Comparison of intravesical chemotherapy regimens after radical nephroureterectomy for upper tract urothelial carcinoma and analysis of risk factors for postoperative recurrence.

OBJECTIVE: Upper tract urothelial carcinoma (UTUC) is a relatively rare but aggressive type of urologic cancer that includes renal pelvic tumors and ureteral tumors with a poor prognosis. Full-length nephroureterectomy plus sleeve bladder resection is the standard treatment for the disease, but patients are prone to recurrence of bladder tumors after surgery. Intravesical infusion therapy is the main means to prevent the recurrence and progression of bladder cancer. Epirubicin and gemcitabine are widely used in clinical practice as first-line or salvage therapy for intravesical chemotherapy; however, the efficacy of these agents is rarely discussed. The purpose of this study was to investigate the effects of epirubicin and gemcitabine on the occurrence of bladder cancer after radical nephroureterectomy for UTUC and to analyze the risk factors affecting the recurrence of postoperative bladder cancer. PATIENTS AND METHODS: A total of 215 patients with diagnosed UTUC and treated in our hospital from June 2019 to August 2021 were retrospectively selected as the research subjects, and they were divided into an observation group (120 cases) and a control group (95 cases) according to different treatment methods. The patients in the control group were treated with epirubicin, while those in the observation group received gemcitabine. All patients were followed up by telephone or outpatient examination for 12 months to record the occurrence of adverse reactions. The occurrence of bladder cancer was recorded at 3 months, 6 months, and 12 months after the surgery. According to the occurrence of bladder cancer after surgery, the patients were divided into a bladder cancer group (63 cases) and a non-bladder cancer group (152 cases). Multivariate Logistic regression analysis was used to analyze the risk factors of bladder cancer after surgery. RESULTS: The total incidence of adverse reactions in the control group was 49.47%, which was higher than that in the observation group with 15.00% (p<0.01). The incidence of bladder tumors in the observation group and the control group was 0.00% and 2.11% at 3 months, 5.00% and 8.42% at 6 months, 13.33% and 15.79% at 12 months, without significant difference (p>0.05). After 12 months of perfusion, the levels of acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) in the two groups were significantly lower than those before perfusion (p<0.05). In the observation group, the levels of these three factors were slightly decreased compared with those in the control group, without a significant difference (p>0.05). Between the bladder cancer and non-bladder cancer groups, there were significant differences in tumor location, number of lesions, tumor stage, preoperative ureteral examination, and preoperative history of bladder cancer (p<0.05). The above indexes were all risk factors for postoperative bladder cancer (p<0.05). CONCLUSIONS: Epirubicin and gemcitabine reduced the occurrence of bladder cancer and effectively inhibited tumor angiogenesis after radical nephroureterectomy for UTUC. The tumor location, number of lesions, tumor stage, preoperative ureteral examination, and preoperative history of bladder cancer were risk factors for postoperative bladder cancer.

Characterization of pyroptosis-related genes in esophageal cancer and construction of a prognostic model.

OBJECTIVE: Esophageal cancer (EC) is a highly malignant digestive system tumor that often lacks evident early symptoms and has a poor prognosis. Pyroptosis, a form of programmed cell death, has been shown to be associated with the occurrence and progression of many malignancies. However, its role in esophageal cancer remains unclear. This work aimed to evaluate the prognostic value of pyroptosis-related genes (PRGs) in EC using data from The Cancer Genome Atlas (TCGA) cohort. MATERIALS AND METHODS: The RNA-seq data from 171 esophageal samples in the TCGA database were employed. Differential expression genes (DEGs) between tumor and non-tumor samples were compared. Protein-protein interaction (PPI) networks were constructed using the STRING database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analyses were performed using the "clusterProfiler" package in R. Furthermore, based on the DEGs, all esophageal cancer cases were classified into three subtypes. A risk model for gene features was established using the LASSO regression method, and EC patients in the TCGA cohort were divided into high-risk and low-risk groups. RESULTS: A total of 614 PRGs were identified. Among them, 32 DEGs (31 upregulated and 1 downregulated) were found between normal esophageal tissue and EC tissue. PPI analysis identified key genes including IL-1ß, CASP1, AIM2, HMGB1, GSDMD, PYCARD, IL-18, BAK1, and TP53. On the other hand, the low-risk group exhibited a significantly higher survival rate than the high-risk group (p < 0.001). Combined with the clinical characteristics of the TCGA cohort, it was found that the risk score was an independent prognostic factor for overall survival (OS) prediction in EC patients. KEGG and GO analyses revealed the enrichment of genes associated with cell proliferation in the high-risk group. CONCLUSIONS: PRGs play a crucial role in the occurrence and development of EC and can be used to predict the prognosis of EC patients.

[Effect of sacubitril/valsartan on cardiac function in heart failure rabbits with preserved ejection fraction].

Objective: To investigate the effect of sacubitril/valsartan on cardiac function in heart failure rabbits with preserved ejection fraction. Methods: Forty-five healthy adult male New Zealand rabbits were divided into sham operation group (n=12) and model group (n=33) by random number table method. HFpEF model was constructed by abdominal aortic constriction in model group. In sham operation group, 1 rabbit died due to anesthesia accident, and 1 rabbit in model group died of acute left heart failure. At 8 weeks of modeling, 3 rabbits were excluded due to the failure to establish the successful model. At the 8th week of modeling, 2 rabbits in sham operation group were selected and sacrificed by random number table method, and 3 rabbits in model group were selected and sacrificed for myocardial histological examination. Then, 9 rabbits in sham operation group and 26 rabbits in model group entered the subsequent experiment. The model group was randomly divided into untreated group (n=8), valsartan intervention group (n=9), and sacubitril/valsartan intervention group (n=9), respectively, drugs were applied per gavage. The feeding and exercise activity of rabbits in each group were evaluated by simple cardiac function classification at baseline, 4 and 8 weeks post intervention. Echocardiography was used to detect interventricular septal thickness at diastole(IVSd), interventricular septal thickness at systolic(IVSs), left ventricular posterior wall of diastolic(LVPWd), left ventricular internal diameter at diastolic(LVIDd), left ventricular internal diameter at systolic(LVIDs), and calculate the left ventricular ejection fraction(LVEF), mitral valve's early diastolic flow velocity(E)/late mitral diastolic maximum flow rate ratio(A) and heart rate at baseline, 4 and 8 weeks post intervention. Serum N terminal B-type natriuretic peptide (NT-proBNP) and angiotensin (Ang)Ⅱ and soluble matrix lysin 2(sST2) content was determined by ELISA at baseline, 4 and 8 weeks post intervention. Eight weeks after intervention, the hearts of rabbits were taken and weighed, and heart mass index (HMI) and left ventricular mass index (LVMI) were calculated. Results: (1) Evaluation results of cardiac function: there were 2, 5, and 2 rabbits with cardiac function grade Ⅰ,Ⅱ and Ⅲ before the drug intervention, and 4, 4, and 1 rabbits with respective cardiac function grade after 8 weeks of intervention in valsartan group (P>0.05). There were 2, 4, and 3 rabbits with heart function gradeⅠ,Ⅱ and Ⅲ before the drug intervention, and 7, 2, and 0 rabbits with respective heart function grade after 8 weeks of intervention in sacubitril/valsartan group(P<0.05). (2) Echocardiographic results: at 8 weeks after drug intervention, IVSd and IVSs of rabbits in untreated group were significantly higher than those in sham operation group, and the ratio of E/A was significantly lower than that in sham operation group(all P<0.01). IVSs of the valsartan group was significantly higher than that of sham operation group, and the ratio of E/A was significantly lower than that of sham operation group(all P<0.01). The E/A ratio in the sacubitril/valsartan group was significantly lower than that in sham operation group(P<0.01). IVSd and IVSs in valsartan group were significantly lower than those in untreated group(all P<0.05), and IVSd in sacubitril/valsartan group was significantly lower than that in untreated group(P<0.01). The IVSd, IVSs, LVPWd, LVIDd, LVIDs, LVEF, E/A ratios were similar between sacubitril/valsartan group and valsartan group(all P>0.05). There was no significant difference in heart rate between the groups(P>0.05). (3) Serum NT-proBNP, Ang Ⅱ and sST2 levels: 4 weeks after drug intervention, untreated group, valsartan group, and sacubitril/valsartan group's serum NT-proBNP levels were significantly higher than that of sham operation group(all P<0.01); serum NT-proBNP was significantly lower in sacubitril/valsartan group than that in untreated group(P<0.01). Four weeks after intervention, serum AngⅡ levels were significantly higher in untreated group, valsartan group, sacubitril/valsartan group than in sham group(all P<0.01), but there was no statistically significant difference between the modeling groups(P>0.05). Four weeks after drug intervention, the serum sST2 contents in untreated group, valsartan group, and sacubitril/valsartan group were significantly higher than in sham operation group(all P<0.01), and which was significantly lower in valsartan group and sacubitril/valsartan group than in untreated group(all P<0.01), which were significantly lower in sacubitril/valsartan group than in valsartan group(P<0.01). Eight weeks after drug intervention, serum NT-proBNP levels were significantly higher in untreated group, valsartan group, and sacubitril/valsartan group than in sham operation group(all P<0.01), which were significantly lower in valsartan group and sacubitril/valsartan group than in untreated group(all P<0.01), which were significantly lower in valsartan group than in sacubitril/valsartan group(P<0.01). Eight weeks after drug intervention, Ang Ⅱ levels were significantly higher in valsartan group and sacubitril/valsartan group than in untreated group(all P<0.01), which tended to be higher in untreated group and valsartan group, tended to be lower in sacubitril/valsartan compared to value at 4 weeks(all P>0.05). Eight weeks after drug intervention, serum sST2 was significantly higher in untreated group and valsartan group than in sham operation group(all P<0.01), which tended to be higher in sacubitril/valsartan group compared to sham operation group(P>0.05), which were significantly lower in valsartan group and sacubitril/valsartan group than in untreated group(all P<0.01), which was significantly lower in sacubitril/valsartan group than in valsartan group(P<0.01). (4) Comparison of whole-heart mass, left ventricular mass, HMI and LVMI: 8 weeks after drug intervention, the whole-heart mass, left ventricular mass, HMI and LVMI were significantly higher in untreated group than in sham operation group(all P<0.01), and the above indexes were also significantly higher in valsartan group than in sham operation group(all P<0.05), tended to be lower in valsartan group compared to untreated group (all P>0.05). HMI and LVMI were lower in sacubitril/valsartan group than in untreated group(all P<0.05). All the above indexes tended to be lower in sacubitril/valsartan group than in valsartan group(all P>0.05). Conclusion: Sacubitril/valsartan is superior to valsartan alone on improving cardiac function in HFpEF rabbits.

Plasma exchange combining with plasma bilirubin adsorption effectively removes toxic substances and improves liver functions of hepatic failure patients.

OBJECTIVE: Hepatic failure (HF) is a kind of complex disease characterizing with liver dysfunction and a few clinical complications. Artificial liver support system (ALSS) has been applied to HF patients to improve dysfunctional liver in recent years. This study aims to evaluate therapeutic effects of ALSS approaches, including plasma exchange (PE), plasma diafiltration (PDF) and plasma bilirubin adsorption (PBA), on liver function of HF patients. PATIENTS AND METHODS: This study is a retrospective analysis involving 516 patients diagnosed as HF between February 2014 and February 2015. Patients were randomly divided into PE, PDF, PE plus PBA, and PDF plus PBA group. Meanwhile, single-drug group and combined-drug group were also divided. The liver functions, capability of removing toxic substances and coagulation functions were evaluated both pre-treatment and post-treatment. The side effects and hospital improvement rate were also observed post-treatment. RESULTS: Hospital improvement rate achieves to 69.6%. TBIL levels and MELD scores were significantly decreased post-treatment compared to pre-treatment (p<0.05). PTA values were significantly increased post-treatment compared to pre-treatment (p<0.05). Reduction value in PE+PBA group was significantly higher compared to PE and PDF group (p=0.002, 0.002, respectively). MELD scores were significantly decreased post-treatment compared to pre-treatment in each group (p<0.05). Combined-drug treatment is superior to single-drug treatment for removing toxic substances and improving liver functions. PE treatment, PDF treatment and PE+PBA treatment induced more side effects compared to PDF+PBA treatment. CONCLUSIONS: PE combining with PBA plays a better role in removing toxic substances, improving liver functions of HF patients.

Association between personal basic information, sleep quality, mental disorders and erectile function: a cross-sectional study among 334 Chinese outpatients.

Male erectile dysfunction (ED) may cause anxiety and depression, while mental disorders and sleep disturbances may also be closely related to ED. However, the exact nature of their relationship remains unclear, and whether personal basic background data affect erectile function is unknown. We conducted a cross-sectional study among Chinese outpatients with ED from January 2012 to December 2014. All the men answered a questionnaire collecting information about mental health status, sleep disturbances and personal data, underwent a physical examination and had a blood sample drawn. Sleep disturbances were assessed on the basis of a 19-item version of the Pittsburgh Sleep Quality Index, which includes questions on sleep patterns during the past month. Among the 462 patients, 128 patients with alcohol abuse, diabetes, hypertension, hyperlipidaemia, psychiatric drugs, neurologic injury or abnormal hormones were excluded from the study; 86.27% and 68.66% of the patients suffered from anxiety and depression respectively. Sleep quality and anxiety symptoms significantly affected erectile function, whereas personal income and education level had no significant effects. Our study suggested that it is necessary to pay attention to the psychological status of patients with ED, especially anxiety disorder. Sleep quality may be an important factor affecting erectile function according to the personal data.

Association of Heavy Rainfall on Genotypic Diversity in V. cholerae Isolates from an Outbreak in India.

The outbreak of waterborne disease cholera has been associated with rainfall and flooding events by contamination of potable water with environmental Vibrio cholerae. The continuation of the epidemic in a region, however, is often due to secondary transmission of the initial outbreak strain through human waste. This paper reports, on the contrary, a rapid shift of genotype from one V. cholerae strain to another one in an epidemic region. V. cholerae isolated from patients during 2005 cholera epidemic in Chennai, India were characterized using PCR identification of toxin genes, antibiogram, and genomic fingerprinting analysis. The results showed that in spite of the similarity of toxin genes and antibiogram, the Vibrio isolates grouped into two different clusters based on the ERIC-PCR fingerprinting. Each cluster corresponded to a distinct peak of cholera outbreak, which occurred after separate heavy rainfall. The results suggest that the rainfall event can bring various genotypes of V. cholerae strains causing multiple outbreaks.

Molecular characterization of Vibrio cholerae outbreak strains with altered El Tor biotype from southern India.

Forty-four Vibrio cholerae isolates collected over a 7-month period in Chennai, India in 2004 were characterized for gene traits, antimicrobial susceptibility and genomic fingerprints. All 44 isolates were identified as O1 El Tor Ogawa, positive for various toxigenic and pathogenic genes viz. ace, ctxB, hlyA, ompU, ompW, rfbO1, rtx, tcpA, toxR and zot. Nucleotide sequencing revealed the presence of cholera toxin B of classical biotype in all the El Tor isolates, suggesting infection of isolates by classical CTXPhi. Antibiogram analysis showed a broad-spectrum antibiotic resistance that was also confirmed by the presence of resistant genes in the genomes. All isolates contained a class 1 integron and an SXT constin. However, isolates were sensitive to chloramphenicol and tested negative for the chloramphenicol resistant gene suggesting a deletion in SXT constin. Fingerprinting analysis of isolates by ERIC- and Box PCR revealed similar DNA patterns indicating the clonal dissemination of a single predominant V. cholerae O1 strain throughout the 2004 outbreak in Chennai. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11274-009-0171-7) contains supplementary material, which is available to authorized users.

Ecology of coliphages in southern California coastal waters.

AIMS: This study aims to investigate the ecology of coliphages, an important microbial pollution indicator. Specifically, our experiments address (i) the ability of environmental Escherichia coli (E. coli) to serve as hosts for coliphage replication, and (ii) the temporal and spatial distribution of coliphages in coastal waters. METHODS AND RESULTS: Water samples from three locations in California's Newport Bay watershed were tested for the presence of coliphages every 2 weeks for an entire year. A total of nine E. coli strains isolated from various sources served as hosts for coliphage detection. Coliphage occurrence was significantly different between freshwater, estuarine and coastal locations and correlated with water temperature, salinity and rainfall in the watershed. The coliphages isolated on the environmental hosts had a broad host-range relative to the coliphages isolated on an E. coli strain from sewage and a US EPA recommended strain for coliphage detection. CONCLUSIONS: Coliphage occurrence was related to the temperature, rainfall and salinity within the bay. The adaptation to a broad host-range may enable the proliferation of coliphages in the aquatic environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding the seasonal variation of phages is useful for establishing a background level of coliphage presence in coastal waters. The broad host-range of coliphages isolated on the environmental E. coli host calls for investigation of coliphage replication in the aquatic environment.

Genetic determinants of virulence, antibiogram and altered biotype among the Vibrio cholerae O1 isolates from different cholera outbreaks in India.

Cholera diarrhea is still a major health challenge for a large part of globe. Global replacement of Vibrio cholerae classical biotype by El Tor biotype, emergence of O139 serogroup and rapid spread of antibiotic resistant strains indicate the continuous evolution in V. cholerae. In this study, 114 V. cholerae O1 serotype Ogawa isolates, collected from different cholera outbreaks in different regions of India between 2004 and 2007 were subjected to biochemical, immunological and molecular characterization. All the isolates were PCR positive for various toxigenic, pathogenic and regulatory genes, viz. ompW, ctxB, rfbO1, tcp, zot, rtxC, ace, hlyA, ompU and toxR. The antibiogram studies of isolates revealed the resistance towards several antibiotics including nalidixic acid, co-trimoxazole, streptomycin, nitrofurantoin and polymyxin B. However, antibiogram of the strains confirmed susceptibility to tetracycline and chloramphenicol in all the isolates. This study also substantiated the wide spread of class 1 integrons and SXT elements (mobile genetic elements for antibiotic resistance) in clinical isolates in India. Sequencing of cholera toxin (ctxB) gene revealed the replacement of traditional ctxB of El Tor biotype with ctxB of classical biotype in all the O1 El Tor strains collected since 2004. In addition, in 2007, a new variant of O1 El Tor strain with further modifications in ctxB of classical biotype is discovered among the Indian isolates.

Transfer of cholera toxin genes from O1 to non-O1/O139 strains by vibriophages from California coastal waters.

AIMS: Vibrio cholerae is an important bacterial pathogen that causes global cholera epidemic. Although they are commonly found in coastal waters around the world, most environmental isolates do not contain cholera toxin genes. This study investigates vibriophages in southern California coastal waters and their ability to transfer cholera toxin genes. METHODS AND RESULTS: Lytic phages infecting V. cholerae were isolated from Newport Bay, California, between May and November, while none was found in winter. Some of the phage isolates can infect multiple environmental V. cholerae strains and El Tor strains. All phages contained double-stranded DNA. Transduction experiments using kanamycin-resistant gene marked CTXPhi demonstrated that some environmental vibriophages can transfer CTXPhi genes from O1 El Tor strain to environmental non-O1/O139 V. cholerae via generalized transduction. CONCLUSIONS: Vibriophages are important components of the natural aquatic ecosystem. They play an important role in influencing the dynamics and evolution of V. cholerae in the environment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the significance of vibriophages in the coastal environment and transduction as one of the mechanisms of pathogenicity evolution among environmental V. cholerae.

Dynamic modeling of photothermal interactions for laser-induced interstitial thermotherapy: parameter sensitivity analysis.

A two-dimensional model was developed to model the effects of dynamic changes in the physical properties on tissue temperature and damage to simulate laser-induced interstitial thermotherapy (LITT) treatment procedures with temperature monitoring. A modified Monte Carlo method was used to simulate photon transport in the tissue in the non-uniform optical property field with the finite volume method used to solve the Pennes bioheat equation to calculate the temperature distribution and the Arrhenius equation used to predict the thermal damage extent. The laser light transport and the heat transfer as well as the damage accumulation were calculated iteratively at each time step. The influences of different laser sources, different applicator sizes, and different irradiation modes on the final damage volume were analyzed to optimize the LITT treatment. The numerical results showed that damage volume was the smallest for the 1,064-nm laser, with much larger, similar damage volumes for the 980- and 850-nm lasers at normal blood perfusion rates. The damage volume was the largest for the 1,064-nm laser with significantly smaller, similar damage volumes for the 980- and 850-nm lasers with temporally interrupted blood perfusion. The numerical results also showed that the variations in applicator sizes, laser powers, heating durations and temperature monitoring ranges significantly affected the shapes and sizes of the thermal damage zones. The shapes and sizes of the thermal damage zones can be optimized by selecting different applicator sizes, laser powers, heating duration times, temperature monitoring ranges, etc.

Effects of dynamic changes of tissue properties during laser-induced interstitial thermotherapy (LITT).

A two-dimensional model including the effects of dynamic changes in the physical properties on tissue temperature and damage was developed to describe laser energy transport, heat transfer, and damage accumulation during laser-induced interstitial thermotherapy (LITT). The Monte Carlo method was used to simulate photon transport in a tissue in the nonuniform optical property field, with the finite difference method used to solve the Pennes bioheat equation to calculate the temperature distribution and the Arrhenius equation used to predict the extent of thermal damage. The numerical results showed that the dynamic changes in the optical properties, thermal properties, and blood perfusion rate significantly affected damage volume accumulation and temperature history and should be included in numerical simulations of the LITT treatment.

PCR detection of pathogenic viruses in southern California urban rivers.

AIMS: To investigate human viral contamination in urban rivers and its impact on coastal waters of southern California, USA. METHODS AND RESULTS: Three types of human viruses (adeno, entero and hepatitis A) were detected using nested- and RT-PCR from 11 rivers and creeks. Faecal indicator bacteria as well as somatic and F-specific coliphage were also tested. Approximately 50% of the sites were positive for human adenoviruses. However, there was no clear relationship between detection of human viruses and the concentration of indicator bacteria and coliphage. Both faecal indicator bacteria and human viral input at beaches near river mouths were associated with storm events. The first storm of the wet season seemed to have the greatest impact on the quality of coastal water than following storm events. CONCLUSIONS: This study provides the first direct evidence that human viruses are prevalent in southern California urban rivers. Urban run-off impacts coastal water quality most significantly during the storm season. SIGNIFICANCE AND IMPACT OF THE STUDY: To protect human health during water recreational activities, it is necessary to develop effective strategies to manage urban run-off during storm events.

Effects of thermal properties and geometrical dimensions on skin burn injuries.

A one-dimensional multi-layer model is presented to characterise the skin burn process resulting from the application of a high temperature heat source to a skin surface. Transient temperatures were numerically calculated using a finite difference method to solve the Pennes bioheat equation. A damage function denoting the extent of burn injury was then calculated using the Arrhenius assumptions. The model was used to predict the effects of thermal physical properties and geometrical dimensions on the transient temperature and damage function distributions. The results show that the epidermis and dermis thicknesses significantly affect the temperature and burn injury distributions, while variations of the initial temperatures and the blood perfusion have little effect.

Giant cell reparative granuloma of the temporal bone.

Giant cell reparative granuloma (GCRG) is an uncommon non-neoplastic lesion that typically occurs in the mandible and maxilla: however, its involvement with the temporal bone is rare. It is usually misdiagnosed as a giant cell tumor. Although regarded as a benign process, GCRG may be locally aggressive. In this paper, we describe two cases of GCRG of the temporal bone and review the pertinent literature published in English. The clinical course, histological evaluation, diagnosis, differential diagnosis, treatment and prognosis of GCRG of the temporal bone were investigated.

Seasonal Abundance and Distribution of Vibrio cholerae in Coastal Waters Quantified by a 16S-23S Intergenic Spacer Probe.

Vibrio cholerae is the causative agent of the severe diarrheal disease cholera and is indigenous to brackish waters. To advance our understanding of the ecology of this bacterium, we have developed a molecular probing method for detection of V. cholerae in coastal waters. Water samples from 7 locations in the Newport Bay watershed, California were sampled monthly for a whole year. V. cholerae concentrations were determined by membrane filtration-colony hybridization using an oligonucleotide probe targeting the 16S-23S intergenic spacer (ITS) region. In addition to V. cholerae concentrations, environmental parameters, including temperature, salinity, total bacterial direct counts, total viable counts, and chlorophyll a concentrations, were determined for each site. V. cholerae was detected year-round throughout the watershed. Regression analysis indicated that the concentration of V. cholerae inversely correlated with salinity (p <0.001). The sampling sites located nearest to the Pacific Ocean had lower concentrations, whereas sites located along the brackish San Diego Creek (salinity 0-12 per thousand) routinely had higher concentrations. V. cholerae concentrations also correlated with temperature (p <0.01) in the watershed, with concentrations ranging from less than 1 CFU mL-1 to 2,930 CFU mL-1 of water. The results of this study indicate that the dynamics of V. cholerae is mainly influenced, out of the parameters measured, by the temperature and salinity of the environment. This information is valuable for understanding the ecology of V. cholerae.

Intense noise-induced apoptosis in hair cells of guinea pig cochleae.

Cells can die by two distinct pathways: apoptosis and necrosis. To explore whether intense noise can induce hair cell (HC) death via the apoptotic pathway, we systematically examined morphological changes in guinea pig cochlear HC nuclei stained with Hoechst 33342, a fluorescent dye specifically labelling the nuclear DNA. A narrow band noise centred at 4 kHz with levels at 110 dB, 115 dB or 120 dB (SPL) was applied for 4 h and the exposed cochleae were collected at various intervals (3 h, 3 or 14 days) after the noise exposure. Auditory function was monitored by measuring thresholds of auditory brain stem responses. In the noise-damaged cochleae, there were two major types of nuclear changes, nuclear condensation appeared as karyorrhexis or karyopyknosis and nuclear swelling. Karyorrhexis and karyopyknosis predominately appeared in the severely damaged cochlear region in the animals exposed to 120 dB noise and examined 3 h after the noise exposure. In contrast, swelling of nuclei occurred in all of the noise-exposed cochleae, and was the feature change in the animals exposed to 110 and 115 dB noise. This pathological change persisted at least for 14 days after the noise exposure. The typical changes of karyorrhexis and karyopyknosis noted in the animals exposed to 120 dB noise were morphologically similar to those nuclear changes described in previous studies for apoptosis, suggesting that the apoptotic process may be involved in intense noise-induced HC death.

Genetic diversity of Vibrio cholerae in Chesapeake Bay determined by amplified fragment length polymorphism fingerprinting.

Vibrio cholerae is indigenous to the aquatic environment, and serotype non-O1 strains are readily isolated from coastal waters. However, in comparison with intensive studies of the O1 group, relatively little effort has been made to analyze the population structure and molecular evolution of non-O1 V. cholerae. In this study, high-resolution genomic DNA fingerprinting, amplified fragment length polymorphism (AFLP), was used to characterize the temporal and spatial genetic diversity of 67 V. cholerae strains isolated from Chesapeake Bay during April through July 1998, at four different sampling sites. Isolation of V. cholerae during the winter months (January through March) was unsuccessful, as observed in earlier studies (J. H. L. Kaper, R. R. Colwell, and S. W. Joseph, Appl. Environ. Microbiol. 37:91-103, 1979). AFLP fingerprints subjected to similarity analysis yielded a grouping of isolates into three large clusters, reflecting time of the year when the strains were isolated. April and May isolates were closely related, while July isolates were genetically diverse and did not cluster with the isolates obtained earlier in the year. The results suggest that the population structure of V. cholerae undergoes a shift in genotype that is linked to changes in environmental conditions. From January to July, the water temperature increased from 3 degrees C to 27.5 degrees C, bacterial direct counts increased nearly an order of magnitude, and the chlorophyll a concentration tripled (or even quadrupled at some sites). No correlation was observed between genetic similarity among isolates and geographical source of isolation, since isolates found at a single sampling site were genetically diverse and genetically identical isolates were found at several of the sampling sites. Thus, V. cholerae populations may be transported by surface currents throughout the entire Bay, or, more likely, similar environmental conditions may be selected for a specific genotype. The dynamic nature of the population structure of this bacterial species in Chesapeake Bay provides new insight into the ecology and molecular evolution of V. cholerae in the natural environment.

Genetic diversity of clinical and environmental isolates of Vibrio cholerae determined by amplified fragment length polymorphism fingerprinting.

Vibrio cholerae, the causative agent of major epidemics of diarrheal disease in Bangladesh, South America, Southeastern Asia, and Africa, was isolated from clinical samples and from aquatic environments during and between epidemics over the past 20 years. To determine the evolutionary relationships and molecular diversity of these strains, in order to understand sources, origin, and epidemiology, a novel DNA fingerprinting technique, amplified fragment length polymorphism (AFLP), was employed. Two sets of restriction enzyme-primer combinations were tested for fingerprinting of V. cholerae serogroup O1, O139, and non-O1, O139 isolates. Amplification of HindIII- and TaqI-digested genomic DNA produced 30 to 50 bands for each strain. However, this combination, although capable of separating environmental isolates of O1 and non-O1 strains, was unable to distinguish between O1 and O139 clinical strains. This result confirmed that clinical O1 and O139 strains are genetically closely related. On the other hand, AFLP analyses of restriction enzyme ApaI- and TaqI-digested genomic DNA yielded 20 to 30 bands for each strain, but were able to separate O1 from O139 strains. Of the 74 strains examined with the latter combination, 26 serogroup O1 strains showed identical banding patterns and were represented by the O1 El Tor strain of the seventh pandemic. A second group, represented by O139 Bengal, included 12 strains of O139 clinical isolates, with 7 from Thailand, 3 from Bangladesh, and 2 from India. Interestingly, an O1 clinical isolate from Africa also grouped with the O139 clinical isolates. Eight clinical O1 isolates from Mexico grouped separately from the O1 El Tor of the seventh pandemic, suggesting an independent origin of these isolates. Identical fingerprints were observed between an O1 environmental isolate from a river in Chile and an O1 clinical strain from Kenya, both isolated more than 10 years apart. Both strains were distinct from the O1 seventh pandemic strain. Two O139 clinical isolates from Africa clustered with environmental non-O1 isolates, independent of other O139 strains included in the study. These results suggest that although a single clone of pathogenic V. cholerae appears responsible for many cases of cholera in Asia, Africa, and Latin America during the seventh pandemic, other cases of clinical cholera were caused by toxigenic V. cholerae strains that appear to have been derived locally from environmental O1 or non-O1 strains.

[Computed tomographic findings of the development of the bone around the vestibular aqueduct in Meniere's disease].

OBJECTIVE: To study the development of the bone around the vestibular aqueduct (VA) in Meniere's disease (MD) by CT. METHOD: The experiment consisted of three groups; normal ear group, non-MD vertigo group and MD group. VA in each group was examined by CT, and the minimum distance between the posterior semicircular canal and the posterior petrous surface where contain the endolymphatic sac. RESULT: VA visualization rate in MD was low, P-P distance in MD group was shorter than that of normal ear group and non-MD vertigo group. CONCLUSION: It is the fundamental pathological anatomy in MD that VA and the bone around VA are maldeveloped.