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Biomedical subjects

S Roth

Publications and source records attributed to S Roth.

At least 145 records · Page 8Linked to original sources

Adenosine receptor blockade and nitric oxide synthase inhibition in the retina: impact upon post-ischemic hyperemia and the electroretinogram.

We preformed this study to determine the effect on ocular blood flow and the electroretinogram of either nitric oxide synthase (NOS) inhibition, adenosine receptor blockade or the combination of both after 1 hr of ocular ischemia. Thirty-seven cats under general anesthesia were subjected to 1 hr of complete ischemia in one eye by raising the intraocular pressure above systolic blood pressure. The other eye in each animal served as a non-ischemic control. Arterial blood gas tension, systemic arterial pressure, body temperature, hematocrit, and anesthetic level were controlled in each experiment. Cats were divided into four groups. Group 1 received normal saline injections [intravenous (i.v.) and intravitreal], Group 2 adenosine receptor blockade (0.1 ml of 0.01 M 8-sulfophenyltheophylline intravitreal) and saline i.v., Group 3 NOS inhibition (30 mg/kg l-NG-nitroarginine-methyl-ester i.v.) and saline intravitreal, and Group 4 intravitreal adenosine receptor blockade and NOS inhibition i.v. A subset of Group 3 received l-arginine to investigate the reversibility of NOS inhibition, after the blood flow measurements were completed. Five minutes after the end of ischemia, blood flows in retina and choroid were measured using injections of radioactively labeled microspheres. Electroretinographic (ERG) studies were carried out before treatment, before ischemia, during ischemia, and 1, 2, 3, and 4 hr after ischemia ended. NOS inhibition significantly reduced basal blood flow in the choroid, and in the retina when combined with adenosine receptor blockade. Adenosine receptor blockade completely attenuated post-ischemic hyperemia in the retina, but retinal hyperemia reappeared when adenosine receptor blockade and NOS inhibition were combined. Adenosine receptor blockade had no effect on ERG recovery after ischemia. NOS inhibition led to a reduction of ERG a- and b-wave amplitudes in control eyes, that could be reversed by l-arginine. Nitric oxide (NO) appears to be a significant factor in the regulation of basal blood flow in the choroid. Adenosine appears to be a major mediator of retinal hyperemia after 60 min of ischemia. Since NOS inhibition appeared to have direct effects on ERG wave amplitudes, short-term ERG studies may be of limited use in assessing the role of NO in postischemic recovery of the retina. Our observations correlate well with the emerging role of NO as a neurotransmitter in the retina.

Analysis of Variance↗

Assessment of a new self-rating scale for post-traumatic stress disorder.

BACKGROUND: In post-traumatic stress disorder (PTSD) there is a need for self-rating scales that are sensitive to treatment effects and have been tested in a broad range of trauma survivors. Separate measures of frequency and severity may also provide an advantage. METHODS: Three hundred and fifty-three men and women completed the Davidson Trauma Scale (DTS), a 17-item scale measuring each DSM-IV symptom of PTSD on 5-point frequency and severity scales. These subjects comprised war veterans, survivors of rape or hurricane and a mixed trauma group participating in a clinical trial. Other scales were included as validity checks as follows: Global ratings, SCL-90-R, Eysenck Scale, Impact of Event Scale and Structured Clinical Interview for DSM-III-R. RESULTS: The scale demonstrated good test-retest reliability (r = 0.86), internal consistency (r = 0.99). One main factor emerged for severity and a smaller one for intrusion. In PTSD diagnosed subjects, and the factor structure more closely resembled the traditional grouping of symptoms. Concurrent validity was obtained against the SCID, with a diagnostic accuracy of 83% at a DTS score of 40. Good convergent and divergent validity was obtained. The DTS showed predictive validity against response to treatment, as well as being sensitive to treatment effects. CONCLUSIONS: The DTS showed good reliability and validity, and offers promised as a scale which is particularly suited to assessing symptom severity, treatment outcome and in screening for the likely diagnosis of PTSD.

Adult↗

Development of a criteria set and a structured interview for disorders of extreme stress (SIDES).

Data regarding the development of a structured interview measuring alterations that may accompany extreme stress are presented. A list of 27 criteria often seen in response to extreme trauma and not addressed by DSM-IV criteria for posttraumatic stress disorder (PTSD) were generated based on a systematic review of the literature and a survey of 50 experts. A structured interview for disorders of extreme stress (SIDES) measuring the presence of these criteria was administered to 520 subjects as part of the DSM-IV PTSD field trials. Inter-rater reliability as measured by Kappa coefficients for lifetime Disorders of Extreme Stress was .81. Internal consistency using coefficient alpha ranged from .53 to .96. Results indicate that the SIDES is a useful tool for investigation of response to extremes stress.

Adolescent↗

Complex PTSD in victims exposed to sexual and physical abuse: results from the DSM-IV Field Trial for Posttraumatic Stress Disorder.

Two hundred thirty four participants in the DSM-IV Posttraumatic Stress Disorder (PTSD) Field Trial who reported sexual and/or physical abuse were evaluated. Participants were categorized according to type of abuse (physical, sexual, both), duration of abuse (acute versus chronic), and onset of abuse (early versus late). Separate logistic regression analyses examined the relationship between age of onset, duration, abuse type, and the complex PTSD (CP) lifetime diagnosis for women and men. Sexually abused women, especially those who also experienced physical abuse, had a higher risk of developing CP, although CP symptoms occurred at a high base rate among physically abused women. The theoretical implications and incremental clinical usefulness of targeting CP symptoms with abused populations are discussed.

Adaptation, Psychological↗

Thematic resolution, PTSD, and complex PTSD: the relationship between meaning and trauma-related diagnoses.

The role of modifying schemas in trauma-focused psychotherapy has received theoretical and clinical attention. However, the relationship of schematic processing to posttraumatic stress disorder (PTSD) diagnosis has not been examined empirically. The current study-compared measures of thematic disruption among individuals with PTSD alone, PTSD with concurrent complex PTSD, and no PTSD. Eighty two participants were interviewed to assess PTSD status, complex PTSD status, traumatic life events, and trauma-related thematic processing. Results indicated that variables quantifying thematic disruption and thematic resolution significantly distinguished those individuals with concurrent PTSD plus complex PTSD from the other two groups. Exploratory analyses indicated that PTSD symptom severity and the interpersonal nature of the trauma were related to thematic disruption.

Adaptation, Psychological↗

Clinical uroselectivity: evidence from patients treated with slow-release alfuzosin for symptomatic benign prostatic obstruction.

OBJECTIVE: To assess the safety profile of slow-release (SR) alfuzosin in the treatment of benign prostatic obstruction (BPO), with special attention to orthostatic blood pressure changes, postural symptoms and efficacy. PATIENTS AND METHODS: Two placebo-controlled studies involving 588 patients (292 receiving SR alfuzosin 5 mg twice daily and 296 a placebo) were pooled; 51% of the patients were > or = 65 years of age and 43% had associated cardiovascular disease including hypertension and/or were receiving concomitant antihypertensive drugs. RESULTS: SR alfuzosin was very well tolerated with an overall incidence of adverse events similar to that of placebo (18.5% and 15.8% of patients, respectively) and an overall incidence of withdrawal from therapy for adverse events lower than that of placebo (3.4% and 5.7%, respectively). Adverse events potentially related to vasodilatation were infrequent with SR alfuzosin (the same incidence as with placebo, i.e. 2.7% of patients) and these adverse events occurred mainly during the first month of alfuzosin treatment. The effect on supine blood pressure was minimal. In the subgroups of elderly and hypertensive patients treated with SR alfuzosin, the cumulative incidence of asymptomatic orthostatic hypotension during the first month of treatment was slightly higher than with placebo with no objective consequences on the incidence of adverse events. The clinical efficacy of SR alfuzosin was confirmed by a significant improvement in urinary symptoms and a significant increase in maximum flow rates. CONCLUSION: SR alfuzosin (10 mg/day) can be administered safely without titration in patients with BPO, even in elderly and hypertensive patients. Its favourable benefit/risk ratio allows alfuzosin to be classified as a clinically uroselective alpha 1-blocker. Specific analysis of orthostatic changes in blood pressure is important when assessing the safety profile of an alpha 1-blocker in patients with BPO.

Adrenergic alpha-Antagonists↗

Concentrations of adenosine and its metabolites in the rat retina/choroid during reperfusion after ischemia.

PURPOSE: Little is known about the nature of biochemical disturbances during reperfusion after retinal ischemia. Previous studies have suggested that adenosine is responsible for regulation of retinal blood flow soon after ischemia has ended. Therefore, in this study we measured concentrations of adenosine and its metabolites in the rat retina/choroid after brief (10 min) or prolonged (60 min) periods of ischemia, and the functional consequences of inhibiting adenosine metabolism. METHODS: Ischemia was produced in anesthetized rats by ligation of the central retinal artery. The eyes were frozen in situ and purine nucleoside concentration was determined by high performance liquid chromatography. The functional effects of pre-ischemic inhibition of xanthine dehydrogenase/xanthine oxidase were assessed by measurement of the electroretinogram before, during, and up to 7 days following 60 min ischemia. RESULTS: Changes in the concentrations of adenosine and its metabolites were significant early in the reperfusion period, and were greater in magnitude and occurred earlier in prolonged, compared to brief, ischemic periods. Concentrations of adenosine, inosine, and hypoxanthine remained elevated for 30 min following the end of 60 min ischemia, and xanthine concentration was significantly elevated until 60 min after the end of either 10 or 60 min of ischemia. The onset of its peak value after ischemia was delayed in comparison to that of adenosine. Ischemia-evoked increases in xanthine concentration were attenuated by inhibition of adenosine deaminase or xanthine oxidase/xanthine dehydrogenase. Pre-ischemic inhibition of xanthine oxidase/xanthine dehydrogenase by oxypurinol (40 or 80 mg/kg intraperitoneally [IP]) resulted in a significant improvement in recovery of the a and b waves of the electroretinogram in comparison to a saline-treated control group. CONCLUSIONS: These results indicate that adenosine is a major component of the biochemical changes that occur after retinal ischemia. Long-lasting increases in xanthine concentration during reperfusion after ischemia could be a source of oxygen free radicals that may contribute to delayed injury of the retina, attempts to decrease xanthine concentration would ideally be initiated within one hour after the end of ischemia.

Adenosine↗

The Y-chromosomal and autosomal male-determining M factors of Musca domestica are equivalent.

In Musca domestica, male sex is determined by a dominant factor, M, located either on the Y, the X or on an autosome. M prevents the activity of the female-determining gene F. In the absence of M, F becomes active and dictates female development. The various M factors may represent translocated copies of an ancestral Y-chromosomal M. Double mutants and germ line chimeras show that MY, MI, MII, MIII and MV perform equivalent functions. When brought into the female germ line, they predetermine male development of the offspring. This maternal effect is overruled by the dominant female-determining factor FD. MI and MII are weak M factors, as demonstrated by the presence of yolk proteins in MI/+ males and by the occurrence of some intersexes among the offspring that developed from transplanted MI/+ and MII/+ pole cells. The arrhenogenic mutation Ag has its focus in the female germ line and its temperature-sensitive period during oogenesis. We propose that MI and Ag represent allelic M factors that are affected in their expression. Analysis of mosaic gonads showed that in M. domestica the sex of the germ line is determined by inductive signals from the surrounding soma. We present a model to account for the observed phenomena.

Animals↗

The anatomy and embryological origins of the fascia of Denonvilliers: a medico-historical debate.

PURPOSE: We reviewed the conflicting theories concerning the anatomy and embryological derivation of Denonvilliers' fascia since its first description in 1836. MATERIALS AND METHODS: An extensive review of the literature for the last 160 years was done. RESULTS: Various studies contributed to the debate on the anatomy and origins of Denonvilliers' fascia. We chose to review these studies because of their sound methodology, large numbers of cases and results, and the high quality of the macroscopic and/or microscopic evidence. CONCLUSIONS: Denonvilliers' fascia consists of a single layer arising from fusion of the 2 walls of the embryological peritoneal cul-de-sac. Histologically, it has a double-layered quality. The fascia of Denonvilliers extends from the deepest point of the interprostatorectal peritoneal pouch to the pelvic floor. A so-called posterior layer is in reality the rectal fascia propria.

Anatomy↗

Unexplained visual loss after lumbar spinal fusion.

Two cases of visual loss after spinal fusion surgery are described. In both cases, surgery was lengthy, the patient's head was placed in a dependent position, and hemodilution and deliberate hypotension were combined. One patient was achondroplastic, the other obese. Possible risk factors associated with ischemic optic neuropathy after anesthesia and surgery are discussed.

Achondroplasia↗

Efficacy and safety of sustained-release alfuzosin 5 mg in patients with benign prostatic hyperplasia. ALGEBI Study Group.

OBJECTIVES: To assess the efficacy and safety of a sustained-release (SR) formulation of alfuzosin, a selective alpha(1)-blocker, in patients with symptomatic benign prostatic hyperplasia (BPH). METHODS: A total of 390 men were randomly assigned to receive SR-alfuzosin (n = 194), 5 mg twice daily without dose titration, or placebo (n = 196) for 12 weeks. Of the patients included, 47% had concomitant cardiovascular disease, mainly hypertension or coronary heart disease. RESULTS: SR-alfuzosin significantly improved urinary symptoms versus placebo assessed using the I-PSS (-31 vs. -18%, p = 0.007) and Boyarsky (-30 vs. -16%, p < 0.001) scores, with a direct correlation between both scores. Maximum flow rate increased significantly with SR-alfuzosin (+2.4 ml/s, i.e. +29%) compared with placebo (+1.1 ml/s, i.e. +14%, p = 0.006). Residual urine was also significantly reduced with SR-alfuzosin. Overall, SR-alfuzosin was as well tolerated as placebo. Nine patients dropped out for adverse events with SR-alfuzosin (4.6%) and 14 (7.1%) with placebo. The incidence of vasodilation-related events (dizziness, postural symptoms, headache) with SR-alfuzosin (3.1%) was similar to that of placebo (3.6%). No first-dose effect was observed compared with placebo. The reduction in supine blood pressure with SR-alfuzosin was minor (< or = 5 mm Hg), both in normotensive and hypertensive patients. CONCLUSION: SR-alfuzosin is an effective treatment of symptoms related to BPH that shows a good safety profile in normotensive and hypertensive patients, without the need of dose titration.

Adrenergic alpha-Antagonists↗

Does the success of ureterointestinal implantation in orthotopic bladder substitution depend more on surgeon level of experience or choice of technique?

PURPOSE: We attempted to determine the relative risk of ureterointestinal anastomosis using 2 antireflux techniques of orthotopic bladder substitution, and we assessed the degree to which success is determined by surgeon experience. MATERIALS AND METHODS: A total of 120 patients underwent surgery, including 74 with the Hautmann (Le Duc) technique and 46 with a somewhat modified Studer (Nesbit/Studer) technique. The urologists who performed the operations were classified as expert, skilled and learner. Evaluation was done retrospectively. All patients in the Studer group, except 3 who died and 1 who was lost to followup, were monitored a minimum of 12 months. RESULTS: There was a 20.4% rate of nonneoplastic obstructions in the 142 ureters reimplanted with the Le Duc technique (Hautmann group). The variation in obstruction rates of 16.7, 18.2 and 25%, respectively, for expert, skilled and learning surgeons was statistically insignificant. Only 3 nonneoplastic obstructions (3.6%) developed in the 83 ureters reimplanted with the Nesbit/ Studer technique (Studer group). The variation in obstruction rates of 5.1, 0 and 3.6%, respectively, for expert, skilled and learner surgeons was statistically insignificant. CONCLUSIONS: The Nesbit/Studer technique results in a generally lower rate of ureterointestinal anastomotic stricture than the Le Duc technique. Using the Le Duc technique there was no statistically significant correlation between incidence of obstruction and surgeon level of experience, indicating that obstruction with this technique probably arises from other factors.

Adult↗

Role of nitric oxide in retinal cell death.

Nitric oxide synthase (NOS), the enzyme that catalyzes the formation of nitric oxide from L-arginine, exists in three major isoforms, neuronal, endothelial, and immunologic. Neuronal and immunologic NOS has been detected in the retina. Neuronal NOS may be responsible for producing nitric oxide in photoreceptors and bipolar cells. Nitric oxide stimulates guanylate cyclase of photoreceptor rod cells and increases calcium-channel currents, which may be significant in the photoresponse. Inducible nitric oxide synthase, found in Müller cells and in retinal pigment epithelium, may be involved in normal phagocytosis of the retinal outer segment, in infectious and ischemic processes, and in the pathogenesis of diabetic retinopathy. Nitric oxide contributes to basal tone in the retinal circulation. To date, findings are conflicting with respect to its role in retinal autoregulation. During glucose and oxygen deprivation, nitric oxide may increase blood flow and prevent platelet aggregation, but it may also mediate the toxic effects of excitatory amino acid release. Nonspecific inhibition of NOS appears to protect the retina from ischemic damage, suggesting an important role of nitric oxide in the pathogenesis of retinal ischemic injury, and possible therapeutic approaches in patients with retinal vascular occlusion.

Animals↗

Tumor necrosis factor production capacity as a potentially useful parameter to monitor disease activity in multiple sclerosis.

The aim of this study was to develop a test allowing to monitor disease activity in patients with multiple sclerosis (MS). A simple, fast and reliable test was used to assess the cytokine production capacity of blood leucocytes. The whole blood test (WBT) involved in vitro stimulation of a whole blood sample with either the mitogen phytohaemagglutinin (PHA), or specific antigens. We focused our attention on the production of tumor necrosis factor alpha (TNF), because of the possible involvement of this cytokine in MS pathogenesis. Under in vitro stimulation with PHA or MBP, TNF production was found to be significantly higher in patients during the clinical relapses than during remissions. The increment of TNF production correlated with the severity of the relapses, as determined by the modification of Kurtzke EDSS scale. Moreover, each clinical relapse appeared to be preceded by a peak of TNF production. We then retrospectively analysed 21 patients with the relapsing-remitting form of the disease, in whom the WBT was performed every 2-4 weeks, for periods ranging from 16 to 52 months. Seventy-three peaks of TNF production (defined as the doubling or more of the individual baseline value, which was found to be stable for each patient during remissions), and 47 relapses, including 36 objective and 11 subjective, were observed. Forty-seven out of the 73 TNF peaks were followed by or concomitant with a clinical relapse. In 10 out of the 26 cases where no relapse followed the TNF peak, another cause (mainly infections) of increased TNF production was found. Thus, by excluding other causes, the specificity of the WBT, i.e., the probability to develop a relapse when a TNF peak was found to be 74.6% (47/63). The sensitivity of the WBT was 100%, since all the 47 relapses were preceded by a TNF peak. Assessment of TNF production capacity by the WBT may thus be useful in the follow-up of MS patients, particularly for the follow-up of various treatments. Information provided by the WBT may also be useful to orientate the therapeutic decision for an incipient relapse. Earlier treatment is likely to result in an improved prevention of neurological damage.

Case-Control Studies↗

Comparison between continuous brain tissue measurement and cerebrovenous measurement of pO2, pCO2 and pH in a porcine intracranial pressure model.

Simultaneous oxygen measurements in brain tissue (p(ti)O2) and hemoglobin saturation measurement in cerebrovenous blood in patients after severe head injury have shown different results regarding the comparability of the findings in respect to CPP and ICP. This is contrast to theoretical expectations. The aim of this study was to compare continuous ptiO2 measurement with oxygen partial pressure measurement in sagittal sinus (pO2cv) during simultaneously performance in an animal intracranial pressure model. For continuous measurement we used a newly available multisensor probe. We placed a Paratrend 7 probe (BSL, High Wycombe, UK) in the left frontoparietal white matter and measured ptiO2, pCO2 (ptiCO2) pH (pHti) and temperature (t(ti)) while simultaneously measuring these parameters (pcvO2, pcvCO2, pHcv, tcv) in the sagittal sinus in 9 pigs under general anaesthesia. A fogarty balloon catheter was placed supracerebellar infratentorial and inflated stepwise in order to increase ICP. The baseline levels of pO2ti, pCO2ti und pHti in the non-injured brain tissue showed a more extended heterogeneity compared to the findings in cerebrovenous blood. Both, pO2ti and pO2cv were significant correlated to the CPP decrease. In both measurement compartments pCO2 was inverse correlated to the course of CPP and seems the course of pH mainly to determine. p(ti)O2 as well as p(cv)O2 showed a close correlation to the CPP course and have proven to be qualified to indicate metabolic information about the relation of cerebral blood flow and metabolic cerebral demands. The measurement of CO2 tension in both measurement compartments shows a distinct heterogeneity of the absolute values and the results are only weak correlated to CPP. Metabolic influence on this parameter could not be revealed in the used experimental approach.

Animals↗

Continuous pO2 and pCO2 measurement in brain tissue and cerebrovenous blood during different inspired oxygen settings. A porcine model.

The clinical use of brain tissue oxygen measurement in patients with severe head injury is increasing. It is important to compare the findings in brain tissue with jugular bulb oximetry, to obtain normal values and to find out limitations of the method. We evaluated a newly available multisensor probe simultaneously in the brain tissue and in the sagittal sinus in a porcine animal model. We placed the Paratrend 7-probe (BSL, High Wycombe, UK) in the left frontoparietal white matter and measured pO2 (ptiO2), pCO2 (pti CO2), pH and temperature while simultaneously measuring these parameters (pcvO2, pcvCO2) in the sagittal sinus in 7 pigs under general anaesthesia during a 100% oxygen enhancement. The relation between oxygen increase in brain tissue and in the sagittal sinus showed a coefficient of correlation (CCmean) r(mean) = 0.96. The quantitative response in brain tissue was much more sensitive than in the sinus. A close correlation between pCO2 in brain tissue and sagittal sinus and the increase of the inspired oxygen was seen: CC ptiCO2 to arterial oxygen pressure (paO2) - r(mean) = 0.67, CC pcvCO2 to paO2 - r(mean) = 0.88. This is important for interpreting measured values and introducing new coefficients for patient monitoring. Newly available continuous brain oxygen measurement methods will allow better understanding of brain metabolism in the future.

Algorithms↗

Randomized trial with early-stage Hodgkin's disease testing 30 Gy vs. 40 Gy extended field radiotherapy alone.

PURPOSE: To evaluate whether or not a total dose (TD) of 30 Gy is sufficient for treatment of assumed subclinical Hodgkin's Disease compared to 40 Gy TD with early stage Hodgkin's Disease (ESHD). METHODS AND MATERIALS: In a prospective multicenter trial, 376 patients with laparotomy-proven ESHD stages PS IA to PS IIB without risk factors such as large mediastinum, massive splenic involvement, extranodal disease, elevated erythrocyte sedimentation rate (ESR), and/or three or more involved lymph node areas were randomly allocated either to receive (ARM A) 40 Gy TD extended field-radiotherapy (EF-RT) or (ARM B) 30 Gy TD EF-RT plus 10 Gy TD involved field-radiotherapy (IF-RT), both arms without any chemotherapy. Three hundred sixty-six of these patients were evaluable for early and long-term response, such as remission status, freedom from treatment failure (FFTF), and overall survival (OAS). For quality control, all planning and verification films as well as dose charts were prospectively reviewed by a panel of four experts, all heads of a radiotherapy department, where protocol violations (PV) were seen either with regard to errors in treatment technique, treatment volume, in TD and/or in dose/time-relationship. RESULTS: Treatment resulted in a complete remission (CR) of 98%; in a 5-year FFTF of 76%, and a 5-year OAS of 97%. There was no difference between the two arms in favor of 40 Gy EF compared to 30 Gy EF regarding FFTF and OAS, without any in field relapse throughout the EF volumes. Expectedly, 5-years FFTF was significantly influenced by the quality of radiotherapeutical procedures: 70% with protocol violations (PV) vs. 82% without PV. CONCLUSION: Subclinical involvement in ESHD without risk factors is sufficiently treated by a TD of 30 Gy without chemotherapy, leading to a 5-years FFTF of 82% and a 5-year OAS of 97% in a multicenter treatment setting, where quality assurance is mandatory.

Adolescent↗