Impact of recombinant human growth hormone (RH-GH) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults. A placebo-controlled trial.

BACKGROUND: Untreated GH-deficient adults have a diversity of dysfunctions (e.g. reduced muscle strength, emotional instability during stress, depressive symptoms) that may cause deleterious effects on quality of life, and may be positively influenced by recombinant human growth hormone (rh-GH) therapy. AIM: To evaluate the impact of a clinical intervention with rh-GH therapy on GH- deficient adults. METHOD: The physical, psychiatric and neuropsychological status of 9 GH-deficient adults was determined before and after the administration of rh-GH (0.250 IU/Kg/week) in a double blind placebo-controlled trial for six months. Patients then received rh-GH for a further period of 6 months and their status was re-evaluated. RESULTS: Rh-GH was significant better than placebo at 6th month (p < 0.05), producing increased serum Insulin like growth factor-I (IGF-I) levels, reduced body mass index (BMI) and body fat, increased lean body mass and water, reduced waist/hip ratio and increased energy expenditure. The rh-GH therapy was also significantly better than placebo on depressive features as measured by the Hamilton Depression Scale (17-items) (p = 0.0431) and the Beck Depression Inventory (p = 0.0431). Neuropsychological evaluations showed significant improvements in measures of Attention: Digit Backward (p = 0.035), Verbal Fluency (FAS) (p = 0.02) and Cognitive Efficiency (WAIS-R tests): Vocabulary (p = 0.027), Picture Arrangements (p = 0.017), and Comprehension (p = 0.01) following rh-GH therapy. CONCLUSION: The clinical, psychiatric, and neuropsychological impairments of untreated GH-deficient adults can be decreased by rh-GH therapy.

A model of persistent partial hindlimb ischemia in the rabbit.

An animal model of resting limb ischemia in the rabbit was developed and studied. Anesthetized rabbits underwent unilateral common iliac artery (CIA) division, allowing comparisons between an experimental (ischemic) and the contralateral control limb in the same animal. The time course and severity of the ischemic insult were measured by quantitating muscle blood flow in seven muscle groups using 57Co-radiolabeled microspheres, limb femoral arteriovenous oxygen differences (AVDO2), and limb arterial pressure. Nine of 20 animals had objective evidence of functional limb impairment judged by abnormal resting posture and/or abnormal gait. Muscle blood flow in the experimental limbs became significantly less than blood flows of corresponding contralateral muscle groups (P less than 0.05) when measured at 1 week after CIA division. By 17 days, mean muscle blood flow had returned to within 82.5% of that of the control limb. AVDO2 increased from 4.8 +/- 0.99 to 8.13 +/- 2.26 ml O2/dl blood following CIA division and remained persistently greater than the control limb value until Day 31. Limb arterial pressure decreased markedly after CIA division and remained significantly depressed beyond 6 weeks when the study was terminated. The reasons for the differential time courses of these parameters of blood flow are discussed. Common iliac artery division in the rabbit appears to produce persistent, partial ischemia at least 17 days in duration, allowing in-depth study of the effects of persistent limb ischemia on muscle cell function in the laboratory setting, as well as permitting the assessment of various therapeutic manipulations for the treatment of prolonged muscle ischemia.