Growth and growth hormone in children during and after therapy for acute lymphoblastic leukaemia

Growth impairment and growth hormone (GH) deficiency have been reported in children treated for acute lymphoblastic leukaemia (ALL). We have studied growth and GH secretion in a group of 50 patients, affected by ALL, during a 2- to 5-year period after diagnosis, and in 12 long-term-survivors. We observed a significant decrease in growth velocity during the 1st year (in particular during the first 6 months) of therapy and a catch-up growth after the end of therapy. Longterm survivors did not exhibit a significant reduction of height standard deviation score (SDS), as compared to height SDS at diagnosis. None of the patients showed GH deficiency. Our data indicate that chemotherapy significantly affects growth of patients treated for ALL, whereas radiotherapy-at the doses used in this study-does not induce GH deficiency, at least not within 9 years after diagnosis.     

Septo-optic dysplasia and growth hormone deficiency: accelerated pubertal maturation during GH therapy

We report four patients (three male, one female) with septo-optic dysplasia and growth hormone deficiency. All had GH therapy for a period of four to eight years until reaching final height. In all four cases bone maturation during puberty was accelerated (1.4 to 1.9 "years"/year), resulting in a final height which was clearly below the predicted height. The progress of pubertal stages was very short in all patients. In three patients TSH and prolactin release after TRH stimulation were increased. These data support a hypothalamic original of the endocrine disorder. Insufficient GH release, even after repeated GHRH stimulation, is in contrast to this assumption. In one case there was a late manifestation of neurohormonal diabetes insipidus, which indicates the possibility of later disease progression. MR imaging of the brain demonstrated variable malformation of the septum pellucidum, chiasma and nervus opticus or the pituitary gland, respectively.     

Growth plate injury of the long bones in treated β-thalassemia

In 12 patients affected by thalassemia major who received an intensive transfusion regimen combined with continuous iron chelation therapy (desferrioxamine 50–80 mg/kg daily), radiologic abnormalities of the long bones were observed similar to those observed in rickets and scurvy. These abnormalities were associated with a growth retardation. The pathogenesis of these lesions is uncertain, but probably the toxic effect of desferrioxamine plays an important role in their development. A relative deficiency of vitamins D and/or C cannot be entirely excluded.     

The effect of growth hormone on the growth failure of chronic renal failure

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX,n=40), GH-treated nephrectomized rats (NX+GH,n=18), sham-operated rats fed ad libitum (SHAMAL,n=27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF,n=10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean±SEM) 49±3 and 54±4 mg/dl, respectively, compared with 16±4 and 19±0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0±3.3 g) and length (3.5±0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2±4.0 g,P<-0.0001 and 4.1±0.2 cm,P<-0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2±5.0 g) and length (3.4±0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81±2 mg/dl versus 55±3 mg/dl in SHAMAL (P0.0001), was not increased in the NX+GH group, 87±3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.     

Crystallisation of calcium oxalate dihydrate in normal urine in presence of sodium copper chlorophyllin

Summary A method is described for the growth of calcium oxalate dihydrate in normal urine. Soluble chlorophyllin, at a concentration of 20 g/ml inhibited the crystallisation and the growth kinetics of the dihydrate crystals. The inhibitory capacity of chlorophyllin was compared with previous results. Data obtained suggest that the food and drug colourant chlorophyllin might be useful in the treatment of calcium oxalate stone disease.     

Naloxone effects on β-endorphin,cortisol, prolactin,growth hormone,HVA and MHPG in plasma of normal volunteers

8 mg of naloxone were administered IV to 14 normal volunteers in a placebo-controlled, double-blind experiment. Plasma levels of -endorphin, cortisol, prolactin, growth hormone, HVA and MHPG were determined before and 45 min after administration. Naloxone elicited significant increases in cortisol and MHPG but did not change plasma levels of the other compounds. In an additional experiment on two subjects, 20 mg of naloxone caused elevations of -endorphin as well as of cortisol. This parallel increase indicates that the linkage between the secretion of -endorphin and ACTH/cortisol may be dose-dependent. The increase in MHPG is in agreement with the hypothesized association of noradrenergic hyperactivity and opiate withdrawal.     

转化生长因子-β1和胰岛素对人鼻中隔软骨细胞增殖和分化影响的研究

目的 了解转化生长因子-β1(transforminggrowth factor-beta 1,TGF-β1)和胰岛素对人鼻中隔软骨细胞增殖和分化的影响。方法 体外培养人鼻中隔软骨细胞,采用四甲基偶氮唑蓝(MTT)代谢和35S-Na2SO4掺入的检测比较不同浓度TGF-β1和胰岛素对人鼻中隔软骨细胞的增殖以及软骨基质蛋白多糖合成的影响,观察TGF-β1和胰岛素对软骨细胞表型的影响。结果在15％血清的培养条件下,TGF-β1和胰岛素均能显著促进软骨细胞增殖,且在各自一定的浓度范围内呈量效关系,联合作用效果累加;TGF-β1、TGF-β1和胰岛素联合作用促使软骨基质蛋白多糖的合成量明显提高;TGF-β1使传代软骨细胞去分化提前。结论一定浓度的TGF-β1、胰岛素和TGF-β1 胰岛素对体外培养的人鼻中隔软骨细胞具有显著的促增殖作用。     

Influence of Growth Hormone on a New Marker of Cartilage Metabolism (Chondrex)

The aim of this study was to evaluate the usefulness of a major secretory protein of human chondrocytes (chondrex) as a potential serum marker of bone responsiveness to growth hormone (GH). The study included 18 children (10 F, 8 M), aged 10.9 ± 2.3 years, bone age 8.8 ± 2.7 years, height −2.3 ± 0.22 SDS, affected by isolated idiopathic GH deficiency (GHD). Serum samples for evaluation of chondrex, total, and bone alkaline phosphatase were taken before and 3 and 6 months following treatment with rhGH. The basal serum level of chondrex did not differ between patients (37 ± 22 ng/ml) and controls (33 ± 9.8 ng/ml). Following 6 months of treatment with rhGH, a significant increase of height velocity SDS (from −2.8 ± 0.5 to 1.3 ± 0.7), total (from 195 ± 47 to 264 ± 79 U/liter) and bone alkaline phosphatase (from 81 ± 21 to 108 ± 30 U/liter) was observed, while chondrex serum level remained unchanged (from 37 ± 22 to 36 ± 29 ng/ml). It was concluded that chondrex cannot be considered a reliable marker of bone responsiveness to GH in the growing child. Received: 19 March 1999 / Accepted: 3 February 2000     

关节－干骺端软骨细胞移植修复兔桡骨缺损

目的研究组织工程软骨移植于成年兔桡骨缺损后的生长、分化与转归特点,以及引导性骨再生和骨缺损的修复机制。方法取自一日龄新生兔关节－干骺端复合物的软骨细胞在几丁质纤维网中增殖21d后装入硅胶管内,套接在成年兔桡骨干1cm的缺损处（实验组12只）;对照组10只在缺损处套接空硅胶管,2只仅填入裸几丁质纤维。术后4周两组各处死3只动物取材,其余在术后16周取材。结果实验组术后4周3只动物的工程软骨组织在骨缺损内形成软骨样组织,术后16周9只动物中有2只动物的缺损愈合。对照组术后4周已开始骨愈合,术后16周9只动物的骨缺损全部愈合。结论新生兔关节－干骺端复合物的软骨细胞在成年兔桡骨缺损区（套管内）未肥大钙化,未再现软骨内化骨过程。缺损内的工程软骨可能因占据空间、阻碍成骨成分进入而中断了骨缺损修复过程。引导性骨再生的机制可能是人工膜管加强了骨膜的天然引导作用而促进了骨愈合。     

Organ-specific acellular matrix for reconstruction of the urinary tract

In urology, replacement of organs or organ segments has proved problematic. Current techniques do not replicate complete organ function, and they cause well-known complications. With the acellular organ-specific matrix we have found a way to regenerate tissue components seen in the normal lower urinary tract. The time required for regeneration depends on the matrix size and function. The matrix is covered by urothelium migrating from the host, after which neovascularization occurs, followed by formation of smooth-muscle cells and nerves. In our studies, normal muscle lining and nerves providing functional tissue were demonstrable and no sign of antigenicity was evident, even after heterologous grafting. The regenerated rat bladder was evaluated by organ bath as well as by in vivo functional tests and demonstrated properties and functions similar to those of host tissue. Besides our obtaining encouraging results in the rat bladder, we also studied the organ-specific acellular matrix in other species (dog and rabbit) and other organ segments (ureter and urethra).