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Biomedical subjects

S Roth

Publications and source records attributed to S Roth.

At least 127 records · Page 7Linked to original sources

[Therapy and follow-up of superficial bladder cancer in in patients less than 30 years of age].

Transitional cell carcinoma of the bladder is relatively uncommon in patients under 30 years old. We treated 11 patients with superficial bladder carcinoma under 30 years of age. In 10 cases gross haematuria was the most common presenting symptom. The pathological reports of the patients revealed grade I, stage Ta transitional cell carcinoma in seven patients, grade I, stage T1 tumour in two patients and bladder myoma and inverted papilloma in two patients each. Four of nine patients with superficial bladder carcinoma stayed free of disease for 1-10 years after initial transurethral resection (TUR). Four patients suffered multiple tumour recurrences 1-4 months after initial TUR, with progressive disease in three cases. One patient was lost to follow-up after primary operation. In the two patients with benign bladder tumours, no recurrences were observed within 12 and 48 months. Owing to the high rates of recurrence (44%) and tumour progression (33%) all patients under 30 years of age should be treated as aggressively as necessary on the basis of the grade and stage of the tumour, in the same way older patients.

Adult

[Diagnosis of urethral diverticulum in women].

Urethral diverticula have proved to be a common cause of recurrent urinary tract infections in female subjects. Positive-pressure urethrography, mostly performed by means of double-balloon catheters, has hitherto been regarded as the method of choice for their detection. Unfortunately, the few existing commercial catheter devices have certain disadvantages, which have led to a lack of acceptance of this important technique and restricted its use. We therefore present an improved tool for positive-pressure urethrography and a synopsis of diagnostic visualization procedures for urethral diverticula in women.

Diverticulum

Functions of glutathione and glutathione disulfide in immunology and immunopathology.

Even a moderate increase in the cellular cysteine supply elevates the intracellular glutathione (GSH) and glutathione disulfide (GSSG) levels and potentiates immunological functions of lymphocytes in vitro. At low GSSG levels, T cells cannot optimally activate the immunologically important transcription factor NF kappa B, whereas high GSSG levels inhibit the DNA binding activity of NF kappa B. The effects of GSSG are antagonized by reduced thioredoxin (TRX). As the protein tyrosine kinase activities p56lck and p59fyn are activated in intact cells by hydrogen peroxide, they are likely targets for GSSG action. These redox-regulated enzymes trigger signal cascades for NF kappa B activation and transduce signals from the T cell antigen receptor, from CD4 and CD8 molecules, and from the IL-2 receptor beta-chain. The effector phase of cytotoxic T cell responses and IL-2-dependent functions are inhibited even by a partial depletion of the intracellular GSH pool. As signal transduction is facilitated by prooxidant conditions, we propose that the well-known immunological consequences of GSH depletion ultimately may be results of the accompanying GSSG deficiency. As HIV-infected patients and SIV-infected rhesus macaques have, on the average, significantly decreased plasma cyst(e)ine and intracellular GSH levels, we also hypothesize that AIDS may be the consequence of a GSSG deficiency as well.

Amino Acid Sequence

Blood flow after retinal ischemia in cats.

PURPOSE: To determine the changes in blood flow in the cat retina after 1 hour of ischemia. METHODS: Blood flow in the retina and choroid of adult cats anesthetized with chloralose, acepromazine, and halothane was measured using sequential injections of radioactively labeled microspheres. Ischemia was induced by elevation of intraocular pressure above systolic arterial pressure. Measurements were carried out before (baseline) and during ischemia, and at 5, 10, 15, 60, 120, and 240 minutes after the return of ocular circulation. In another two series of cats, blood flow was measured at comparable time periods without ischemia (controls). Arterial blood gas tension, systemic arterial pressure, hematocrit, and anesthetic level were controlled in each experiment. RESULTS: Retinal blood flow was decreased to 6%, and choroidal blood flow to 0.6%, of baseline value during ischemia. Within 5 minutes of the return of ocular circulation, retinal blood flow was approximately 200% of baseline, and choroidal blood flow was 108% of baseline. Blood flow 1 hour after the return of ocular circulation was not significantly different from baseline. There was no late decrease in blood flow after the ischemic period. CONCLUSION: As does cerebral ischemia, retinal ischemia results in a hyperemic response but no delayed hypoperfusion. The mechanism of this effect is unknown.

Animals

The effects of enflurane on ocular blood flow.

Although general anesthesia is frequently chosen for eye surgery or experimental studies of ocular blood flow, there are few data available describing its effects on ocular blood flow. In a previous study in cats, we reported that enflurane produced significant increases in preretinal oxygen tension, indicating an increase in oxygen availability in the retina. To examine whether this effect was due to an increase in retinal or choroidal blood flow, we used radioactively labeled 15 microns microspheres of Ce 141, Sn 113, Ru 103, or Nb 95, to measure ocular blood flow in cats during enflurane anesthesia. In 10 adult cats, retinal blood flow measured 75 +/- 13, 90 +/- 9 and 88 +/- 11 ml x 100 g-1 x min-1 (mean +/- S.E.M.) at 0.5, 1.0, and 1.5 MAC enflurane, respectively (1 MAC is the concentration at which 50% of subjects do not move in response to a standardized stimulus). Corresponding values for choroidal blood flow were 1275 +/- 124, 876 +/- 106 and 842 +/- 102 ml x 100 g-1 x min-1 (mean +/- S.E.M.) at 0.5, 1.0, and 1.5 MAC enflurane, respectively. The decrease in choroidal blood flow was significant between 0.5 and 1.0 MAC. These results differ from those in our previous investigation of the effects of halothane on ocular blood flow. With halothane, retinal blood flow increased and choroidal blood flow decreased throughout the entire dose range (0.5, 1.0, and 1.5 MAC). We conclude that inhalational anesthetic agents produce significant but different effects upon ocular blood flow.

Anesthesia, Inhalation

Bladder substitutes, bile acids and the risk of colorectal cancer: an experimental study.

There is a large body of evidence relating the causation of colon cancer to bile acids. Using an animal model, we attempted to address the question, i.e., the incidences of carcinogenesis in the colon as consequences of resection of different bowel segments, predominantly employed in the construction of various forms of intestinal bladder substitutes. 60 male Wistar rats were operated. Group 1 served as control, in group 2, 20 cm of terminal ileum was resected, and rats in group 3 underwent resection of the distal 10 cm of the ileum and 7 cm of the proximal colon. All rats were killed 6 months after surgery and the colon was removed. After examination under 40-fold magnification, in the absence of tumors, 3 biopsies were performed at predetermined positions and underwent histological processing. Even if no tumor was found it would be incorrect to conclude that these results would have an appeasing relevance. The complex and highly different fecal bile acid profiles of the rat compared to man makes it impossible in this context to draw analogies between the rat model and human colonic carcinogenesis. Furthermore, 6 months of observation in the rat might be too short for 'spontaneous' colonic carcinogenesis. Nevertheless, there exists evidence from epidemiological studies to implicate bile acids as an etiological factor in the development and growth of colorectal cancer. Therefore, the importance of colorectal cancer in urologic surgery patients must be kept in perspective. In this direction, further studies are required besides the application of known appropriate preventive measures.

Animals

Mutations of the fizzy locus cause metaphase arrest in Drosophila melanogaster embryos.

We describe the effects of mutations in the fizzy gene of Drosophila melanogaster and show that fizzy mutations cause cells in mitosis to arrest at metaphase. We show that maternally supplied fizzy activity is required for normal nuclear division in the preblastoderm embryo and, during later embryogenesis, that zygotic fizzy activity is required for the development of the ventrally derived epidermis and the central and peripheral nervous systems. In fizzy embryos, dividing cells in these tissues arrest at metaphase, fail to differentiate and ultimately die. In the ventral epidermis, if cells are prevented from entering mitosis by using a string mutation, cell death is prevented and the ability to differentiate ventral epidermis is restored in fizzy; string double mutant embryos. These results demonstrate that fizzy is a cell cycle mutation and that the normal function of the fizzy gene is required for dividing cells to exit metaphase and complete mitosis.

Animals

Mechanisms of dorsal-ventral axis determination in Drosophila embryos revealed by cytoplasmic transplantations.

The establishment of the dorsal-ventral pattern in Drosophila embryos depends on a signal transduction process: a putative extracellular ligand released into the perivitelline space surrounding the embryo binds to the Toll receptor. Toll activation triggers the formation of the nuclear gradient of dorsal protein, the morphogen of the dorsal-ventral axis. Here, I analyse the dorsal protein distribution and the expression of zygotic dorsal-ventral genes in Toll- embryos that have been injected with wild-type cytoplasm under a variety of different injection conditions. Injections into two positions within a single embryo lead to the formation of two dorsal-ventral patterns in one embryo, allowing the analysis of interactions between pattern-forming processes. The results of single and double injections suggest that the spatial information for the embryonic dorsal-ventral axis is largely derived from spatial cues present in the extraembryonic compartment, which restrict the release of the putative Toll ligand. They argue against a Toll-dependent pattern-formation process employing local self-enhancement and lateral inhibition to enhance a weak initial asymmetry. The putative Toll ligand appears to originate from a ventrally restricted zone which extends along the entire anterior-posterior axis. Ligand diffusion or its graded release are required to determine the slope of the nuclear dorsal protein gradient. Both the Toll receptor and the putative ligand of Toll are in excess in wild-type embryos. Since spatial information for the embryonic dorsal-ventral axis is already present in the vitelline membrane or the perivitelline space, it is most likely generated during oogenesis. Oogenic pattern formation is also responsible for the perpendicular orientation the dorsal-ventral axis maintains with respect to the anterior-posterior axis.

Animals

Micronucleus assay in lymphocytes as a tool to biomonitor human exposure to aneuploidogens and clastogens.

The analysis of micronuclei (MN) in cultured human lymphocytes is, in principle, able to detect exposure to clastogens and aneuploidogens alike. There is, however, no clear evidence from human biomonitoring studies or animal experiments showing that in vivo exposure of resting lymphocytes to an aneuploidogen could actually be expressed as MN in cultured lymphocytes. In vitro, a pulse treatment of human lymphocytes with vinblastine, an aneuploidogen, did result in MN induction even if performed before mitogen stimulation, although a much more pronounced effect was obtained in actively dividing lymphocyte cultures. On the other hand, it is probable that a considerable portion of "spontaneous" MN contain whole chromosomes, their contribution increasing with age. It also seems that cytochalasin B, used for the identification of second cell cycle interphase cells in the MN assay, is able to slightly increase the level of MN with whole chromosomes. If MN harboring chromosome fragments represent a minority of the total MN frequency, there may be difficulties in detecting a weak effect in this fraction of MN against the background of MN with whole chromosomes. This would reduce the sensitivity of the assay in detecting clastogens, unless MN with whole chromosomes and chromosome fragments are distinguished from each other. That a problem may exist in sensitivity is suggested by the difficulty in demonstrating MN induction by smoking, an exposure capable of inducing chromosome aberrations. The sensitivity of the lymphocyte MN assay could be increased by detecting kinetochore or centromere in MN, or by automation, allowing more cells to be analyzed.

Aneuploidy

Does detubularization improve continence in bladder replacement?

Camey in the seventies promoted bladder replacement. In 1987, the French Association of Urology gave us the opportunity to review 729 Tubularized Ileocystoplasty (Camey operation) [1]. The day time continence was excellent or acceptable (mild stress incontinence) on 91% of the patients, the night time continence was excellent (no pads, no leakage) or acceptable (one pad or less than 3 wakes at night) for 44% of the patients (56% had to use a device). Since 1985, the detubularization attempted to improve the continence rate. Today, the review of the literature shows that day time continence has not changed and the night time continence improved less than 20% arising from 44% to 60%. Bladder replacement after prostatocystectomy has been proved to be superior to continent urinary diversion in patients whose urethral and external sphincter can be preserved. Day time continence is excellent in tubularized and detubularized bowel reservoirs. Night time continence, in 30 to 50% of patients, remains an unresolved problem also in detubularized low pressure reservoirs, even if they are of great capacity. The literature is therefore too optimistic when describing night time continence in 85% of the patients. These results are stated in spite of the absence of sensitivity in the neobladder, the loss of reflexic increase in sphincteric activity during bladder filling, and the low sphincteric tonus during sleeping. These optimistic results are due to lack of unanimous criteria for evaluating continence after bladder replacement and not taking into consideration as continence failure the abundant although not frequent nighttime incontinence. In order to improve continence, muscle reeducation and artificial sphincter implantation are the most adequate solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans

Rapid suppression of spontaneous ventricular arrhythmias during oral amiodarone loading.

OBJECTIVE: To determine the time course of effects of amiodarone during an oral loading period. DESIGN: A prospective, nonrandomized study. SETTING: Arrhythmia referral center at a university hospital. PATIENTS: Fifty patients with refractory sustained ventricular tachycardia (n = 44) or ventricular fibrillation (n = 6) and frequent (greater than or equal to 30/h) ventricular premature complexes. INTERVENTION: Oral amiodarone, 1200 mg/d for 14 days and 400 mg/d thereafter. MEASUREMENTS: Ambulatory electrocardiographic monitorings, 12-lead electrocardiograms, and amiodarone blood levels on days 3, 5, 7, 9, 11, 13, and 28. RESULTS: Dramatic reductions of ventricular arrhythmias were noted during the first 72 hours of the therapy. Average ventricular premature complexes/h, couplets/h, and nonsustained ventricular tachycardias/24 h were 524 +/- 1224/h, 16 +/- 61/h, and 167 +/- 611/24 h, respectively, at baseline, and reduced to 140 +/- 243/h, 11 +/- 50/h, and 33 +/- 117/24 h, respectively, on day 3 (P less than 0.05 for all). Subsequent reductions of ventricular arrhythmias from day 3 to day 13 were more gradual but were still significant (P less than 0.05). A significant reduction of ventricular arrhythmias (greater than or equal to 70% reduction of ventricular premature complexes and greater than or equal to 90% reduction of nonsustained ventricular tachycardias) was noted in 50% of patients on day 3, in 65% on day 7, and in 83% on day 13. Prolongation of the QT interval exhibited a similar time course. There were no further differences in reduction of ventricular premature complexes or QT intervals between day 13 and day 28. CONCLUSIONS: Oral amiodarone given in loading doses produces rapid and dramatic reductions in spontaneous ventricular arrhythmias within 72 hours. Subsequent reductions of spontaneous arrhythmia were gradual and less dramatic.

Administration, Oral

Immunorecognition of different ganglioside epitopes on human normal and melanoma tissues.

There is increasing evidence that cell-surface gangliosides play a role in tumor growth, progression and metastases. In order to determine the frequency of ganglioside GD3 in patients with metastatic malignant melanoma for further therapeutic trials, GD3 ganglioside expression was determined in 119 tissue samples. Of these melanomas, 93% (111/119) were R-24-positive, which indicates the value of this diagnostic marker for melanoma. To study the structural epitopes of gangliosides, 10 ganglioside antibodies with defined specificities and affinities were tested on over 100 fresh-frozen tissue specimens of human normal and melanoma tissues. All the antibodies tested recognize the ganglioside GD3, but vary in their cross-reactivity with other gangliosides. According to their epitope specificity, they can be divided into 5 groups. For example, the antibodies Z-21 and A-4 react like the previously established MAb R-24 with gangliosides GD3 and GQlb, and one MAb (Q-4) detects all gangliosides containing 2 connected sialic acids (GD3, GD2, GDlb, GTlb, GQlb). Specificity on TLC does not always correlate with specificity to melanoma tissues and vice-versa. For example, MAb A-4, which recognizes only GD3 and GQlb on TLC, shows no specific reactivity on tissues. Furthermore, antibodies with the same ganglioside specificity do not have the same staining pattern on human tissues. For example, MAb Z-21, which is directed against the same gangliosides as MAb R-24 on TLC, does not cross-react with as many neuroectodermal tissues as MAb R-24. Because of their distinct properties, some of these antibodies may be even more useful for immunodiagnosis and immunotherapy of malignant melanoma than MAb R-24.

Antibodies, Monoclonal

The effects of isovolumic hemodilution on ocular blood flow.

Techniques by which retinal blood flow may be increased safely are potentially important in the treatment of retinal vascular disease. It was hypothesized that hemodilution, which increases cerebral blood flow, would also increase retinal blood flow. To investigate the physiological effects of hemodilution in the eye, ocular blood flow was measured in 14 cats using the radioactively labeled microsphere method. After the animals were anesthetized with halothane and oxygen, intraocular and systemic arterial pressure were recorded; blood flows were measured before and after isovolumic hemodilution to a hematocrit of 20-22% using 6% hydroxyethyl starch (a synthetic plasma expander with a molecular weight of 450 in 0.9% saline). In hemodiluted cats, retinal blood flow increased 71% from its baseline value (36.7 +/- 6.4 ml 100 g-1 min-1 to 62.9 +/- 6.4 ml 100 g-1 min-1, mean +/- S.E.M., P < 0.0001). Calculated retinal O2 delivery remained approximately constant, as the increased blood flow countered a significant decrease in arterial O2 content. Choroidal blood flow decreased (1297 +/- 140 ml 100 g-1 min-1 to 1051 +/- 144 ml 100 g-1 min-1) but the change was not statistically significant. Blood flows in the iris and sclera were not significantly altered. Hemodilution increased retinal blood flow without causing a redistribution in ocular blood flow.

Animals