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Objective: To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells. Methods: The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis. Results: SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals ( P <0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA ( P <0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased ( P <0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged ( P >0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion: SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.

As we know, benign paroxysmal positional vertigo is a peripheral vestibular disorder,while vestibular migraine is a central vestibular disease. Although they are two different independent diseases, patients often choose to consult otolaryngology and neurology. The clinical manifestations of some patients with these two diseases are similar and the diagnosis is easy to be confused, but the treatment methods are completely different, and incorrect treatment methods will inevitably affect the curative effect and prognosis. Vestibular migraine is characterized by a diversity of clinical manifestations and signs, and the migraine symptoms of some patients do not match with the vestibular symptoms. There are 30% of vestibular migraine patients who showed isolated paroxysmal vertigo/dizziness and nystagmus, which is easily confused with benign paroxysmal positional vertigo and needs to be identified. Under the framework of the international classification of vestibular diseases, according to the new guideline of nystagmus examination and classification issued by Barany Association and new diagnostic criteria of two diseases, differential diagnosisof benign paroxysmal positional vertigo from vestibular migrainecan make up for one-sided understanding caused by the specialization of disciplines, improve thediagnosis and treatment of vestibular diseases, and thus reduce the misdiagnosis and mistreatment.

Fecal calprotectin and indole were studied in 134 subjects with recurrent CDI before and after FMT. Reduced fecal calprotectin (p = 0.0353, 95% CI 0.1305-0.1439) and rising levels of indole (p < 0.0001, 95% CI < 0.0001-0.0003) predicted successful treatment. A ratio of recal calprotectin/indole may provide prognostic value for FMT (p = 0.0004, 95% CI 0.22-0.87)., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore the spectrum of causes for patients with vertigo or dizziness in the Department of Neurology, and provide a reference for diagnosis and treatment of patients with vertigo or dizziness. Methods: Clinical data of patients in the Department of Neurology, Baotou Central Hospital between January 2016 and September 2017 was retrospectively analyzed. The target group under study was diagnosed based on the uniform diagnostic criteria. Results: A total of 9 200 patients with a chief complaint of vertigo or dizziness were included. The ratio of male to female was 1∶1.8, with an age range of 19 to 85 years. The different etiology was as follows: benign paroxysmal positional vertigo (BPPV) (3 148 cases, 34.22%), persistent postural-perceptual dizziness (PPPD) (2 006 cases, 21.80%), vertigo caused by cerebrovascular diseases (1 463 cases, 15.90%), vestibular neuritis (741 cases, 8.05%), vestibular migraine (536 cases, 5.83%), vestibular paroxysmia (336 cases, 3.65%), Ménière disease (187 cases, 2.03%), drug-induced vertigo (96 cases, 1.04%), neurological degenerative diseases (74 cases, 0.80%), sudden sensorineural hearing loss (51 cases, 0.55%), multiple sclerosis and neuromyelitis optica (21 cases, 0.23%), other reasons (22 cases, 0.24%), unknown reasons (519 cases, 5.64%). Conclusions: Dizziness is resulted from various causes, and BPPV is the most common reason. Vertigo caused by cerebrovascular diseases appears to gradually increase along with age. PPPD is very common in clinical practice, so clinicians needs to be highly aware of BPPV and PPPD. Although those dizziness diseases have a low incidence, they should not be ignored. There are still certain proportion of vertigo patients whose diagnosis are undetermined.

Eleven published studies of the etiology of travellers' diarrhea (TD) were reviewed define the etiology of TD and to exam newly developed technology such as Real-Time multiplex polymerase chain reaction (PCR) to identify multiple pathogens in one assay to define the cause of TD. Using PCR methods bacterial pathogens were found in 72% of patients acquiring diarrhea in Latin America and in 80% in travellers with illness acquired in Southeast Asia). In these studies, enterotoxigenic Escherichia coli as the predominant pathogen (42% in Latin America and 28% in Southeast Asia). Ciprofloxacin-resistant Campylobacter was commonly associated with TD in Southeast Asia. Multiplex PCR has improved the detection of enteropathogens and allowed better assessment returning travellers hospitalized with TD and those with persistent diarrhea., (© International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Faecal microbiota transplantation (FMT) has become routine in managing recurrent C. difficile infection (CDI) refractory to antibiotics., Aim: To compare clinical response and improvements in colonic microbiota diversity in subjects with recurrent CDI using different donor product., Methods: Seventy-two subjects with ≥3 bouts of CDI were randomised in a double-blind study to receive fresh, frozen or lyophilised FMT product via colonoscopy from 50 g of stool per treatment from eight healthy donors. Recipients provided stools pre- and 7, 14 and 30 days post-FMT for C. difficile toxin and, in a subset, microbiome composition by 16S rRNA gene profiling., Results: Overall resolution of CDI was 87% during 2 months of follow-up after FMT. Stool samples before FMT had significantly decreased bacterial diversity with a high proportion of Proteobacteria compared to donors. Cure rates were highest for the group receiving fresh product seen in 25/25 (100%), lowest for the lyophilised product 16/23 (78%; P = 0.022 vs. fresh and 0.255 vs. frozen) and intermediate for frozen product 20/24 (P = 0.233 vs. fresh). Microbial diversity was reconstituted by day 7 in the subjects receiving fresh or frozen product. Improvement in diversity was seen by day 7 in those randomised to lyophilised material with reconstitution by 30 days., Conclusions: Comparative efficacy in faecal microbiota transplantation was observed in subjects receiving fresh or frozen faecal product from the same donors. The lyophilised product had a slightly lowered efficacy compared with fresh product, but it resembled other treatments in microbial restoration 1 month after faecal microbiota transplantation., (© 2017 John Wiley & Sons Ltd.)

BACKGROUND: Cryotherapy and hyperthermia are effective treatments for several diseases, especially for liver cancers. Thermal conductivity is a significant thermal property for the prediction and guidance of surgical procedure. However, the thermal conductivities of organs and tissues, especially over the temperature range of both cryotherapy and hyperthermia are scarce., Objective: To provide comprehensive thermal conductivity of liver for both cryotherapy and hyperthermia., Materials and Methods: A hot probe made of stain steel needle and micron-sized copper wire is used for measurement. To verify data processing, both the least square method and the Monte Carlo inversion method are used to determine the hot probe constants, respectively, with reference materials of water and 29.9 % Ca 2 Cl aqueous solution. Then the thermal conductivities of Hanks solution and pork liver bathed in Hanks solution are measured., Results: The effective length for two methods is nearly the same, but the heat capacity of probe calibrated by the Monte Carlo inversion is temperature dependent. Fairly comprehensive thermal conductivity of porcine liver measured with these two methods in the target temperature range is verified to be similar., Conclusion: We provide an integrated thermal conductivity of liver for cryotherapy and hyperthermia in two methods, and make more accurate predictions possible for surgery. The least square method and the Monte Carlo inversion method have their advantages and disadvantages. The least square method is available for measurement of liquids that not prone to convection or solids in a wide temperature range, while the Monte Carlo inversion method is available for accurate and rapid measurement.

Background: Cell survival upon cryopreservation is affected by the cooling rate. However, it is difficult to model the heat transfer process or to predict the cooling curve of a cryoprotective agent (CPA) solution due to the uncertainty of its convective heat transfer coefficient (h)., Objective: To measure the h and to better understand the heat transfer process of cryovials filled with CPA solution being plunged in liquid nitrogen., Materials and Methods: The temperatures at three locations of the CPA solution in a cryovial were measured. Different h values were selected after the cooling process was modeled as natural convection heat transfer, the film boiling and the nucleate boiling, respectively. And the temperatures of the selected points are simulated based on the selected h values. h was determined when the simulated temperature best fitted the experimental temperature., Results: When the experimental results were best fitted, according to natural convection heat transfer model, h(1) = 120 W/(m(2)·K) while due to film boiling and nucleate boiling regimes h(f) = 5 W/(m(2)·K) followed by h(n) = 245 W/(m(2)·K). These values were verified by the differential cooling rates at the three locations of a cryovial., Conclusion: The heat transfer process during cooling in liquid nitrogen is better modeled as film boiling followed by nucleate boiling.

Aims: To detect any functional abnormality in the brainstem auditory pathway in late preterm babies born of small-for-gestational age (SGA) using maximum length sequence brainstem evoked response., Study Design: The response was recorded and analyzed at term in 38 SGA (birthweight <3rd centile) babies born at 33-36 week gestation. The results were compared with 40 age-matched babies born of appropriate-for-gestational age (AGA) (birthweight >10th centile). None of the subjects had major perinatal problems., Results: All wave latencies and interpeak intervals in the SGA group were slightly longer than those in the AGA group at most click rates. Wave III latency was significantly longer than that in the AGA group at 227/s (P < 0.05), and wave V latency was at 227 and 910/s (P < 0.05 and 0.05). Of the interpeak intervals, only the I-V interval in the SGA group was significantly longer than that in the AGA group at the highest rate 910/s (P < 0.05). The amplitudes of waves I, III and V in the SGA group all tended to be smaller than those in the AGA group at all click rates 91-910/s. The wave V amplitude was significantly smaller at most click rates (227-910/s, all P < 0.05). The slopes of all wave latency-, interval-, and amplitude-rate functions were similar in SGA and AGA groups., Conclusions: There were marginal abnormalities in MLS BAER of low-risk late preterm SGA babies, suggesting a mild degree of maturational delay in the brainstem. Intrauterine growth retardation occurring in late preterm babies has a minor effect on neural maturation of the immature brainstem., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

The purpose of this study was to determine the presence of Clostridium difficile infection (CDI) and risk factors for infection in hospitalized patients with diarrhea in a cancer hospital in Beijing, China. A total of 277 patients with hospital-associated diarrhea (HAD) were studied of which 41 (15%) were positive for fecal C. difficile toxin A/B. For each CDI case identified, a control with HAD but negative C. difficile specimen was enrolled to look for CDI risk factors. Receipt of cancer chemotherapy occurred in 20 (49%) patients with CDI and 9 (22.0%) patients with non-CDI HAD (OR3.39, 95%CI 1.78-10.05). Median length of chemotherapy before HAD developed was 39 days for those with CDI and 22 days for patients with CDI-negative HAD (P = 0.0391). The study found that CDI is commonly seen in cancer patients in China with increasing risk for patients who receive chemotherapy., (Copyright © 2013. Published by Elsevier Ltd.)

Pitahaya or dragon fruit [Hylocereus undatus (Haw.) Britton & Rose] is one of the most popular tropical fruits in the world. In China, it is widely planted in Guangdong, Guangxi, Hainan, and Taiwan. In July 2011, a new pitahaya disease was found in Conghua City and Yunfu City, Guangdong Province, China, characterized by many small, circular, reddish brown spots over the diseased stems. The spots continuously expanded, and ultimately formed large areas of canker on stems. It is similar to pitahaya stem canker disease caused by Neoscytalidium dimidiatum in Taiwan (1). Pieces of tissues were collected from the lesion margins. After surface disinfestations with 1% sodium hypochloride for 1 min and rinsing in sterile water three times, the diseased tissues were placed on potato dextrose agar medium plates (PDA) and incubated at 28°C for 3 days. A dark, fast-growing fungus was isolated from all samples. For identification, single-spore cultures were grown on PDA in an incubator at 28°C. After 5 days, colonies with dark gray to black aerial mycelium formed. The colonies produced abundant conidia that occurred in arthric chains in aerial mycelium. The conidia were disarticulating, cylindrical-truncate, oblong-obtuse to doliform, dark brown, zero- to one-septate, and averaged 7.56 (5.46 to 10.30) × 6.20 (3.79 to 8.93) μm. The teleomorph was never observed in PDA culture. Based on these characteristics, the fungus was identified as N. dimidiatum (Penz.) Crous & Slippers (2). The internal transcribed spacer (ITS) regions of rDNAs from two isolates were amplified by primers ITS1 and ITS4 (3), and then sequenced. Both sequences were completely identical and 579 bp long (GenBank Accession Nos. JX128103 and JX128104), with 99% identity to that of N. dimidiatum previously deposited (Accession No. HQ439174). To confirm its pathogenicity, six healthy detached stems of pitahaya designed as two replicates were inoculated by injecting 10 μl of conidia suspension (1 × 10 6 conidia per ml). Three stems were inoculated with sterile water as controls. The inoculated stems were kept in an incubator at 28°C in dark. The stems exhibited the same symptoms as described above after 10 days post inoculation, whereas no symptoms developed on the control stems. The fungus was reisolated from the lesions of the inoculated stem. These results indicated that N. dimidiatum was the pathogen of pitahaya brown spot disease. To our knowledge, this is the first report of brown spot caused by N. dimidiatum on H. undatus on the Chinese mainland. References: (1) M. F. Chuang et al. Plant Dis. 96:906, 2012. (2) P. W. Crous et al. Stud. Mycol. 55:235, 2006. (3) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, New York, 1990.

Background: Traveler's diarrhea is the most common medical complaint of international visitors to developing regions. Previous findings suggested that noroviruses (NoVs) are an underappreciated cause of traveler's diarrhea. METHODS. In the present study, we sought to define the presence of NoVs in 320 acute diarrheic stool samples collected from 299 US students who traveled to Guadalajara, Cuernavaca, or Puerto Vallarta, Mexico, during the period from 2007 through 2008. Conventional and quantitative real-time polymerase chain reaction assays were used to detect and determine NoV loads in stool samples. NoV strains were characterized by purification of viral RNA followed by sequencing of the viral capsid protein 1 gene. Sequences were compared using multiple sequence alignment, and phylogenetic trees were generated to evaluate the evolutionary relatedness of the viral strains associated with cases of traveler's diarrhea., Results: NoV RNA was detected in 30 (9.4%) of 320 samples. Twelve strains belonged to genogroup I, and 18 strains belonged to genogroup II. NoV prevalence was higher in the winter season than in the summer season (23% vs 7%, respectively; P = .001). The cDNA viral loads of genogroup I viruses were found to be 500-fold higher than those of genogroup II strains. Phylogenetic analysis revealed a diverse population of NoV strains over different locations and years., Conclusions: NoV strains are important causes of traveler's diarrhea in Mexico, especially during the wintertime, and US students in Mexico may represent a suitable group for future NoV vaccine efficacy trials.

Aim: This was an in vitro study to analyse the susceptibility of Clostridium difficile isolates to rifampin and rifaximin., Methods: Stool samples from patients who had nosocomial diarrhoea and C difficile toxin B at a university hospital between August 2006 and December 2007 were cultured for C difficile. Susceptibility of C difficile isolates to rifaximin and rifampin was determined by agar dilution and E strips, respectively. C difficile isolates were analysed via PCR for genes encoding toxins A and B, for binary toxin (BT), and for partial deletions of the tcdC gene (tcdC-del)., Results: Rifaximin exhibited high-level activity against 359 C difficile isolates, with MIC(50) <0.01 microg/ml and MIC(90) 0.25 microg/ml; rifampin had MIC(50) <0.002 microg/ml and MIC(90) 4 microg/ml. Among isolates analysed, 55 (15%) were positive for BT and tcdC-del. 28 (8% of 359) isolates were resistant to rifampin (> or = 32 microg/ml), of which 6 (2% of 359) were resistant to rifaximin and rifampin with MIC values > or = 32 microg/ml. 2 of the 28 isolates resistant to rifampin were A(+)/B(+)/BT(+)/tcdC-del(+), 5 were A(+)/B(+)/BT(-)/tcdC-del(+), 4 were A(+)/B(+)/BT(+)/tcdC-del(-), 13 were A(+)/B(+)/BT(-)/tcdC-del(-), and 4 had no detectable toxin genes. Of the 11 isolates resistant to rifaximin alone, 1 was A(+)/B(+)/BT(-)/tcdC-del(+), 2 were A(+)/B(+)/BT(+)/tcdC-del(-), 6 were A(+)/B(+)/BT(-)/tcdC-del(-), and 2 had no detectable toxin genes., Conclusions: The study demonstrates that rifaximin has high-level activity against C difficile in vitro. Determination of resistance to rifampin by E strip did not predict rifaximin resistance.

Identification of a population at high risk for Clostridium difficile infection (CDI) would enable CDI prevention strategies to be designed. The purpose of this study was to create a clinical risk index that would predict those at risk for CDI. A CDI risk index was therefore developed, based on a cohort of hospital patients given broad-spectrum antibiotics, and divided into a development and validation cohort. Logistic regression equations helped identify significant predictors of CDI. A scoring algorithm for CDI risk was created using identified risk factors and collapsed to create four categories of CDI risk. The area under the receiver operating characteristic (aROC) curve was used to measure goodness-of-fit. Among 54 226 patients, 392 tested positive for C. difficile. Age 50-80 years [odds ratio (OR: 0.5; P<0.0116)], age >80 years (OR: 2.5; P<0.0001), haemodialysis (OR: 1.5; P=0.0227), non-surgical admission (OR: 2.2; P<0.0001) and increasing length of stay in the intensive care unit (OR: 2.1; P<0.0001) were significantly associated with CDI. A simple risk index using presence of significant variables was significantly associated with increasing risk for CDI in both development (OR: 3.57; P<0.001; aROC: 0.733) and validation (OR: 3.31; P<0.001; aROC: 0.712) cohorts. An OR-derived risk index did not perform as well as the simple risk index. This easily implemented risk index should allow stratification of patients into risk group categories for development of CDI and help fashion preventive strategies.

In vitro inhibitory activity of rifaximin is directed against Gram-positive and Gram-negative, aerobic and anaerobic bacteria. It is effective in the treatment of gastrointestinal infections when given orally because of the high concentration of the drug remaining in the gut lumen. Laboratory investigations have been carried out to assess the in vitro activity of rifaximin on different bacterial strains isolated from both human and domestic animals. The objective of this project is to review the in vitro and in vivo activity of rifaximin against bacterial infection with Gram-negative rods, Gram-positive rods and Gram-positive cocci and their resistance to rifaximin. The available data suggest that rifaximin is active in vitro and in vivo in the treatment of bacterial infection of adults and children., (Copyright (c) 2005 S. Karger AG, Basel.)

The development of rifaximin- and rifampicin-resistant intestinal coliforms was studied in 27 subjects receiving rifaximin for 3 days by plating stool samples on media containing rifaximin 200 mg/L or rifampicin 64 mg/L before treatment (day 0), after treatment was completed (day 3), and after a further 2 days (day 5). The susceptibility of enterococci grown on day 0 and day 3 was also studied in 71 subjects. Significant increases in antimicrobial-resistant coliform flora were not seen in either the rifaximin-treated or the placebo-treated subjects. Enterococci recovered pre- and post-treatment showed similar susceptibilities. Rifaximin did not select for significant resistance in the Gram-negative and Gram-positive intestinal flora during therapy.

Aim: To examine the process of change in hearing threshold during the neonatal period after perinatal hypoxia-ischaemia., Methods: The threshold of brainstem auditory evoked responses (BAER) was measured serially during the first month after birth in 92 term babies who suffered hypoxia-ischaemia., Results: The mean BAER threshold in these babies was significantly increased on day 1 (ANOVA p < 0.001). The elevated threshold decreased progressively on days 3 and 5, but was still significantly higher than that in normal controls (p < 0.01). The elevation continuously decreased more slowly on days 10 and 15, and to a near normal level on day 30. Threshold elevation was seen in 31.7% of the babies on day 1, and 34.5% during the first three days. The rate of elevation decreased progressively thereafter. On day 30, 10.6% of the subjects still had increased thresholds. Moderate to severe elevation occurred mainly during the first week and severe elevation occurred predominately on day 1. Threshold elevation starting after days 3-5 is likely to be due to middle-ear disorders. As a whole, during the first month, 44.6% (41/92) of the babies studied had threshold elevation. BAER threshold was correlated weakly with the stage of hypoxic-ischaemic encephalopathy on days 1 and 3. The threshold was significantly higher in babies with severe encephalopathy than in those with mild or moderate encephalopathy during the first 3 d of life., Conclusion: Hearing threshold is elevated in about one-third of term babies after hypoxia-ischaemia. The elevated threshold decreases progressively after birth, and returns to normal by one month in most babies. The threshold correlates weakly with the severity of encephalopathy.

Aim: To clarify further the influence of intrauterine growth retardation (IUGR) on early neural development., Methods: In 30 small-for-gestational age (SGA) preterm infants at term, brainstem auditory-evoked responses (BAERs) were recorded with clicks of different repetition rates. All infants had a birthweight < 3rd centile, without any other major perinatal complications., Results: Compared with the BAER in 36 appropriate-for-gestational age (AGA) term infants, the preterm SGA infants did not show any abnormalities at 21 s(-1) clicks, except for a slight increase in wave III amplitude. At 51 s(-1) clicks, there was an increase in III-V/I-III interval ratio (ANOVA p < 0.05). At 91 s(-1), the I-III interval shortened, whereas the III-V interval and III-V/I-III interval ratio increased (all p < 0.05). Wave V amplitude tended to increase slightly at all repetition rates of clicks used, although this increase did not reach statistical significance. The III-V interval and III-V/I-III interval ratio in the preterm SGA infants at different click rates correlated inversely with occipitofrontal head circumference at the time of testing, i.e. the smaller the head the longer the III-V interval (all p < 0.01). Wave III amplitude at 21 s(-1) also correlated inversely with head circumference (p < 0.01), suggesting that the slight increase in this amplitude in the preterm SGA infants is related to their relatively small head size., Conclusion: There were no major abnormalities in the BAER up to 91 s(-1) clicks at term in preterm SGA infants. The slight increase in III-V interval at high-rate stimulation suggests a subtle degree of central neural dysfunction, which is associated with small head size following IUGR.

Background: Simple methods for detecting secretory immunoglobulin A (sIgA) immune responses following natural enteric infection and oral immunization are needed., Methods: Fourteen students from the United States acquiring enterotoxigenic Escherichia coli (ETEC) diarrhea in Mexico were studied for fecal immunoglobulin A (IgA) response to their homologous infecting ETEC and to heat-labile (LT) toxin of ETEC using Dot-Blot microfiltration and enzyme-linked immunosorbent assay (ELISA) methods. Paired stool samples were collected on the day of presentation and 5 days later., Results: Twelve of 14 (86%) patients with ETEC diarrhea (5 heat-stable [ST]/LT positive, 4 LT-only, and 5 ST-only) developed sIgA antibodies directed against their homologous ETEC and 6 (66%) of the 9 patients harboring ST/LT or LT-only strains developed sIgA LT-antibody responses. Single fecal samples from 9 healthy controls were negative for ETEC specific antibodies., Conclusions: Patients with diarrhea due to noninvasive ST/LT ETEC and LT ETEC commonly produce a specific sIgA antibody response early in the illness. We feel that the methods employed will be useful to detect antibodies during natural infection by enteric pathogens and following oral enteric vaccine administration.

Unlabelled: This study examined whether high presentation rates of clicks while recording brainstem auditory evoked responses (BAER) can improve the detection of central auditory impairment in asphyxiated neonates using the BAER. The BAER was analysed at different presentation rates of clicks within the first week after birth in 38 term neonates who suffered perinatal asphyxia. At the routinely used 21 s(-1) clicks all BAER wave latencies increased significantly (ANOVA, p < 0.05-0.01). After excluding five neonates who had a significantly elevated BAER threshold, only wave V latency increased slightly (p < 0.05). The interpeak intervals of I-V and III-V also increased slightly (both p < 0.05). Similar results were found at 51 s(-1) clicks. As the clicks were increased to 91 s(-1), the III-V interval increased more significantly (p < 0.01) and the III-V/I-III interval ratio also increased significantly (p < 0.01). In particular, wave V amplitude reduced more significantly than that in normal term controls (p < 0.01). Compared with values in the controls, wave V amplitude reduced by 4.5%, 12.2% and 24.7% at 21, 51 and 91 s(-1) clicks, respectively., Conclusion: Although a moderate increase in the rate (e.g. 51 s(-1)) while recording the BAER did not improve the detection of hypoxic-ischaemic auditory impairment, a significant increase (e.g. 91 s(-1)) did, which mainly indicates an abnormal reduction in wave V amplitude.

Rifaximin is a poorly absorbed rifamycin derivative under investigation for treatment of infectious diarrhea. Adult students from the United States in Mexico and international tourists in Jamaica were randomized to receive either rifaximin (400 mg twice per day) or ciprofloxacin (500 mg twice per day) for 3 days, following a double-blinded model, from June 1997 to September 1998. A total of 187 subjects with diarrhea were studied. Time from initiation of therapy to passage of last unformed stool was comparable for those receiving rifaximin or ciprofloxacin (median, 25.7 hours versus 25.0 hours, respectively). There was no significant difference in the proportion of subjects in the 2 groups with respect to clinical improvement during the first 24 hours (P=.199), failure to respond to treatment (P=.411), or microbiological cure (P=.222). The incidence of adverse events was low and similar in each group. Rifaximin is a safe and effective alternative to ciprofloxacin in the treatment of traveler's diarrhea.

Unlabelled: Seventy preterm babies who were born with a birthweight <1500 g were studied with brainstem auditory evoked responses (BAER) at 37-42 wk of postconceptional age. The data were compared with those of normal term neonates to determine the prevalence of hearing impairment in preterm very low birthweight (VLBW) babies when they reached term. The BAER was recorded with click stimuli at 21 s(-1). Wave I and V latencies increased significantly (ANOVA p < 0.01 and 0.001). I-V and III-V intervals also increased significantly (p < 0.05 and 0.001). Wave V amplitude and V/I amplitude ratio did not differ significantly from those in the normal term controls. Ten of the 70 VLBW babies had a significant elevation in BAER threshold (>30 dB normal hearing level). Eleven had an increase in I-V interval (>2.5 SD above the mean in the normal controls) and one had a decrease in V/I amplitude ratio (<0.45). These results suggest that 14% (10/70) of the VLBW babies had a peripheral hearing impairment and 17% (12/70) a central impairment. Three babies had both an increase in I-V interval and an elevation in BAER threshold, suggesting that 4% (3/70) had both peripheral and central impairments. Thus, the total prevalence of hearing impairment was 27% (19/70)., Conclusion: About one in four preterm VLBW babies has peripheral and/or central hearing impairment at term. VLBW and its associated unfavourable perinatal factors predispose the babies to hearing impairment.

Objective: The Houston Department of Health and Human Services (HDHHS) has a centralized process for notifying and setting up follow-up appointments for women with abnormal Pap smears who are clients of HDHHS health centers. Faculty and a student from the University of Texas School of Public Health and HDHHS personnel jointly conducted a study to evaluate the process and performance of the system., Methods: The study examined two subpopulations: women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions (ASCUS/LGSIL) and women with high-grade squamous intraepithelial lesions or atypical glandular cells of undetermined significance (HGSIL/AGCUS). A retrospective study was conducted of data on women attending eight HDHHS clinics during the period from February 1996 through August 2000. Records of 1,216 women referred for evaluation of abnormal Pap smears were reviewed. Process effectiveness was measured by the number of successful contacts made and the number of appointments set up. Performance was measured by compliance with referral appointments. Predictors included race/ethnicity, age, co-existence of a sexually transmitted disease, number of prior referrals, type of patient visit, and health center attended., Results: HDHHS staff successfully notified 95.6% of women with ASCUS/LGSIL and 97.9% of women with HGSIL/AGCUS. Using performance criteria as outcome measures, high-risk women requiring targeted interventions were identified. Overall, 84.2% of women scheduled appointments. Among those with ASCUS/LGSIL, women identified as African American were 53% less likely to accept an appointment and 45% less likely to show up for the appointment than those identified as Hispanic or "other." Age and type of patient visit appeared to be significantly associated with patient compliance behavior., Conclusion: The study describes the effectiveness of a centralized patient follow-up process for women at risk for cervical cancer.

Enteroaggregative Escherichia coli (EAEC) has been reported to cause traveler's diarrhea and persistent diarrhea in children in developing countries and in immunocompromised patients. To clarify the prevalence of EAEC in traveler's diarrhea, we studied 636 US, Canadian, or European travelers with diarrhea: 218 in Guadalajara, Mexico (June--August 1997 and 1998), 125 in Ocho Rios, Jamaica (September 1997--May 1998), and 293 in Goa, India (January 1997--April 1997 and October 1997--February 1998). Stool samples were tested for conventional enteropathogens. EAEC strains were identified by use of the HEp-2 assay. EAEC was isolated in 26% of cases of traveler's diarrhea (ranging from 19% in Goa to 33% in Guadalajara) and was second only to enterotoxigenic E. coli as the most common enteropathogen in all areas. Identification of EAEC reduced the number of cases for which the pathogen was unknown from 327 (51%) to 237 (37%) and explained 28% of cases with unknown etiology. EAEC was a major cause of traveler's diarrhea in 3 geographically distinct study areas.

The emergence of resistant enteropathogens has been reported worldwide. Few data are available on the contemporary in vitro activities of commonly used antimicrobial agents against enteropathogens causing traveler's diarrhea (TD). The susceptibility patterns of antimicrobial agents currently available or under evaluation against pathogens causing TD in four different areas of the world were evaluated. Pathogens were identified in stool samples from U.S., Canadian, or European adults (18 years of age or older) with TD during 1997, visiting India, Mexico, Jamaica, or Kenya. MICs of 11different antimicrobials were determined against 284 bacterial enteropathogens by the agar dilution method. Ciprofloxacin, levofloxacin, ceftriaxone, and azithromycin were highly active in vitro against the enteropathogens, while traditional antimicrobials such as ampicillin, trimethoprim, and trimethoprim/sulfamethoxazole showed high levels and high frequencies of resistance. Rifaximin, a promising and poorly absorbable drug, had an MIC at which 90% of the strains tested were inhibited of 32 microg/ml, 250 times lower than the concentration of this drug in the stools. Amdinocillin, nalidixic acid, and doxycycline showed moderate activity. Fluoroquinolones are still the drugs of choice for TD in most regions of the world, although our study has a limitation due to the lack of Escherichia coli samples from Kenya and possible bias in selection of the patients for evaluation. Azithromycin and rifaximin should be considered as promising new agents. The widespread in vitro resistance of the traditional antimicrobial agents reported since the 1980s and the new finding of resistance to fluoroquinolones in Southeast Asia are the main reasons for monitoring carefully the antimicrobial susceptibility patterns worldwide and for developing and evaluating new antimicrobial agents for the treatment of TD.

Thirty-nine healthy US students without diarrheal disease and who had not received prophylactic or therapeutic antibiotics were monitored for emergence of trimethoprim-resistant gram-negative fecal flora for a 3-week period after arrival in Guadalajara, Mexico. During this time period, most students showed no change in total fecal gram-negative bacteria (p > 0.05) but showed an increasing level of trimethoprim (TMP) resistance (p < 0.01) among fecal coliforms. Escherichia coli was the TMP-resistant organism isolated in 18 of 39 (46%) healthy students. These 18 TMP-resistant E. coli were also resistant to ampicillin (44%), azithromycin (11%), chloramphenicol (39%), ciprofloxacin (11%), doxycycline (89%), erythromycin (100%), furazolidone (72%), levofloxacin (17%), trimethoprim-sulfamethoxazole (89%) and trovafloxacin (17%). In the absence of prophylactic and therapeutic antibiotics, increased acquisition of TMP-resistant gram-negative fecal flora in this developing country is probably due to poor sanitary conditions and the recurrent and heavy exposure to antimicrobial-resistant indigenous flora as a result of contaminated food and drink.

Maximum length sequence brainstem auditory evoked response (BAER) was studied within the first week after birth in 28 term neonates who had perinatal hypoxia-ischemia, or asphyxia. In the BAER recorded using conventional averaging techniques (click rate 21/s), the only abnormality was a slight increase in III-V interval, in addition to an increase in wave latencies when including those who had an elevated threshold (t test, all p<0.05). In the maximum length sequence BAER, however, both the III-V and I-V intervals in the asphyxiated infants were significantly increased at all the 91/s, 227/s, 455/s, and particularly 910/s click rates (p<0.05-0.001). The I-III interval was also increased significantly at 455/s and 910/s click rates (both p< 0.05). Wave V amplitude was significantly reduced at all the click rates used (ANOVA, p<0.05-0.001), particularly at 910/s, which sometimes was the only abnormality indicative of brain damage. Both the amplitude ratios V/I and V/III were significantly decreased at 455/s and 910/s click rates (p<0.01 or 0.001). A general trend was that BAER abnormalities after hypoxia-ischemia became more prominent as click rate was increased. Significant abnormalities occurred mainly at very high click rates (455/s and 910/s), which can be achieved using the maximum length sequence technique but not by using conventional averaging techniques. Thus, this technique, which can be used at the cribside, appears to be a better method for the early detection of brain damage after hypoxia-ischemia than using conventional averaging techniques, enhancing the diagnostic value of the BAER.

Rifaximin showed moderately high MICs (the MIC at which 90% of the isolates tested were inhibited = 50 microg/ml) for 145 bacterial enteropathogens from patients with traveler's diarrhea acquired in Mexico during the summers of 1997 and 1998. Rifaximin concentrations in stool the day after oral administration (800 mg daily for 3 days) were high (average, 7,961 microg/g), proving the value of the drug.

As part of a traveler's diarrhea study carried out in Guadalajara, Mexico, and Goa, India, we conducted a case control study to evaluate fecal markers of enteric inflammation in three groups. Forty-five cases of enteroaggregative Escherichia coli (EAEC) diarrhea were compared to 56 controls with enterotoxigenic E. coli (ETEC) diarrhea, and 126 controls with diarrhea without identifiable pathogens. For EAEC cases we found fecal leukocytes, occult blood, and lactoferrin in 13 (28.9%), 14 (31.1%), and 27 (60.0%) patients, respectively; for ETEC controls they were 15 (26.8%), 16 (28.6%), and 15 (26.8%) respectively; and for patients without identifiable pathogens 19 (15.1%), 34 (27.0%) and 27 (21.4%) were seen for the presence of a positive fecal lactoferrin test in EAEC cases was statistically significant compared to both control groups. The study provides evidence that EAEC infection is associated with an intestinal inflammatory response.

We examined stool samples from travelers for secretory immunoglobulin A (sIgA) to enteroaggregative Escherichia coli (EAEC) during episodes of acute diarrhea. Ten paired samples from 10 patients with diarrhea caused by EAEC were examined for the presence of specific sIgA by dot blot and Western blot immunoassays. Five samples were positive by dot blotting, and two samples were positive by Western blotting.

The relationship between enterotoxigenic Escherichia coli (ETEC) and travelers' diarrhea was examined in a high-risk area in 1992-1997. Toxin patterns, colonization-factor antigens (CFAs), and in vitro antimicrobial susceptibility were determined. In total, 928 US students with diarrhea acquired in Guadalajara, Mexico, were screened for enteric pathogens. Diagnosis of ETEC infection was done with oligonucleotide probes. ETEC was isolated in 19.9% of the travelers with diarrhea. CFAs were identified in 51% of the ETEC strains. The highest CFA frequency was observed among heat-stable isolates. Ampicillin, furazolidone, and sulfisoxazole resistance of ETEC increased during the study period. ETEC isolation rates and CFA patterns varied little during the 6 years of the study, which has implications for immunoprophylactic strategies. The finding that differences in the results of ribotyping and plasmid analysis change over time suggests that multiple strains of ETEC were responsible for the illness in the region studied.

The lipid extract of the temperate red alga Rhodymenia pertusa has yielded four eicosanoid metabolites, three of which are new natural products. Using principally NMR and MS techniques, their structures were deduced as 5R,6S-dihydroxy-7(E),9(E),11(Z),14(Z)-eicosatetraenoic acid (5R,6S-diHETE), 5R*,6S*-dihydroxy-7(E),9(E),11(Z),14(Z),17(Z)-eicosapentaenoic acid (5R*,6S*-diHEPE), 5-hydroxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid (5-HETE), 5-hydroxy-6(E),8(Z),11(Z),14(Z),17(Z)-eicosapentaenoic acid (5-HEPE). The co-occurrence of these metabolites strongly suggests that R. pertusa contains a unique 5R-lipoxygenase system acting on both arachidonic and eicosapentaenoic acids.

Background: Between December 6, 1994 and March 10, 1996, a study of the etiology of diarrhea was carried out among 332 travelers to five all-inclusive hotels in Negril, Jamaica., Methods: Stool specimens were collected and sent to Montego Bay for laboratory analysis. Escherichia coli strains isolated at the Jamaican laboratory were sent to Houston for toxin testing., Results: A recognized enteropathogen was found in 118 of the 332 (35.5%) cases. Enterotoxigenic E. coli (ETEC) were the most commonly identified pathogen (87/332; 26.2%) followed by Salmonella (4.2%) and Shigella (4.2%). Clustering of etiologically defined cases was studied at each hotel. A cluster was defined as 2 or more cases with the same pathogen identified in the same hotel within 7 days. In the 3 hotels with the highest number of cases of diarrhea, enteropathogens were part of a cluster in 65 of 99 cases (65.7%) of diarrhea of which an etiologic agent was identified. In the other 2 hotels, only 4 of 20 cases (20%) occurred in clusters., Conclusions: A total of 25 clusters of travelers' diarrhea cases was detected at the five hotels during the study period. Seventeen of 25 (68%) ETEC isolations occurred as part of a clustering of diarrhea cases. The largest outbreak of pathogen-identified diarrhea consisted of 7 cases of ETEC producing both heat-stable and heat-labile enterotoxins. In the Jamaican hotels with all inclusive meal packages most diarrhea cases occurred as small clusters, presumably as the result of foodborne outbreaks.

This study sought to determine whether a specific polymerase chain reaction (PCR) for enterotoxigenic Escherichia coli (ETEC) toxins after chaotropic extraction of DNA from stool would increase the detection of ETEC over that of conventional oligonucleotide probe hybridization of 5 E. coli colonies per stool sample (a standard method). By DNA hybridization, 29 (21%) of 140 patients were positive for ETEC, and 59 (42%) of 140 were positive for ETEC when PCR was used. Sensitivity of the PCR assay was confirmed through spiked stool experiments to be approximately 100-1000 ETEC colonies per sample. Specificity of the assay was determined by showing an absence of ETEC by the PCR technique in a subgroup of 48 subjects and by confirming the presence of ETEC DNA of positive samples by dot blot procedure. PCR technique detected significantly more ETEC infections in these subjects than did the hybridization method (P<.0001).

Brainstem auditory evoked response (BAER) was studied in term neonates using maximum length sequences (MLS), which allows presentation of acoustic stimuli at much higher rate than possible with conventional averaging technique. The response waveforms, especially for waves III and V, were well defined at the click rates of 91-455/s. Wave latencies and interpeak intervals at various click rates were all significantly longer and wave V amplitude was smaller in the neonates than in the adults. As click rate was increased, wave latencies increased and amplitudes progressively reduced. The slopes of wave latency-rate functions were progressively steeper for the later waves. The slopes of both III-V and I-V interval-rate functions were significantly steeper in the neonates than in the adults, indicating greater rate-dependent changes in the central components of the neonatal MLS BAER. These rate-dependent changes in the neonatal MLS BAER are generally similar to those in neonatal conventional BAER, although there are some differences. The results indicate that the neonatal brainstem can process rapid acoustic stimulation up to 455/s, although this ability remains immature.

Conductive hearing loss, produced by otitis media with effusion, is widespread in young children. However, little is known about its short- or long-term effects on hearing or the brain. To study the consequences of a conductive loss for the perception and processing of sounds, we plugged the left ear canal of ferrets for 7-15 months during either infancy or adulthood. Before or during plugging, the ferrets were trained to perform a binaural task requiring the detection of a 500 Hz tone, positioned 90 degrees to the right, that was masked by two sources of broad-band noise. In one condition ("control"), both noise sources were 90 degrees right and, in the second condition ("bilateral"), one noise source was moved to 90 degrees left. Normal ferrets showed binaural unmasking: tone detection thresholds were lower (mean 10.1 dB) for the bilateral condition than for the control condition. Both groups of ear-plugged ferrets had reduced unmasking; the mean residual unmasking was 2.3 dB for the infant and 0.7 dB for the adult ear-plugged animals. After unplugging, unmasking increased in both groups (infant, 7.1 dB; adult, 6.9 dB) but not to normal levels. Repeated testing during the 22 months after unplugging revealed a gradual return to normal levels of unmasking. These results show that a unilateral conductive hearing loss, in either infancy or adulthood, impairs binaural hearing both during and after the hearing loss. They show scant evidence for adaptation to the plug and demonstrate a recovery from the impairment that occurs over a period of several months after restoration of normal peripheral function.

The purpose of this study was to determine the role of enteroaggregative Escherichia coli (EAEC) in the development of traveler's diarrhea and the clinical response of patients with EAEC diarrhea following treatment with ciprofloxacin. Sixty-four travelers with diarrhea and no other recognized enteropathogen were enrolled in treatment studies in Jamaica and Mexico from July 1997 to July 1998. EAEC was isolated from 29 travelers (45.3%). There was a significant reduction in the duration of posttreatment diarrhea in the 16 patients treated with ciprofloxacin, as compared with that in the 13 patients who received placebo (mean of 35.3 versus 55.5 hours; P = .049). There was a nonsignificant reduction in the mean number of unformed stools passed during the 72 hours after enrollment in the ciprofloxacin-treated group (5.6), as compared with that in the placebo group (7.5) (P = .128). This study provides additional evidence that EAEC should be considered as a cause of antibiotic-responsive traveler's diarrhea.

Two new antiinflammatory macrolides, lobophorins A and B (1 and 2), have been isolated from fermentation broths of a marine bacterium isolated from the surface the Caribbean brown alga Lobophora variegata (Dictyotales). The new compounds, distantly related to antibiotics of the kijanimicin class, are potent inhibitors of topical PMA-induced edema in the mouse ear assay when administered either topically or IP.

Brain stem auditory electrophysiology was assessed in children long after purulent meningitis by examining the central components of brain stem auditory evoked response (BAER) at different presentation rates of clicks. Children with peripheral hearing loss were excluded from this study to avoid any possible influence of the loss on the measurements of BAER central components. Of the 70 children who had recovered from meningitis 2 to 8 years earlier, 9 (12.9%) showed abnormalities in BAER central components--mainly a slight reduction of wave V amplitude, at the click presentation rate of 10/s. Of the remaining 61 children who did not show any obvious abnormalities in the BAER at 10/s, an abnormally prolonged I-V interval and a reduced amplitude of wave V were seen in 5 children (8.2%) at the click rate of 90/s. The total BAER abnormality rate was therefore 20.0% (14/70 cases). The results suggest that most children who survive purulent meningitis have a favorable outcome for the brain stem auditory pathway, with about 1 in 5 having mild dysfunction or a suboptimal outcome in the pathway.

Background: Few data have been published recently on the etiology of outpatient pediatric diarrhea in the US., Methods: We determined the etiology of acute, nondysenteric diarrhea among 147 children between 2 and 11 years old presenting to 9 outpatient clinics in various regions of the US between August, 1991, and August, 1993. Enteropathogens were sought by conventional laboratory methods. The various diarrheagenic Escherichia coli were sought., Results: A recognized etiologic agent was detected in the stools of 89 (60.5%) children and 15 (10) patients had multiple agents detected. Rotavirus was found in 43 (29.3%) of the children, with a spring and winter peak in occurrence. Giardia lamblia was identified in 22 (15%) cases with a spring peak. HEp-2 cell-adherent E. coli were found in 15 (10.2%). Other agents found included: enteric adenovirus in 7 (4.8%); Salmonella in 5 (3.4%); enterohemorrhagic E. coli in 5 (3.4%); enteropathogenic E. coli in 2 (1.4%); enterotoxigenic E. coli in 2 (1.4%); Entamoeba histolytica in 1 (0.70%); and Campylobacter jejuni in 1 (0.7%)., Conclusions: In addition to the presence of conventional enteropathogens, diarrheagenic E. coli (HEp-2 cell-adherent E. coli, enterohemorrhagic E. coli, enteropathogenic E. coli and enterotoxigenic E. coli) were associated with endemic pediatric diarrhea in the US.

Data from 213 cases of simultaneous carotid endarterectomy and coronary artery bypass grafting (CEN/CABG) were analyzed (1980-1996). There were 154 males (72.3%), and 59 females (27.7%), (mean age: 65. 6 years, range: 42-83). One hundred and thirty-two patients (62.0%) had angina, 58 (37.2%) had myocardial infarction, and 23 (10.8%) had congestive heart failure. Symptomatic cerebrovascular disease was present in 89 patients (41.7%). One hundred and twenty-two patients (57.2%) had three-vessel coronary artery disease, 41 (19.2%) had left main disease, and 27 (12.6%) had a low ejection fraction (ejection fraction /=75% diameter reduction) stenosis was present in 168 (78.8%) of the operated carotid arteries. The contralateral internal carotid artery was severely stenosed or occluded in 35 patients (16.4%). The hospital mortality rate was 5. 6% (12 patients). The cause of death was cardiac in ten patients (4. 6%), and neurologic in two (1%). Eleven patients (5.1%) developed a stroke postoperatively; eight strokes were ipsilateral to the operated artery, and six were permanent. Myocardial infarction occurred in five patients (2.3%). Independent predictors of early mortality were age >62 years, hypertension, and postoperative stroke (p < 0.05). Male sex was the only independent predictor of neurologic morbidity (p < 0.05). Late follow-up data were obtained for 163 (81.0%) patients (mean: 54.8 months, range: 1-168). Four (9. 3%) out of the 43 late deaths were attributed to strokes. There were three (1.8%) late ipsilateral strokes, and five (3.1%) contralateral strokes. The 5- and 10-year survival probabilities were 75 +/- 4%, and 52 +/- 6.9%. The freedom from late ipsilateral neurologic morbidity at 5 and 10 years were 97 +/- 1.7% and 90 +/- 4.0%, respectively. Taken together, the results indicate that combined carotid endarterectomy and coronary artery bypass grafting can be performed safely in this high-risk group of patients. Excellent long-term freedom from stroke can be expected.

Background/aims: Bacterial enteropathogens, the major cause of travelers' diarrhea, are customarily treated with antibacterial drugs. Rifaximin, a nonabsorbed antimicrobial was examined as treatment for travelers' diarrhea., Methods: A randomized, prospective, double-blind clinical trial was carried out in 72 US adults in Mexico. Patients with acute diarrhea received one of three doses of rifaximin (200, 400 and 600 mg t.i.d.) or trimethoprim/sulfamethoxazole (TMP/SMX, 160 mg/800 mg b.i.d.) for 5 days. Results were compared with data from 2 placebo-treated historical control populations., Results: The shortest duration of treated diarrhea was seen in the group receiving 200 mg rifaximin t. i.d (NS). Clinical failure to respond to treatment occurred in 6 of 55 (11%) rifaximin-treated subjects versus 5 of 17 (29%) of TMP/SMX-treated subjects (NS). Sixteen of twenty (80%) of the enteropathogens isolated from the rifaximin-treated subjects and 7 of 7 (100%) from the TMP/SMX group were eradicated by treatment (NS). Sixteen of twenty-four (67%) enteropathogens identified were susceptible to TMP and all 24 were inhibited by

Changes in brainstem auditory evoked response (BAER) with varying stimulus repetition primarily represent neural processes concerning the efficacy of synaptic transmission in the brainstem auditory pathway. In this study the BAER to different rates of clicks was recorded from 16 term neonates. The results were compared with those from 16 adults to examine whether the degree of maturation of synaptic transmission of the neonatal brainstem auditory pathway parallels that of general function of the pathway. All BAER wave latencies and interpeak intervals increased linearly and wave amplitudes reduced with increasing click rate. The absolute rate-dependent changes in BAER measures were much greater in the neonates than in the adults, reflecting a significant immaturity in the efficacy of synaptic transmission in the neonatal auditory brainstem and in the ability of the neonatal brainstem to process rapid acoustic stimulation. When the data obtained at higher click rates at various age groups were analyzed as percentages, using the BAER measurements at conventionally used slow rate (21/s) of clicks as the denominators, the changing rates (%), or relative changes, of most BAER measures at higher rates in the neonates were still greater than those in the adults. Therefore, the rate-dependent BAER changes in the neonates are relatively less mature than general aspects of the BAER, reflected by the BAER elicited with conventionally used slow rates of clicks. These findings suggest that synaptic efficacy in the neonatal brainstem auditory pathway is relatively less mature than general function of the pathway and thus may be more susceptible to unfavourable perinatal conditions.

We devised two screening systems to detect cell wall transglycosylation inhibitors. One screen utilizes a mutant of Enterococcus faecalis strain A256 that is dependent on vancomycin or moenomycin for growth. In the absence of transglycosylation inhibitors the strain fails to grow, while in the presence of inhibitors, cells are rescued. A second screening organism E. faecalis strain MDD212 utilizes a translational fusion of the lacZ gene to the vanH promoter in a derivative of E. faecalis that contains a vancomycin resistance determinant. Induction of beta-galactosidase occurs when cells are exposed to inhibitors of transglycosylation. Our natural products drug source of fungal fermentations was tested with these screens. Several cultures that produced the same family of compounds, called the thielavins, were detected. Thielavin B inhibited the formation of peptidoglycan in an in vitro assay, suggesting that these screening systems can detect compounds that interfere with cell wall transglycosylation.

Maturation of peripheral hearing and auditory brainstem following perinatal asphyxia was investigated by longitudinal recording of brainstem auditory evoked potentials (BAEP) during the first year of life in affected infants. The general maturational course of the BAEP following asphyxia was similar to that in a control group of infants with normal births, although there were some abnormalities in the BAEP Response threshold elevation seen in a few asphyxiated infants improved significantly during the first 3 months. The interpeak intervals in the asphyxiated infants did not differ significantly from that of the control-group infants except in the first month, when the I-V and III-V intervals were significantly prolonged in the severe asphyxia group. In contrast, wave V amplitude and V/I ratio were always smaller when compared to that of the control-group infants. Amplitude reduction of wave V was more sustained than the prolonged I-V interval. Persistent hearing loss and brainstem auditory impairment were seen in 6.8% and 14.6% of the asphyxiated infants, respectively. These findings suggest that asphyxia does not interfere significantly with the maturation of the auditory system in most asphyxiated infants and that sustained peripheral hearing loss and brainstem impairment occur only in a small proportion of affected infants.