Evaluation of cadaveric pericardium in the rat for the surgical treatment of Peyronie's disease.

OBJECTIVES: To evaluate the intermediate-term efficacy of cadaveric pericardium (Tutoplast) as a grafting material in the surgical correction of Peyronie's disease using a rat model. Peyronie's disease is a connective tissue disorder of the tunica albuginea. When less invasive modalities fail to correct the penile deformity, surgical excision of the plaque and coverage with various grafting materials has been advocated. MFETHODS:Twenty male Sprague-Dawley rats (300 to 325 g) constituted the study population. The animals were divided into two groups: group 1, control rats (n = 10) and group 2, rats that underwent wedge excision of the tunica albuginea and replacement with cadaveric pericardial grafts (n = 10). All rats underwent electrical stimulation of the cavernosal nerve to assess erectile function after 4 months. Tissues obtained after death were stained with trichrome and Verhoff's van Giesen for collagen and elastic fibers. RESULTS: Erectile function as studied by cavernosal nerve stimulation was not significantly different in either group (P >0.05), and histologic studies of penile cross sections of the pericardial graft group revealed a mild to moderate degree of fibrosis surrounding the patch at 4 months. CONCLUSIONS: We found that pericardial cadaveric grafts in a rat model are a suitable tunica albuginea substitute. They allow for penile expansion after cavernosal nerve stimulation and are strong enough to withstand normal intracorporeal pressures. Our early experimental data in the rat support the use of pericardial cadaveric material for coverage of excised Peyronie's plaques. However, long-term follow-up in humans is mandatory.

Regulation of major histocompatibility complex class II antigens on human alveolar macrophages by granulocyte-macrophage colony-stimulating factor in the presence of glucocorticoids.

Alveolar macrophages (AM) present antigen poorly to CD4+ T cells and respond weakly to interferon-gamma (IFN-gamma) for up-regulation of major histocompatibility complex (MHC) class II and costimulatory molecule expression. In atopic asthma, however, AM exhibit enhanced antigen-presenting cell (APC) activity. Since granulocyte-macrophage colony-stimulating factor (GM-CSF) is increased in the airways of asthmatic patients, we have investigated its role in modulating the APC function of AM. The effects of glucocorticoids were also studied since earlier studies showed optimal induction of MHC antigens on monocytes by GM-CSF in their presence. GM-CSF in the presence, but not the absence, of dexamethasone enhanced the expression of HLA-DR, -DP and -DQ antigens by AM. However AM and monocytes differed in the optimal concentration of steroid required to mediate this effect (10-10 m and 10-7 m, respectively). Induction of MHC antigens was glucocorticoid specific and independent of IFN-gamma. These studies suggest the existence of an IFN-gamma-independent pathway of macrophage activation, which may be important in regulating APC function within the lung.

GM-CSF increases the ability of cultured macrophages to support autologous CD4+ T-cell proliferation in response to Dermatophagoides pteronyssinus and PPD antigen.

Previous studies have demonstrated an infiltration of monocytes and increased levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the asthmatic lung. To study the possible effects of this cytokine upon the differentiation and function of these newly recruited monocytes, we have developed a model in which monocytes isolated from human peripheral blood were differentiated into macrophages in serum in the presence or absence of GM-CSF. After 7 days, the macrophages increased in size and granularity, had increased phagocytic activity, and expressed various adhesion molecules, CD14 and major histocompatibility complex (MHC) class II. The effects of GM-CSF on antigen presentation by cultured macrophages on the antigen-specific proliferative response of CD4+ T cells to Dermatophagoides pteronyssinus or purified protein derivative of tuberculin and the mitogen phytohaemagglutinin was determined. CD4+ T-cell proliferation was reduced when either antigen was presented by macrophages cultured in serum alone, compared with the values obtained with freshly isolated monocytes. However, CD4+ cell proliferation was comparable to that observed with monocytes when antigen was presented by macrophages which had been pre-cultured with 50 U/ml GM-CSF. CD4+ T-cell proliferation to phytohaemagglutinin was similar when all three populations were used as accessory cells. High numbers of macrophages partially suppressed CD4+ T-cell proliferation in response to antigen presented by monocytes, but there was no significant difference between macrophages cultured in the presence or absence of GM-CSF. This data suggests that GM-CSF directs monocyte differentiation into macrophages with an antigen-presenting, rather than a suppressive, phenotype. Elevated levels of GM-CSF in the asthmatic lung may therefore maintain recently recruited monocytes in an inflammatory and T-cell activating state.

Evaluation of fluid absorption during laser prostatectomy by breath ethanol techniques.

PURPOSE: Laser prostatectomy has evolved as a less invasive method of relieving bladder outlet obstruction due to prostatic enlargement. The elimination of adenomatous tissue by laser induced coagulation necrosis theoretically avoids the sequelae of fluid absorption noted during traditional transurethral resection of the prostate. However, to our knowledge no accurate determination of fluid absorption during laser prostatectomy has been performed to date. MATERIALS AND METHODS: A technique previously described to determine the amount of irrigant absorbed during transurethral resection of the prostate measures breath ethanol levels using a standard alcohol breath analyzer during the procedure after a predetermined amount of ethanol is added to the irrigant fluid. This method was used in 4 men undergoing laser prostatectomy. RESULTS: All 4 subjects had ethanol levels of 0 throughout the operation, indicating that little or no irrigant fluid was absorbed. CONCLUSIONS: We demonstrated in a quantitative manner that fluid absorption during laser prostatectomy is almost nil and patients are, indeed, at no risk for the transurethral resection syndrome.

Isolation and characterisation of a subpopulation of human chorionic cytotrophoblast using a monoclonal anti-trophoblast antibody (NDOG2) in flow cytometry.

Human cytotrophoblast cells, isolated from term amniochorion by enzymic digestion and Percoll gradient centrifugation, were characterised by flow cytometry. A panel of 12 anti-trophoblast monoclonal antibodies was screened for labelling of these cells in flow cytometry and the results compared with immunoperoxidase labelling of cytospin preparations and tissue sections. All 12 antibodies were positive for trophoblast on tissue sections, 11/12 were positive on cytospins but only two (NDOG2 and GB25) gave consistent results in flow cytometry. Two-colour labelling with NDOG2 and W6/32, an antibody to HLA-A, -B, -C, demonstrated that 88% of the NDOG2-positive cells also express Class I major histocompatibility complex (MHC) antigens. The NDOG2-positive cytotrophoblast subpopulation was isolated by flow cytometry in sufficient purity (greater than 95%) and yield (3.1 x 10(6)) for use in functional studies in vitro.

Involvement of protein kinase C in mouse mammary gland development.

The relationship between kinase C activity and mammary gland differentiation was investigated by following kinase activity throughout the mouse reproductive cycle and by pharmacologically perturbing the kinase, while monitoring biochemical differentiation. Protein kinase C activity declined during pregnancy and remained low throughout lactation, suggesting an inverse relationship with milk protein expression. This negative association was further supported by the use of quercetin (50-100 mumol/l) and gossypol (50 mumol/l), which are both protein kinase C inhibitors. These compounds doubled alpha-lactalbumin levels in mammary explants cultured with hormones. However, a phorbol ester, known to activate protein kinase C, had no effect on alpha-lactalbumin production, although it did stimulate this milk protein 2.5-fold in the presence of the calcium ionophore, A23187. In the absence of raised calcium levels, protein kinase C activity therefore appeared to be inversely correlated with biochemical differentiation; but, in the presence of increased calcium concentrations, both calcium and the kinase acted synergistically to augment hormone-induced alpha-lactalbumin expression.