Management of arthritis of the hip in the young adult.

Arthritis of the hip in the young adult can be a disabling condition. Recent years have witnessed extensive research related to the management of this condition. This article reviews the current status with regard to aetiology, diagnosis and treatment of arthritis of the hip in the young adult.

High concentration of leptin stimulates myeloid differentiation from human bone marrow CD34+ progenitors: potential involvement in leukocytosis of obese subjects.

OBJECTIVE AND DESIGN: As well as its involvement in control of adipose mass and body energy balance, several reports suggest a link between leptin and hemopoiesis. To test its putative role in human hemopoiesis, we developed a homologous system, ie recombinant human leptin treatment of purified CD34+ progenitors from adult human bone marrow. RESULTS: Leptin (50-100 ng/ml) significantly stimulated the appearance of granulocyte-macrophage colonies in the presence or absence of erythropoietin. The concentration of leptin required for this effect was rather high but within the range of plasma leptin levels observed in obesity. Two results further support the hypothesis that leptin may be involved in the leukocytosis associated with obesity: (i) leptin concentrations in bone marrow and plasma of subjects studied were highly correlated; (ii) leptin and leukocyte count were correlated only in obese subjects. Paracrine effects of locally released leptin from bone marrow adipocytes could also be involved in the regulation of hemopoiesis, a hypothesis supported by marrow immunocytochemistry revealing the close association of CD34+ cells with adipocytes and by previous demonstration that leptin is secreted at a high level by these cells. CONCLUSION: These results indicate that leptin acts on human multilineage CD34+ cells and that high plasma leptin levels associated with obesity could participate in the differentiation of granulocytes from hemopoietic progenitors.

High expression of leptin by human bone marrow adipocytes in primary culture.

Adipocytes participate in the microenvironment of the bone marrow (BM), but their exact role remains to be determined. It has recently been shown that leptin, a hormone secreted from extramedullary adipocytes, could be involved in hematopoiesis. Therefore we have developed a primary culture system of human BM adipocytes to characterize their differentiation and determine whether leptin is also secreted from these adipocytes. BM cells were cultured with fetal calf and horse sera. In the presence of dexamethasone, cells with vesicles containing lipids appeared within 15 days. They expressed glycerol phosphate dehydrogenase activity and a lipolytic activity in response to isoproterenol, but expressed neither the adrenergic beta3 receptor nor the mitochondrial uncoupling protein UCP1. The addition of insulin alone to the culture media did not promote adipocyte differentiation. Leptin was expressed and secreted at high levels during adipocyte differentiation. Acute exposure of differentiated adipocytes to insulin had little effect on leptin expression whereas forskolin strongly inhibited it. These results show that although human BM adipocytes differ from extramedullary adipose tissues in their sensitivity to different effectors, they are a secondary source of leptin production. They suggest that BM adipocytes could contribute to hematopoiesis via the secretion of leptin in the vicinity of hematopoietic stem cells.

Effects of oral versus transdermal estrogen on the growth hormone/insulin-like growth factor I axis in younger and older postmenopausal women: a clinical research center study.

To compare the effects of oral vs. transdermal estrogens on GH secretion and levels of circulating insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) in younger vs. older postmenopausal women, we conducted a placebo-controlled, cross-over trial of 6 weeks of oral conjugated estrogen (1.25 mg daily) or transdermal estradiol (100 micrograms/day) administered in random order and separated by an 8-week, treatment-free interval. Sixteen healthy postmenopausal women, ages 49-75 yr, were studied on an NIH-funded General Clinical Research Center grant. Data were analyzed for the combined group as well as in the younger ( 62 yr, n = 8). Spontaneous GH secretion, as assessed by 12-h overnight blood sampling at 20-min intervals; GH responsiveness to i.v. bolus injection of GHRH; and levels of serum IGF-I and IGFBP-3, before and after GHRH stimulation, were measured at enrollment and after 6 weeks of each estrogen treatment. Before estrogen treatment, spontaneous nocturnal GH secretion and morning IGF-I levels tended to be lower, IGFBP-3 levels did not differ, and GHRH-stimulated GH levels were significantly reduced in older vs. younger postmenopausal women. Oral estrogens increased spontaneous GH secretion, decreased serum IGF-I levels, and did not alter IGFBP-3 levels, whereas transdermal estrogens did not alter nocturnal GH secretion or morning IGF-I levels and decreased IGFBP-3 levels only in the older women. GHRH-stimulated GH levels were similar before and after oral or transdermal estrogen treatment. In contrast, after, GHRH administration, IGF-I levels were decreased only with oral estrogens, whereas IGFBP-3 levels were decreased with both oral (younger women only) and transdermal (younger and older women) estrogens. We conclude that, in postmenopausal women, oral and transdermal estrogens exert differing effects on the GH/IGF-I axis, but neither form of estrogen completely reverses the known age-related reductions in spontaneous or GHRH-stimulated GH and IGF-I.

Body weight gain after VMH lesions in adult female rats guanethidine-sympathectomized at birth.

The role of the sympathetic nervous system in body weight gain produced by lesions of the ventromedial nucleus of the hypothalamus (VMH) was studied in adult female rats that had been sympathectomized from birth for 3 weeks with daily injections of guanethidine (0.01 ml/g body weight) starting the second day after birth. Female littermates injected with 0.15 M NaCl served as controls. Body weight gain during the dynamic phase after the VMH lesion was the same in the sympathectomized and control groups of rats, whereas the treated rats gained weight at a slower rate than the controls in the static phase. The increase in food intake stimulated by the VMH lesion peaked sooner and remained elevated longer in the controls than in the experimental animals despite the similar increases in body weight gain. These results indicate that the sympathetic nervous system may play an important role in body weight gain during the static phase following a VMH lesion in adulthood.

Effect of testosterone enanthate on testis size.

We treated chronically 39 normal men with a depot androgen, testosterone enanthate (200 mg. intramuscularly), to assess its potential as a male contraceptive agent. Careful examination and quantification of testicular volume were done before, during and after several dose regimens of androgen therapy. After 4 months of weekly or bimonthly treatment with testosterone enanthate testicular volume decreased by 19.0 plus or minus 2.1 and 16.5 plus or minus 3.4 per cent, respectively. Decrease in testicular volume was related directly to decrease in sperm count. A total of 17 subjects on either weekly or bimonthly injections failed to suppress sperm counts to less than 5 million per cc after 16 weeks; testicular volume was not significantly less than control at this time. Four to 12 weeks of additional weekly injections decreased sperm counts to less than 5 million per cc in 13 of the 17 patients and decreased testicular volume by 23.0 plus or minus 4.8 per cent. The 16 additional weeks of less frequent injections (every 3 or 4 weeks) resulted in an increase in testicular volume with a return to normal size after treatment was discontinued.