Final adult height in children with Prader-Willi syndrome with and without human growth hormone treatment

Short stature is characteristic of children with Prader-Willi syndrome (PWS). While previous studies have demonstrated acceleration of linear height velocity with growth hormone (GH) treatment, the long-term benefit on final adult height (AH) has not been reported. The objective of this study was to compare AH attained in PWS subjects with and without GH treatment. We reviewed the records of 21 children (aged 8.3 +/- 2.7 years) with PWS and confirmed GH deficiency that attained AH after receiving human GH treatment (0.25 +/- 0.06 mg/kg/week) for a period of 7.9 +/- 1.7 years. A group of 39 non-GH-treated adults with matched initial height standard deviation score (SDS) at age 6.8 +/- 1.3 years was used as control. In the GH-treated group the mean initial height and AH-SDS was -1.9 +/- 1.7 and -0.3 +/- 1.2 respectively (P < 0.0001), whereas the mean initial and AH-SDS in the control group was -1.9 +/- 1.3 and -3.1 +/- 1 respectively (P < 0.0001). Scoliosis was seen in 43% and 39% in the GH-treated and control group respectively. Premature adrenarche (PA) was noticed in 57% of GH-treated group. Six subjects in the control group but none of the GH-treated subjects developed type 2 diabetes mellitus. Our data show that administration of GH to children with PWS restores linear growth and final AH without significant adverse effects other than PA. Further studies will be necessary to determine related morbidity and mortality in individuals with PWS that reached final AH with or without GH treatment.     

Hesperidin,a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions

Aim: Diabetic neuropathy (DN) is one of the most common long-term complications of diabetes mellitus and clinically can be characterized by an elevated nociceptive response with electrophysiological conduction abnormalities. The present investigation was designed to evaluate the neuroprotective effect of hesperidin against STZ induced diabetic neuropathic pain in laboratory rats.

Materials and methods: DN was induced in Sprague–Dawley rats (150–200?g) by intraperitoneal administration of streptozotocin (STZ) (55?mg/kg, p.o.). Rats were divided into various groups, namely, STZ control (vehicle), hesperidin (25, 50, and 100?mg/kg, p.o.), insulin (10?IU/kg, s.c.), and combination of hesperidin (100?mg/kg, p.o.) with insulin (10?IU/kg, s.c.) for 4 weeks. Various behavioral (allodynia and hyperalgesia), biochemical parameters [oxido-nitosative stress, Na–K–ATPase, aldose reductase (AR)], and molecular changes (TNF-α and IL-1β) along with hemodynamic changes were determined.

Results: Rats treated with hesperidin (50 and 100?mg/kg, p.o., 4 weeks) significantly reduced (p?p?p?Conclusion: In combination with insulin, hesperidin not only attenuated the diabetic condition but also reversed neuropathic pain via control over hyperglycemia as well as hyperlipidemia to down-regulate generation of free radical, release of pro-inflammatory cytokines as well as elevation in membrane bound enzyme.     

Constraints on Compliance and the Impact of Health Information in Rural Pakistan

The provision of information, which is a common public health strategy, may be ineffective if recommendations are not privately optimal for message recipients. This paper evaluates the response to a hygiene information campaign in rural Pakistan. In a theoretical model, baseline hygiene and health proxy for preferences, prices, and wealth, which jointly moderate the impact of information. We show that people with good baseline hygiene and health respond differentially to the hygiene message. This result, which does not appear to arise through differential learning, suggests that practical constraints limit the adoption of hygiene recommendations. Information provision may exacerbate health inequality under these conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

Terpenoid tetrahydroisoquinoline alkaloids emetine, klugine, and isocephaeline inhibit the activation of hypoxia-inducible factor-1 in breast tumor cells

Klugine (1), isocephaeline (2), and emetine (4) inhibited hypoxia-inducible factor-1 (HIF-1) activation by hypoxia in T47D breast tumor cells (IC(50) values 0.2, 1.1, and 0.11 muM, respectively). Compounds 1, 2, and 4 inhibited both hypoxia- and iron chelator-induced HIF-1 activation by blocking HIF-1alpha protein accumulation.     

Delivery of testosterone replacement therapy

Optimal testosterone replacement therapy remains a considerable challenge for the estimated five out of 1000 men in the general community with androgen deficiency. Oral delivery is not possible due to rapid first pass metabolism and short half-life. Testosterone derivatives have been developed to enhance intrinsic androgenic potency, prolong duration of action, or improve oral bioavailability of synthetic androgens. Structural modification of testosterone include 17 beta-esterification, 17 alpha-alkylation, 1-methylation, addition of a 19-normethyl group, and 7 alpha-methylation. Currently, oral (testosterone undecanoate), transcutaneous (Andropatch, Virormone, Testoderm (ALZA Corp), Testogel), sublingual (testosterone cyclodextrin), intramuscular (Sustanon, Primoteston Depot), and fused crystalline testosterone pellet preparations are available for clinical use. Transbuccal testosterone systems have also been developed for clinical use and require twice daily application. Suspensions of biodegradable microspheres consisting of a polyglycolide-lactide matrix laden with testosterone can deliver stable, physiological levels of testosterone for 2 to 3 months. Micronized testosterone has low oral bioavailability requiring high daily doses. 7 alpha-Methyl 19-nortestosterone, a potent, synthetic androgen free of hepatotoxicity, has tissue-specific selectivity, being susceptible to aromatization but not 5 alpha-reduction, thereby potentially avoiding intraprostatic androgen amplification.     

Fundamental perceptions about palliative care among young generations living in Dhaka city,Bangladesh: A short survey

Background: Palliative care is the practical care which seeks toward maximization of quality of life intended for people and families in front of life-threatening illnesses. Though the concept of palliative care is not new, still it is not eminent in Bangladesh. As young generations are future representatives of any society, their basic concepts and knowledge should be clear and broad.

Objective: The endeavor of the study was to ascertain the level of basic concepts and knowledge of young generations living in Dhaka city, Bangladesh about palliative care.

Method: A cross-sectional survey study of young adults (those are living in Dhaka city, Bangladesh) was conducted from April 2016 to November 2016. Information regarding their knowledge and concepts was collected by self-made questionnaire by literature review.

Results: The study was conducted with the total number of 3152 young adults (n?=?3152). Among them 55.01% were male and 44.98% were female. It was found that their age range was between 20 and 28 and most of them (n?=?1643) were between 23 and 25 years. It was also found that 40.31% knew about the concept of palliative care and 62% of their information source was Internet and 14% from books and 8% from health professionals and 12% from mass media and 4% others. And a larger portion of them which was 59.69%, did not know the concept of palliative care. Among those 40.31% young adults who knew about palliative care, 46% believed their concepts were clear about palliative care and 54% thought their concepts were not clear. And astoundingly 78% assumed that palliative care only deals with cancer patients. It is important to notice in the study that, young males are comparatively more aware then young females.

Conclusion: The findings reveal that most of the young adults living in Dhaka city do not have clear concepts and knowledge about palliative care. There should be more awareness-related programs on this aspect.     

Albumin and furosemide for acute lung injury

Citation

Martin GS, Moss M, Wheeler AP, Mealer M, Morris JA, Bernard GR: A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Crit Care Med 2005, 33:1681–1687 [1].

Background

Hypoproteinemia is a common condition in critically ill patients, associated with the development of acute lung injury and acute respiratory distress syndrome and subsequent worse clinical outcomes. Albumin with furosemide benefits lung physiology in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome, but the independent pharmacologic effects of these drugs are unknown.

Methods

Objective

To determine the independent pharmacologic effects of albumin and furosemide in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome.

Design

Randomized, double-blinded, placebo-controlled multicentered trial.

Setting

Eleven medical, surgical, and trauma intensive care units including 190 beds within two university hospital systems.

Subjects

Forty mechanically ventilated patients with acute lung injury/acute respiratory distress syndrome, whose serum total protein concentrations were <6.0 g/dL were included. Patients were excluded for hemodynamic instability or significant renal or hepatic failure.

Intervention

Subjects were equally randomly allocated to receive furosemide with albumin or furosemide with placebo for 72 hrs, titrated to fluid loss and normalization of serum total protein concentration.

Outcomes

The primary outcome was change in oxygenation from baseline to day 1, with secondary physiologic and clinical outcomes.

Results

There were no differences in baseline characteristics of the subjects in relation to group assignment. Albumin-treated patients had greater increases in oxygenation (mean change in Pao2/Fio2: +43 vs. -24 mm Hg at 24 hrs and +49 vs. -13 mm Hg at day 3), serum total protein (1.5 vs. 0.5 g/dL at day 3), and net fluid loss (-5480 vs. -1490 mL at day 3) throughout the study period (all p < .05). Fluid bolus administration to control patients reduced net negative fluid balance; control patients more frequently developed hypotension and had fewer shock-free days, which translated to differences in organ failure at study end. Apart from more frequent hypotension in the control group, there were no adverse events. There were seven deaths in the treatment group and nine in the control group (35% vs. 45% mortality rate; p = .52).

Conclusion

The addition of albumin to furosemide therapy in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome significantly improves oxygenation, with greater net negative fluid balance and better maintenance of hemodynamic stability. Additional randomized clinical trials are necessary to examine mechanisms and determine the effect on important clinical outcomes, such as the duration of mechanical ventilation.