Differences in LH receptor down-regulation between rat and mouse Leydig cells: effects of 3',5'-cyclic AMP and phorbol esters.

The role of cyclic AMP and phorbol esters in luteinizing hormone (LH) receptor down-regulation in Leydig cells has been studied. Dibutyryl cyclic AMP (db-cAMP) (0.01, 0.1 and 1 mM), forskolin (80 microM) and cholera toxin (1.19 nM) caused a 30-50% loss of [125I]hCG binding sites and an inhibition of receptor-[125I]hCG complex internalization in mouse tumour Leydig (MA10, MLTC-1) cells during 2 h. In contrast, db-cAMP had no effect on the level of binding sites or internalization of the hormone receptor complex in rat testis Leydig cells or a rat tumour (R2C) Leydig cell. Phorbol 12-myristate 13-acetate (PMA) at concentrations from 10(-9) to 10(-5) M had no effect on hormone binding or hormone-receptor complex internalization in any of the Leydig cells. In contrast a 2 h preincubation of MLTC-1 cells with 10(-7) M PMA caused a loss of subsequent LH-stimulated cyclic AMP and pregnenolone production. These results indicate that LH receptor down-regulation is mediated by cyclic AMP dependent kinase, but not protein kinase C, in mouse Leydig cells. No down-regulation of rat Leydig cell LH receptor occurs with either kinase.     

Can people with severe mental retardation consent to mutual sex?

One of the most pressing issues confronting service providers who work with people with severe mental retardation is how to negotiate mutual sex behaviors which occur among this population. Uncertainty surrounding whether individuals have the capacity to consent, fear of legal repercussion, and staff not understanding what their responsibilities and roles should be, each contribute to the difficulty which the service provider experiences. This article examines in detail all aspects of consent and ways for determining consent as well as the responsibilities an interdisciplinary team has for managing mutual sex behaviors.     

Ainhum (dactylolysis spontanea): A Radiological survey of 6000 patients

Dactylolysis spontanea is an idiopathic condition affecting the fifth toe, and sometimes other toes, that is frequently bilateral, with lesions in different stages. Between 1977 and 1999, a total 6000 radiographic studies of the feet were reviewed in a mainly African American population in Chicago, Illinois. After an initial screening based on the Cole criteria, 581 patients were selected and re-examined, and amplification techniques were performed. After reviewing the complementary exams, 102 patients were diagnosed with dactylolysis spontanea or ainhum. Soft-tissue constriction was the most frequently presented radiological sign on the initial screening. Kurtosis at the digit plantar fold and marked rotation of the fifth toe were normal findings in asymptomatic patients. Demographics, comorbidities, and radiological findings were analyzed in the selected population. Associated diseases occurring in these patients appeared to have no specific etiologic correlation with ainhum. African Americans and the dark-skinned population are affected exclusively by this condition, presumably due to the fibrogenic tendency of these individuals. Early diagnosis and accurate staging of ainhum are facilitated by radiological examination of the feet. The findings suggest that this condition is underdiagnosed and overlooked because its low prevalence and variable clinical presentations that might mimic more common etiologies, including localized trauma.     

Ambulatory Phlebectomy Versus Compression Sclerotherapy: Results of a Randomized Controlled Trial

BACKGROUND: Although no randomized controlled trial has assessed the effects of either compression sclerotherapy or ambulatory phlebectomy, both techniques are used to treat varicose veins worldwide. We performed a randomized controlled trial to compare recurrence rates of varicose veins and complications after compression sclerotherapy and ambulatory phlebectomy. METHODS: From September 1996 to October 1998, we randomly allocated 49 legs to compression sclerotherapy and 49 legs to ambulatory phlebectomy. Our primary outcome parameters were as follows: recurrence rates at 1 and 2 years and complications related to therapy. Eighty-two patients were included, of whom 16 were included with both of their legs. The number of treated legs was therefore 98, but two patients were lost to follow-up. RESULTS: One year recurrence amounted to 1 out of 48 for phlebectomy and 12 out of 48 for compression sclerotherapy (P<0.001); at 2 years, six additional recurrences were found, but then solely for compression sclerotherapy (P<0.001). Significant differences in complications occurring more in phlebectomy than in compression sclerotherapy therapy were blisters, teleangiectatic matting, scar formation, and bruising from bandaging. CONCLUSION: Our results show that ambulatory phlebectomy is an effective therapy for varicose veins of the leg. Recurrence rates are significantly lower than for compression sclerotherapy therapy. If varicose veins persist 4 weeks after compression sclerotherapy, it can be argued that to reduce the risk of future recurrence ambulatory phlebectomy should be considered as the better treatment option.     

Cerebellar nuclear afferents--where do they originate? A re-evaluation of the projections from some lower brain stem nuclei

Summary Cerebellar nuclear afferents from some caudal brain stem nuclei in the cat were studied by means of retrograde transport after implantation of the wheat germ agglutinin-horseradish peroxidase complex in crystalline form in the cerebellar nuclei. The findings give evidence that projections to the cerebellar nuclei from certain nuclei of the reticular formation proper (e.g., from the gigantocellular reticular nucleus) are very modest, while there appears to be no or extremely few cerebellar nuclear afferents from the paramedian reticular, spinal trigeminal, gracile, cuneate and external cuneate nuclei. Previous tracer studies have given evidence that also the pontine and red nuclei send very few, if any, fibres to the cerebellar nuclei. All these brain stem regions are known to project to the cerebellar cortex. This relative lack of mossy fibre collaterals to the cerebellar nuclei is discussed with references to previous literature on the distribution of cerebellar nuclear afferents, and the problem of how the cerebellar nuclei are facilitated is considered.Abbreviations Br.c. superior cerebellar peduncle (brachium conjunctivum) - Br.p. middle cerebellar peduncle (brachium pontis) - C.r. interior cerebellar peduncle (restiform body) - HRP horseradish peroxidase - L left - N.c. cuneate nucleus - N.c.e. external cuneate nucleus - N.c.t. nucleus of corpus trapezoideum - NIA anterior interposed nucleus - NIP posterior interposed nucleus - NL lateral (dentate) nucleus - N.l.l. nuclei of lateral lemniscus - NM medial (fastigial) nucleus - N.m.X. dorsal motor vagal nucleus - N.mes. mesencephalic trigeminal nucleus - N.r.l. lateral reticular nucleus (nucleus of the lateral funiculus) - N.r.p. paramedian reticular nucleus - N.r.t. reticular tegmental pontine nucleus - N V, VI, VII, XII root fibres of cranial nerves - Ol.s. superior olive - P.h. nucleus praepositus hypoglossi - Py pyramid - R right - R.gc. gigantocellular reticular nucleus - R.l. lateral reticular nucleus of Meessen and Olszewski - R.p.c. caudal pontine reticular nucleus - R.pc. parvicellular reticular nucleus - R.v. ventral reticular nucleus - Tr.sp.V. spinal tract of the trigeminal nerve - T.s. solitary tract surrounded by nucleus of solitary tract - V.m. medial vestibular nucleus - WGA wheat germ agglutinin - WGA-HRP wheat germ agglutinin-horseradish peroxidase conjugate - V, VI, VII, X, XII motor nuclei of cranial nerves     

Effect of the Aldehyde Dehydrogenase Inhibitor, Cyanamide, on the Ex Vivo Sensitivity of Murine Multipotent and Committed Hematopoietic Progenitor Cells to Mafosfamide (Asta Z 7557)

The ex vivo sensitivity of murine multipotent (CFU-GEMM) and committed (CFU-Mk, CFU-GM, BFU-E and CFU-E) hematopoietic progenitor cells to mafosfamide was quantified with and without concurrent exposure to cyanamide, an inhibitor of aldehyde dehydrogenase activity. In the absence of cyanamide, CFU-GEMM, CFU-Mk and CFU-GM were approximately equisensitive to mafosfamide while the erythroid progenitors were more sensitive to the drug. Cyanamide potentiated the cytotoxicity of mafosfamide toward CFU-GEMM and CFU-Mk, but not toward CFU-GM, BFU-E and CFU-E. Cellular aldehyde dehydrogenases are known to catalyze the oxidation of 4-hydroxycyclophos-phamide/aldophosphamide, the major intermediate in cyclophosphamide and mafosfamide activation, to the relatively nontoxic acid, carboxyphosphamide. Thus, our findings indicate that 1) murine CFU-GEMM contain the relevant aldehyde dehydrogenase activity, and 2) the relevant aldehyde dehydrogenase activity is retained upon differentiation to progenitors committed to the megakaryocytoid lineage, but lost upon differentiation to progenitors committed to the granulocytoid/monocytoid and erythroid lineages. The relative insensitivity of CFU-GM to mafosfamide is apparently due to a cellular determinant that influences their sensitivity to all cross-Unking agents since CFU-GM were found to be relatively insensitive to non-oxazaphosphorine cross-linking agents as well.     

S-nitrosocaptopril. I. Molecular characterization and effects on the vasculature and on platelets

We have synthesized an S-nitrosylated derivative of captopril, S-nitrosocaptopril, that manifests nitrosovasodilatory activity, inhibits angiotensin converting enzyme activity and inhibits platelet aggregation. The direct vasodilatory effects of S-nitrosocaptopril reflect the effects of the thionitrite bond, the presence of which does not in any way influence S-nitrosocaptopril's ability to inhibit angiotensin converting enzyme. Thionitrite stimulation of both vascular and platelet soluble guanylate cyclase activity leads to increases in intracellular cyclic GMP that are accompanied by vasodilatation and platelet inhibition, respectively. S-nitrosocaptopril is a novel hybrid molecule that has potential use in the treatment of hypertension regardless of renin status, angina pectoris and congestive heart failure.     

Impact of gestrinone on the course of asymptomatic endometriosis

A new drug, gestrinone, was subjected to the first double blind, randomised placebo controlled trial of any treatment of endometriosis. The disease deteriorated in eight (47%) of the 17 patients prescribed placebo (95% confidence limits 23% and 71%) compared with none of the 18 patients prescribed gestrinone (p = 0.002). There was a difference in elimination of the endometriosis in the gestrinone group compared with placebo but this was not statistically significant (p = 0.057). There was a significant difference in improvement of the disease in the gestrinone group compared with placebo (p = 0.004), confirming that gestrinone is an effective treatment of endometriosis. Endometriosis deteriorates in at least 23% of patients; as it is impossible to predict in whom this will happen, treatment appears to be warranted in all cases.