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Biomedical subjects

R J Bosch

Publications and source records attributed to R J Bosch.

50 records · Page 3Linked to original sources

A possible role for calcitonin-gene-related peptide in the regulation of the smooth muscle tone of the bladder and penis.

We investigated the effect of calcitonin-gene-related peptide (CGRP) on bladder contractions and penile erection in 12 dogs. In a system in which the arteries were tied bilaterally to ensure delivery of high drug levels to the bladder, arterial injections of CGRP significantly reduced the peak intravesical pressure of bladder contractions induced by pelvic nerve stimulation or arterial injection of carbachol. When given intravenously, CGRP had no effect on bladder contractions consequent to neural stimulation. Intravesical instillation of CGRP, however, reduced the bladder contractions significantly. Histologic staining showed CGRP-immunoreactive nerve fibers within the smooth muscle layers of the bladder wall. Intracavernous CGRP increased cavernous arterial flow and induced cavernous smooth muscle relaxation and venous outflow occlusion. Muscarinic blockade had no effect on the canine intracavernous pressure response to intracavernous injection of CGRP. Histologic staining for CGRP-immunoreactivity showed nerve-fiber-like staining within the cavernous arterial wall, the nerves running near the cavernous arteries, and the cavernous smooth muscles. Our results suggest a possible role for CGRP in the regulation of the smooth muscle tone of the bladder and penis.

Animals↗

Local and systemic effects of chronic intracavernous injection of papaverine, prostaglandin E1, and saline in primates.

To compare the local and systemic effects of chronic intracavernous injection of papaverine, prostaglandin E1, and saline on erectile tissue, eight pigtail monkeys underwent 75 injections over a nine-month period. Monkeys were divided into three groups; each group received papaverine (10 mg.), prostaglandin E1 (20 micrograms.), or saline (one ml.). The erectile response was closely observed for two hours after each injection to monitor the onset, degree, and duration of erection. Liver function tests were performed every three months to detect early systemic metabolic changes. After sacrifice, the simian penises were perfused in situ and examined histologically with both light and electron microscopy. Papaverine resulted in an initially strong erectile response, but this was maintained throughout the length of the study in only two monkeys. In contrast, prostaglandin E1 resulted in tumescence that was maintained in all monkeys over the nine-month period. In addition, the papaverine group had elevated liver enzymes and significant histologic changes with loss of normal architecture on both light and electron microscopy. The other two groups showed only minimal histologic changes or none.

Alprostadil↗

Treatment of benign prostatic hyperplasia by androgen deprivation: effects on prostate size and urodynamic parameters.

The possible effect of medical androgen deprivation in the treatment of benign prostatic hyperplasia has been studied in 12 patients. Six patients received the luteinizing hormone-releasing hormone agonist buserelin and 6 others received the antiandrogen cyproterone acetate. The treatment resulted in an average decrease in prostatic size of 29 per cent after 12 weeks as measured by ultrasonography. This decrease led to an increase in peak urinary flow rate, a reduction in residual urine volume and a decrease in daytime voiding frequency. However, it caused no decrease in urethral resistance but only an increase in the bladder contraction strength. After discontinuation of the treatment the prostates showed regrowth to the initial sizes within 6 to 36 weeks. The urodynamic changes were reversed as well. Although statistically significant, the urodynamic changes were minimal from a clinical viewpoint and did not lead to an unobstructed state after 12 weeks of treatment. For this reason the clinical indication for use of medical androgen deprivation in benign prostatic hyperplasia patients will remain limited for the time being.

Androgen Antagonists↗

Endogenous digoxin-like immunoreactivity and erythrocyte sodium transport in uraemic patients undergoing dialysis.

1. Erythrocyte Na+ transport (Na+ pump activity, co-transport, countertransport and passive Na+ efflux) and intracellular Na+ concentration were studied in 10 normal individuals and in 29 uraemic patients on chronic haemodialysis, before and after a haemodialysis session. Eight of them fulfilled the criteria of hypertension. 2. Normotensive patients before haemodialysis were classified in two groups: group 1 (pump-) with decreased erythrocyte Na+ pump activity, and group 2 (normal pump) with normal erythrocyte Na+ pump activity. Group 1 showed, compared with controls, a normal intracellular Na+ concentration and a decreased co-transport, but no difference in either countertransport or passive Na+ efflux. After haemodialysis this difference disappeared. Before haemodialysis, group 2 showed a high intracellular Na+ concentration, but activities of the Na+ transport systems studied were similar to those of controls. After haemodialysis, cell Na+ concentration decreased to a level not significantly different from that of controls. 3. Both before and after haemodialysis, hypertensive patients showed Na+ transport system activities and an intracellular Na+ concentration similar to those of controls. 4. Endogenous digoxin-like immunoreactivity (EDLI) and erythrocyte Na+ transport were studied in five normotensive and five hypertensive patients, before and after haemodialysis. EDLI in plasma was similar in both groups before and after haemodialysis. No correlation was found between EDLI and erythrocyte Na+ pump activity. 5. These results suggest the existence in some dialysed uraemic patients of alterations in erythrocyte Na+ fluxes, which may be corrected by haemodialysis. EDLI and erythrocyte Na+ fluxes do not seem to be markers of secondary hypertension in these patients.

Adult↗

Surgical treatment of locally advanced (T3) prostatic carcinoma: early results.

The fate of 48 patients with clinical stage T3 prostatic carcinoma after attempted curative surgical management was studied. In 23 of these patients positive frozen sections of the lymph nodes were found at pelvic lymphadenectomy and orchiectomy was performed. The median interval to progression was 61 months. Radical prostatectomy was performed in the remaining 25 patients. In 4 of these patients positive lymph nodes were found on paraffin sections but no additional treatment was given. Over-all, total tumor removal as defined by negative lymph nodes and negative margins of resection could be achieved in 14 of the 48 patients (29 per cent). During the same period 34 patients with clinical state T less than 3 prostatic carcinoma were treated in a similar manner. Orchiectomy was done in 4 patients because of positive frozen sections of the lymph nodes and radical prostatectomy was done in 30, including 1 in whom positive paraffin sections of the lymph nodes were found but no additional treatment was given. An attempt was made to study the impact of several prognostic factors by comparing the probability of progression between patients with stage pT3 disease with (T3pT3N0) or without (T less than 3pT3N0) extracapsular tumor growth as determined by preoperative rectal examination (36 versus 27 per cent progression at 3 years), with or without positive margins of resection (45 versus 20 per cent progression at 3 years) and with or without involvement of the seminal vesicles (47 versus 18 per cent progression at 3 years). Our results suggest that a certain proportion of patients with clinical stage T3 disease will benefit from radical prostatectomy. This is to be expected especially in patients with stage T3pT3N0 cancer and negative margins.

Aged↗

Benign prostatic hyperplasia treated by castration or the LH-RH analogue buserelin: a report on 6 cases.

This article presents the clinical data of 5 patients treated by castration and 1 patient treated with an LH-RH analogue to relieve chronic urinary retention due to benign prostatic hyperplasia (BPH). Besides the clinical data related to prostatism, prostatic volume was studied in 4 of the 5 patients by means of transrectal ultrasonography. All 5 patients showed a marked decrease of prostatic volume, which averaged 31.4% (range 19-55%) after 2-3 months. This correlated well with a relief of urinary obstruction. In all 5 patients, the indwelling catheters could be removed, symptoms decreased or disappeared and all 5 patients became free of residual urine. LH-RH analogues, because of the reversibility of their effect, may be more acceptable for the treatment of BPH than castration. At this moment however, it remains unknown whether prostatic volume will increase again after cessation of androgen withdrawal.

Aged↗

[Post-phlebitis cutaneous calcinosis. Histochemical study].

A case of cutaneous localized calcinosis of the left upper limb is reported and classified as dystrophic calcinosis because the antecedent of superficial phlebitis. This kind of manifestation is rare in relationship with the frequence of superficial inflammatory processus of veins.

Adolescent↗

A practical approach to the molecular biology of kidney diseases: from basic science to bed side.

Nowadays, the term "Molecular Biology" (MB) is generally a pplied to the biochemical processes that involve genes and the expression of proteins for which specific genes code. In recent years, astonishing advances have occurred in this field. Currently, there are many important powerful techniques allowing scientists to study the molecular mechanisms involved in many human genetic diseases. Furthermore, it is important to underline that the possibilities are not limited to the diagnosis and study of these genetic diseases. Indeed, by studying gene expression, MB also allows the molecular study of many acquired diseases such as viral hepatitis and cancer.Therefore, these major advances in the knowledge of gene biology are facilitating the arrival of a new era of gene therapy. This article will describe the most important techniques currently used in MB. Firstly, techniques involved in recombinant DNA technology will be discussed and these will include the study of DNA and the possibility of identifying the expression of abnormal genes, e.g. to identify individuals for paternity. Secondly, a description of techniques designed to study the expression of genes and their regulation will follow and they involve the study of RNA. Thirdly, the impact of genetic molecular studies as tools for medical diagnosis will be discussed and analysed. Finally, a discussion concerning the rational basis for gene therapy and its future perspectives is included. In this article, we have focused on technical or diagnostic aspects ofMolecular Biology. Although Ethics are also an interesting issue to deal with, theseissues are far beyond the scope of this review.

DNA Fingerprinting↗

Parathyroid hormone-related protein: roles in the glomerulus.

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) produce similar biological effects through the PTH/PTHrP receptor. Less is known about the physiological role of PTHrP which was first identified as the agent of the humoral hypercalcemia of malignancy. Despite the widespread production of PTHrP in healthy individuals, the concentration of the protein is below the detectable limit of current assays, suggesting that PTHrP normally functions locally in an autocrine or paracrine manner. Thus, some differences in their biological activities have been described, and they may be related to the presence of different receptors. In this regard, a second receptor which binds selectively to PTH has also been found. Recent studies have demonstrated the expression of both PTH/PTHrP receptor and protein in the renal glomeruli. Moreover, there are convincing data that support a direct role of PTH and PTHrP in modulating renal blood flow and glomerular filtration rate. This multifunctional protein, PTHrP, also has a proliferative effect on mesangial cells, supporting the notion that it may play a role in the normal glomerulus and in injured kidney.

Animals↗

Parathyroid hormone-related protein as a renal regulating factor. From vessels to glomeruli and tubular epithelium.

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) produce similar biological effects through the PTH/PTHrP receptor. Less is known about the physiological role of PTHrP, which was first identified as the agent of the humoral hypercalcemia of malignancy. Despite the widespread production of PTHrP in healthy individuals, the concentration of the protein is below the detectable limit of current assays, suggesting that PTHrP normally functions locally in an autocrine or paracrine manner. Thus, some differences in their biological activities have been described and they may be related to the presence of different receptors. In this regard, a second receptor that binds selectively to PTH has also been found. Recent studies have demonstrated the expression of both PTH/PTHrP receptor and protein in the renal glomeruli. Moreover, there are convincing data that support a direct role of PTH and PTHrP in modulating renal blood flow and glomerular filtration rate. This multifunctional protein, PTHrP, also has a proliferative effect on both glomerular mesangial cells and tubular epithelial cells. Increases in the expression of PTHrP have been observed in several experimental models of nephropathies, suggesting that PTHrP upregulation is a common event associated with the mechanism of renal injury and repair.

Glomerular Filtration Rate↗

Angiosarcoma arising on rhinophyma.

We report an 82-year-old man who presented with a tumor which had developed over the previous year on the right nasal ala of a rhinophyma. Histopathological, immunohistochemical, and electron microscopic study confirmed the diagnosis of angiosarcoma on the head and neck. He was treated with radiotherapy of the tumor and cervical adenopathy, which developed later. The possible etiological and pathogenetic role of lymphedema due to inflammatory flares of rosacea on the nose is discussed, together with the histological and immunohistochemical data leading to the diagnosis of this tumor.

Aged↗

Gene transfer into the mammalian kidney: microtransplantation of retrovirus-transduced metanephric tissue.

Our previous observation that embryonic kidney tissue can develop and differentiate when transplanted into the parenchyma of mouse kidneys in the postnatal period provided an avenue for transferring novel genes into the mammalian kidney in vivo. Mouse metanephric tissue was infected ex vivo with a replication defective retrovirus which transduces the gene for beta-galactosidase. Seven to 21 days after transplantation of this tissue into neonatal and adult mouse kidneys, the expression of the gene, controlled by the viral long-terminal repeat promoter, was noted in approximately one-third of implants. Gene expression occurred predominantly in glomerular epithelial cells, but also in interstitial cells and in vascular structures. Polymerase chain reaction amplification of renal genomic DNA indicated the presence of viral DNA in 9 of 10 kidneys which had received metanephric implants into the neonatal renal cortex. These studies demonstrate the feasibility of short-term gene transfer into and expression within the mammalian kidney.

Animals↗

Gene transfer into the mammalian kidney: direct retrovirus-transduction of regenerating tubular epithelial cells.

Gene transfer using retroviral vectors requires cell replication for insertion of the DNA provirus. Since the mitotic index of the mammalian kidney is very low, renal tubular cell replication was induced in adult rats as part of a regenerative response to the nephrotoxic injury induced by an intraperitoneal injection of folic acid. At 48 h, at the time of maximum 3H-thymidine incorporation, the left kidney was directly injected with a suspension of the Psi2 BAG retrovirus which transduces the beta-galactosidase gene. At 1-7 weeks after virus administration the left kidney was harvested. Using the polymerase chain reaction to amplify viral DNA, successful gene transfer was achieved in 8 of 15 kidneys. In 6 of 10 kidneys assessed histochemically positive staining for beta-galactosidase activity was detected in the cytoplasm of tubular epithelial cells. There was no evidence of gene expression in glomerular, vascular or endothelial cells. All analyses were negative in vehicle-injected kidneys and in the kidneys of animals which did not receive pretreatment with folic acid. These studies demonstrate the feasibility of gene transfer into the adult kidney provided that replication of specific cell types can be achieved.

Animals↗