Diagnosis,treatment and prevention of type 2 diabetes mellitus in children and adolescents

During the last two decades, there have been several reports of an increasing incidence of type 2 diabetes mellitus (T2DM) in children and adolescents, especially among those belonging to minority ethnic groups. This trend, which parallels the increases in prevalence and degree of pediatric obesity, has caused great concern, even though T2DM remains a relatively rare disease in children. Youth T2DM differs not only from type 1 diabetes in children, from which it is sometimes difficult to differentiate, but also from T2DM in adults, since it appears to be an aggressive disease with rapidly progressive β-cell decline, high treatment failure rate, and accelerated development of complications. Despite the recent research, many aspects of youth T2DM still remain unknown, regarding both its pathophysiology and risk factor contribution, and its optimal management and prevention. Current management approaches include lifestyle changes, such as improved diet and increased physical activity, together with pharmacological interventions, including metformin, insulin, and the recently approved glucagon-like peptide-1 analog liraglutide. What is more important for everyone to realize though, from patients, families and physicians to schools, health services and policy-makers alike, is that T2DM is a largely preventable disease that will be addressed effectively only if its major contributor (i.e., pediatric obesity) is confronted and prevented at every possible stage of life, from conception until adulthood. Therefore, relevant comprehensive, coordinated, and innovative strategies are urgently needed.     

Efficacy of tolterodine in preventing urge incontinence immediately after prostatectomy

Purpose: Urgency and urge incontinence are frequently observed after prostatectomy. Although symptoms ameliorate within a relatively short time, they usually cause significant stress and anxiety to the patient as far as their duration is concerned. Aim of our study was to determine the efficacy of tolterodine in preventing urgency and urge incontinence after catheter removal in patients that underwent prostatectomy for benign prostate hyperplasia. Patients and methods: Twenty-seven patients with moderate/severe lower urinary tract symptoms due to benign prostatic enlargement, scheduled for prostatectomy, were randomised into two groups, Group A (14 pts) received tolterodine 2 mg b.i.d starting the day of surgery, while group B patients received no such treatment. Tolterodine treatment was discontinued 15 days after catheter removal. All patients completed the International Prostatic Symptom Score (IPSS) and the International Continence Society (ICS-BPH) forms the day before surgery, and three times more, one, fifteen and thirty days after catheter removal. Results: Pre-operative total 1PSS and frequency of urgency/urge incontinence as determined by questions 3 and 4 of the ICS-BPH questionnaire were equally distributed between groups. Tolterodine was well tolerated and no adverse effects were reported. Post-operative IPSS and QoL scores did not differ between groups. However, the frequency of urge incontinence both the first day and fifteen days after catheter removal was significantly lower in the tolterodine group (16.6% vs. 69.2%, p=0.004 and 8.3% vs. 38.4%, p=0.039, respectively). Conclusion: Tolterodine was well tolerated in all patients and had a beneficial effect regarding the postoperative urge incontinence. Trials of a larger scale could determine which patients would benefit more, especially according to the presence of storage lower urinary tract symptoms prior to surgery.     

Endoscopic management and long-term follow-up of Dieulafoy's lesions in the upper GI tract

BACKGROUND: The aim of this study was to retrospectively evaluate the short-and long-term effectiveness of different methods of endoscopic treatment for bleeding Dieulafoy's lesions. METHODS: Patients were allocated into 2 groups according to the hemostatic method applied: (1) injection group (epinephrine and/or ethanolamine oleate), and (2) thermal coagulation group (heat probe), either alone or combined with epinephrine injection. The combination of epinephrine and ethanolamine oleate was used in 5 patients, epinephrine alone in 3, ethanolamine oleate alone in one, heat probe and epinephrine in 8, and heat probe alone in 1 patient. RESULTS: Dieulafoy's lesions were found in 18 (1%) of 1750 patients with acute nonvariceal upper GI bleeding. Comorbid conditions were present in 5 (28%) patients. Initial hemostasis was achieved endoscopically in 13 patients (72%) and permanent hemostasis in 17 patients (94%). Bleeding recurred in 5 patients (2 with concomitant disease) in the injection group; 3 were successfully retreated by heat probe coagulation and epinephrine injection, 1 with hemoclip application and 1 by surgery. There was no recurrent bleeding in thermal treatment group. Thermal treatment was significantly superior to injection (p = 0.0029). CONCLUSIONS: Endoscopic thermal coagulation with or without epinephrine injection should be the initial treatment of choice for Dieulafoy's lesions. Mortality is lowest in patients with no significant comorbidity and an unremarkable medical history.     

Effects of renin-angiotensin system blockers on renal outcomes and all-cause mortality in patients with diabetic nephropathy: an updated meta-analysis

BackgroundIn contrast to previous studies, recent data questioned the ability of renin-angiotensin-aldosterone system (RAAS) blockers to delay progression of diabetic nephropathy. This study evaluated the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in patients with diabetic nephropathy.MethodsA systematic literature search of MEDLINE/PubMed and EMBASE databases was performed to identify randomized trials published up to June 2007 comparing the effects of ACEIs or ARBs with placebo and/or a regimen not including a RAAS blocker on the incidence of end-stage renal disease (ESRD), doubling of serum creatinine (DSC), or death from any cause in patients with diabetic nephropathy. Treatment effects were summarized as relative risks (RRs) using the Mantel-Haenszel fixed-effects model.ResultsOf the 1,028 originally identified studies, 24 fulfilled the inclusion criteria (20 using ACEIs and 4 using ARBs). Use of ACEIs was associated with a trend toward reduction of ESRD incidence (RR 0.70; 95% confidence interval (CI) 0.46-1.05) and use of ARBs with significant reduction of ESRD risk (RR 0.78; 95% CI 0.67-0.91). Both drug classes were associated with reduction in the risk of DSC (RR 0.71; 95% CI 0.56-0.91 for ACEIs and RR 0.79; 95% CI 0.68-0.91 for ARBs) but none affected all-cause mortality (RR 0.96; 95% CI 0.85-1.09 for ACEIs and RR 0.99; 95% CI 0.85-1.16 for ARBs).ConclusionTreatment of patients with diabetic nephropathy with a RAAS blocker reduces the risks of ESRD and DSC, but does not affect all-cause mortality. These findings are added to the evidence of a renoprotective role of RAAS blockers in such patients.American Journal of Hypertension (2008). doi:10.1038/ajh.2008.206American Journal of Hypertension (2008); 21, 8, 922-929. doi:10.1038/ajh.2008.206.     

Epicardial Coronary Spasm in Women With Angina Pectoris and Unobstructed Coronary Arteries Is Linked With a Positive Family History: An Observational Study

Purpose

Coronary spasm is frequently found in patients with angina and unobstructed coronaries. The pathophysiology is incompletely understood, although sex differences have been described. Often a positive family history (PFH) is encountered. We assessed the relationship between sex, coronary spasm, and a PFH for cardiovascular disease.

Diabetic nephropathy and antihypertensive treatment: what are the lessons from clinical trials?

Diabetic nephropathy is the most serious problem among current issues in nephrology, as 40% of the cases of end-stage renal disease are due to this entity. The close relationship between type 2 diabetes and hypertension makes the problem even more severe. The knowledge of the intrarenal effects of angiotensin II and the greater effect of angiotensin converting enzyme inhibitors (ACEI) on reducing albuminuria suggested in the past a trend toward preferable use of these drugs in diabetic nephropathy. The first relevant clinical trials yielded rather poor conclusions because of lack of blind randomization and short duration. Subsequent double-blind studies with adequate numbers of patients and sufficient duration underlined the importance of blood pressure (BP) control as well as the rather poor response of diabetic nephropathy to any treatment. In most of these studies, the changes in albuminuria or microalbuminuria were a substitute end point for the renal function. Three clinical trials using angiotensin II receptor blockers (ARB), planned specifically to monitor the progression of renal damage, have been recently published. They showed better renal protection by ARB, as compared with placebo or calcium channel blockers (CCB), beyond or independently of the BP reduction. Nevertheless, these recent trials, like the previous ones with similar results, invariably demonstrate slightly better control of BP in the groups of the active drug. Another issue is that the vast majority of the patients need so many nonstudy drugs to keep their pressure under control, that the isolation of advantageous effects of certain drugs seems unrealistic.     

Age-related changes in oral motor-control strategies during unpredictable load demands in humans

To investigate age-related changes in oral motor strategies in response to unpredictable load demands. Sixty-five healthy children (aged 3–17 yr) were divided into five age-groups based on their dental eruption stages and compared with a group of healthy adults (aged 18–35 yr). Each participant was asked to perform a standardized motor control task involving ‘pulling’ and ‘holding’ a force transducer with the anterior teeth. Different loads were attached to the force transducer in an unpredictable manner. The temporal force profile was divided into two time-segments (an initial segment and a later segment). The peak force and peak force rate during the initial time-segment, and the holding force and intra-trial variability (coefficient of variation) during the later time-segment, were measured. The results showed no differences in the peak force, peak force rate, holding force, and force variability in children compared with adults. However, the trends in the data evaluated using a segmented regression analysis showed that a breakpoint (abrupt change) consistently occurred in the late-mixed dentition group (age 9–11 yr) for most of the outcome variables. The results indicate that while the motor control strategies in children appear to be similar to those in adults, there is a shift in the oral motor developmental trend during the late-mixed dentition stage.     

An update on red blood cell storage lesions,as gleaned through biochemistry and omics technologies

Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high‐energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affect RBC morphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long‐stored RBCs and promote the rapid clearance of up to one‐fourth of long‐stored RBCs from the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of stored RBCs have observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects.