An approach to protein restriction in children with renal insufficiency

Children with mild to moderate renal insufficiency may be at an increased risk for developing glomerulosclerosis and subsequent renal failure. Low protein diets (LPD) have been shown to delay the progression of renal insufficiency in laboratory animals and may be of benefit in adult humans. The nutritional costs of a LPD in adults are reportedly minimal. We review the protein and caloric requirements of growing children and discuss the potential harmful effects and benefits of an LPD in this population. We also discuss dietary adherence and the difficulty of designing an LPD for children. We conclude that the protein content of a typical American diet can safely be reduced to, but not below, the recommended daily allowance for protein if diets are carefully planned, patients and their parents extensively counseled, and if dietary supplements are given to help meet the caloric and vitamin-mineral nutrient needs of growing children. In addition, ongoing nutritional assessment, counseling, and frequent monitoring of growth, diet and biochemical indicators of protein status are essential for maintaining the health of these children.     

Pyridinium crosslinks of collagen as a marker of bone resorption rates in children and adolescents: Normal values and clinical application

The aim of our study was to establish normal values of urinary pyridinoline (Pyr) and deoxypyridinoline (DPyr) excretion for children aged 3–18 years, examine the biological variability of the marker, and assess its clinical value for pediatric patients with growth hormone deficiency. Pyr and DPyr was measured in first void urine samples from 692 healthy subjects (340 boys, 352 girls) by high-performance liquid chromatography. At sampling, age, body height, and weight was recorded for all individuals. Short-term variability in crosslinks excretion was examined in four healthy children. The clinical value of the marker was studied in seven patients with growth hormone (GH) deficiency. In childhood, crosslinks excretion exceeded normal adult values by about fivefold and declined during puberty. In the age range of 13–18 years, gender-related differences in Pyr and DPyr levels were observed, presumably resulting from the earlier onset of puberty in girls. Urinary levels of Pyr and DPyr were highly correlated both in males and females. Pyr/DPyr ratio was significantly higher in adolescents than children, suggesting enhanced release of Pyr from extraosseous sources. In both genders, neither age nor anthropometric variables showed a linear effect on crosslinks excretion. The range of within-subject, short-term variability in urinary Pyr and DPyr was relatively high (CV: 6%–21%), indicating that single measurements of crosslinks excretion may not adequately reflect bone resorption rates in children. Pyr and DPyr levels were significantly lower in GH-deficient patients and normalized during human growth hormone (hGH) therapy. Significant correlations between growth velocity (GV) and crosslinks levels were found, but individual prediction of GV increment during hGH treatment may be inaccurate. Pyr/DPyr ratio was not related to GV. It is concluded that measurement of urinary Pyr and DPyr excretion in children may be a valuable tool to assess bone resorption rates in population-based studies. In individual patients, however, only qualitative evaluation of disease severity and response to treatment seems justified.     

Pulsed CO2 laser tissue ablation: effect of tissue type and pulse duration on thermal damage

Tissue removal by infrared lasers is accompanied by thermal damage to nonablated tissue. The extent of thermal damage can be controlled by a choice of laser wavelength, irradiance, and exposure duration. The effect of exposure duration has been studied in vivo by using CO2 lasers with pulse widths that vary from 2 microseconds to 50 msec. Pulse widths of 50 msec, typical of a shuttered, continuous-wave CO2 laser, produce damage regions 750 micron wide in normal guinea pig skin; the use of a 2-microseconds-long pulse reduced this damage zone to as little as 50 micron. Using 2-microseconds-long pulses, in vitro studies showed that the minimum zone of thermal damage varied significantly with tissue type. The thermal denaturation of these tissues has been studied and correlated with damage. The effect of denaturation temperature and pulse duration on the width of the damage zone is explained by a simple model.     

Secretogranin I (chromogranin B) mRNA accumulation is hormonally regulated in GH3B6 rat pituitary tumor cells

Secretogranin I (SgI; chromogranin B) belongs to a class of acidic tyrosine-sulfated secretory proteins believed to play a role in the secretory process of endocrine cells. Our aim here was to compare the levels of SgI mRNA to that of prolactin (PRL) and growth hormone (GH), using rat pituitary cell lines. As far as the constitutive expression is concerned, we found a positive correlation between SgI mRNA and PRL mRNA levels. However, the neuropeptide TRH (50 nM) inhibited the accumulation of SgI mRNA in GH3B6 cells whereas, as expected, it induced a rapid and sustained increase in PRL mRNA accumulation. By contrast, 17β-estradiol (1 nM) stimulated the accumulation of both SgI and PRL mRNAs, with the same EC₅₀ (18–59 pM). Reciprocally, treatment with dexamethasone (100 nM) reduced the level of SgI and PRL mRNAs to 23% and 29% of control, respectively, but led to a 2.1-fold increase in the GH mRNA level. Altogether, the present work shows that SgI gene expression is subject to multiple hormonal regulations and occasionally parallels the regulation of the PRL gene but never that of the GH gene, under the conditions tested.     

Interactions between growth hormone and dexamethasone in skeletal growth and bone structure of the young mouse

Summary The present study investigated the interactions of growth hormone (GH) and glucocorticoid on skeletal growth and bone structure in young mice. The purpose of this study was to examine the possible prevention by GH of the damage inflicted by dexamethasone (Dex) at sites of skeletal growth and ossification. Dex (1 mg/kg) with or without rat GH (rGH) or bovine GH (bGH), 1 mg/kg, was given for 4 weeks, from age 3–7 weeks, to female ICR mice. Tibiae, humerus, and vertebrae were analyzed morphometrically and biochemically. Growth, as determined by the mouse weight, tibial length, and humerus protein content was found to be compromised by dexamethasone. This was prevented by rGH or bGH. The epiphyseal growth plate width, trabecular bone volume, cortical bone width, mineral bone content, and alkaline and acid phosphatase activity were decreased by dexamethasone. These were prevented by rGH or by bGH. The findings of the present study suggest that in the mouse, GH can decrease or even avoid some of the pathological features in growing bones inflicted by high-dose glucocorticoid treatment.     

Relationship between growth hormone and Somatomedin-C levels in untreated acromegaly, after surgery and radiotherapy and during medical therapy with Sandostatin (SMS 201–995)

Abstract. Several conflicting reports have been published with regard to the relationships between circulating growth hormone (GH), Somatomedin-C (SM-C) levels and clinical activity during different stages of therapy of acromegaly. We did not find a significant correlation between (fasting, post-prandial and mean 24-h) plasma GH and SM-C concentrations in twenty-two untreated acromegalic patients. There was a statistical significant correlation, however, if only the GH levels below 100 μg l^-1 were considered (n=18 patients, P<0·01). The distribution of molecular forms of GH (‘little’, ‘big’ and ‘big-big’) did not differ between the four patients with GH levels above 100 μg l^-1 and in four patients with levels between 40 μg l^-1 and 80 μg l^-1. Therefore, it is suggested that GH levels of 80–100 μg l^-1 maximally activate Somatomedin-C production in man and that further increases in GH in general will not result in a further increase in SM-C generation. There was a significant correlation between GH and SM-C levels in forty-nine acromegalic patients after surgery and/or radiotherapy (P<0·001). In twenty-three of thirty-one patients with elevated SM-C levels the disease was subjectively still active, while this was the case in none of the patients with normal SM-C levels. In eight patients the disease was considered not to be clinically active any more, despite slightly increased SM-C levels. During long-term therapy of ten acromegalic patients for 16–108 weeks (mean 66±10) with 200–300 μg Sandostatin subcutaneously, clinical activity of the disease disappeared well before mean 24–h GH and SM-C levels reached the normal levels. There was a close correlation between mean 24-h GH and SM-C levels during Sandostatin therapy (P<0·001). ‘Clinical cure’ during this medical treatment was reached in five patients, as reflected by disappearance of subjective complaints, normalization of SM-C levels and 24-h mean GH levels of 2·8±0·2 μg l^-1. Conclusions: (i) in untreated acromegaly, circulating GH and SM-C levels correlate well up to GH concentrations of 100 μg l^-1. A further increase in GH does not result in a corresponding further increase in SM-C levels, suggesting a maximally activated production, without further GH-dependent capacity. (ii) Clinical ‘cure’ of acromegaly often occurs before normalization of the circulating SM-C levels. (iii) The measurement of plasma SM-C concentrations can be used well to adjust the dose and frequency of Sandostatin administration in acromegaly. This avoids the need of measuring extensive 24-h GH profiles.     

劳动姿势对流量－容积曲线的影响─—波速学说的进一步验证

用“点值法”对健康工人４７３例［轻体力劳动工人（简称轻工）２４８例，重体力劳动工人（简称重工）２２５例］。作了流量一容积曲线和常规通气功能检查。结果表明：重工男女在４０岁以后其高肺容积流量下降，３０岁以后低肺容积流量上升，而且这些改变有随年龄增长而更加明显的倾向；轻工仅有个别年龄组的低肺容积流量上升。对７名健康坐位工作者模拟劳动的前倾姿势作多次通气功能检查，亦有明显高肺容积流量下降和低肺容积流量上升的现象，这一事实提示波速学说亦可应用于颈和躯干前倾进行重体力劳动工人的通气行为。     

船舶噪声对豚鼠耳蜗微音电位响应曲线的影响

在排除电场干扰伪迹后，耳蜗微音电位响应曲线可以作为反映近全耳蜗电生理功能的一项测试指标。能方便而迅速地完成测试，结果可靠。船舶噪声暴露后，显示耳蜗损伤频带主要在３．１５～８ｋＨｚ范围。这与人噪声性听力损失的特征非常类似。     

包甲素合成类似物的过筛试验

本文采用豚鼠离体纵长肌累积剂量-效应曲线法,求解离常数(KD)及最大效应(Emax)值,以氨甲酰胆碱为标准药,对14个莨菪烷类化合物进行比较,结果表明:6β-乙酰氧基去甲莨菪烷,3α-对甲苯甲酰氧基-6β-乙酰氧基莨菪烷及3α,6β-二乙酰氧基莨菪烷三化合物有明显的M受体激动作用。其构-效关系提示:6β-乙酰氧基是M激动作用的关健结构,N位上的CH_3能削弱这一作用。