Concordance rate for Type II diabetes mellitus in monozygotic twins: actuarial analysis

Summary To determine the concordance rate for Type II (non-insulin-dependent) diabetes mellitus in monozygotic twin pairs, initially ascertained discordant for diabetes, we carried out a prospective study on 44 non-diabetic subjects, each of whom had a sibling twin with diabetes (21 men, 23 women, median age 55 years, interquartile range 47–65). The subjects were referred as discordant for Type II diabetes. The twin pairs were part of the British Diabetic Twin Study and ascertained between May 1968 and January 1998. These subjects underwent an OGTT at time of referral and periodically thereafter. The mean follow-up was 8 years (range 0–18 years) and data were collected until January 1996. The percentage of twins who developed Type II diabetes was assessed by standard actuarial life-table methods and the pairwise concordance rate, that is the proportion of concordant pairs over the sum of concordant and discordant pairs, was calculated. The observed rates of concordance for Type II diabetes at 1, 5, 10, and 15 years follow-up were 17, 33, 57, and 76 %, respectively. The concordance rate for any abnormality of glucose metabolism (either Type II diabetes or impaired glucose tolerance) at 15 years follow-up was 96 %. The concordance rate for Type II diabetes in monozygotic twins is very high even in twins initially ascertained discordant for diabetes. [Diabetologia (1999) 42: 146–150] Received: 16 March 1998 and in revised form: 26 August 1998     

HIV-related characteristics among female partners of injecting drug users in Kelantan,Malaysia: a descriptive study

Kelantan, a northeastern state in Peninsular Malaysia, is one of the states that has been acutely hit by injecting drug user (IDU)-driven HIV epidemic, in addition to having a high number of infected women in Malaysia. This cross-sectional study describes the socio-demographic characteristics, HIV risk factors, risk perception, and adoption of preventive behaviors among female partners of IDUs in Kelantan. Out of 101 women, the majority of them are from low socioeconomic background and have no other risk factors besides heterosexual HIV transmission from their male IDU partners. Although 45.5% have not been tested for HIV and more than half (53.5%) of them did not use condoms during sexual intercourse, only 44.6% of the women perceived themselves to be at risk of being infected with HIV. Most of the women (86.1%) were willing to undergo voluntary counseling and testing (VCT). Female partners of IDUs continue to be vulnerable to HIV due to having sexual contact with IDUs, and also due to their socioeconomic position in the community. To prevent HIV transmission among female partners of IDUs, consolidating HIV prevention efforts from multiple approaches is needed.     

Investigation of optical neuro-monitoring technique for detection of maintenance and emergence states during general anesthesia

The American Society of Anesthesiologist recommends peripheral physiological monitoring during general anesthesia, which offers no information regarding the effects of anesthetics on the brain. Since no “gold standard” method exists for this evaluation, such a technique is needed to ensure patient comfort, procedure quality and safety. In this study we investigated functional near infrared spectroscopy (fNIRS) as possible monitor of anesthetic effects on the prefrontal cortex. Anesthetic drugs, such as sevoflurane, suppress the cerebral metabolism and alter the cerebral blood flow. We hypothesize that fNIRS derived features carry information on the effects of anesthetics on the prefrontal cortex (PFC) that can be used for the classification of the anesthetized state. In this study, patients were continuously monitored using fNIRS, BIS and standard monitoring during surgical procedures under sevoflurane general anesthesia. Maintenance and emergence states were identified and fNIRS features were identified and compared between states. Linear and non-linear machine learning algorithms were investigated as methods for the classification of maintenance/emergence. The results show that changes in oxygenated (HbO₂) and deoxygenated hemoglobin (HHb) concentration and blood volume measured by fNIRS were associated with the transition between maintenance and emergence that occurs as a result of sevoflurane washout. We observed that during maintenance the signal is relatively more stable than during emergence. Maintenance and emergence states were classified with 94.7% accuracy with a non-linear model using the locally derived mean total hemoglobin, standard deviation of HbO₂, minimum and range of HbO₂ and HHb as features. These features were found to be correlated with the effects of sevoflurane and to carry information that allows real time and automatic classification of the anesthetized state with high accuracy.     

Osteoprotegerin and the receptor activator of NF-kappa B ligand in the serum and synovial fluid. A comparison of patients with longstanding rheumatoid arthritis and osteoarthritis

We examined OPG and soluble RANKL in the serum (sOPG, sRANKL) and synovial fluid (synOPG, synRANKL) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). OPG and RANKL were measured in 85 patients (44 with RA, 41 patients with OA) in serum and synovial fluid as well. For measuring of OPG and RANKL ELISA tests were used. The results of OPG and RANKL were compared with clinical and radiological scores. We found a negative correlation for OPG and RANKL in synovial fluids: not only for the whole group of patients (P< 0.003, r=–0.32), but also for the subgroups (RA: P<0.04, r=–0.28, OA: P<0.002, r=–0.54). SRANKL and synRANKL were positively correlated in the whole group (P<0.01, r=0.25) and in the OA group (P<0.02, r=0.35); the RA group was showing a trend (P<0.063, r=0.24), however. Serum OPG was lower in RA, synOPG higher in OA. The difference between the two patient groups was only significant for synOPG (P<0.03, r=0.056), but not for sOPG (P<0.09, r=0.19), sRANKL (P<0.43, r=0.85) or synRANKL (P<0.11, r=0.22). The synOPG:synRANKL ratio was significantly correlated with the Larsen score (P<0.004, r=0.38). Synovial OPG is significantly decreased in rheumatoid joints, whereby synovial RANKL is increased. Lower synOPG could reflect a lower protective effect on bone, thus leading to an earlier and more pronounced bone destruction in RA. However, the effect of different mediators for joint destruction in RA and OA seems not to be important to the pathophysiological changes in the joints. The upregulation of serum OPG might be the result of the inflammation; in contrast, an upregulation of RANKL could not be found in the serum of patients with RA and OA.     

A national survey of surgical antibiotic prophylaxis in Turkey.

OBJECTIVE: To assess the quality of antibiotic prophylaxis for clean and clean-contaminated elective surgical procedures. DESIGN: A cross-sectional, country-wide survey. SETTING: Thirty-six hospitals in 12 cities in Turkey. PARTICIPANTS: Four hundred thirty-nine surgeons from 6 different specialties who performed selected procedures of interest. METHODS: A random sample of surgeons from different hospitals was selected. A standardized data collection form was used to record the type of procedure, the names, doses, timing of the first doses, and duration of antibiotics, important decisive factors, and problems in the management of prophylactic antibiotic use for surgical procedures. RESULTS: Fifty-five percent of surgeons addressed completed the survey. For clean-contaminated procedures, 6% of surgeons did not use antibiotic prophylaxis, whereas 88% used more than a single dose. Inappropriate antibiotics were chosen for 32% of procedures. In 39% of procedures, the first dose of antibiotics was not administered during induction of anesthesia. Duration of prophylaxis was longer than 24 hours in 80% and longer than 48 hours in 46% of all procedures. Only 112 surgeons (26%) were using definitely appropriate prophylaxis in all ways. Multivariate analysis revealed that surgeons in university hospitals (OR, 2.353; CI95, 1.426-3.884; P = .001) and general surgeons (OR, 4.986; CI95, 2.890-8.604; P < .001) used antibiotic prophylaxis more appropriately. Patients not covered by health insurance (OR, 0.417; CI95 0.225-0.772; P < .001) were associated with inappropriate prophylaxis. CONCLUSION: Given the high frequency of antibiotics prescribed for surgical prophylaxis in Turkey, adherence to surgical prophylaxis guidelines is urgently needed.     

Antibodies to IA-2 and GAD65 in type 1 and type 2 diabetes: isotype restriction and polyclonality

OBJECTIVE: To determine the isotypes and clonality of antibodies to GAD (GADA) and IA-2 (IA-2A) in patients with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied the following consecutive series of patients who attended a diabetes center for antibodies to GADA and IA-2A: 52 newly diagnosed type 1 diabetic patients, 199 type 2 diabetic patients, 200 control patients, and a cohort of 34 nondiabetic identical twins of patients with type 1 diabetes (15 of whom developed diabetes) who were followed prospectively. RESULTS: GADA or IA-2A were detected in 37 (71%) type 1 diabetic patients compared with only 10 (5%) type 2 diabetic patients (P<0.0001). Both GAD and IA-2 antibodies, regardless of the type of diabetes, were usually subclass restricted to IgG1 and were polyclonal. IgM, IgG3, and IgE isotypes were also detected, but all isotypes of GADA and IA-2A were less prevalent than IgG1 (P<0.017 for either antibody). There was no evidence of spreading or switching of isotypes before the onset of type 1 diabetes. CONCLUSIONS: These observations suggest that the pathogenesis of antigen-specific antibodies in type 1 and type 2 diabetes is similar and probably involves a chronic nonrandom antigen-driven polyclonal B-cell activation that is consistent with a Th1-type immune response.     

Effect of systemic glucocorticoid therapy on bone metabolism and the osteoprotegerin system in patients with active Crohn's disease

BACKGROUND AND AIMS: Osteoporosis may occur in 25-30% of patients with Crohn's disease. Its pathogenesis is not completely understood. Both systemic inflammation in acute disease and treatment with systemic glucocorticoids have been implicated. The aim of the present study was to investigate changes in bone density and biochemical markers of bone metabolism before and during a 3-month period of high-dose glucocorticoid treatment for acute flare-up of Crohn's disease. METHODS: Twenty-five patients with active Crohn's disease requiring systemic glucocorticoid treatment (prednisolone, 60 mg/day) were investigated. Lumbar spine and femoral neck bone mineral densitometry was performed at baseline and again after 3 months. Clinical examinations including evaluation of the Crohn's disease activity index and measurement of the biochemical markers osteocalcin, deoxypyridinoline, osteoprotegerin and the soluble receptor activator of NF-kappaB ligand were performed prior to, and at 1, 2 and 12 weeks following steroid administration.RESULTS Median lumbar bone mineral density decreased significantly during the observation period by 1.04% from -0.84 (t score; range, -2.8 to +0.57) to -0.95 (range, -3.1 to +0.40; P = 0.022), while bone density of the total femur decreased by 2.9% from -0.83 (range, -2.61 to +1.86) to -0.90 (range, -2.65 to +0.19; P = 0.01). Serum levels of osteocalcin, a bone formation marker, and osteoprotegerin, an anti-resorptive cytokine produced by osteoblasts, decreased after the first 2 weeks of treatment and reached baseline levels after 3 months. No significant change was found for the bone resorption marker deoxypyridinoline, while soluble receptor activator of NF-kappaB ligand, a cytokine promoting bone resorption, tended to increase during steroid treatment. CONCLUSION: A decrease in bone mineral density in patients with Crohn's disease appears to result, at least in part, from a short-term effect of systemic glucocorticoid. Modulation of osteoclastogenesis by the receptor activator of NF-kappaB ligand/osteoprotegerin cytokine system and decreased osteoblastic function may be the underlying molecular basis.     

Identification of a novel mutation in hereditary vitamin D resistant rickets causing exon skipping

OBJECTIVE Hereditary vitamin D resistant rickets (HVDRR) is an autosomal recessive disorder resulting in target organ resistance to the actions of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃). In many cases, this disorder has been shown to be due to mutations in the gene encoding vitamin D receptors (VDR). In a patient with characteristic features of this disorder, we investigated the functional defect and sequenced the coding region of the gene for mutations. DESIGN Skin fibroblasts from patient and control were used to measure binding of 1,25(OH)₂D₃ and functional responses to the hormone. These cells were also used to prepare RNA from which cDNA was prepared and sequenced. Furthermore, genomic DNA was prepared from the fibroblasts and the intronlexon boundarles sequenced. PATIENT A child with classic features of HVDRR with alopecia diagnosed as having rickets due to resistance to 1,25(OH)₂D₃. MEASUREMENTS Nuclear association of 1,25(OH)₂D₃ was determined in patient and control cells and the functional response to 1,25(OH)₂D₃ was assessed by measurement of 25-hydroxyvitamln D-24-hydroxylase(24-hydroxylase) activity. VDR cDNA and genomic DNA prepared from patient and control cells were sequenced. RESULTS Cells from the patient with HVDRR had undetectable amounts of VDR compared to control cells and did not show induction of 24-hydroxylase activity following treatment with 1,25(OH), D₃. Sequencing of the VDR coding region after RT-PCR of RNA revealed an absence of exon 4 in patient RNA which was not due to a deletion in genomic DNA but was caused by exon skipping during RNA processing. In addition, the deletion of exon 4 sequences from RNA leads to a frameshift in translation resulting in a premature stop codon. Amplification of genomic DNA around the intron/exon boundary of exon 4 revealed a point mutation in the 5’donor splice site of intron 4. CONCLUSION In this study, we have identified a novel mutation in the gene for vitamin D receptors in a patient with the Characteristic phenotype of hereditary vitamin D resistant rickets. The mutation at the + 5 position in intron 4 is most likely to cause skipping of exon 4 in this patient.