羧乙基锗倍半氧化物对正常和异丙基肾上腺素损伤培养乳鼠心肌细胞的影响

羧乙基锗倍半氧化物(Ge—132)能促进培养乳鼠心肌细胞DNA和RNA的合成,提高超氧化物歧化酶(SOD)的活性,维持细胞膜结构的稳定。异丙基肾上腺素可使心肌细胞乳酸脱氢酶(LDH)释放增加,细胞搏动停止,超微结构显示肌膜和线粒体严重受损。Ge—132可显著减少异两基肾上腺素引起心肌细胞释放LDH,维持细胞的搏动功能和超微结构的完整。     

固相法合成心肌兴奋肽及其类似物

用Boc-和Tos-基团分别保护氨基和侧链胍基,以1%交联度聚苯乙烯二苯甲氨基树脂为载体,用DCC固相法合成肽,HF断裂肽树脂键和去除侧链保护基团,粗产物经高效液相层析纯化,合成了心肌兴奋肽Phe-Met-Arg-Phe-NH_2及其类似物Phe-Pro-Arg-Phe-NH_2,并观察了此二种肽对大鼠血压和心率的影响。     

Acute multifocal hemorrhagic retinal vasculitis

The authors present a series of seven patients with acute visual loss associated with mild anterior uveitis, multifocal retinal vasculitis, retinal capillary nonperfusion, retinal hemorrhage, disc swelling, and vitreitis. Oral prednisone was of some benefit in these patients and oral acyclovir was generally ineffective. Neovascular complications including retinal, disc, choroidal, and iris new vessels were common, requiring photocoagulation in five patients. Horseshoe tears developed in two patients in zones of uninvolved retina but retinal detachment did not occur. The etiology remains unknown, although it may represent either a localized ocular form of Beh?et's disease or other systemic syndrome, infection with a herpes group virus other than zoster varicella virus, or a manifestation of an undefined infectious agent.     

Short-term treatment of short stature and subnormal growth rate with human growth hormone

Forty-eight children with short stature, growth rate less than 4 cm/yr, and normal growth hormone response to secretagogues were given exogenous human growth hormone (hGH) for 6 months to determine its effect on the short-term growth rate in these children. All except three had an increase in growth rate with hGH therapy. The mean +/- SD pretreatment growth rate (3.4 +/- 0.8 cm/yr) was significantly less than either the growth rate during 6 months of hGH therapy (6.9 +/- 2.6 cm/yr) or after therapy (4.1 +/- 1.8 cm/yr). Several patterns of response were observed after treatment was stopped: the mean growth rate in 22 children decreased after treatment but remained above basal rates, the mean growth rate in seven children was similar to the rates during treatment, and the mean growth rate in 16 children was less than basal rates. Twenty children received therapy for an additional 6 months and had a mean increase in growth rate from 3.6 +/- 1.3 to 6.7 +/- 2.4 cm/yr. The decreased growth rate after discontinuation of treatment and increased rate with resumption of therapy indicates that maintenance of the increased growth rate might be dependent on continuation of hGH therapy.     

Growth-stimulating effects of human growth hormone therapy in patients with Turner syndrome

We determined the effect of pituitary human growth hormone treatment on the growth rate of 52 children with Turner syndrome. The pretreatment growth rate was 3.2 +/- 0.8 cm/yr. Growth hormone treatment (0.2 IU/kg three times per week) resulted in enhancement of the growth rate to 5.9 +/- 1.4 cm/yr for the first year of therapy. The bone age advanced approximately 1 year during the year of therapy. The growth hormone therapy was discontinued at 12 months, and the mean growth rate decreased to pretreatment levels, 3.1 +/- 1.9 cm/yr; 26 of 41 patients actually had post-treatment growth rates that were less than the pretreatment rate. Glucose tolerance tests at 6-month intervals did not indicate an effect of hGH treatment on glucose intolerance. Several patients had glucose intolerance that preceded hGH treatment, but this remained stable during treatment; glucose intolerance likely was related to obesity in this group of patients. Basal and hGH-stimulated somatomedin C levels (32 patients) correlated with age of the patient but not with growth rate during therapy. We conclude that hGH therapy can accelerate the growth rate of patients with Turner syndrome. The growth rate increased to "normal" levels and was dependent on continued treatment with hGH. If the response continues, long-term treatment of Turner syndrome may result in increased adult height.     

Global strategies to reduce the price of antiretroviral medicines: evidence from transactional databases

Objective

To estimate the impact of global strategies, such as pooled procurement arrangements, third-party price negotiation and differential pricing, on reducing the price of antiretrovirals (ARVs), which currently hinders universal access to HIV/AIDS treatment.

Methods

We estimated the impact of global strategies to reduce ARV prices using data on 7253 procurement transactions (July 2002–October 2007) from databases hosted by WHO and the Global Fund to Fight AIDS, Tuberculosis and Malaria.

Findings

For 19 of 24 ARV dosage forms, we detected no association between price and volume purchased. For the other five ARVs, high-volume purchases were 4–21% less expensive than medium- or low-volume purchases. Nine of 13 generic ARVs were priced 6–36% lower when purchased under the Clinton Foundation HIV/AIDS Initiative (CHAI). Fifteen of 18 branded ARVs were priced 23–498% higher for differentially priced purchases compared with non-CHAI generic purchases. However, two branded, differentially priced ARVs were priced 63% and 73% lower, respectively, than generic non-CHAI equivalents.

Conclusion

Large purchase volumes did not necessarily result in lower ARV prices. Although current plans for pooled procurement will further increase purchase volumes, savings are uncertain and should be balanced against programmatic costs. Third-party negotiation by CHAI resulted in lower generic ARV prices. Generics were less expensive than differentially priced branded ARVs, except where little generic competition exists. Alternative strategies for reducing ARV prices, such as streamlining financial management systems, improving demand forecasting and removing barriers to generics, should be explored.     

Management of Obesity in Adults with CKD

Obesity is a leading public health problem that currently affects over 650 million individuals worldwide. Although interest in the adverse effects of obesity has grown exponentially in recent years, less attention has been given to studying its management in individuals with CKD. This relatively unexplored area should be considered a high priority because of the rapid growth and high prevalence of obesity in the CKD population, its broad impact on health and outcomes, and its modifiable nature. This article begins to lay the groundwork in this field by providing a comprehensive overview that critically evaluates the available evidence related to obesity and kidney disease, identifies important gaps in our knowledge base, and integrates recent insights in the pathophysiology of obesity to help provide a way forward in establishing guidelines as a basis for managing obesity in CKD. Finally, the article includes a kidney-centric algorithm for management of obesity that can be used in clinical practice.     

Pulmonary Function in Scleroderma

Pulmonary function tests were performed in 45 patients with scleroderma. Thirteen patients (29%) were found to have restrictive disease, 12 patients (27%) were found to have obstructive disease, and 19 patients (42%) had small airway disease (SAD). Smoking did not seem to be a factor underlying either obstructive or small airway disease in these patients. A low diffusing capacity was most common in patients with restrictive disease and rarely the only abnormality in pulmonary function. SAD was usually found in patients who had normal chest radiographs and no pulmonary symptoms and was often the only abnormality. SAD is therefore an early and sensitive indicator of pulmonary involvement in scleroderma.     

Histopathologic factors conducive to experimental ventricular tachycardia

Ventricular tachyarrhythmia is the leading cause of sudden cardiac death. Determination of the substrates conducive to the initiation of this arrhythmia remains an important clinical goal. The purpose of this study was to correlate histopathologic findings, specifically: pattern (heterogeneous versus homogeneous infarct morphology), distribution (viable epicardial and/or endocardial rim), and infarct size, with susceptibility to the initiation of sustained ventricular tachycardia employing programmed electrical stimulation in two canine models of experimental myocardial infarction. Twenty-one adult dogs were randomly divided into two groups: 12 dogs underwent two-stage, 2-hour occlusion of the proximal left anterior descending coronary artery and nine animals underwent permanent, complete occlusion of the left anterior descending coronary artery with latex embolization. With programmed ventricular pacing with two premature ventricular extrastimuli, initiation of ventricular tachycardia was attempted, open chest, two weeks after infarction. Electrophysiologic evaluation of the infarct type correlated significantly with the histologic morphology of the infarction (p less than 0.001). The presence of a viable epicardial rim was an extremely important variable for ability to induce sustained ventricular tachycardia (p = 0.04). The presence of an endocardial rim was not significant (p = 1.0). Infarct size alone was only marginally related to ventricular tachycardia inducibility (p = 0.08). Nonuniform infarcts were more conducive to the initiation of sustained ventricular tachycardia than were homogeneous infarcts (p = 0.025). The presence of a large, nonuniform infarct correlated best with inducibility (p = 0.0002). Thus in these experimental models, specific infarct morphologies correlate significantly with susceptibility to inducible sustained ventricular tachyarrhythmias.