Characterization of 33 488 children and adolescents with type 1 diabetes based on the gender‐specific increase of cardiovascular risk factors

Schwab KO, Doerfer J, Marg W, Schober E, Holl RW. Characterization of 33 488 children and adolescents with type 1 diabetes based on the gender‐specific increase of cardiovascular risk factors. Objectives: Characterization of children with type 1 diabetes (T1DM) regarding number and gender distribution of cardiovascular risk factors (cvRF) and of total cholesterol/high‐density lipoprotein cholesterol ratio (TC/HDL‐C ratio) for risk assessment. Methods: 33488 patients ≤18 years were included in this cross‐sectional analysis and placed into 5 categories by their number of cvRF. Dyslipidemia (TC >200 mg/dL, >5.17 mmol/L; and/or HDL‐C <35 mg/dL, <0.91 mmol/L; and/or LDL‐C >130 mg/dL, >3.36 mmol/L), elevated systolic and/or diastolic blood pressure (BP) ≥90th percentile, obesity >97th percentile, active smoking, and HbA1c ≥7.5% were considered as cvRF. Results: 65% had no or 1 cvRF. HbA1c ≥7.5% was the most frequently occurring cvRF followed by BP ≥90th percentile, dyslipidemia, smoking, and BMI >97th percentile. Age at diabetic onset ranged from 7.7 to 9.2 years and diabetes duration from 4.1 to 6.6 years. CvRF showed differences in disfavour of females except smoking and HDL‐C <35 mg/dL (0.91 mmol/L). Rate of females was 45% with 0 cvRF and 60% with 4 to 5 cvRF. TC/HDL‐C ratio showed no clear association to the number of cvRF. Conclusions: 35% of a pediatric T1DM population develops 2 or more cvRF thus increasing their cv risk in adulthood. With increasing numbers of cvRF, the percentage of girls is rising from 45% to 60% which might contribute to an assimilation of survival rates in female and male adults. TC/HDL ratio does not predict the extent of cardiovascular risk in pediatric T1DM.     

Clearance of inulin,diodrast, chloride and phosphate under mercurial diuresis: Intensive study of a patient in severe cardiac failure

A patient in severe cardiac decompensation was subjected to clearance tests of inulin, diodrast, chloride and phosphate over a period of eight weeks. The urinary output, daily weight and clearance figures, together with the $\text{U}\text{P}$ ratios of inulin, chloride and phosphate were tabulated. The $\text{U}\text{P}$ chloride was plotted against the $\text{U}\text{P}$ inulin in order to assess the reabsorption of chloride in the distal tubules in terms of water reabsorbed by the proximal tubules. The same was done in the case of phosphate.Similar determinations were made under conditions resulting from the administration of mercupurin, and the data were plotted and compared with data drawn from experiences with normal individuals in varying degrees of water diuresis.Evidence was found to support the idea that the oliguria of cardiac decompensation is not the function of a decreased filtration rate, and that the large outputs associated with mercurial diuresis are not the results of an increase in filtration rate. It, therefore, appeared probable that the fluid retention of cardiac decompensation should be considered, as referring directly to the renal tubules, and that the action of the mercurial diuretic was first on the proximal tubules and second and specifically upon the behavior of the distal tubules toward chloride.     

Neuropathology of subarachnoid phenol-glycerin

Summary An analysis is presented of the neuropathological findings in a 39-year-old man with severe multiple sclerosis who received two subarachnoid injections of phenol in glycerin for the relief of spastic paraparalysis in flexion contracture and of the findings in a single root from another patient. The morphology and extent of the pathological processes are described.Extensive damage to both anterior and posterior roots involving fibres of all sizes, accompanied by localized arachnoiditis, was observed.The effect on spasticity was excellent, but it was obtained at the expense of destruction of sensory roots which was more extensive than was necessary and desirable.

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Zusammenfassung Die neuropathologischen Befunde eines 39 jährigen Mannes mit schwere multipler Sklerose, der zwei subarachnoidale Injektionen von Phenolglycerin zur Milderung der spastischen Paraparese in Beugekontraktur erhalten hatte, werden erörtert; der Befund an einer einzelnen Wurzel bei einem anderen Patienten wird mitgeteilt. Morphologie und Ausdehnung der pathologischen Veränderungen werden beschrieben. Es wurden ausgedehnte Schädigungen sowohl der Vorder- als auch der Hinterwurzeln beobachtet, die Fasern aller Kaliber betrafen und von lokalisierter Arachnoiditis begleitet waren. Die Wirkung auf die Spastizität war ausgezeichnet, sie erfolgte jedoch auf Kosten der Zerstörung sensibler Wurzeln, die ausgedehnter war, als notwendig und wünschenswert erschien.

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With 4 Figures in the Text     

Impact of mutations at residue I223 of the neuraminidase protein on the resistance profile, replication level, and virulence of the 2009 pandemic influenza virus

Amino acid substitutions at residue I223 of the neuraminidase (NA) protein have been identified in 2009 pandemic influenza (pH1N1) variants with altered susceptibilities to NA inhibitors (NAIs). We used reverse genetics and site-directed mutagenesis to generate the recombinant A/Québec/144147/09 pH1N1 wild-type virus (WT) and five (I223R, I223V, H275Y, I223V-H275Y, and I223R-H275Y) NA mutants. A fluorimetry-based assay was used to determine 50% inhibitory concentrations (IC(50)s) of oseltamivir, zanamivir, and peramivir. Replicative capacity was analyzed by viral yield assays in ST6GalI-MDCK cells. Infectivity and transmission of the WT, H275Y, and I223V-H275Y recombinant viruses were evaluated in ferrets. As expected, the H275Y mutation conferred resistance to oseltamivir (982-fold) and peramivir (661-fold) compared to the drug-susceptible recombinant WT. The single I223R mutant was associated with reduced susceptibility to oseltamivir (53-fold), zanamivir (7-fold) and peramivir (10-fold), whereas the I223V virus had reduced susceptibility to oseltamivir (6-fold) only. Interestingly, enhanced levels of resistance to oseltamivir and peramivir and reduced susceptibility to zanamivir (1,647-, 17,347-, and 16-fold increases in IC(50)s, respectively) were observed for the I223R-H275Y recombinant, while the I223V-H275Y mutant exhibited 1,733-, 2,707-, and 2-fold increases in respective IC(50)s. The I223R and I223V changes were associated with equivalent or higher viral titers in vitro compared to the recombinant WT. Infectivity and transmissibility in ferrets were comparable between the recombinant WT and the H275Y or I223V-H275Y recombinants. In conclusion, amino acid changes at residue I223 may alter the NAI susceptibilities of pH1N1 variants without compromising fitness. Consequently, I223R and I223V mutations, alone or with H275Y, need to be thoroughly monitored.     

Non‐steroidal antiandrogen monotherapy compared with luteinizing hormone‐releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer: a Cochrane systematic review

To assess the effects of non‐steroidal antiandrogen monotherapy compared with luteinizing hormone‐releasing hormone agonists or surgical castration monotherapy for treating advanced hormone‐sensitive stages of prostate cancer. We searched the Cochrane Prostatic Diseases and Urologic Cancers Group Specialized Register (PROSTATE), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science with Conference Proceedings, three trial registries and abstracts from three major conferences to 23 December 2013, together with reference lists, and contacted selected experts in the field and manufacturers. We included randomized controlled trials comparing non‐steroidal antiandrogen monotherapy with medical or surgical castration monotherapy for men in advanced hormone‐sensitive stages of prostate cancer. Two review authors independently examined full‐text reports, identified relevant studies, assessed the eligibility of studies for inclusion, extracted data and assessed risk of bias as well as quality of evidence according to the GRADE working group guidelines. We used Review Manager 5.2 for data synthesis and the fixed‐effect model as primary analysis (when heterogeneity was low with I² < 50%); we used a random‐effects model when confronted with substantial or considerable heterogeneity (when I² ≥50%). A total of 11 studies involving 3060 randomly assigned participants were included in the present review. Use of non‐steroidal antiandrogens resulted in lower overall survival times (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.05–1.48, six studies, 2712 participants) and greater clinical progression (1 year: risk ratio [RR] 1.25, 95% CI 1.08–1.45, five studies, 2067 participants; 70 weeks: RR 1.26, 95% CI 1.08–1.45, six studies, 2373 participants; 2 years: RR 1.14, 95% CI 1.04–1.25, three studies, 1336 participants), as well as treatment failure (1 year: RR 1.19, 95% CI 1.02–1.38, four studies, 1539 participants; 70 weeks: RR 1.27, 95% CI 1.05–1.52, five studies, 1845 participants; 2 years: RR 1.14, 95% CI 1.05–1.24, two studies, 808 participants), compared with medical or surgical castration. The quality of evidence for overall survival, clinical progression and treatment failure was rated as moderate according to GRADE. Use of non‐steroidal antiandrogens increased the risk for treatment discontinuation as a result of adverse events (RR 1.82, 95% CI 1.13–2.94, eight studies, 1559 participants), including events such as breast pain (RR 22.97, 95% CI 14.79– 35.67, eight studies, 2670 participants) and gynaecomastia (RR 8.43, 95% CI 3.19–22.28, nine studies, 2774 participants) The risk of other adverse events, such as hot flushes (RR 0.23, 95% CI 0.19–0.27, nine studies, 2774 participants) was decreased when non‐steroidal antiandrogens were used. The quality of evidence for breast pain, gynaecomastia and hot flushes was rated as moderate according to GRADE. The effects of non‐steroidal antiandrogens on cancer‐specific survival and biochemical progression remained unclear. Non‐steroidal antiandrogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival, clinical progression, treatment failure and treatment discontinuation resulting from adverse events. Evidence quality was rated as moderate according to GRADE; therefore, further research is likely to have an important impact on results for patients with advanced but non‐metastatic prostate cancer treated with non‐steroidal antiandrogen monotherapy.     

High Exercise Levels Are Related to Favorable Sleep Patterns and Psychological Functioning in Adolescents: A Comparison of Athletes and Controls

PurposeTo investigate whether chronic vigorous exercising is related to improved sleep and psychological functioning, and whether this association varies with gender. Both lay and scientific opinions hold that physical activity is an efficient remedy and preventative measure for poor sleep. However, empirical evidence on adolescents is very limited.MethodsA total of 434 adolescents (258 athletes, 176 controls; mean age 17.2 years) took part in the study. Weekly hours spent exercising were 17.69 hours and 4.69 hours, respectively. To assess sleep patterns and psychological functioning, participants completed a sleep log for 7 consecutive days and several self-rating questionnaires.ResultsCompared with controls, athletes reported better sleep patterns including higher sleep quality, shortened sleep onset latency, and fewer awakenings after sleep onset, as well as less tiredness and increased concentration during the day. Athletes reported significantly lower anxiety and fewer depressive symptoms. Compared with males, females reported fewer variations in sleep. Male controls had particularly unfavorable scores related to sleep and psychological functioning.ConclusionsFindings suggest that chronic vigorous exercising is positively related to adolescents' sleep and psychological functioning. Results also indicate that males with low exercise levels are at risk for increased sleep complaints and poorer psychological functioning.