PubMed Health⌕ Search

Biomedical subjects

Julian H Barth

Publications and source records attributed to Julian H Barth.

15 recordsLinked to original sources

The use of metformin for women with PCOS undergoing IVF treatment.

BACKGROUND: Metformin appears to improve reproductive function in some women with polycystic ovary syndrome (PCOS). We wished to explore the effect of metformin in women with PCOS undergoing IVF. METHODS: A randomized, placebo-controlled, double-blind study was carried out between 2001 and 2004. Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were randomized to receive metformin (MET), 850 mg, or placebo (PLA) tablets twice daily from the start of the down-regulation process until the day of oocyte collection. The primary outcome was to be an improvement in the overall fertilization rate. RESULTS: One-hundred and one IVF/ICSI cycles were randomized to receive metformin (52) or to receive placebo (49). There was no difference in the total dose of rFSH required per cycle (median dose: MET = 1200 U, PLA = 1300 U; P = 0.937). The median number of oocytes retrieved per cycle (MET = 17.2, PLA = 16.2; P = 0.459) and the overall fertilization rates (MET = 52.9%, PLA = 54.9%; P = 0.641) did not differ. However, both the clinical pregnancy rates beyond 12 weeks gestation per cycle (MET = 38.5%, PLA = 16.3%; P = 0.023) and per embryo transfer (MET = 44.4%, PLA = 19.1%; P = 0.022) were significantly higher in those treated with metformin. Furthermore, a significant decrease in the incidence of severe ovarian hyperstimulation syndrome (OHSS) was observed (MET = 3.8%, PLA = 20.4%; P = 0.023), and this was still significant after adjustment for BMI, total rFSH dose and age (OR = 0.15; 95% CI: 0.03, 0.76; P = 0.022). CONCLUSION: Short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS.

Adult↗

Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study.

BACKGROUND: It has been reported that women with polycystic ovary syndrome (PCOS) benefit from metformin therapy. METHODS: A randomized, placebo-controlled, double-blind study of obese (body mass index >30 kg/m2), oligo-/amenorrhoeic women with PCOS. Metformin (850 mg) twice daily was compared with placebo over 6 months. All received the same advice from a dietitian. The primary outcome measures were: (i) change in menstrual cycle; (ii) change in arthropometric measurements; and (iii) changes in the endocrine parameters, insulin sensitivity and lipid profile. RESULTS: A total of 143 subjects was randomized [metformin (MET) = 69; placebo (PL) = 74]. Both groups showed significant improvements in menstrual frequency [median increase (MET = 1, P < 0.001; PL = 1, P < 0.001)] and weight loss [mean (kg) (MET = 2.84; P < 0.001 and PL = 1.46; P = 0.011)]. However, there were no significant differences between the groups. Logistic regression analysis was used to analyse the independent variables (metformin, percentage of weight loss, initial BMI and age) in order to predict the improvement of menses. Only the percentage weight loss correlated with an improvement in menses (regression coefficient = 0.199, P = 0.047, odds ratio = 1.126, 95% CI 1.001, 1.266). There were no significant changes in insulin sensitivity or lipid profiles in either of the groups. Those who received metformin achieved a significant reduction in waist circumference and free androgen index. CONCLUSIONS: Metformin does not improve weight loss or menstrual frequency in obese patients with PCOS. Weight loss alone through lifestyle changes improves menstrual frequency.

Adult↗

Testosterone measurement by isotope-dilution liquid chromatography-tandem mass spectrometry: validation of a method for routine clinical practice.

BACKGROUND: Immunoassay is unsatisfactory for measuring the testosterone concentrations typically found in women. Bench-top tandem mass spectrometers are a viable alternative technology for measurements in the clinical laboratory. METHODS: We used stable-isotope dilution liquid chromatography-tandem mass spectrometry (ID/LC-MS/MS) to measure testosterone in plasma and serum. The sample volume was 50 muL in duplicate; preparation and analysis were carried out in a single tube, and a batch of 192 tubes was analyzed in 17.5 h. RESULTS: Intra- and interassay imprecision was <15% in the range 0.3-49 nmol/L. Recovery of testosterone added to samples at concentrations of 0.625-20 nmol/L was 96% (CV = 12%; n = 26). Six samples were serially diluted with double charcoal-stripped serum to demonstrate linearity. Correlation (r(2)) with isotope-dilution gas chromatography-mass spectrometry for 20 pools of clinical samples (range, 0.5-38.5 nmol/L) was 0.99. Correlations with our extraction RIA were 0.97 for clinical samples from men (range, 8-46.3 nmol/L) and 0.66 for samples from women (range, 0.7-3.0 nmol/L), but were 0.35 for male samples containing <3 nmol/L testosterone and 0.77 for female samples containing >8 nmol/L. Various steroids added to double charcoal-stripped serum showed no interference at the retention time of the testosterone peak. CONCLUSIONS: The ID/LC-MS/MS method has improved accuracy compared with immunoassay. The low sample volume and simplicity, rapidity, and robustness of the method make it suitable for use as a high-throughput assay in routine clinical biochemistry laboratories.

Chromatography, High Pressure Liquid↗

Children's residential weight-loss programs can work: a prospective cohort study of short-term outcomes for overweight and obese children.

OBJECTIVE: The evidence base for child obesity treatment is weak. Children's weight-loss camps, despite their popularity, have not been properly evaluated. This study evaluated the effectiveness of a residential weight-loss camp program for overweight and obese children. METHODS: A total of 185 overweight children (mean age: 13.9 years) enrolled in 1 of 4 consecutive programs between 1999 and 2002 (intervention group) were compared with 94 children of similar ages who were not camp attendees, ie, 38 overweight children and 56 normal-weight children. The intervention group attended a 6-week (maximum) summer residential weight-loss camp. The program included a daily schedule of six 1-hour, skill-based, fun, physical activity sessions, moderate dietary restriction, and group-based educational sessions. All children were assessed for body weight, height, and other anthropometric measures, blood pressure, aerobic fitness, self-esteem, and selected sports skills. RESULTS: Campers, who stayed for a mean of 29 days, lost 6.0 kg, reduced their BMI by 2.4 units, and reduced their BMI SD scores by 0.28. Fat mass decreased significantly (from 42.7 to 37.1 kg), whereas fat-free mass did not change. In contrast, both comparison groups gained weight during this period. Camp attendees also showed significant improvements in blood pressure, aerobic fitness, and self-esteem. Longer durations of stay were associated with greater improvements in outcomes. CONCLUSIONS: In the short term at least, this weight-loss program was effective across a range of health outcomes. Ongoing research is examining the maintenance of these improvements. Future research should investigate whether benefits can be generalized across weight-loss camps and how the intervention can be adapted to nonresidential, term-time settings.

Adolescent↗

Plasma homocysteine in polycystic ovary syndrome: does it correlate with insulin resistance and ethnicity?

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and premature coronary artery disease (CAD). Hyperhomocysteinaemia is a recognized risk factor for atherosclerosis, particularly among migrant South Asians, and has recently been shown to be correlated positively with the degree of insulin resistance/hyperinsulinaemia. OBJECTIVES: To compare total plasma homocysteine (Hcy) in PCOS with controls from ethnic groups at high and low risk of insulin resistance. METHODS: Case control study of three ethnic groups, Sri Lankans (SL), British Asians (BA) and white Europeans (C), with and without PCOS at specialist centres in Sri Lanka and Yorkshire, UK. Fasting total plasma Hcy concentration was analysed by fluorescence polarization immunoassay and examined for any correlation with age, body mass index (BMI), central obesity, fasting insulin and insulin sensitivity [calculated by the Quantitative Insulin Sensitivity Check Index (QUICKI) method], lipids and testosterone in each ethnic group. RESULTS: Eighty SL with PCOS and 45 controls, 47 BA with PCOS and 11 controls, and 40 C with PCOS and 22 controls were studied. Both Asian groups with PCOS were younger than affected Europeans (P = 0.008). Sri Lankans with PCOS had significantly lower BMI values than other affected groups: mean +/- SEM (SL) 26.3 +/- 0.95; (BA) 30.59 +/- 7.54; (C) 32.1 +/- 5.95 kg/m2 (P = 0.006). However, waist : hip ratios (WHR) of Sri Lankans with PCOS were similar to others: mean +/- SEM (SL) 0.97 +/- 0.01 (BA) 1.04 +/- 0.02 (C) 0.92 +/- 0.01, P = 0.33. Mean plasma Hcy was significantly higher in all PCOS groups than in their ethnically matched controls (Student's t-test): (SL) 10.2 +/- 1.9 vs 9.0 +/- 3.8, P = 0.01; (BA) 7.9 +/- 1.9 vs 6.8 +/- 2.5, P < 0.0001; (C) 8.3 +/- 2.3 vs 6.8 +/- 1.5, P = 0.0007 micromol/l. Sri Lankans with PCOS had significantly greater Hcy concentrations than British Asians and Europeans with PCOS [P = 0.001; single-factor analysis of variance (anova)] and also significantly greater fasting insulin concentrations [(SL) 242.9 +/- 38.9; (BA) 89.4 +/- 8.9; (C) 48.6 +/- 4.8 pmol/l (P = 0.0003)] and significantly lower QUICKI [(SL) 0.308 +/- 0.004; (BA) 0.335 +/- 0.005; (C) 0.375 +/- 0.002 (P = 0.0007)]. Fasting plasma Hcy correlated best with fasting insulin (r = 0.56, P = 0.0001) and QUICKI (r =-0.53, P < 0.0001) in Sri Lankans with PCOS. Hcy in PCOS subjects from all three ethnic groups correlated significantly with fasting insulin following adjustment for age, BMI and WHR (r = 0.45, P = 0.0001), but this was not evident in the controls (r =-0.32, P = 0.1). CONCLUSIONS: Elevation of fasting plasma homocysteine in PCOS varies with ethnicity and correlates significantly with fasting insulin. High homocysteine in young Sri Lankans with PCOS has major implications for their long-term risk for atherosclerosis.

Adult↗

Acne and hirsuties in teenagers.

Acne and body hair are both cutaneous responses to androgenic stimulation. They are normal events in adolescent girls. There is considerable variation in the evolution of the two conditions. The sebaceous gland is exquisitely sensitive to androgens, and acne appears with the onset of puberty, peaks in prevalence in the teenage years and gradually improves thereafter. Hair growth on the face, trunk and limbs develops more slowly and generally peaks in the 20s. Indications for endocrine investigation include very severe acne, onset of acne and hirsuties in the very early stage of puberty (Tanner stage 3) and systemic virilism. Treatment for acne and hirsuties can be either topical or systemic. The choice of therapy is based on the severity of the disease rather than the results of endocrine investigation. Further, since PCO is related to impaired glucose tolerance, advice relating to lifestyle changes should be offered to prevent the development of diabetes.

Acne Vulgaris↗

An audit of the laboratory interpretation of growth hormone response to insulin-induced hypoglycaemia in the assessment of short stature in children.

INTRODUCTION: Measurement of serum growth hormone (GH) concentration in response to insulin-induced hypoglycaemia remains an important investigation in the assessment of pituitary disease. METHODS: In this audit, laboratories were presented with aliquots of sera with GH concentrations likely to be found in an insulin stress test (IST). They were invited to analyse the specimens for GH and comment on their results. RESULTS AND DISCUSSION: A number of laboratories appeared to be using out-of-consensus cut-off concentrations that sometimes were unrelated to the bias of their GH assay. The specimens were chosen to mimic those seen in an IST that was clearly not indicative of GH deficiency, so there was reasonable consensus in the interpretation of results. However, five laboratories (9.6%) did indicate that their results were equivocal.

Acromegaly↗

Surveys on the use of cardiac markers in the UK.

BACKGROUND: Troponin measurements are now central to the diagnosis of acute coronary syndromes and for the stratification of the severity of cardiac disease. Some laboratories have quickly adopted the new testing strategies, which include troponin measurement for the diagnosis of acute myocardial infarction, while others are still developing appropriate protocols for cardiac testing that they can support financially. However, it is not known how widespread is the adoption of these new strategies across the UK. METHODS: The National Audit Committee of the Association of Clinical Biochemists commissioned two surveys in 1999 and 2001 to assess the status of cardiac markers currently being offered by laboratories in the UK and how this service might develop in the future. RESULTS: The results show that many laboratories are continuously adapting and improving their cardiac marker testing in line with current recommendations for acute myocardial infarction. Although most laboratories are confident in the use of troponin measurement in the diagnosis of myocardial infarction, they are less confident in the use of biochemical markers in assessing prognostic outcome in the other cardiac conditions. CONCLUSIONS: Finance, staffing and equipment constraints may offer significant impediments to troponin testing with a 1-h turnaround time.

Chemistry, Clinical↗

Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome (PCOS) among South Asians and Caucasians: is there a difference?

OBJECTIVE: Polycystic ovary syndrome (PCOS) is more prevalent in South Asian women residing in the UK than in Caucasians. Insulin resistance (IR) is central to the pathogenesis of PCOS, while type 2 diabetes is commoner in South Asians. We aimed to determine a possible ethnic difference in the clinical and biochemical characteristics of South Asian vs. Caucasian women with PCOS. PATIENTS AND DESIGN: A case-control cross-sectional observational study of consecutive women with anovular PCOS (47 South Asians, 40 Caucasians) and their age-matched controls (11 South Asians and 22 Caucasians). MEASUREMENTS: Index subjects: a questionnaire-based interview on clinical symptoms and family history; anthropometric measurements, clinical observations of the presence and degree of acne, hirsutism and acanthosis nigricans; transvaginal pelvic ultrasound; biochemical analyses of fasting blood sugar, fasting plasma insulin, fasting lipids, testosterone, and SHBG concentrations. CONTROL GROUP: age- and weight-matched unrelated women from the same ethnic backgrounds without PCOS seeking treatment for male infertility were studied by similar methods to those used with the index subjects. RESULTS: South Asians with PCOS presented at a younger age (age 26 +/- 4 vs. 30.1 +/- 5 years, P = 0.005). Body mass index (BMI) and waist : hip ratios were similar in the two affected cohorts. More South Asians had oligomenorrhoea commencing at a younger age. Hirsutism (Ferriman Gallwey score 18 vs. 7.5, P = 0.0001), acne, acanthosis nigricans and secondary infertility were significantly more prevalent in South Asians. The fasting glucose was similar (4.52 +/- 0.08 vs. 4.62 +/- 0.09 mmol/l, P = 0.25), the fasting insulin higher (89.4 +/- 8.9 vs. 48.6 +/- 4.8 pmol/l, P = 0.0001) and insulin sensitivity (IS) lower (0.335 +/- 0.005 vs. 0.357 +/- 0.002, P = 0.0001) among South Asians. Serum SHBG was significantly less in South Asians (35 +/- 3.3 vs. 55 +/- 9.4 nmol/l, P = 0.02), while serum testosterone was similar (2.69 +/- 0.11 vs. 2.64 +/- 0.13 nmol/l, P = 0.37). CONCLUSIONS: We conclude that South Asians with anovular PCOS seek treatment at a younger age, have more severe symptoms, and have higher fasting insulin concentrations and lower insulin sensitivity than Caucasians.

Adult↗

Wrong biochemistry results: two case reports and observational study in 5310 patients on potentially misleading thyroid-stimulating hormone and gonadotropin immunoassay results.

BACKGROUND: Immunoassays are used in almost all medical and surgical specialties, but they suffer from interference from proteins such as antibodies in some patients' sera. Such interferences are usually reported in the literature only as case reports after the introduction of a new assay. METHODS: We undertook a prospective observational study on 5310 patients for whom the common immunoassay tests for thyroid-stimulating hormone (TSH) and/or gonadotropins were requested. All TSH and gonadotropin results were critically assessed for a mismatch between the clinical details and analytical results to identify samples suspected of analytical unreliability. These were tested further by three approaches to screen for interference. RESULTS: From the 5310 sets of results, 59 patients' samples were identified as suspect and were tested further. Analytically incorrect results were found in 28 (0.53% of the total studied). The magnitude of interference varied, but in 23 of 28 patients (82%), it was considered large enough to have a potentially adverse effect on cost and/or the clinical care of these patients. Two cases, described in detail, illustrate the adverse effect of error on patient care and cost, and the second highlights the difficulties and limitations of current approaches for identifying interference and inaccuracy in immunoassays. CONCLUSIONS: Because millions of TSH/gonadotropin tests are carried out in UK hospital laboratories alone, our data suggest that thousands of patients could be adversely affected by errors from interferences. Early identification of interference in cases with unusual results could be valuable.

Aged↗