Complementary medicine must be research led and evidence based.
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Complementary Therapies↗
Biomedical subjects
K Thomas
Publications and source records attributed to K Thomas.
Concordance of the toxicity of pharmaceuticals in humans and in animals.
This report summarizes the results of a multinational pharmaceutical company survey and the outcome of an International Life Sciences Institute (ILSI) Workshop (April 1999), which served to better understand concordance of the toxicity of pharmaceuticals observed in humans with that observed in experimental animals. The Workshop included representatives from academia, the multinational pharmaceutical industry, and international regulatory scientists. The main aim of this project was to examine the strengths and weaknesses of animal studies to predict human toxicity (HT). The database was developed from a survey which covered only those compounds where HTs were identified during clinical development of new pharmaceuticals, determining whether animal toxicity studies identified concordant target organ toxicities in humans. Data collected included codified compounds, therapeutic category, the HT organ system affected, and the species and duration of studies in which the corresponding HT was either first identified or not observed. This survey includes input from 12 pharmaceutical companies with data compiled from 150 compounds with 221 HT events reported. Multiple HTs were reported in 47 cases. The results showed the true positive HT concordance rate of 71% for rodent and nonrodent species, with nonrodents alone being predictive for 63% of HTs and rodents alone for 43%. The highest incidence of overall concordance was seen in hematological, gastrointestinal, and cardiovascular HTs, and the least was seen in cutaneous HT. Where animal models, in one or more species, identified concordant HT, 94% were first observed in studies of 1 month or less in duration. These survey results support the value of in vivo toxicology studies to predict for many significant HTs associated with pharmaceuticals and have helped to identify HT categories that may benefit from improved methods.
Animals↗
Health-care inequalities: an Indian perspective.
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Delivery of Health Care↗
The effects of an alpha-2 adrenergic agonist, guanfacine, on rCBF in human cortex in normal controls and subjects with focal epilepsy.
Alpha-2 noradrenergic agonists may have wide applicability in the treatment of pre-frontal cortex deficits in primates and behavioral dysfunction in man. We have undertaken this study to determine the effect of an alpha-2 agonist, guanfacine, on regional cerebral blood flow (rCBF) in humans. Three subject groups were evaluated: normal controls, subjects with frontal lobe epilepsy (FLE), and subjects with temporal lobe epilepsy (TLE). All underwent a number of PET scans using 15O-water, with half before and half after a single dose of guanfacine. A wide area of increased rCBF was seen in the frontal lobe, maximal at the central region, following guanfacine in controls and subjects with TLE. Smaller areas of decrease in rCBF were seen in the posterior temporal-occipital cortex. In the FLE group a decrease in rCBF was seen in the dorsal prefrontal cortex on the epileptogenic side with only small increases seen in the mid- to anterior temporal perisylvian areas. The ability of alpha-2 agonists to enhance performance of tasks reliant on prefrontal cortex, without improving tasks believed to rely on intact temporal-hippocampal function, may be explained by these results. Epileptogenic zones appear to create both direct and indirect changes in patterns of drug response. Further studies on the cognitive properties of these agents in humans should be encouraged.
Adrenergic alpha-2 Receptor Agonists↗
Medicaid and African American outpatient mental health treatment.
The present study tested the hypothesis that Medicaid-financed African Americans would be more likely to receive outpatient mental health treatment than African Americans whose treatment was financed by private insurance. The hypothesis was confirmed: when compared with privately insured persons eligible for care under either fee-for-service or managed care, the Black-White gap in outpatient service use was significantly smaller under Medicaid. There was no racial difference in outpatient treatment rates among the uninsured. The often-noted difference between Blacks and Whites in the likelihood of receiving outpatient mental health treatment is confined largely to the privately insured.
Black or African American↗
Effect of premedication guidelines and leukoreduction on the rate of febrile nonhaemolytic platelet transfusion reactions.
Platelet transfusion reactions were prospectively studied in haematology/oncology patients at five university teaching hospitals over three consecutive summers. The initial summer study provided baseline information on the use of premedications and the rate of platelet transfusion reactions (fever, chills, rigors and hives). Most (73%) platelet recipients were premedicated and 30% (95% CI 28-33%) of transfusions were complicated by reactions. The second study followed implementation of guidelines for premedicating platelet transfusions. Despite a marked reduction in premedication (50%), there was little change in the platelet transfusion reaction rate, 26% (95% CI 24-29%), or the type of reactions. The third study followed implementation of prestorage platelet leukoreduction while maintaining the premedication guidelines. The reaction rate decreased to 19% (95% CI 17-22%). For nonleukoreduced platelets, there was a statistically significant association between the platelet age and reaction rate (P = 0.04). For leukoreduced platelets, there was no statistically significant association between platelet age and reaction rate (P = 0.5). Plasma reduction of nonleukoreduced platelet products also reduced the reaction rate. These prospective studies document a high rate of platelet transfusion reactions in haematology/oncology patients and indicate premedication use can be reduced without increasing the reaction rate. Prestorage leukoreduction and/or plasma reduction of platelet products reduces but does not eliminate febrile nonhemolytic platelet transfusion reactions.
Blood Preservation↗
Medicolegal aspects of vesicovaginal fistulae.
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Female↗
Towards a minimum dataset in urology.
OBJECTIVE: To establish and prospectively collect data for a minimum dataset in urology by agreeing a dataset amongst a group of urologists, designing structured forms around the data items and implementing them in clinical practice. METHODS: Consultant urologists decided the initial dataset. Structured forms, which incorporated the dataset items, were designed. These forms were piloted before implementation in two urology departments. They were used to document clinical information instead of writing this in the traditional medical record. After use forms were 'scanned' before being filed in the medical record, thus storing the data in an electronic format. RESULTS: Nine forms were designed; inpatient and outpatient activity was captured separately. There were six outpatient forms; a generic new patient form and five specific follow-up forms (lower urinary tract symptoms, oncology, erectile dysfunction, female urology and stones). Three generic inpatient forms were designed. The forms were used by nine registrars, five senior house officers and six clinical nurse practitioners, who required minimal training. CONCLUSION: It is possible to agree a minimum dataset amongst a relatively small group of urologists. The information can be acquired prospectively using structured forms instead of the traditional medical record. This locally agreed dataset could form the basis for a national consensus on a minimum dataset in urology.
Data Collection↗
Fatigue of abdominal and paraspinal muscles during sustained loading of the trunk in the coronal plane.
OBJECTIVE: To measure fatigue-related changes in the electromyographic signals of trunk muscles during lateral bend loading, and to determine the effects of load magnitude, gender, and contraction time on these changes. DESIGN: A factorial experimental design. SETTING: A research laboratory. PARTICIPANTS: Twenty-four healthy volunteers (12 men, 12 women; mean age +/- SD, 22.9 +/- 3.1 yrs). INTERVENTION: Subjects sustained lateral bend loads at 20%, 40%, and 60% of their maximal exertion. OUTCOME MEASURES: Median frequency and total power of the power spectrum of the electromyographic signals. RESULTS: Trunk muscles' median frequency signals decreased and their total power increased as contraction time increased. These changes became more pronounced as the magnitude of loading increased. Men and women showed a similar rate of median frequency decline, but the total power of signals in men was larger than that in women. All muscles showed signs of fatigue, except that at 20% of maximal exertion only thoracic erector spinae fatigued significantly. CONCLUSIONS: Endurance training of paraspinal and abdominal muscles may be useful in preventing low back pain associated with lateral bend loading. The risk of back pain is similar in both genders and is higher with larger load magnitude and longer contraction time.
Adult↗
Inhibition of ovulation by a novel progestogen (drospirenone) alone or in combination with ethinylestradiol.
OBJECTIVE: To investigate ovulation inhibition with drospirenone, a novel progestogen that has a profile similar to natural progesterone, when given alone or in combination with ethinylestradiol. METHOD: Hormonal parameters (LH, FSH, 17beta-estradiol and progesterone) and peripheral parameters (cervical score, spinnbarkeit and crystallization), as well as follicle size assessed by ultrasonography, were measured in two groups of healthy women. Forty-eight women aged 19-35 years were randomly assigned to receive 0.5 mg, 1.0 mg, 2.0 mg or 3.0 mg of drospirenone over a single treatment cycle, and 52 women aged 20-35 years were randomized to receive either 2 mg drospirenone/30 microg ethinylestradiol or 3 mg drospirenone/30 microg ethinylestradiol over three treatment cycles. Baseline measurements were taken during a control pretreatment cycle. RESULTS: Adequate ovarian suppression with drospirenone alone was evident at dose levels of 2 and 3 mg, and at 3 mg all subjects had anovulatory cycles. Although both combined preparations (2 mg and 3 mg drospirenone/30 microg ethinylestradiol) inhibited the hypothalamic-pituitary-ovarian axis, follicular maturation leading to escape ovulation was observed in three subjects in the 2 mg drospirenone/30 microg ethinylestradiol group. Only one of these ovulations was considered to be definitely the result of treatment failure. All cycles in the 3 mg drospirenone/30 microg ethinylestradiol group were anovulatory. No statistically significant difference was found between treatment groups. CONCLUSION: The combination of 3 mg drospirenone/30 microg ethinylestradiol (Yasmin, Schering AG) reliably inhibits ovulation, with a low frequency of follicular maturation, and provides a reasonable safety margin.
Adult↗
The value of Chlamydia trachomatis antibody testing as part of routine infertility investigations.
Laparoscopy is considered the gold standard for the evaluation of tubal disease but it is an invasive and costly procedure. Chlamydia trachomatis antibody testing is simple and inexpensive and causes minimal inconvenience to the patient. Using the micro-immunofluorescence technique we assessed the significance of positive serology. There was a marked association between the titre and the likelihood of tubal damage. In the group with low titres (1 in 32) there was only a 5% incidence of tubal damage; however, there was a progressive increase in the incidence of tubal damage in those with higher titres. Twenty out of 57 patients with titres higher than 1 in 32 had tubal damage (35%). The difference between the two groups was statistically significant (P < 0.0001, chi(2) test). By using C. trachomatis antibody testing more widely it may be possible to reduce the number of laparoscopies performed. It should therefore become an integral part of the fertility work-up.
Anti-Bacterial Agents↗
Inhibin and activin production and subunit expression in human placental cells cultured in vitro.
Inhibins and activins are dimeric proteins, with each subunit being one of three related protein subunits (alpha, betaA or betaB). The mRNA levels of these subunits were studied quantitatively during in-vitro differentiation of human cytotrophoblast cells into syncytium, using Northern blot analysis and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. The corresponding protein concentrations were determined by specific enzyme-linked immunosorbent assays for inhibin A, B, pro alphaC and activin A in cellular protein extracts and culture medium (n = 5). Immunofluorescence studies showed syncytium formation after 48 h. The alpha subunit was present before plating and increased at 48 h (P<0.001) while the betaA subunit was weak before plating and increased at 24 h. The betaB subunit was not detected. With respect to corresponding protein synthesis, inhibin A (alpha + betaA) had risen after 48 h in cellular protein extract and after 72 h in culture medium, while activin A (betaA + betaB) was detected after 24 h, with no significant variations in culture medium. There was a good correlation between inhibin A and alpha subunit expression (r = 0.736, P<0.001), as well as between activin A and betaA subunit expression (r = 0.755, P<0.001). This study showed that mRNA expression parallels protein synthesis of inhibin and activin in trophoblast cells. Inhibin A synthesis appears to be dependent on alpha subunit mRNA expression, rather than on the betaA subunit which controls activin A synthesis. This study has also shown that isolated cytotrophoblast cells do not produce dimeric inhibin. However, during the transformation of cytotrophoblast cells into syncytium, betaA subunit mRNA expression may be an indicator of cell aggregation, while alpha subunit mRNA expression may be an indicator of cell fusion.
Activins↗
Factious desaturation due to isosulfan dye injection.
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Biopsy↗
Development of a serological test for Haemophilus ducreyi for seroprevalence studies.
We developed a new enzyme immunoassay (rpEIA) for use in determining the seroprevalence of chancroid. Three highly conserved outer membrane proteins from Haemophilus ducreyi strain 35000 were cloned, overexpressed, and purified from Escherichia coli for use as antigens in the rpEIA. Serum specimens from patients with and without chancroid were assayed to determine optimum sensitivity and specificity and to establish cutoff values. On the basis of these data, rpEIA was found to be both sensitive and specific when used to test a variety of serum specimens from patients with genital ulcers and urethritis and from healthy blood donors.
Antibodies, Bacterial↗
Multiple screening for fetal Down's syndrome with the classic triple test, dimeric inhibin A and ultrasound.
The aim of the study was to determine whether inhibin combined with ultrasound improves the classic second trimester triple test. Eighteen Down's syndrome and 200 euploid pregnancies were included. Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and estriol (E3), measured between 15 and 20 weeks' gestation by radioimmunoassay, were retrieved. Inhibin A was tested with a specific two-monoclonal-antibody ELISA. Ultrasound was performed between 15 and 25 weeks' gestation: femur length, nuchal thickness and morphological abnormalities were assessed. Statistical analysis used a multivariate discriminant analysis. Except for the classic triple test parameters, only inhibin and the standard deviation score (SDS) for femur length allowed us to make a statistically significant distinction between euploid and Down's syndrome pregnancies. For a 5% false-positive rate, the classic triple test sensitivity was 61%. When E3 was replaced with inhibin A, the sensitivity increased to 77.8% and to 66.7% with SDS femur length. Combining hCG, AFP, SDS femur length and inhibin A gave a sensitivity of 66.7% for a false-positive rate of 2.5%. In conclusion, the classic triple test can be more significantly improved by replacing E3 with inhibin than by including ultrasound. However, a combination of ultrasound and inhibin enhances both the sensitivity and specificity of the test. In Down's syndrome screening, the biological parameters improve sensitivity while ultrasound is a better indication of specificity.
Amniocentesis↗
Gonadotropins, prolactin, inhibin A, inhibin B, and activin A in human fetal serum from midpregnancy and term pregnancy.
Using specific enzyme-linked immunosorbent assays we measured inhibin A, inhibin B, and activin A in relation to LH, FSH, and PRL in normal human fetal midpregnancy serum obtained by in utero cord venipuncture (n = 25) and compared these results to those in fetal serum from term pregnancies (n = 23). We also tested serum from fetuses with intrauterine growth retardation (n = 6) or trisomy 21 (n = 6). We found no measurable inhibin A, except in three midpregnancy males (3 of 14). Inhibin B, however, was detected in midpregnancy male fetuses (167+/-67 pg/mL) and was higher than that in females (16+/-12 pg/mL). It was present in male term fetuses (125+/-32 pg/mL), but not in females. The activin A levels did not significantly differ between term and midpregnancy males and females. LH and FSH were detected in midpregnancy male fetuses (4.4+/-3.3 and 0.77+/-0.49 mIU/mL, respectively), with higher levels in females (33.0+/-23.2 and 54.4+/-27.7 mIU/mL, respectively), and were suppressed at term. PRL did not exhibit sexual difference, but showed a higher level at term (322.4+/-113.8 ng/mL) than at midpregnancy (33.0+/-26.1 ng/mL). Comparison of inhibin B with FSH levels showed correlation coefficients of -0.565 at midpregnancy vs. +0.445 at term. Serum from fetuses with intrauterine growth retardation or trisomy 21 did not show any different hormonal profiles. These data suggest that inhibin B is probably an additional factor in FSH inhibition at midpregnancy, whereas activin A is not associated with any change in the different studied populations. We speculate that inhibin A could be a method to detect maternal blood contamination in cord venipuncture.
Activins↗
The incidence and significance of testicular microlithiasis in a subfertile population.
The objective of this study was to assess the frequency of testicular microlithiasis (TM) in infertile men who underwent testicular ultrasound and to determine any causative or associated factors. The case notes of 159 consecutive patients who were referred for testicular ultrasound in the investigation of male factor infertility were reviewed. Microcalcification was found in 10 cases (6.2%). This was unilateral in all cases and six patients had clinical evidence of a varicocele. Five cases had minimal calcification and five had marked TM. On patient had a past history of testicular maldescent and another of testicular torsion. Sperm function (as assessed by sperm count, motility and the sperm migration test) was variable within the 10 patients and there was no correlation with hormone profiles or testicular size. There was a statistical difference between a number of investigations in those patients with minimal degrees of calcification and those with TM (sperm migration test (SMT), namely sperm migration and sperm motility (p < 0.05, Mann-Whitney U test)). The results showed a higher than expected incidence of TM. Patients with marked TM seemed to have poorer sperm function than those with minimal calcification. There was a high incidence of co-existing pathology, for instance scrotal varicocele and cryptorchidism, although the numbers in this study were small and further studies need to be carried out to determine the exact nature and significance of this condition.
Gonadal Steroid Hormones↗
Conservative management of triplet pregnancy after delivery of one foetus.
This paper intends to demonstrate that the conservative management of triplet pregnancy after delivery of one foetus is a feasible and reasonable approach. Three cases of triplet pregnancy with successful conservative management after miscarriage of one foetus, are presented and compared with cases in the literature. The route of delivery, as well as the role of tocolysis, cerclage, prophylactic antibiotic therapy and corticosteroids are discussed. Guidelines for conservative treatment are proposed. The deliveries of our three pregnancies were delayed by 63, 44 and 22 days respectively. Foetal and neonatal evolution are normal in five of the remaining foetuses. Only one intrauterine death is observed. No maternal complications with sequelae are reported. After abortion of the first triplet, contractions often persist and the birth of the two remaining foetuses may be unavoidable. Nevertheless, in our experience, confirmed by some reports in the literature, prolongation of the pregnancy after expulsion of the first foetus is possible. It can be achieved by cervical cerclage associated with tocolytic and antibiotic therapy. This management is not associated with significantly increased foetal-maternal morbidity.
Abortion, Spontaneous↗