Effect of intravesical capsaicin and vehicle on bladder integrity control and spinal cord injured rats

PURPOSE: To determine the acute effect of intravesical capsaicin on bladder mucosal integrity in normal and spinal cord injured (SCI) rats. MATERIALS AND METHODS: Intravesical reagents were instilled in 5 groups of age and weight matched female rats: 1) control + normal saline solution (NSS), 2) control + ethanol (EtOH), 3) control + capsaicin/EtOH, 4) SCI + NSS, 5) SCI + capsaicin/EtOH. Intravesical instillations were performed 4 weeks after a standard T10 SCI. Intravesical capsaicin (1 mM.) was dissolved in 30% EtOH/NSS. The animals (n = 3 each group) were sacrificed at 30 minutes, 24 hours, 72 hours, and 7 days after intravesical instillation. Whole bladders were harvested, fixed in 10% buffered formalin, and paraffin embedded. Tissue blocks were blind coded and sectioned (5 microns thickness) for histopathological analysis. All sections were initially stained with hematoxylin and eosin (H & E). Specific staining for mucin carbohydrate moieties included periodic acid-Schiff (PAS) and alcian blue. Also, immunohistochemical staining for GP51 (a urinary glycoprotein) was performed. RESULTS: Control and SCI rats exhibited similar bladder mucosal histology by H & E and mucin specific stains. Instillation of saline demonstrated no effect on bladder histology, whereas instillation of intravesical capsaicin induced a profound acute effect of thinning of the epithelium, submucosal edema, and diminished presence of GP51. EtOH produced similar pathological findings, but to a lesser degree than capsaicin. Intravesical capsaicin demonstrated a similar effect in both control and SCI animals. The peak effect was seen after 30 minutes and continued for 24 hours. Partial recovery was noted after 72 hours and complete recovery was evident by 1 week. CONCLUSIONS: The control and SCI rats demonstrated a histologically similar mucosa and glycosaminoglycan layer. The effect of saline instillation on the mucosa was negligible. Intravesical capsaicin dissolved in 30% ethanol/NSS had a profound effect on the bladder urothelium submucosa that was more pronounced than that seen with the ethanol vehicle alone in normal animals.     

Intrinsic dynamics and mechanosensory modulation of non-nutritive sucking in human infants

The rate constants of acetylcholine receptor channels (AChR) desensitization and recovery were estimated from the durations and frequencies of clusters of single-channel currents. Diliganded-open AChR desensitize much faster than either unliganded- or diliganded-closed AChR, which indicates that the desensitization rate constant depends on the status of the activation gate rather than the occupancy of the transmitter binding sites. The desensitization rate constant does not change with the nature of the agonist, the membrane potential, the species of permeant cation, channel block by ACh, the subunit composition (epsilon or gamma), or several mutations that are near the transmitter binding sites. The results are discussed in terms of cyclic models of AChR activation, desensitization, and recovery. In particular, a mechanism by which activation and desensitization are mediated by two distinct, but interrelated, gates in the ion permeation pathway is proposed.     

Personal performance profiles: a useful adjunct to quality assurance in cervical cytology

The purpose of this study was to determine whether the morphology of the midface differed in subjects with a retrognathic midfacial appearance (Class III malocclusions) using a combination of morphometric and cephalometric analyses. After obtaining appropriate consent, lateral cephalographs of 133 children of European-American descent, ages 5-11 years, were compared: 73 had Class III malocclusion, 60 had normal (Class I) occlusion. The cephalographs were traced and subdivided into seven age- and sex-matched groups. Average geometries based upon seven nodes (pterygoid point, PTS; rhinion, RO; posterior nasal spine, PNS; midpalatal point, MPP; anterior nasal spine, ANS; subspinale, A; prosthion, Pr), scaled to an equivalent size, were compared using a Procrustes routine. Euclidean distance matrix analysis (EDMA) was employed to localize differences in morphology. Bivariate analyses on unscaled data utilizing nine linear and six angular measurements were also undertaken. Results from Procrustes and EDMA analyses indicated that although the overall midfacial configurations differed statistically (P < 0.05), only about half of the seven age sub-groups maintained significance. Similarly, only four of the nine linear measures (PNS-MPP, MPP-ANS, A-Pr and PTS-RO) and two of the six angular parameters (PTS-RO-ANS and ANS-A-Pr) tested were significantly different (P < 0.05). Therefore, midfacial morphometric variability and morphological diversity may mask statistical differences. It is concluded that the midface may be the defining craniofacial component in the final appearance of Class III malocclusions compared to other craniofacial components, including the cranial base and mandible.     

Cell death and oxidative damage in inflammatory myopathies

AIMS: To evaluate the independent prognostic value of apoptotic versus proliferative fractions in a series of 92 patients with non-Hodgkin's lymphomas (NHL). METHODS AND RESULTS: Apoptotic fractions were quantified by use of the TdT (terminal deoxynucleotidyl-transferase)-mediated in-situ end-labelling technique (TUNEL), the percentage of positive cells constituting the apoptotic index (AI). Proliferative rate was expressed as percentage of Ki67 positive cells (Ki67 LI). Tissues were also stained for p53 protein with the DO-1 antibody. Patients were followed up until death (n = 33) or for an average of 63 months (n = 56). AI increased with malignancy grade and proliferative activity but was not related to location, cell of origin, clinical stage, bone marrow involvement and p53 expression. In multivariate analysis, overall survival was independently influenced by grade, stage, p53 LI and chemotherapy. The independent predictors of disease-free survival were Ki67 LI location and chemotherapy. AI turned out to be the only independent (negative) predictor of post-relapse survival. On the other hand, a low Ki67 LI increased the risk of relapse (logistic regression analysis) whereas a low p53 LI increased the probability of complete response. CONCLUSIONS: Our results suggest that the combined assessment of apoptotic fraction, proliferative rate and p53 expression may provide important prognostic information independent of other clinicopathological parameters in NHL.     

MR analysis of lung volume and thoracic dimensions in patients with emphysema before and after lung volume reduction surgery

OBJECTIVE: This study was performed to assess the accuracy of determining lung volume in patients with emphysema using MR imaging and then to investigate changes in thoracic dimensions after lung volume reduction surgery. SUBJECTS AND METHODS: Fast gradient-echo breath-hold MR imaging through the entire thorax at full inspiration and expiration was performed in 21 patients with severe emphysema and was performed again in nine of the patients who underwent surgery. Lung volumes were determined using a semiautomated computerized method of delineating the lungs and summing cross-sectional areas. These summed areas were compared with volumes measured on plethysmography and CT. Postoperative changes in thoracic structure were determined by measuring anteroposterior and transverse lung dimensions and lung height before and after surgery. RESULTS: The correlation coefficients and SEM for determining inspiratory lung volume were MR imaging versus plethysmography, r = .77, SEM = -12% (volume measured as less on MR imaging); CT versus plethysmography, r = .86, SEM = -13% (volume measured as less on CT); and MR imaging versus CT, r = .87, SEM = 4% (volume measured as greater on MR imaging). The correlation coefficients and SEM for determining expiratory volume on MR imaging versus plethysmography were r = .77, SEM = 6% (volume measured as greater on MR imaging). After surgery, decreases were found in all thoracic dimensions, and such decreases were greatest at expiration. CONCLUSION: MR measurements of lung volume are comparable with those of CT and differ from those of plethysmography. Changes in thoracic dimensions after lung volume reduction surgery are consistent with improved respiratory mechanics.     

Immunocytochemical colocalization of specific immunoglobulin A with sendai virus protein in infected polarized epithelium

Thrombocytopenia is often the dose-limiting toxicity for radionuclide therapy. Prediction of platelet counts after therapy is important for treatment planning. Simple prediction methods based on linear correlation between radiation dose and blood count nadir have been insufficient because they have not considered time, because of the complicated hierarchical structure of the hematopoietic system in which platelets are not directly injured by low dose rate radiation and because of changing radiation dose rates to marrow with time. This study addresses these problems using a cell kinetics model. METHODS: The model consists of compartments for progenitor cells, megakaryocytes, platelets and stromal cells. A linear quadratic formula was used for progenitor cell survival. Stromal cells were described by a model based on a maximum likelihood estimate for cellular damage, repair and proliferation. Reported values for murine cellular turnover rates and radiosensitivity of progenitor cells were used in the model calculations. Experimental mice received 4 Gy of external beam radiation for tumor implantation and 12.4-23.3 MBq 67Cu-2-iminothiolane-BAT-Lym-1 (BAT = 6-[p-(bromoacetamido) benzyl]-1,4,8,11-tetra-azacyclotetradecane-N,N',N',N'-tetraacet ic acid) 19-30 days later. Blood counts were measured three times each week. RESULTS: The model predicted the severity of thrombocytopenia, and the time of the nadir corresponded to measured values in mice. For a dose of 14.2 MBq 67Cu-2-iminothiolane-BAT-Lym-1 that induced a platelet nadir of 20% of baseline (Grade II), the model predicted that at least 20 days were needed before a second 14.2-MBq injection if a subsequent nadir of <10% of baseline (Grade IV) was to be avoided. CONCLUSION: The nadir and duration of thrombocytopenia predicted by the model were similar to those observed in the mice. Predicted information could be useful for planning the dose and timing of fractionated radionuclide therapy. This model provides a stepping stone for future development of a predictive model for patients.     

Carbon dioxide laser surgery for snoring: results in 192 patients

Laser-assisted uvulopalatoplasty has been introduced as an alternative to uvulopalatopharyngoplasty for treatment of snoring and potentially of obstructive sleep apnea syndrome. Between July 1994 and June 1996, 192 patients underwent 227 laser-assisted uvulopalatoplasty procedures. Loud habitual snoring was evaluated in 42 women (21.8%) and 150 men (78.2%), who were then treated with laser-assisted uvulopalatoplasty. Among the 192 patients (227 procedures), with ages from 18 to 81 years (mean 42.6 years), 15.6% (30 patients) had more than one laser-assisted uvulopalatoplasty treatment. In our series, 80 patients (42.1%) had a history of obstructive sleep apnea syndrome in addition to snoring. Laser-assisted uvulopalatoplasty treatment in patients with loud snoring resulted in elimination of snoring in 61%, partial improvement of snoring in 26%, and no improvement in 13%. The overall success rate was 87%. The mean body mass index was significantly higher in the patients with no response after the operation (27.9 kg/m2) compared with that in the patients with a good response (25.9 kg/m2). Obese (body mass index >30 kg/m2) patients were more likely to have no response to laser-assisted uvulopalatoplasty treatment of snoring than patients with an ideal body weight (body mass index <25 kg/m2) (p < 0.01). We conclude that the body mass index may be of significant value in the postoperative success rate of laser-assisted uvulopalatoplasty for the treatment of snoring.     

Ethionine toxicity in vitro: the correlation of data from rat hepatocyte suspensions and monolayers with in vivo observations

The hepato-steatogenic compound ethionine has been used to investigate the correlations between in vivo and in vitro toxicity data. The aim was to find a suitable model of toxicity in hepatocyte suspensions or monolayers in vitro, which could predict the known toxicity of ethionine in vivo and which could be implemented in screening compounds of unknown toxicity. Thus a variety of markers of cytotoxicity, metabolic competence and liver-specific functions were investigated in rat hepatocyte suspensions and monolayers and compared with in vivo data in the rat. The following markers were measured in the appropriate system: (1) Neutral red uptake; 3-(4,5 dimethyl)thiazol-2-yl,-2,5-diphenyl tetrazolium bromide (MTT) reduction; lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) leakage (cytotoxicity). (2) ATP levels, protein synthesis and glutathione (GSH) levels (metabolic competence). (3) Urea and triglyceride synthesis and beta-oxidation (liver specific functions). Ethionine (0-30 mM) did not affect the markers of direct cytotoxicity, except neutral red uptake, which was reduced by 18 and 30 mM ethionine after 20 h in culture. ATP and GSH depletion occurred in hepatocyte suspensions at the highest concentrations of ethionine (20 and 30 mM) after 1 h. In monolayers, GSH levels were reduced after 4 h, but not 20 h. Urea synthesis was increased in hepatocyte suspensions from 1 to 3 h by 10-30 mM ethionine and reduced after 20 h in cultured hepatocytes (18-30 mM). Protein synthesis was reduced and beta-oxidation was increased in ethionine-treated hepatocyte suspensions. Unfortunately, there was no measurable effect on triglyceride accumulation within cells (the major biochemical change in vivo) in either system. Ethionine treated hepatocytes in suspension showed the same rate of triglyceride synthesis and transportation out of cells as control cells. Thus, hepatocyte suspensions were able to mimic the early biochemical effects of ethionine in vivo (ATP and GSH depletion, inhibition of protein synthesis) and some effects on urea synthesis, but monolayer cultures appeared to be less sensitive to the toxicity of ethionine. However, neither in vitro system was able to model the effects of ethionine on the accumulation of triglycerides in vivo.