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Biomedical subjects

J Navarro

Publications and source records attributed to J Navarro.

At least 307 records · Page 17Linked to original sources

Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer.

We report the second interim analysis of data from a randomized prospective trial comparing the prophylactic effect of 15 courses of 50 mg. doxorubicin, 50 mg. thiotepa or 150 mg. bacillus Calmette-Guerin instilled intravesically against recurrences and progression of superficial transitional cell bladder cancer. Of 202 enrolled patients 176 currently are evaluable with a mean follow-up of 3 years (range 3 to 97 months). The number of patients with recurrences was significantly lower in the bacillus Calmette-Guerin arm (9 of 67) compared to the doxorubicin (23 of 53, p equals 0.002) and thiotepa (20 of 56, p equals 0.003) arms. The over-all recurrence index per 100 patient-months also was lower for the bacillus Calmette-Guerin versus the thiotepa and doxorubicin groups (0.53 versus 1.55 and 1.7, respectively). Bacillus Calmette-Guerin also was superior in preventing recurrences and progression of high risk tumors, that is stage T1, grade 3 or multiple growths, associated or not with carcinoma in situ. In the stage T1 category 19 of 32 (60%) tumors recurred under treatment with doxorubicin, 11 of 33 (33%) with thiotepa and 6 of 49 (12%) with bacillus Calmette-Guerin. Toxicity to intravesical bacillus Calmette-Guerin was higher compared to the other drugs but it was not limiting: bladder irritability and malaise occurred in 42% of the patients, granulomatous cystitis in 16.4% and bladder contraction in 1.4% (1 of 64). The latter complication occurred in a patient whose stage T1m grade 2 tumors had recurred 3 times, who underwent 3 transurethral bladder resections within 15 months and who had received thiotepa for 4 months after having been removed from the study 11 months after entry. Three patients in the doxorubicin group (5.6%) underwent radical cystectomy for local urothelial progression. One patient (1.8%) in the same group died of distant progression. Our preliminary results suggest that at the dose, periodicity and duration used in the study bacillus Calmette-Guerin is significantly superior to the chemotherapeutic agents doxorubicin and thiotepa for the prophylaxis of recurrence and retardation of progression in superficial transitional cell bladder tumors.

Administration, Intravesical↗

Sperm chromosome studies in an infertile man with partial, complete asynapsis of meiotic bivalents.

Meiotic and sperm chromosome studies were carried out in two semen samples from an infertile man with a 46,XY karyotype, oligoasthenoteratozoospermia and abundant exfoliation of spermatogenic cells. Meiotic preparations showed partial, complete asynapsis in a large proportion of metaphase I figures observed, and absence of metaphase II figures, while 24 of the 30 sperm chromosome karyotypes analysed were normal. The remaining sperm karyotypes were as follows: one with structural abnormalities, one with both structural abnormalities and hypohaploidy and four with hypohaploidy. The total frequency of chromosomal abnormalities (6.7%) is similar to that obtained by us in normal men (10.9%). The frequency of spermatozoa with structural abnormalities (6.7%) was not significantly different from that obtained by us in normal men (6.9%). These results suggest that, in some cases, asynaptic spermatogenic cells do not proceed further than metaphase I and only normal germ cells continue spermatogenesis.

Adult↗

Visceral neuropathies responsible for chronic intestinal pseudo-obstruction syndrome in pediatric practice: analysis of 26 cases.

Twenty-six children aged from 1 day to 15 years (18 boys and 8 girls) with visceral neuropathies are analyzed. Clinical symptomatology is dominated by abdominal distension, attacks of occlusion, abdominal pain, and malnutrition. Intestine bacterial overgrowth is frequent. From aspiration biopsies, surgical rectal biopsies, and, in some cases, ileal or ileocolic biopsies, histopathological studies revealed two patterns. One group had abnormalities of the myenteric plexus identified by conventional light microscopic studies, with two patterns: [myenteric plexus hyperplasia (9 patients), characterized by large ganglionic nodes, penetration into the mucosal zone, and altered argyrophilic neurons]. Clinically this pattern was observed in four patients with multiple endocrine neoplasia syndrome with risk of medullary thyroid carcinoma. The second pattern observed was characterized by glial cell hyperplasia (15 patients). Ganglion cells are present but are small and sparse, often infiltrated by collagen tissue; Schwann nerve fibers are hypertrophic. Eleven patients presented with neonatal intestinal obstruction. The second group is characterized by normal conventional light microscopic examination, but silver stains revealed important abnormalities of argyrophobic cells (one case) or argyrophilic cells (one case). In the two groups, most of the patients needed intestinal derivation and prolonged nutritional support with total parenteral nutrition.

Adolescent↗

Microscopic colitis: a new cause of chronic diarrhea in children?

From a retrospective study on children who underwent colonoscopy or rectosigmoidoscopy with multiple level biopsies, we selected five patients whose rectocolonic endoscopic aspect was normal and contrasting with the presence of a microscopic colitis on biopsies. These five children had chronic diarrhea (mean duration of 14 months), associated with vomiting (three cases), abdominal pain (two cases), anorexia (two cases), abdominal distension (two cases), and weight loss (four cases). Symptomatic treatment was used in all children: loperamide (one case), trimebutine (three cases), and aluminium and magnesium silicate (two cases). One child received sulfasalazine for 2 months. After 1 year, all patients had normal stools. Rectosigmoidoscopy was performed in four patients and was normal. Biopsies obtained in three cases were normal in two cases and showed a persistent microscopic colitis in one case. Microscopic colitis may be a distinct cause of chronic diarrhea in children.

Biopsy↗

Duodenogastric reflux in children: measurement of phospholipids and trypsin in gastric content.

The duodenogastric reflux (DGR) is a suspected cause in some esogastric pathologies in adults: esophagitis, peptic gastric ulcers, stress ulcers, ulcers secondary to drugs, gastric cancer, and gastritis. The toxic substances of the reflux are essentially bile acids, lysolecithin, and trypsin. A number of diagnostic methods have been proposed in the adult. This study suggests a diagnosis technique for DGR in the child. Fasting gastric juice was collected by gastric intubation during 1 h and three substances were measured: phospholipids as markers of biliary reflux, trypsin as a marker of pancreatic reflux, and sialic acid as a marker of the degradation of gastric mucus. The sialic acid enabled us to evaluate some of the toxicity of DGR on the stomach. The study of 49 child subjects permitted us to show the existence, in the normal child, of biliopancreatic markers in the stomach under fasting conditions through a physiological DGR; to define the norms in the child, varying according to three age groups: 0-2 months, 2-12 months, and 1-4 years (the maximum values for an age above 4 years seemed to correspond to those in the adult); and to suggest the existence of a pathological DGR in children with antral gastritis or ulcers.

Age Factors↗

Newly synthesized calsequestrin, destined for the sarcoplasmic reticulum, is contained in early/intermediate Golgi-derived clathrin-coated vesicles.

We have examined the possible role of clathrin-coated vesicles (CVs) in the genesis of the sarcoplasmic reticulum (SR) in developing chick skeletal myotubes. Calsequestrin (CSQ) a luminal Ca2+ binding protein of the terminal SR cisternae, is contained within the vesicle lumen of skeletal muscle CVs in substantial amounts, approximately four molecules/CV. Employing 3-day cultures of chick skeletal myotubes we demonstrate that after a 30-min labeling with [35S]methionine and cysteine, radioactivity in CSQ remains high in the CVs 45 min later and then declines, while labeled CSQ in the SR continues to rise. No CSQ appears to be secreted. All of the CSQ in both the CVs and SR is sensitive to the activity of endoglycosidase H, and a significant fraction also binds to wheat germ agglutinin. Based on these results, we discuss the hypothesis that a selective CV-mediated pathway exists in developing skeletal muscle cells for the transport of CSQ from the early/intermediate Golgi apparatus to the SR.

Acetylcholinesterase↗

Mucinous metaplasia to neoplastic lesions in endometrial samples with cytohistologic correlation.

Seven cases of endometrial mucinous metaplasia and five of well-differentiated mucinous adenocarcinoma of the endometrium were studied. Cytologic specimens were obtained by Isaacs endometrial sampler, avoiding endocervical contamination. The histologic diagnosis between the intermediate type of mucinous metaplasia and the well-differentiated mucinous adenocarcinoma posed no problems. DNA analyses of the histologic samples showed a euploid pattern in benign and intermediate types of metaplasia, while well-differentiated mucinous adenocarcinoma showed a hyperdiploid pattern. The cytologic diagnosis of benign mucinous metaplasia should be suggested in the presence of abundant mucinous cells in endometrial samples in the absence of nuclear abnormalities.

Adenocarcinoma, Mucinous↗

Expression of fragile sites in human sperm and lymphocyte chromosomes.

Sperm and lymphocyte chromosome studies in a normal, fertile male have shown a high degree of coincidence between chromosome lesions and fragile sites in both types of cells. In this donor we also found that some fragile sites expressed in sperm chromosomes coincided with those expressed in lymphocyte chromosomes. These results indicate that the chromosome lesions expressed in sperm do not occur at random and that they are not technical artifacts. The fragility expression in sperm chromosomes could reflect in vivo conditions. The presence in some sperm metaphases of acentric fragments suggests that chromosome fragility can result in the loss of chromosome fragments or give rise to de novo structural rearrangements. However, the incidence of sperm with chromosomal abnormalities observed in this man was within the normal range.

Adult↗

Promotion of fetal liver engraftment by T cells in a murine semiallogeneic model without graft-versus-host reaction.

Graft failure following transplantation with T cell-depleted bone marrow or with tissue naturally devoid of T cells, such as fetal liver (FL), suggests an important role for T cells in ensuring sustained hematopoietic stem cell engraftment. Whether T cells act by eliminating host residual immune cells--or, alternatively, by helping stem cell growth and differentiation--is still to be determined. The purpose of this study was to analyze the effect of T cell supplementation to the FL graft, using a semiallogeneic murine model where the graft-versus-host reaction is absent. Lethally irradiated C3H/OuJ mice were grafted with 10(6) FL cells from (C3H/OuJ x BALB/c) F1 hybrid mice, with or without 10(6) isogeneic mature T cells (FL and FL + T groups). Recipient animals were then monitored for survival and for hematologic and immune reconstitution. Eight days postgrafting, the number of multipotent stem cells in the spleen was significantly higher in FL + T as compared with FL recipient mice. Addition of T cells to the FL graft provided a faster recovery of hematological parameters and a significant increase in short-term survival (25.5% 6 weeks of survival in the FL group, as opposed to 55.5% 6 weeks of survival in the FL + T group, P less than 0.01). By contrast, immunological functions, as assessed by mitogen responses, were quite similar in both groups of animals. Overall a promoting effect of T cells in early stem cell engraftment was clearly demonstrated in this murine model, where GVHR is absent. These results provide in vivo support for a direct T cell effect on hematopoiesis.

Animals↗

Intravesical therapy comparing BCG, adriamycin, and thiotepa in 200 patients with superficial bladder cancer: a randomized prospective study.

This report presents the second interim analysis of data from a randomized prospective trial that compares the prophylactic effect of 15 intravesical instillations of 50 mg Doxorubicin (ADM), 50 mg of Thiotepa (TTPA), or 150 mg of Bacillus Calmette-Guérin (BCG) against recurrence and progression of superficial transitional cell bladder cancer. Of 202 enrolled patients, 176 patients are currently evaluable after a mean follow-up of 3 years (range, 3-97 months). The number of patients with recurrence was significantly lower in the BCG group (9/67) than in the ADM group (23/53, p = 0.002) or the TTPA group (20/56, p = 0.003). The overall recurrence index per 100 patient-months was also significantly lower for the BCG group (BCG vs. ADM, p = 0.07; BCG vs. TTPA, p = 0.001; TTPA vs. ADM, not significant). BCG was superior in preventing recurrence and progression of high risk tumors (T1, G2-3, multiple growth, and tumors associated with carcinoma in situ). The recurrence in this group of high risk tumors was for ADM treated patients 12/17, for TTPA treated patients 10/17 and for BCG treated patients 5/23 (BCG vs. ADM, p = 0.002; BCG vs. TTPA, p = 0.016; TTPA vs. ADM, not significant). Toxicity of intravesical BCG was higher than that of the other drugs, but not limiting the treatment. Bladder irritability occurred in 42% of the patients, granulomatous cystitis in 16.4%, and bladder contraction in 1.5% of the patients. Two patients of the ADM group (2/53 = 3.8%) underwent radical cystectomy for local urothelial progression. One patient (1.9%) in the same group died of distant metastases. The preliminary results suggest that BCG is significantly superior to the chemotherapeutic agents ADM and TTPA when used as an adjuvant intravesical therapy in superficial bladder cancer.

Administration, Intravesical↗

[Neurocristopathy. The association of Hirschsprung's disease-ganglioneuroma with autonomic nervous system dysfunction in 2 children].

Two children with the coexistence of long segment Hirschsprung's disease, ganglioneuroblastoma with Ondine's curse in one case and autonomic nervous system impairment in the other are presented. All lesions may be related to aberrations of neural crest cell growth, their migration, or differentiation. A genetic etiology, and the link between Hirschsprung's disease and multiple endocrine adenomatosis is discussed. The combination of Hirschsprung's disease and a neurocristopathy strongly suggests that exploration of the autonomic nervous system and APUD system be carried out.

Autonomic Nervous System Diseases↗

Crohn's disease lesions in the upper gastrointestinal tract: correlation between clinical, radiological, endoscopic, and histological features in adolescents and children.

The incidence of Crohn's disease (CD) lesions in the upper gastrointestinal (GI) tract of both adults and children is frequently underestimated. In this prospective study, a total of 31 children suspected of having Crohn's disease were systematically examined to identify upper digestive tract lesions. They all underwent barium transit endoscopy with multiple-level biopsies. Typical clinical symptoms suggestive of upper GI tract involvement were found in 5 children (16%), radiological signs in only one child (3%), endoscopic lesions in 13 children (42%), and specific granulomas in 12 children (39%). In eight of these 12 children, the biopsies were taken from macroscopically normal areas of the esophagogastroduodenal mucosa. One of the 31 children had no abnormal radiological and endoscopic features suggestive of CD on the distal small bowel and the colon. There was no correlation between the clinical, radiological, and histological data. Endoscopy plus biopsy provided a positive diagnosis in 39% of cases and a confirmation of the diagnosis in 87% of cases. Endoscopic and histological evidence of CD of the upper GI tract is often present despite an absence of clinical symptoms or radiological changes. Upper GI tract endoscopy with multiple biopsies may be important in the evaluation of this condition and even in some cases for the establishment of the diagnosis.

Adolescent↗