smokers compared to non-smokers. In the large group of individuals the random sampling method was possible to use in 80% of the cases. In the residual 20% one or several of the metabolite concentrations were too low or unmeasurable. CONCLUSIONS: Our study demonstrates that the random urine caffeine phenotyping method is possible to use in as many as 80% of the individuals when based on dietary caffeine. Our approach should prove applicable in most countries with widely spread caffeine consumption. The method is useful in larger studies of drug metabolising enzyme activities and minimises the time consumption and costs.

Caffeine↗
PubMed1999

Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer.

The development of prostate cancer is dependent on heredity, androgenic influences, and exposure to environmental agents. A high intake of dietary fat is associated with an increased risk of prostate cancer, either through influence on steroid hormone profiles or through production of carcinogenic compounds that require biotransformation by enzymes. The polymorphic glutathione S-transferase (GST), N-acetyltransferase (NAT), and cytochrome P450 (CYP) enzymes are of particular interest in prostate cancer susceptibility because of their ability to metabolize both endogenous and exogenous compounds, including dietary constituents. Association between different NAT2, CYP2D6, CYP2C19 and GSTP1 genotypes and prostate cancer was studied in a Swedish and Danish case-control study comprising 850 individuals. The combined Swedish and Danish study population was analysed by polymerase chain reaction for the NAT2 alleles *4, *5A, *5B, *5C, *6 and *7, and for the CYP2D6 alleles *l, *3 and *4. The Swedish subjects were also analysed for the CYP2C19 alleles *1 and *2, and the GSTP1 alleles *A, *B and *C. No association was found between prostate cancer and polymorphisms in NAT2, CYP2D6, CYP2C19 or GSTP1. An association between CYP2D6 poor metabolism and prostate cancer was seen among smoking Danes; odds ratio 3.10 (95% confidence interval 1.07; 8.93), P = 0.03, but not among smoking Swedes; odds ratio 1.19 (95% confidence interval 0.41; 3.42), P = 0.75. Smoking is not a known risk factor for prostate cancer, and the association between CYP2D6 poor metabolism and prostate cancer in Danish smokers may have arisen by chance.

Acetylation↗
PubMed1999

Incontinence in women. Don't suffer it.

BACKGROUND: Urinary incontinence is a distressing and embarrassing condition suffered by at least 1 in 10 women. Incontinence is not just a disease of the elderly: 40% of women aged 30 to 50 suffer from incontinence and a surprising 11% of young women who have never borne children may also experience it. OBJECTIVE: Incontinence unlike other chronic diseases can be cured in up to 70% of patients. DISCUSSION: The cost of incontinence is immense. Studies based on health care costs of urine incontinence in the USA indicate expenses as high as 2% of the national health care budget. Australia spends nearly 1 billion dollars per year on incontinence aids and this represents only a fraction of the total cost of incontinence.

Australia↗