Urethro-vesical function during spinal shock

Summary Twenty spinal shock patients were investigated with simultaneous urethrovesical, anal and rectal pressure recordings and EMG of the external urethral and anal sphincters. Dynamic and static urethral pressure profiles (UPP) were carried out with empty and full bladder. Baldder filling was accompanied by an increased resistance in the internal sphincter zone, which in turn was paralleled in the majority of cases by an elevation of pressure in the membranous urethra without concomitant increase of its EMG activity. This is suggestive of an increased sympathetic activity in the bladder neck area and in the smooth muscle component of the external urethral sphincter. Dynamic pullthrough UPP's displayed higher resistances in the membranous urethra than static interrupted UPP's pointing to the role played by the urethral muscosal receptors in eliciting artefactual results. Higher pressures were recorded in the juxtabulbar portion of the membranous urethra than in its mid portion pointing to a gradient of pressure within the external urethral sphincter itself. The amount of EMG activity recorded in the anal and urethral sphincters at rest was somewhat decreased; high pressures and distinct reflex activity were recorded in both sphincters showing that they escape spinal shock characterized primarily by areflexia. After defining spinal shock a rational explanation based upon neuroanatomical and neurophysiological findings is offered as to why somatic activity of the sacral segments escapes it as evidenced by clincial, urodynamic, and electromyographic recordings.     

Draize rabbit eye test compatibility with eye irritation thresholds in humans: a quantitative structure-activity relationship analysis.

Draize rabbit eye test scores, as modified maximum average score (MMAS), for 68 pure bulk liquids were adjusted by the liquid-saturated vapor pressure P. These 68 adjusted scores, as log (MMAS/P), were shown to be completely equivalent to eye irritation thresholds (EIT), expressed as log (1/EIT), for 23 compounds in humans. Thus, for the first time the Draize eye test in rabbits for pure bulk liquids is shown to be perfectly compatible with eye irritation thresholds in humans. The total data set for 91 compounds was analyzed by the general solvation equation of Abraham. Values of log (MMAS/P) or log (1/EIT) could be fitted to a five-parameter equation with R2 = 0.936, SD = 0.433, AD = 0.000, and AAD = 0.340 over a range of 9.6 log units. When divided into a training set of 45 compounds, the corresponding equation could be used to predict the remaining 46 compounds in a test set with AD = -0.037 and AAD = 0.345 log units. Thus, the 91-compound equation can now be used to predict further EIT values to around 0.4 log units. It is suggested that the mechanism of action in the Draize test and in the human EIT involves passive transfer of the compound to a biophase that is quite polar, is a strong hydrogen bond base, a moderate hydrogen bond acid, and quite hydrophobic. The biophase does not resemble water or plasma, but resembles an organic solvent such as N-methylformamide.     

Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis.

PURPOSE: Molecular antagonists of the inhibitor of apoptosis protein survivin have shown promise as novel anticancer strategies for triggering tumor cell apoptosis, dysregulating mitotic progression, and inhibiting tumor growth in preclinical models. However, how survivin couples to the cell death machinery has remained elusive, and the relevant cellular targets of survivin antagonists have not been completely elucidated. Experimental Design: Human umbilical vein and dermal microvascular endothelial cells were infected with replication-deficient adenoviruses encoding survivin (pAd-Survivin), green fluorescent protein (pAd-GFP), or a phosphorylation-defective survivin Thr(34)-->Ala (pAd-T34A) dominant negative mutant. The effect of wild-type or mutant survivin was investigated on capillary network stability, endothelial cell viability, and caspase activation in vitro and on kinetics of tumor growth and development of angiogenesis in a breast cancer xenograft model in vivo. The cell death pathway initiated by survivin targeting was mapped with respect to cytochrome c release, changes in mitochondrial transmembrane potential, and apoptosome requirements using mouse embryonic fibroblasts deficient in Apaf-1 or caspase-9. RESULTS: Adenoviral transduction of endothelial cells with pAd-Survivin inhibited growth factor deprivation- or ceramide-induced apoptosis, reduced caspase-3 and -7 generation, and stabilized three-dimensional capillary networks in vitro. Conversely, expression of pAd-T34A caused apoptosis in umbilical vein and dermal microvascular endothelial cells and resulted in caspase-3 activity. Cell death induced by survivin targeting exhibited the hallmarks of mitochondrial-dependent apoptosis with release of cytochrome c and loss of mitochondrial transmembrane potential and was suppressed in Apaf-1 or caspase-9 knockout mouse embryonic fibroblasts. When injected in human breast cancer xenografts, pAd-T34A inhibited growth of established tumors and triggered tumor cell apoptosis in vivo. This was associated with a approximately 60% reduction in tumor-derived blood vessels by quantitative morphometry of CD31-stained tumor areas, and appearance of endothelial cell apoptosis by internucleosomal DNA fragmentation in vivo. CONCLUSIONS: Survivin functions as a novel upstream regulator of mitochondrial-dependent apoptosis, and molecular targeting of this pathway results in anticancer activity via a dual mechanism of induction of tumor cell apoptosis and suppression of angiogenesis.     

Pyloric volume: an important factor in the surgeon’s ability to palpate the pyloric “olive” in hypertrophic pyloric stenosis

Objective. The objective of this study was to determine whether the size of the pyloric mass is one of the factors in the surgeon's ability to palpate the pyloric “olive”. Materials and methods. The ultrasonographic images and medical records of 60 infants with surgically confirmed hypertrophic pyloric stenosis (HPS) were reviewed. The pyloric diameter (PD) and pyloric length (PL) were measured and the pyloric volume (PV) was calculated using the equation PV = 1/4π× (PD)²× PL. Based on the pediatric surgeon's physical examination the infants were divided into two groups: those with and those without palpable pyloric masses. Results. Infants with a palpable pyloric mass had an average pyloric volume of 3.33 ± 1.76 mm³, which was statistically larger than those whose hypertrophied pylorus could not be palpated (average volume 2.59 ± 2.07 mm³, P < 0.01). There was no statistically significant age difference between the two groups. Conclusion. Clinical skill of the examiner and other clinical aspects (patient cooperation, etc.) determine palpability of the pylorus in HPS. The size of the hypertrophied pylorus is also an important factor affecting the clinican's ability to palpate the pyloric mass. Received: 29 December 1995 Accepted: 7 June 1996     

DMAIC methodology for achieving public satisfaction with health departments in various districts of Punjab and optimizing CT scan patient load in urban city hospitals

The health care delivery system in Pakistan is in a process of rapid growth, and it consists of public and private sectors. The provincial government is preliminarily responsible for providing health care facilities within its province except in federally administered areas. In Pakistan, there are three tiers of governmental healthcare delivery systems, which comprise government, semi-government, and parastatal organizations. The purpose of this study is to understand the rapid increase in influx of patients in major city hospitals of the Punjab province. The reasons for patient flow towards the major city areas can vary, but our point of focus is mainly on those patients who are prescribed to get a computed tomography (CT) scan done for better diagnosis and early treatment, including but not limited to roadside accident cases. The study targets the define, measure, analyze, improve and control (DMAIC) problem solving approach to assess the potential cause of CT patient flow and the challenges that the health department is facing to cater to such a patient niche and process while minimizing the congestion in city government hospitals. The approach in this study summarizes with numerous quality tools like Voice of Customer (VOC) which is customer feedback, Customer Output Process Input and Supplier (COPIS) processes use for high-level process map to know what your customer value, Approver Resource Member Interested (ARMI) chart which is use to analyze the stakeholders on management of the project, evaluation with the help of fishbone diagram and house of quality, and for process improvement methodology we use the team brainstorming technique and the kaizen 5-why technique. The technique came up with an idea of a public-private partnership (PPP) project—partnership between public agency and private firm, as the health care industry in Punjab province is going through budgetary issues. In a PPP project, the Government will allocate the space to a private firm to build the facility on their own and provide quality service for CT scan diagnosis to the public of Punjab. The study identified the top 10 critical factors that the patients have expected from the government to be provided on priority. The Kaizen process improvement methodology has been adopted to provide the possible solution of government budgetary issues. The set of tools in this study can be adopted by other PPP projects to enhance the project performance.     

Synthesis and free radical scavenging activity of coumarin derivatives containing a 2-methylbenzothiazoline motif

Coumarin and benzothiazole scaffolds can be found in a number of natural or synthetic antioxidants. In an effort to develop a novel radical scavenger and potential antioxidant, a series of coumarin derivatives containing 2‐methylbenzothiazoline motif and related compounds was synthesized and evaluated for their DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) and ABTS^?+ (2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) radicals scavenging activities. Among them, 7‐hydroxy‐3‐(2‐methyl‐2,3‐dihydrobenzo[d]thiazol‐2‐yl)‐2H‐chromen‐2‐one ( 3e ) has shown a significant free radical scavenging activity. From the structure–activity point of view, it was found that phenolic coumarin ring and benzothiazoline moiety in target compounds may contribute to the scavenging activity against free radicals.     

A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia

Rational

A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia.

Objective

The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia.

Methods

In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8.

Results

Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699)?=?37.366, p?<?0.001] as well as negative scores [F(2.439,92.675)?=?16.623, p?<?0.001] and general psychopathology [F(1.767,67.158)?=?4.602, p?=?0.017], but not positive subscale scores [F(1.348, 51.218)?=?0.048, p?=?0.893] compared to placebo. In a multiple regression analysis controlling for positive, extrapyramidal, and depressive symptoms, treatment group (standardized β?=??0.640) significantly predicted changes in primary negative symptoms. The side effect profile did not differ significantly between the two groups.

Conclusion

Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.