Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

Destructive ocular myiasis in a noncompromised host

A case of destructive ocular myiasis resulting in complete loss of the globe in two days time is documented. To the best of our knowledge this is the first report of such a severe involvement in a healthy and non-compromised host. Mechanical removal and good local hygiene helped heal the wound. The larvae were isolated to be that of Chrysomyia bezziana (screwworm fly). This is possibly the first report of destructive ocular myiasis caused by Chrysomyia bezziana from the Indian subcontinent and the second in world literature. Infestation of human eyes with larvae of flies (myiasis) has been reported. Serious consequences of destructive myiasis are seen in emaciated and diseased patients. Only one report of total destruction of the globe by maggots of Chrysomyia bezziana exists in the literature. As in previous communications, the patient in this report had no predisposing factors both systemic and local. We here in document a case of orbital myiasis leading to rapid destruction of the globe within two days in a healthy and a non-compromised patient.     

CD31 (JC70) expression in plasma cells: an immunohistochemical analysis of reactive and neoplastic plasma cells.

AIMS: To investigate the immunohistochemical expression of CD31 (JC70) in normal and neoplastic plasma cells. METHODS: Plasma cells in bone marrow biopsies and extramedullary locations were examined. All extramedullary biopsies were formalin fixed and paraffin embedded. The bone marrow biopsies were fixed in formal acetic acid and embedded in paraffin wax. Twenty multiple myelomas (12 bone marrow and eight extramedullary deposits), 10 extramedullary plasmacytomas, and 30 biopsies with reactive plasma cells (10 bone marrow, 20 extramedullary biopsies) were stained with anti-CD31 (JC70) using the streptavidin-biotin detection system with diaminobenzidine as a chromogen. Antigen retrieval in bone marrow biopsies was achieved by pressure cooking. In all other biopsies, antigen retrieval was achieved by microwave pretreatment. RESULTS: All 20 extramedullary cases with reactive plasma cells showed intense membrane staining. Focal staining was detected in reactive plasma cells in bone marrow biopsies. Five of 10 plasmacytomas showed membrane staining. None of the cases of multiple myeloma, either medullary or extramedullary, showed any immunoreactivity for CD31. CONCLUSIONS: CD31, a member of the immunoglobulin supergene family of cell adhesion molecules, is strongly expressed in extramedullary reactive plasma cells, focally in bone marrow reactive plasma cells, and occasionally in extramedullary plasmacytomas.     

Characterization of the large-conductance Ca-activated K channel in myocytes of rat saphenous artery

We used the patch-clamp method to characterize the BK channel in freshly isolated myocytes from the saphenous branch of the rat femoral artery. Single-channel recordings revealed that the BK channel had a conductance of 187 pS in symmetrical 150 mM KCl, was blocked by external tetraethylammonium (TEA) with a KD(TEA) of approx. 300 microM at +40 mV, and by submicromolar charybdotoxin (CTX). The sensitivity of the BK channel to Ca was especially high (KD(ca) approx. 0.1 microM at +60 mV) compared to skeletal muscle and neuronal tissues. We also investigated the macroscopic K current, which under certain conditions is essentially sustained by BK channels. This conclusion is based on the findings that the macroscopic current activated upon depolarization follows a single exponential time course and is virtually fully blocked by 100 nM CTX and 5 mM external TEA. We made use of this occurrence to assess the voltage and Ca dependence of the macroscopic BK current. In intact myocytes, the BK channel showed a strong and voltage-dependent reduction of the outward current (62% at +40 mV), most likely due to block by intracellular Ba and polyamines. The results obtained from macroscopic and unitary current indicate that approx. 2.5% of the BK channels are active under physiological conditions, sustaining approx. 20 pA of outward current. Given the high input resistance of these cells, few BK channels are required to open in order to cause a significant membrane hyperpolarization, and thus function to limit the contraction resulting from acute increases in intravascular pressure, or in response to hypertensive pathologies.     

Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone

BACKGROUND: Suppression of spermatogenesis to azoospermia is required for effective hormonal male contraception, but the degree of suppression varies between ethnic groups. We here report the first study of hormonal suppression of spermatogenesis in two African centres using a regimen of oral progestogen with depot testosterone. METHODS A total of 31 healthy men (21 black) were recruited in Cape Town and 21 men in Sagamu, Nigeria. Subjects were randomized to take either 150 or 300 micro g desogestrel daily p.o. with testosterone pellets. In Cape Town, desogestrel was administered for 24 weeks with 400 mg testosterone re-administered 12 weekly. In Sagamu, desogestrel was administered for 52 weeks with 200 mg testosterone (later increased to 400 mg) re-administered 12-weekly. RESULTS: In Cape Town, 22 men completed at least 20 weeks treatment. Azoospermia was achieved in 8/10 and 8/12 men in the 150 micro g and 300 micro g desogestrel groups. Four men in Sagamu withdrew. Azoospermia was achieved in all 17 men in the two groups. There were no significant changes in lipoprotein or haemoglobin concentrations in any group. CONCLUSION: These data demonstrate that the combination of oral desogestrel with depot testosterone is an effective regimen for suppression of spermatogenesis in African as in Caucasian and Chinese men, with azoospermia achieved in a total of 83/98 (85%) men.     

Berberine modulates crucial erectogenic biomolecules and alters histological architecture in penile tissues of diabetic rats

Berberine is an isoquinoline alkaloid, found in several plants. Diabetes induces erectile dysfunction (ED) via reduction in some hormones and enzymes implicated in sexual function. This study aimed to investigate the role of berberine on crucial biomolecules linked to penile function in diabetic rats. Sixty-three (63) adult male rats were used and distributed into nine groups (each = 7). Group I–IV normal rats administered with citrate buffer (pH 4.5), sildenafil citrate (SD, 5.0 mg/kg), 50 and 100 mg/kg of berberine, respectively, via oral gavage. Rats in groups V–IX were diabetic rat with ED treated with buffer, SD, 50 and 100 mg/kg of berberine, and acarbose (25 mg/kg ACA) respectively. The result revealed that histological architecture in penile tissues were altered in diabetic groups treated with berberine, sildenafil citrate and acarbose when compared to the diabetic control group. Treatment with berberine, increased testosterone, luteinizing hormone and follicle-stimulating hormone in diabetic rat with ED. Also, reduced prolactin level and acetylcholinesterase, angiotensin-1 converting enzyme, adenosine deaminase and arginase activities were observed in berberine treated diabetic rat with ED. Molecular docking analysis revealed that berberine had strong binding affinities for these enzymes. Thus, berberine could represent a potential therapeutic agent for diabetes-induced ED.     

Indications for pediatric keratoplasty in India.

PURPOSE: To study the associations and indications for pediatric keratoplasty. METHODS: We undertook a retrospective analysis of 415 grafts performed in 393 children, aged 12 years or younger between January 1993 and December 1997. The parameters evaluated were demographic data, socioeconomic status, preoperative diagnosis, and any systemic or ocular associations. RESULTS: Of the 415 eyes operated on, 296 (71.32%) eyes underwent keratoplasty for acquired nontraumatic corneal opacities, 51 (12.28%) had congenital corneal conditions, 45 (10.85%) were regrafts, and 23 (5.54%) eyes had acquired traumatic corneal opacities. The cause of corneal opacification in the acquired nontraumatic group was infectious keratitis in 215 (72.63%) eyes and keratomalacia in 81 (27.36%) eyes. Systemic associations with the onset of the opacity in the acquired nontraumatic group were fever in 74 (25%) cases, diarrhea in 56 (18.9%) cases, and malnutrition in 98 (33.1%) cases. Seventeen (4.32%) children belonged to the lower middle class, 64 (16.28%) were in the upper lower class, and 312 (79.38%) were from the lower socioeconomic families based on the Kuppuswamy scale. CONCLUSIONS: Infectious keratitis is the major indication for pediatric keratoplasty in India. In the majority of the cases, the occurrence of corneal opacification is associated with poverty.