Evaluation of metabolic risk markers in polycystic ovary syndrome (PCOS). Adiponectin, ghrelin, leptin and body composition in hirsute PCOS patients and controls

OBJECTIVE: Polycystic ovary syndrome (PCOS) patients are abdominally obese and are at increased risk of developing the metabolic syndrome. Low adiponectin and ghrelin levels in PCOS patients could be caused by insulin resistance as well as high testosterone levels. DESIGN: Adiponectin and ghrelin levels were evaluated in 51 hirsute PCOS patients referred to the outpatient clinic of an academic, tertiary care medical centre and in 63 weight-matched female controls. Relationships between adiponectin, ghrelin, leptin, body composition, testosterone and insulin were examined. METHODS: Measurements of body composition including waist-hip-ratio (WHR), body mass index (BMI) and whole body dual-energy X-ray absorptiometry scan measures of body fat mass. Measurements of fasting levels of adiponectin, ghrelin, leptin, androgen status, oestradiol, lipid variables and insulin during follicular phase. RESULTS: Adiponectin levels were significantly decreased in obese PCOS patients compared with weight-matched controls (geometric mean (-2 to 2 s.d.) 5.3 (2.5-11.1) vs 7.3 (3.0-17.4) mg/l, P<0.05). Mean ghrelin was significantly lower in hirsute PCOS patients than in controls (0.6 (0.3 to 1.4) vs 0.8 (0.4 to 1.7) microg/l, P<0.001) and this remained significant after subdividing subjects according to waist circumference and BMI. During multiple regression analysis, testosterone correlated positively with adiponectin and negatively with ghrelin independent of BMI, WHR and total fat mass. CONCLUSION: Obese hirsute PCOS patients demonstrated significantly lower adiponectin levels than weight-matched controls suggesting a very high risk for the metabolic syndrome. Furthermore, ghrelin levels were decreased in hirsute PCOS patients and showed a significant, negative correlation with testosterone independent of body composition.     

Clinical interest: a study of the influence on general practitioners' prescribing

PURPOSE: To analyse the association between general practitioners' clinical interest and prescribing rates in four clinical areas: dyspepsia, depression, headache and diabetes. METHODS: Data concerning general practitioners' prescribing during 2004 were retrieved from a pharmacy database and linked with data from a physician questionnaire and the National Health Insurance Register. To counterbalance differences in practice populations all 1-year prevalences of prescribing were standardised according to age and gender. Participants were asked 'To what extent do you find the following areas interesting from a professional point-of- view?' Four rating categories were used. The association between clinical interest and standardised prescribing rates was investigated using logistic regression, the Kruskal-Wallis test and a trend test. RESULTS: A total of 68 (72%) single-handed general practitioners representative of the total group completed the questionnaire. We observed a two-fold ratio between the 90% and the 10% percentiles of the 1-year prevalences of antisecretory drugs, antidepressants, migraine drugs as well as anti-diabetics. The variation in prescribing of antidepressant and antisecretory drugs was far above chance level. No significant association with clinical interest could, however, be observed for any of the four clinical areas. CONCLUSION: General practitioners' prescribing of the four classes of medical drugs varied considerably. However, only part of this variation was based on chance. This study did not confirm our hypothesis that general practitioners' level of clinical interest in one area corresponds with their prescribing of drugs used within that area.     

Culture of multiple peroperative biopsies and diagnosis of infected knee arthroplasties

Prosthetic joint infections remain difficult to diagnose. In 1981, Kamme & Lindberg described a diagnostic procedure with five peroperative biopsies in patients with total hip arthroplasty (Clin Orthop Relat Res 1981;154:201-7). Its usefulness, however, has not been ascertained for other prosthetic joints undergoing surgical revision. Therefore, we undertook a retrospective study of 120 surgical revisions in 118 patients with knee arthropasties where such biopsies had been obtained. Cases were categorized into three groups based on information available prior to revision and peroperative inspection: prosthetic joint infection (n = 26), aseptic loosening (n = 58), and mechanical problems (n = 36). Fifteen sets were positive, 13 had significant growth (i.e. > or =3 biopsies with the same microbe/s), and 2 had insignificant growth (< or =2 positive biopsies). Excluding the group with a mechanical problem, the sensitivity for infection was 12/26 (46%), the specificity 58/58 (100%), the positive predictive value 12/12 (100%), and the negative predictive value 58/72 (81%). In the group with infection there was a trend towards less exposure to antibiotics in cases with positive cultures than cases with negative cultures. The Kamme & Lindberg procedure is applicable also to knee arthroplasties, but the low sensitivity and negative predictive value underline the need for new diagnostic methods.     

Risk scores for type 2 diabetes can be applied in some populations but not all

OBJECTIVE: Risk scores based on phenotypic characteristics to identify individuals at high risk of having undiagnosed diabetes have been developed in Caucasian populations. The impact of known risk factors on having undiagnosed type 2 diabetes differs between populations from different ethnic origin, and risk scores developed in Caucasians may not be applicable to other ethnic groups. This study evaluated the performance of one risk score in nine populations of diverse ethnic origin. RESEARCH DESIGN AND METHODS: Data provided by centers from around the world to the DETECT-2 project were used. The database includes population-based surveys with information on at least 500 people without known diabetes having a 75-g oral glucose tolerance test. To date, 52 centers have contributed data on 190,000 individuals from 34 countries. In this analysis, nine cross-sectional studies were selected representing diverse ethnic and regional backgrounds. The risk score assessed uses information on age, sex, blood pressure treatment, and BMI. RESULTS: This analysis included 29,758 individuals; 1,805 individuals had undiagnosed diabetes. The performance of the risk score varied widely, with sensitivity, specificity, and percentage needing further testing ranging between 12 and 57%, 72 and 93%, and 2 and 25%, respectively, with the worse performance in non-Caucasian populations. This variation in performance was related to differences in the association between prevalence of undiagnosed diabetes and components of the risk score. CONCLUSIONS: A typical risk score developed in Caucasian populations cannot be applied to other populations of diverse ethnic origins.     

Rs710521[A] on chromosome 3q28 close to TP63 is associated with increased urinary bladder cancer risk

Single nucleotide polymorphism (SNP) rs710521[A], located near TP63 on chromosome 3q28, was identified to be significantly associated with increased bladder cancer risk. To investigate the association of rs710521[A] and bladder cancer by new data and by meta-analysis including all published data, rs710521 was studied in 1,425 bladder cancer cases and 1,740 controls that had not been included in previous studies. Blood samples were collected from 1995 to 2010 in Germany (n?=?948/1,258), Hungary (n?=?262/65), Venezuela (n?=?112/190) and Pakistan (n?=?103/227) supplemented by a meta-analysis of 5,695 cases and 40,187 controls. Detection of a A/G substitution (rs710521) on chromosome 3q28, position 191128627 was done via fast real-time polymerase chain reaction (rt-PCR). Rs710521[A] is associated with increased risk in the unadjusted analysis (OR?=?1.21; 95% Cl?=?1.04-1.40; P?=?0.011) and in the recessive model adjusted for age, gender, smoking habits and ethnicity (OR?=?1.23; 95% Cl?=?1.05-1.44; P?=?0.010). No difference between individuals occupationally exposed versus not occupationally exposed to urinary bladder carcinogens was observed concerning the relevance of rs710521[A]. Similarly, rs710521[A] did not confer different susceptibility in smokers and non-smokers. Performing a meta-analysis of 5,695 cases and 40,187 controls including all published studies on rs710521, a convincing association with bladder cancer risk was obtained (OR?=?1.18; 95% Cl?=?1.12-1.25; P?相似文献   

Nitric oxide modulation of low-frequency oscillations in cortical vessels in FHM--a NIRS study

Background.— The pathophysiological alterations in patients with familial hemiplegic migraine (FHM) are not yet fully known. The headache characteristics in patients with FHM mutations have been examined in a series of glyceryl trinitrate (GTN) provocation studies in FHM patients, but the cortical vascular response to GTN in FHM patients has never been investigated before. Objective.— To investigate changes in spontaneous low‐frequency oscillations (LFO) of cortical vessels in response to the nitric oxide donor GTN by near‐infrared spectroscopy in FHM patients. Methods.— Twenty‐three FHM patients without known mutations and 9 healthy controls received a continuous intravenous infusion of GTN 0.5 µg/kg/minute over 20 minutes. Using near‐infrared spectroscopy, we recorded oxygenated hemoglobin (oxyHb) LFO amplitude bilateral at the frontal cortex at baseline and 15 minutes and 40 minutes after start of the GTN infusion. Results.— GTN changed oxyHb LFO amplitude in FHM patients (P = .002), but not in healthy controls (P = .121). Only in FHM patients with coexisting common migraine types did GTN infusion induced changes in LFO amplitudes (P < .001), where post‐hoc analysis revealed an increase in LFO amplitude 15 minutes (P = .003) and 40 (P = .013) minutes after start of infusion compared with baseline. Interestingly, GTN infusion induced no changes in LFO amplitude in patients with a pure FHM phenotype (P = .695). Conclusion.— FHM patients with a mixed phenotype (coexisting common type of migraine) showed an increase in oxyHb LFO amplitude during GTN infusion, whereas FHM patients with pure phenotype showed no changes. These data suggest possible differences in frontal cortical nitric oxide vascular sensitivity between FHM patients with a mixed phenotype and patients with pure FHM.     

Therapy with pembrolizumab in treatment-naïve patients with nonmetastatic,mismatch repair deficient colorectal cancer

Therapy with immune checkpoint inhibitors (ICI) is effective in patients with metastatic mismatch-repair deficient (dMMR) colorectal cancer (CRC); however, data on treatment with neoadjuvant ICI in patients with locally advanced CRC are limited. From March 2019 to June 2020, five Danish oncological centers treated 10 patients with a treatment-naïve dMMR CRC with preoperative pembrolizumab, 9 with a nonmetastatic, unresectable colon cancer and 1 with a locally advanced rectum cancer. All 10 patients were evaluated regularly at a multidisciplinary team (MDT) meeting, and they all had a radical resection after a median of 8 cycles (range 2-13) of pembrolizumab. A microscopic evaluation of the resected tumors revealed no remaining tumor cells in five patients, while five still had tumor cells present. The patients were given no additional therapy. No recurrences were reported after a median follow-up of 26 months (range 23-38.5 months). Biopsies from Danish patients with CRC are routinely screened for dMMR proteins. In 2017, data from the Danish Colorectal Cancer Group showed that 19% (565/3000) of the patients with colon cancer and 1.5% (19/1279) of those with rectum cancer had an dMMR tumor. Among the patients with MMR determination, 26% (99/384) patients had a T4 dMMR colon cancer; thus, the 10 patients treated with neoadjuvant pembrolizumab comprised about 9% of the patients with a T4 dMMR colon cancer (9/99) and 5% of patients with dMMR rectal cancer (1/19). Therapy with pembrolizumab was feasible and effective. Larger prospective trials are needed to confirm our findings.