Differentiating normal hyaline cartilage from post-surgical repair tissue using fast gradient echo imaging in delayed gadolinium-enhanced MRI (dGEMRIC) at 3 Tesla

The purpose was to evaluate the relative glycosaminoglycan (GAG) content of repair tissue in patients after microfracturing (MFX) and matrix-associated autologous chondrocyte transplantation (MACT) of the knee joint with a dGEMRIC technique based on a newly developed short 3D-GRE sequence with two flip angle excitation pulses. Twenty patients treated with MFX or MACT (ten in each group) were enrolled. For comparability, patients from each group were matched by age (MFX: 37.1 ± 16.3 years; MACT: 37.4 ± 8.2 years) and postoperative interval (MFX: 33.0 ± 17.3 months; MACT: 32.0 ± 17.2 months). The Δ relaxation rate (ΔR1) for repair tissue and normal hyaline cartilage and the relative ΔR1 were calculated, and mean values were compared between both groups using an analysis of variance. The mean ΔR1 for MFX was 1.07 ± 0.34 versus 0.32 ± 0.20 at the intact control site, and for MACT, 1.90 ± 0.49 compared to 0.87 ± 0.44, which resulted in a relative ΔR1 of 3.39 for MFX and 2.18 for MACT. The difference between the cartilage repair groups was statistically significant. The new dGEMRIC technique based on dual flip angle excitation pulses showed higher GAG content in patients after MACT compared to MFX at the same postoperative interval and allowed reducing the data acquisition time to 4 min.     

Sildenafil Prevents Cardiovascular Changes after Bone Marrow Fat Embolization in Sheep

Background: Sudden, intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anesthetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Selective pulmonary vasodilation may be an appropriate prophylactic or therapeutic measure. The effect of sildenafil (phosphodiesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated.

Methods: Bone cement (polymethylmethacrylate) was injected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals received a bolus injection (0.7 mg/kg) of sildenafil, with continuous infusion (0.2 mg [middle dot] kg-1 [middle dot] h-1) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat.

Results: Fat embolism was associated with a transient increase (21 +/- 7mmHg) in pulmonary arterial pressure. A transient decrease in arterial blood pressure and temporary increases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1).     

Long-term follow-up of submucosal tunnel and serosa-lined extramural tunnel ureter implantation in ileocaecal continent cutaneous urinary diversion (Mainz pouch I)

OBJECTIVE: To assess upper urinary tract complications and renal function in patients with a submucosal tunnel and serosa-lined extramural tunnel ureter implantation during the long-term follow-up of ileocaecal continent cutaneous urinary diversion (Mainz pouch I). PATIENTS AND METHODS: In all, 458 patients who had diversion with the ileocaecal pouch were analysed in a retrospective follow-up study. Uretero-intestinal implantation was done using a submucosal tunnel (ST) in 809 reno-ureteric units (RUs) and by the serosa-lined extramural tunnel (ET) technique in 74 RUs. The median age of the patients at the time of surgery was 47.1 years, and the median follow-up was 89.0 months. RESULTS: For the ST, there was anastomotic obstruction in 59 RUs (7.3%) at a median of 16.8 months after diversion; the obstruction-free intervals at 1, 5 and 10 years were 97%, 93% and 91%, respectively. Obstruction rates were 13.9% for previously dilated upper tracts and 17.1% in patients with a neurogenic bladder. Serum creatinine levels were < or =1.6 mg/dL in 97% of the patients at the latest follow-up. For ET, there was anastomotic obstruction in three RUs (4.1%) at a median of 17.2 months after diversion. Obstruction-free intervals at 1, 5 and 10 years were 100%, 96% and 96%. Preoperative dilation of the upper tracts did not reduce the obstruction rate (3.1%), but it was 7.1% in patients with a neurogenic bladder. Serum creatinine levels were < or =1.6 mg/dL in 98% of the patients at the latest follow-up. CONCLUSIONS: The ET gives lower obstruction rates than the ST, especially when upper tracts are dilated and in patients with a neurogenic bladder. Renal function remained stable with both techniques in the long term.     

Prevalence,incidence, and natural course of anorexia and bulimia nervosa among adolescents and young adults

We aimed to assess the prevalence, incidence, age-of-onset and diagnostic stability of threshold and subthreshold anorexia nervosa (AN) and bulimia nervosa (BN) in the community. Data come from a prospective-longitudinal community study of 3021 subjects aged 14–24 at baseline, who were followed up at three assessment waves over 10 years. Eating disorder (ED) symptomatology was assessed with the DSM-IV/M-CIDI at each wave. Diagnostic stability was defined as the proportion of individuals still affected with at least symptomatic eating disorders (EDs) at follow-ups. Baseline lifetime prevalence for any threshold ED were 2.9 % among females and 0.1 % among males. For any subthreshold ED lifetime prevalence were 2.2 % for females and 0.7 % for males. Symptomatic expressions of EDs (including core symptoms of the respective disorder) were most common with a lifetime prevalence of 11.5 % among females and 1.8 % among males. Symptomatic AN showed the earliest onset with a considerable proportion of cases emerging in childhood. 47 % of initial threshold AN cases and 42 % of initial threshold BN cases showed at least symptomatic expressions of any ED at any follow-up assessment. Stability for subthreshold EDs and symptomatic expressions was 14–36 %. While threshold EDs are rare, ED symptomatology is common particularly in female adolescents and young women. Especially threshold EDs are associated with a substantial risk for stability. A considerable degree of symptom fluctuation is characteristic especially for subthreshold EDs.     

Association of 18 Confirmed Susceptibility Loci for Type 2 Diabetes With Indices of Insulin Release, Proinsulin Conversion, and Insulin Sensitivity in 5,327 Nondiabetic Finnish Men

OBJECTIVE

We investigated the effects of 18 confirmed type 2 diabetes risk single nucleotide polymorphisms (SNPs) on insulin sensitivity, insulin secretion, and conversion of proinsulin to insulin.

RESEARCH DESIGN AND METHODS

A total of 5,327 nondiabetic men (age 58 ± 7 years, BMI 27.0 ± 3.8 kg/m²) from a large population-based cohort were included. Oral glucose tolerance tests and genotyping of SNPs in or near PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, LOC387761, CDKN2B, IGF2BP2, CDKAL1, HNF1B, WFS1, JAZF1, CDC123, TSPAN8, THADA, ADAMTS9, NOTCH2, KCNQ1, and MTNR1B were performed. HNF1B rs757210 was excluded because of failure to achieve Hardy-Weinberg equilibrium.

RESULTS

Six SNPs (TCF7L2, SLC30A8, HHEX, CDKN2B, CDKAL1, and MTNR1B) were significantly (P < 6.9 × 10⁻⁴) and two SNPs (KCNJ11 and IGF2BP2) were nominally (P < 0.05) associated with early-phase insulin release (InsAUC_0–30/GluAUC_0–30), adjusted for age, BMI, and insulin sensitivity (Matsuda ISI). Combined effects of these eight SNPs reached −32% reduction in InsAUC_0–30/GluAUC_0–30 in carriers of ≥11 vs. ≤3 weighted risk alleles. Four SNPs (SLC30A8, HHEX, CDKAL1, and TCF7L2) were significantly or nominally associated with indexes of proinsulin conversion. Three SNPs (KCNJ11, HHEX, and TSPAN8) were nominally associated with Matsuda ISI (adjusted for age and BMI). The effect of HHEX on Matsuda ISI became significant after additional adjustment for InsAUC_0–30/GluAUC_0–30. Nine SNPs did not show any associations with examined traits.

CONCLUSIONS

Eight type 2 diabetes–related loci were significantly or nominally associated with impaired early-phase insulin release. Effects of SLC30A8, HHEX, CDKAL1, and TCF7L2 on insulin release could be partially explained by impaired proinsulin conversion. HHEX might influence both insulin release and insulin sensitivity.Impaired insulin secretion and insulin resistance, two main pathophysiological mechanisms leading to type 2 diabetes, have a significant genetic component (1). Recent studies have confirmed 20 genetic loci reproducibly associated with type 2 diabetes (2–13). Three were previously known (PPARG, KCNJ11, and TCF7L2), whereas 17 loci were recently discovered either by genome-wide association studies (SLC30A8, HHEX-IDE, LOC387761, CDKN2A/2B, IGF2BP2, CDKAL1, FTO, JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, THADA, ADAMTS9, NOTCH2, KCNQ1, and MTNR1B), or candidate gene approach (WFS1 and HNF1B). The mechanisms by which these genes contribute to the development of type 2 diabetes are not fully understood.PPARG is the only gene from the 20 confirmed loci previously associated with insulin sensitivity (14,15). Association with impaired β-cell function has been reported for 14 loci (KCNJ11, SLC30A8, HHEX-IDE, CDKN2A/2B, IGF2BP2, CDKAL1, TCF7L2, WFS1, HNF1B, JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, KCNQ1, and MTNR1B) (6,12,13,16–38). Although associations of variants in HHEX (16–22), CDKAL1 (6,21–26), TCF7L2 (22,27–30), and MTNR1B (13,31,32) with impaired insulin secretion seem to be consistent across different studies, information concerning other genes is limited (12,18–25,27,33–38). The mechanisms by which variants in these genes affect insulin secretion are unknown. However, a few recent studies suggested that variants in TCF7L2 (22,39–42), SLC30A8 (22), CDKAL1 (22), and MTNR1B (31) might influence insulin secretion by affecting the conversion of proinsulin to insulin. Variants of FTO have been shown to confer risk for type 2 diabetes through their association with obesity (7,16) and therefore were not included in this study.Large population-based studies can help to elucidate the underlying mechanisms by which single nucleotide polymorphisms (SNPs) of different risk genes predispose to type 2 diabetes. Therefore, we investigated confirmed type 2 diabetes–related loci for their associations with insulin sensitivity, insulin secretion, and conversion of proinsulin to insulin in a population-based sample of 5,327 nondiabetic Finnish men.     

Modulation of associative human motor cortical plasticity by attention

The role of attention in generating motor memories remains controversial principally because it is difficult to separate the effects of attention from changes in kinematics of motor performance. We attempted to disentangle attention from performance effects by varying attention while plasticity was induced in human primary motor cortex by external stimulation in the absence of voluntary movement. A paired associative stimulation (PAS) protocol was employed consisting of repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with single-pulse transcranial magnetic stimulation (TMS) over the optimal site for activation of the right abductor pollicis brevis muscle (APB) to generate near-synchronous events in the left primary motor cortex. In experiment 1, the spatial location of attention was varied. PAS failed to induce plasticity when the subject's attention was directed to their left hand, away from the right target hand the cortical representation of which was being stimulated by PAS. In experiment 2, the grade of attention to the target hand was manipulated. PAS-induced plasticity was maximal when the subject viewed their target hand, and its magnitude was slightly reduced when the subject could only feel their hand. Conversely, plasticity was completely blocked when the subject's attention was diverted from the target hand by a competing cognitive task. A similar modulation by attention was observed for PAS-induced changes in the duration of the silent period evoked by TMS in voluntarily contracted muscle. Associative plasticity in the human motor cortex depends decisively on attention.