Hormonal approaches to preservation and restoration of male fertility after cancer treatment

It is important to develop methods to prevent or reverse the sterility caused by chemotherapy or radiation therapy for cancer in men. Using a rat model, we have shown that infertility after testicular exposure to moderate doses of radiation and some chemotherapeutic agents occurs as a result of the inability of spermatogonia to differentiate. There is evidence that this phenomenon also occurs in men. Spermatogenesis and fertility can be restored in rats following treatment with radiation or some chemotherapeutic agents by suppressing testosterone with gonadotropin releasing hormone (GnRH) agonists or antagonists either before or after the cytotoxic insult. However, species differences exist in the testicular response to radiation or GnRH antagonist therapy, so rescue protocols that work in rodents do not work in nonhuman primates. The applicability of this procedure to humans is still largely unknown. In rodents, suppression of testosterone with GnRH analog treatment also appears to enhance the success of spermatogonial transplantation-an option when all stem cells are killed by cytotoxic therapy.     

Hypothesis: Uric acid, nephron number, and the pathogenesis of essential hypertension

BACKGROUND: Essential hypertension affects more than 25% of the world's population. Genetic, physiologic, and epidemiologic studies provide clues to its origins, but a clear understanding has been elusive. Recent experimental and clinical studies have implicated uric acid in the onset of essential hypertension. METHODS: In a retrospective chart review, we identified 95 children with confirmed, new onset hypertension, and evaluated the cause of hypertension and parental history of hypertension, birth weight, and serum uric acid. In an open-label, cross-over trial we treated 5 children with confirmed essential hypertension with allopurinol as single treatment agent, and screened for change in blood pressure by casual and ambulatory methods. In tissue culture experiments, we evaluated the effect of uric acid on glomerular endothelial cell function. RESULTS: Elevation of serum uric acid is related to the onset of essential hypertension in children, reduced birth weight, and endothelial dysfunction. Normalization of uric acid appears to ameliorate new onset essential hypertension. CONCLUSION: These findings, combined with animal model data, support the hypothesis that uric acid has a key role in the pathogenesis of early onset essential hypertension, and may unify some of the disparate theories of the origins of essential hypertension.     

Comparing wound complication rates following closure of hip wounds with metallic skin staples or subcuticular vicryl suture: a prospective randomised trial

PURPOSE: To compare 2 methods of wound closure-metallic staples or 3-0 undyed vicryl-according to postoperative wound complication rates. METHODS: Patients who underwent surgery for proximal femoral fractures were randomised to have wound closure with metallic staples or with subcuticular vicryl suture. Wounds were regularly examined postoperatively and only those with positive wound swabs were regarded as wound infections. RESULTS: Five infections and one superficial wound dehiscence occurred in the patients who had wound closure with metallic staples. The complication rate was significantly higher for this group compared with the group who had wound closure with subcuticular vicryl suture (p<0.025). CONCLUSION: Superficial wound complication rates are higher for wounds closed with metallic staples compared to wounds closed with subcuticular vicryl.     

Tennis elbow--outcome following the Garden procedure: a retrospective study

PURPOSE: From 1993 to 1999, 17 patients (18 elbows) underwent the Garden procedure for clinically diagnosed tennis elbow. Non-operative treatment was ineffective for these patients. METHODS: The study group consisted of 10 men and 7 women, with a mean age of 49.6 years. Follow-up duration ranged from 18 months to 6 years, with a mean of 37 months. Patients' pain, activity level, and hand grip strength were evaluated postoperatively. RESULTS: 14 (77.8%) elbows had an excellent or good result, 2 elbows had a fair result, and another 2 elbows had a poor result and required revision surgery. Most patients had immediate relief of elbow pain, returned to work early, and did not notice any weakness of hand grip strength or radial wrist extension. There were no significant complications. CONCLUSION: The Garden procedure produced good results for tennis elbow with minimal morbidity in an unselected group of patients. This retrospective study supports the view that the underlying lesion in tennis elbow is in the origin of extensor carpi radialis brevis.     

Hyperimmunoglobulinaemia E syndrome: pulmonary imaging features

Hyperimmunoglobulinaemia E (hyper-IgE) syndrome (Job's syndrome) is a rare disease that presents with recurrent cutaneous and sinopulmonary infections, and which begins in infancy and is associated with extreme hyper-IgE. The pulmonary imaging features typically consist of recurrent alveolar lung infections, pneumatocoeles and, occasionally, pneumothorax. Various other causes of pneumatocoeles in children can be excluded on the basis of clinical history and other data. Computed tomography may add valuable information for the management of these patients.     

Disruption of the blood-brain barrier and neuronal cell death in cingulate cortex,dentate gyrus,thalamus, and hypothalamus in a rat model of Gulf-War syndrome

We investigated the effects of a combined exposure to restraint stress and low doses of chemicals pyridostigmine bromide (PB), N, N-diethyl-m-toluamide (DEET), and permethrin in adult male rats, a model of Gulf-War syndrome. Animals were exposed daily to one of the following for 28 days: (i) a combination of stress and chemicals (PB, 1.3 mg/kg/day; DEET, 40 mg/kg/day; and permethrin, 0.13 mg/kg/day); (ii) stress and vehicle; (iii) chemicals alone; and (iv) vehicle alone. All animals were evaluated for: (i) the disruption of the blood-brain barrier (BBB) using intravenous horseradish peroxidase (HRP) injections and endothelial barrier antigen (EBA) immunostaining; (ii) neuronal cell death using H&E staining, silver staining, and glial fibrillary acidic protein (GFAP) immunostaining; and (iii) acetylcholinesterase (AChE) activity and m2-muscarinic acetylcholine receptors (m2-AChR). Animals subjected to stress and chemicals exhibited both disruption of the BBB and neuronal cell death in the cingulate cortex, the dentate gyrus, the thalamus, and the hypothalamus. Other regions of the brain, although they demonstrated some neuronal cell death, did not exhibit disruption of the BBB. The neuropathological changes in the above four brain regions were highly conspicuous and revealed by a large number of HRP-positive neurons (21-40% of total neurons), a decreased EBA immunostaining (42-51% reduction), a decreased number of surviving neurons (27-40% reduction), the presence of dying neurons (4-10% of total neurons), and an increased GFAP immunostaining (45-51% increase). These changes were also associated with decreased forebrain AChE activity and m2-AchR (19-25% reduction). In contrast, in animals exposed to stress and vehicle or chemicals alone, the above indices were mostly comparable to that of animals exposed to vehicle alone. Thus, a combined exposure to stress and low doses of PB, DEET, and permethrin leads to significant brain injury. The various neurological symptoms reported by Gulf-War veterans could be linked to this kind of brain injury incurred during the war.