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S Ward

Publications and source records attributed to S Ward.

At least 91 records · Page 5Linked to original sources
PubMed2000

spe-29 encodes a small predicted membrane protein required for the initiation of sperm activation in Caenorhabditis elegans.

Caenorhabditis elegans spermatids complete a dramatic morphogenesis to crawling spermatozoa in the absence of an actin- or tubulin-based cytoskeleton and without synthesizing new gene products. Mutations in three genes (spe-8, spe-12, and spe-27) prevent the initiation of this morphogenesis, termed activation. Males with mutations in any of these genes are fertile. By contrast, mutant hermaphrodites are self-sterile when unmated due to a failure in spermatid activation. Intriguingly, mutant hermaphrodites form functional spermatozoa and become self-fertile upon mating, suggesting that spermatids can be activated by male seminal fluid. Here we describe a mutation in a fourth gene, spe-29, which mimics the phenotype of spe-8, spe-12, and spe-27 mutants. spe-29 sperm are defective in the initiation of hermaphrodite sperm activation, yet they maintain the ability to complete the morphogenetic rearrangements that follow. Mutant alleles of spe-12, spe-27, and spe-29 exhibit genetic interactions that suggest that the wild-type products of these genes function in a common signaling pathway to initiate sperm activation. We have identified the spe-29 gene, which is expressed specifically in the sperm-producing germ line and is predicted to encode a small, novel transmembrane protein.

Animals↗
PubMed2000

Inadequate treatment of nosocomial infections is associated with certain empiric antibiotic choices.

OBJECTIVE: The purpose of this study was to determine the impact of scheduled changes of antibiotic classes, used for the empirical treatment of suspected or documented Gram-negative bacterial infections, on the occurrence of inadequate antimicrobial treatment of nosocomial infections. DESIGN: Prospective observational study. SETTING: Medical (19-bed) and surgical (18-bed) intensive care units in an urban teaching hospital. PATIENTS: A total of 3,668 patients requiring intensive care unit admission were prospectively evaluated during three consecutive time periods. INTERVENTIONS: During each time period, one antibiotic class was selected for the empirical treatment of Gram-negative bacterial infections as follows: time period 1 (baseline period) (1,323 patients), ceftazidime; time period 2 (1,243 patients), ciprofloxacin; and time period 3 (1,102 patients), cefepime. MEASUREMENTS AND MAIN RESULTS: The overall administration of inadequate antimicrobial treatment for nosocomial infections decreased during the course of the study (6.1%, 4.7%, and 4.5%; p = .15). This was primarily because of a statistically significant decrease in the administration of inadequate antibiotic treatment for Gram-negative bacterial infections (4.4%, 2.1%, and 1.6%; p < .001). There were no statistically significant differences in the overall hospital mortality rate among the three time periods (15.6%, 16.4%, and 16.2%; p = .828) despite a significant increase in severity of illness as measured with Acute Physiology and Chronic Health Evaluation (APACHE) II scores (15.3 +/- 7.6, 15.7 +/- 8.0, and 20.7 +/- 8.6; p < .001). The hospital mortality rate decreased significantly during time period 3 (20.6%) compared with time period 1 (28.4%; p < .001) and time period 2 (29.5%; p < .001) for patients with an APACHE II score > or = 15. CONCLUSIONS: These data suggest that scheduled changes of antibiotic classes for the empirical treatment of Gram-negative bacterial infections can reduce the occurrence of inadequate antibiotic treatment for nosocomial infections. Reducing inadequate antibiotic administration may improve the outcomes of critically ill patients with APACHE II scores > or = 15.

APACHE↗
PubMed2000

Exhaled ethane, a marker of lipid peroxidation, is elevated in chronic obstructive pulmonary disease.

Ethane is a product of lipid peroxidation and can be measured in the exhaled air as an index of oxidative stress. Oxidant/antioxidant imbalance is important in the pathogenesis of chronic obstructive pulmonary disease (COPD). Therefore, we measured exhaled ethane in 22 patients with COPD (mean age +/- SEM, 59 +/- 8 yr; 19 male) and compared it with other noninvasive markers of oxidative stress and inflammation such as carbon monoxide (CO), measured electrochemically, and nitric oxide (NO), measured by chemiluminescence. Exhaled ethane was collected during a flow and pressure-controlled exhalation into a reservoir, discarding dead space air contaminated with ambient air. A sample of the collected expired air was analyzed by chromatography. Compared with normal subjects (n = 14; eight men; age, 33 +/- 2.8 yr), patients with COPD not on steroid treatment (n = 12; FEV(1), 58 +/- 6%) had elevated levels of exhaled ethane (2.77 +/- 0.25 and 0.88 +/- 0.09 ppb, respectively, p < 0.05), CO (5.96 +/- 0.50 and 2.8 +/- 0.25 ppm, p < 0.05) and NO (11.86 +/- 0.53 and 6.77 +/- 0.50 ppb, p < 0.05) levels. Ethane was correlated to FEV(1) (r = -0.67, p < 0.05). Patients receiving steroid treatment (n = 10; FEV(1), 56 +/- 2%) had lower levels of ethane (0.48 +/- 0.05 ppb) than did steroid-treated patients, whereas CO (5.99 +/- 0.63 ppm) and NO (9.11 +/- 0.53 ppb) levels were similar in the two treatment groups. Exhaled ethane is elevated, correlates with FEV(1), and is significantly lower in patients treated with steroids, so it may be complementary to the use of NO and CO in assessing and monitoring oxidative stress in COPD.

Biomarkers↗
PubMed2000

Discordant amino acid profiles in monochorionic twins with twin-twin transfusion syndrome.

To test the hypothesis that discordant growth in monochorionic (MC) twins occurs at least in part due to disparity in placental amino acid transporter function, we measured plasma amino acid levels by HPLC in maternal and fetal blood samples collected at birth from gestational age matched twins with (n = 12) and without (n = 12) twin-twin transfusion syndrome (TTTS). In the donor twin, fetal plasma concentrations and feto-maternal ratios of five essential amino acids-valine (p < 0.001), leucine (p < 0.001), iso-leucine (p < 0.05), histidine (p < 0.001) and L-arginine (p < 0. 001)-were lower than the recipient and non-TTTS twin pairs. Fetal concentrations of the nonessential amino acids taurine (p < 0.001), serine (p < 0.01), glycine (p < 0.001) and tyrosine (p < 0.05) were also markedly lower in the donor than the recipient and non-TTTS twin pairs. In contrast, the fetal alanine level in the donor twin was higher than the recipient (664 +/- 64 versus 396 +/- 23 microM; p < 0.001) and the non-TTTS twin pairs (p < 0.01). No such differences between amino acid profiles in non-TTTS MC twin pairs were found. Maternal plasma amino acid levels between TTTS and non-TTTS groups were comparable. This study provides the first evidence that certain amino acids in the donor twin of chronic TTTS differ significantly from those of the co-twin while others were comparable between twin pairs. These data, therefore, argue against inter-twin transfusion as the sole cause of growth restriction of the donor twin and suggests instead that impaired placental transport of amino acids may be a likely mechanism.

Amino Acids↗
PubMed2000

Broad oxygen tolerance in the nematode Caenorhabditis elegans.

This study examined the effects of oxygen tensions ranging from 0 to 90 kPa on the metabolic rate (rate of carbon dioxide production), movement and survivorship of the free-living soil nematode Caenorhabditis elegans. C. elegans requires oxygen to develop and survive. However, it can maintain a normal metabolic rate at oxygen levels of 3.6 kPa and has near-normal metabolic rates at oxygen levels as low as 2 kPa. The ability to withstand low ambient oxygen levels appears to be a consequence of the small body size of C. elegans, which allows diffusion to supply oxygen readily to the cells without requiring any specialized respiratory or metabolic adaptations. Thus, the small size of this organism pre-adapts C. elegans to living in soil environments that commonly become hypoxic. Movement in C. elegans appears to have a relatively minor metabolic cost. Several developmental stages of C. elegans were able to withstand up to 24 h of anoxia without major mortality. Longer periods of anoxia significantly increased mortality, particularly for eggs. Remarkably, long-term exposure to 100 % oxygen had no effect on the metabolic rate of C. elegans, and populations were able to survive for a least 50 generations in 100 % (90 kPa) oxygen. Such hyperoxic conditions are fatal to most organisms within a short period.

Anaerobiosis↗
PubMed2000

A comparative analysis of patients with early-onset vs late-onset nosocomial pneumonia in the ICU setting.

STUDY OBJECTIVE: To compare the clinical outcomes of critically ill patients developing early-onset nosocomial pneumonia (NP; ie, within 96 h of ICU admission) and late-onset NP (ie, occurring after 96 h of ICU admission). DESIGN: Prospective cohort study. SETTING: A medical ICU and a surgical ICU from a university-affiliated urban teaching hospital. PATIENTS: Between July 1997 and November 1998, 3, 668 patients were prospectively evaluated. INTERVENTION: Prospective patient surveillance and data collection. RESULTS: Four hundred twenty patients (11.5%) developed NP. Early-onset NP was observed in 235 patients (56.0%), whereas 185 patients (44.0%) developed late-onset NP. Among patients with early onset NP, 114 patients (48. 5%) spent at least 24 h in the hospital prior to ICU admission, compared to 57 patients (30.8%) with late-onset NP (p = 0.001). One hundred eighty-three patients (77.9%) with early-onset NP received antibiotics prior to the development of NP, as compared to 162 patients (87.6%) with late-onset NP (p = 0.010). The most common pathogens associated with early-onset NP were Pseudomonas aeruginosa (25.1%), oxacillin-sensitive Staphylococcus aureus (OSSA; 17.9%), oxacillin-resistant S aureus (ORSA; 17.9%), and Enterobacter species (10.2%). P aeruginosa (38.4%), ORSA (21.1%), Stenotrophomonas maltophilia (11.4%), OSSA (10.8%), and Enterobacter species (10.3%) were the most common pathogens associated with late-onset NP. The ICU length of stay was significantly longer for patients with early-onset NP (10.3 +/- 8.3 days; p < 0.001) and late-onset NP (21. 0 +/- 13.7 days; p < 0.001), as compared to patients without NP (3.5 +/- 3.2 days). Hospital mortality was significantly greater for patients with early-onset NP (37.9%; p = 0.001) and late-onset NP (41.1%; p = 0.001) compared to patients without NP (13.1%). CONCLUSIONS: Both early-onset and late-onset NP are associated with increased hospital mortality rates and prolonged lengths of stay. The pathogens associated with NP were similar for both groups. This may be due, in part, to the prior hospitalization and use of antibiotics in many patients developing early-onset NP. These data suggest that P aeruginosa and ORSA can be important pathogens associated with early-onset NP in the ICU setting. Additionally, clinicians should be aware of the common microorganisms associated with both early-onset NP and late-onset NP in their hospitals in order to avoid the administration of inadequate antimicrobial treatment.

Adult↗
PubMed2000

The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting.

STUDY OBJECTIVE: To evaluate the relationship between the adequacy of antimicrobial treatment for bloodstream infections and clinical outcomes among patients requiring ICU admission. DESIGN: Prospective cohort study. SETTING: A medical ICU (19 beds) and a surgical ICU (18 beds) from a university-affiliated urban teaching hospital. PATIENTS: Between July 1997 and July 1999, 492 patients were prospectively evaluated. INTERVENTION: Prospective patient surveillance and data collection. RESULTS: One hundred forty-seven patients (29.9%) received inadequate antimicrobial treatment for their bloodstream infections. The hospital mortality rate of patients with a bloodstream infection receiving inadequate antimicrobial treatment (61.9%) was statistically greater than the hospital mortality rate of patients with a bloodstream infection who received adequate antimicrobial treatment (28.4%; relative risk, 2. 18; 95% confidence interval [CI], 1.77 to 2.69; p < 0.001). Multiple logistic regression analysis identified the administration of inadequate antimicrobial treatment as an independent determinant of hospital mortality (adjusted odds ratio [AOR], 6.86; 95% CI, 5.09 to 9.24; p < 0.001). The most commonly identified bloodstream pathogens and their associated rates of inadequate antimicrobial treatment included vancomycin-resistant enterococci (n = 17; 100%), Candida species (n = 41; 95.1%), oxacillin-resistant Staphylococcus aureus (n = 46; 32.6%), coagulase-negative staphylococci (n = 96; 21.9%), and Pseudomonas aeruginosa (n = 22; 10.0%). A statistically significant relationship was found between the rates of inadequate antimicrobial treatment for individual microorganisms and their associated rates of hospital mortality (Spearman correlation coefficient = 0.8287; p = 0.006). Multiple logistic regression analysis also demonstrated that a bloodstream infection attributed to Candida species (AOR, 51.86; 95% CI, 24.57 to 109.49; p < 0.001), prior administration of antibiotics during the same hospitalization (AOR, 2.08; 95% CI, 1.58 to 2.74; p = 0.008), decreasing serum albumin concentrations (1-g/dL decrements) (AOR, 1.37; 95% CI, 1.21 to 1.56; p = 0.014), and increasing central catheter duration (1-day increments) (AOR, 1.03; 95% CI, 1.02 to 1.04; p = 0.008) were independently associated with the administration of inadequate antimicrobial treatment. CONCLUSIONS: The administration of inadequate antimicrobial treatment to critically ill patients with bloodstream infections is associated with a greater hospital mortality compared with adequate antimicrobial treatment of bloodstream infections. These data suggest that clinical efforts should be aimed at reducing the administration of inadequate antimicrobial treatment to hospitalized patients with bloodstream infections, especially individuals infected with antibiotic-resistant bacteria and Candida species.

Aged↗
PubMed2000

Talcosis associated with IV abuse of oral medications: CT findings.

OBJECTIVE: Our objective was to evaluate the CT appearance of talcosis associated with IV abuse of oral medications and to compare the findings of talcosis related to methylphenidate with those findings seen with other drugs. MATERIALS AND METHODS: The CT scans of 12 patients with talcosis (seven men, five women), 33-54 years old (mean age, 44 years), were analyzed retrospectively. Seven patients had abused methylphenidate; five patients had no history of abuse. The diagnosis of talcosis was made histologically in 11 patients and at funduscopy in one patient. CT was performed with 1- to 1.5-mm collimation (n = 10 patients) or 5- to 10-mm collimation (n = 2). RESULTS: The predominant abnormalities seen on CT consisted of a diffuse fine nodular pattern (n = 2), a combination of nodules and lower lobe panacinar emphysema (n = 3), and ground-glass attenuation (n = 2). Emphysema was the only abnormality seen in the remaining five patients (lower lobe panacinar, n = 4; upper lobe centrilobular, n = 1). No significant difference in the prevalence of nodules and ground-glass attenuation was seen between the methylphenidate and non-methylphenidate groups. Lower lobe panacinar emphysema was more common in methylphenidate abusers (six [86%] of seven patients) than in non-mnethylphenidate drug abusers (one [20%] of five, p<0.05, Fisher's exact test). CONCLUSION: The CT manifestations of talcosis consist of a fine micronodular pattern, ground-glass attenuation, and emphysema. A significantly increased prevalence of lower lobe panacinar emphysema is seen in IV drug addicts who abuse methylphenidate.

Adult↗
PubMed1999

Genetic and environmental conditions that increase longevity in Caenorhabditis elegans decrease metabolic rate.

Mutations that increase the longevity of the soil nematode Caenorhabditis elegans could define genes involved in a process specific for aging. Alternatively, these mutations could reduce animal metabolic rate and increase longevity as a consequence. In ectotherms, longevity is often negatively correlated with metabolic rate. Consistent with these observations, environmental conditions that reduce the metabolic rate of C. elegans also extend longevity. We found that the metabolic rate of long-lived C. elegans mutants is reduced compared with that of wild-type worms and that a genetic suppressor that restored normal longevity to long-lived mutants restored normal metabolic rate. Thus, the increased longevity of some long-lived C. elegans mutants may be a consequence of a reduction in their metabolic rate, rather than an alteration of a genetic pathway that leads to enhanced longevity while maintaining normal physiology. The actual mechanism responsible for the inverse correlation between metabolic rate and longevity remains unknown.

Animals↗