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Biomedical subjects

S Ward

Publications and source records attributed to S Ward.

At least 109 records · Page 6Linked to original sources
PubMed1999

Equatorius: a new hominoid genus from the Middle Miocene of Kenya.

A partial hominoid skeleton just older than 15 million years from sediments in the Tugen Hills of north central Kenya mandates a revision of the hominoid genus Kenyapithecus, a possible early member of the great ape-human clade. The Tugen Hills specimen represents a new genus, which also incorporates all material previously referable to Kenyapithecus africanus. The new taxon is derived with respect to earlier Miocene hominoids but is primitive with respect to the younger species Kenyapithecus wickeri and therefore is a late member of the stem hominoid radiation in the East African Miocene.

Animals↗
PubMed1999

Heroes to zero?

Explore the source record for details and available documents.

Community-Institutional Relations↗
PubMed1999

Multiple conformations of the acylenzyme formed in the hydrolysis of methicillin by Citrobacter freundii beta-lactamase: a time-resolved FTIR spectroscopic study.

Time-resolved infrared difference spectroscopy has been used to show that the carbonyl group of the acylenzyme reaction intermediate in the Citrobacter freundii beta-lactamase-catalyzed hydrolysis of methicillin can assume at least four conformations. A single-turnover experiment shows that all four conformations decline during deacylation with essentially the same rate constant. The conformers are thus in exchange on the reaction time scale, assuming that deacylation takes place only from the conformation which is most strongly hydrogen bonded or from a more minor species not visible in these experiments. All conformers have the same (10 cm-1) narrow bandwidth compared with a model ethyl ester in deuterium oxide (37 cm-1) which shows that all conformers are well ordered relative to free solution. The polarity of the carbonyl group environment in the conformers varies from 'ether-like' to strongly hydrogen bonding (20 kJ/mol), presumably in the oxyanion hole of the enzyme. From the absorption intensities, it is estimated that the conformers are populated approximately proportional to the hydrogen bonding strength at the carbonyl oxygen. A change in the difference spectrum at 1628 cm-1 consistent with a perturbation (relaxation) of protein beta-sheet occurs slightly faster than deacylation. Consideration of chemical model reactions strongly suggests that neither enamine nor imine formation in the acyl group is a plausible explanation of the change seen at 1628 cm-1. A turnover reaction supports the above conclusions and shows that the conformational relaxation occurs as the substrate is exhausted and the acylenzymes decline. The observation of multiple conformers is discussed in relation to the poor specificity of methicillin as a substrate of this beta-lactamase and in terms of X-ray crystallographic structures of acylenzymes where multiple forms are not apparently observed (or modeled). Infrared spectroscopy has shown itself to be a useful method for assessment of the uniqueness of enzyme-substrate interactions in physiological turnover conditions as well as for determination of ordering, hydrogen bonding, and protein perturbation.

Bacterial Proteins↗
PubMed1999

Hydrogen bonding and protein perturbation in beta-lactam acyl-enzymes of Streptococcus pneumoniae penicillin-binding protein PBP2x.

A soluble form of Streptococcus pneumoniae PBP2x, a molecular target of penicillin and cephalosporin antibiotics, has been expressed and purified. IR difference spectra of PBP2x acylated with benzylpenicillin, cloxacillin, cephalothin and ceftriaxone have been measured. The difference spectra show two main features. The ester carbonyl vibration of the acyl-enzyme is ascribed to a small band between 1710 and 1720 cm-1, whereas a much larger band at approx. 1640 cm-1 is ascribed to a perturbation in the structure of the enzyme, which occurs on acylation. The protein perturbation has been interpreted as occurring in beta-sheet. The acyl-enzyme formed with benzylpenicillin shows the lowest ester carbonyl vibration frequency, which is interpreted to mean that the carbonyl oxygen is the most strongly hydrogen-bonded in the oxyanion hole of the antibiotics studied. The semi-synthetic penicillin cloxacillin is apparently less well organized in the active site and shows two partially overlapping ester carbonyl bands. The penicillin acyl-enzyme has been shown to deacylate more slowly than that formed with cloxacillin. This demonstrates that the natural benzylpenicillin forms a more optimized and better-bonded acyl-enzyme and that this in turn leads to the stabilization of the acyl-enzyme required for effective action in the inhibition of PBP2x. The energetics of hydrogen bonding in the several acyl-enzymes is discussed and comparison is made with carbonyl absorption frequencies of model ethyl esters in a range of organic solvents. A comparison of hydrolytic deacylation with hydroxaminolysis for both chymotryspin and PBP2x leads to the conclusion that deacylation is uncatalysed.

Acylation↗
PubMed1999

Evolution of sperm size in nematodes: sperm competition favours larger sperm.

In the free-living rhabditid nematode Caenorhabditis elegans, sperm size is a determinant of sperm competitiveness. Larger sperm crawl faster and physically displace smaller sperm to take fertilization priority, but not without a cost: larger sperm are produced at a slower rate. Here, we investigate the evolution of sperm size in the family Rhabditidae by comparing sperm among 19 species, seven of which are hermaphroditic (self-fertile hermaphrodites and males), the rest being gonochoristic (females and males). We found that sperm size differed significantly with reproductive mode: males of gonochoristic species had significantly larger sperm than did males of the hermaphroditic species. Because males compose 50% of the populations of gonochoristic species but are rare in hermaphroditic species, the risk of male-male sperm competition is greater in gonochoristic species. Larger sperm have thus evolved in species with a greater risk of sperm competition. Our results support recent studies contending that sperm size may increase in response to sperm competition.

Animals↗
PubMed1999

Congenital bronchial atresia--presentation of three cases and a pictorial review.

Congenital bronchial atresia (CBA) is a rare anomaly that results from a congenital focal obliteration of a proximal segmental or subsegmental bronchus with the normal development of distal structures. The short atretic segment leads to accumulation of mucus within the distal bronchi to form a bronchocoele and underventilation of the affected part of the lung. The clinical and radiographic features of three cases of CBA are reported and the literature is reviewed. Radiologically, CBA is characterized by the presence of a branching opacity, the bronchocoele, radiating from the hilum surrounded by an area of hyperlucency. These features can be recognized on the chest radiograph but are more clearly defined by computed tomography. Fibreoptic bronchoscopy (FOB) is often required to exclude acquired proximal bronchial obstruction by tumour, foreign body or inflammatory stricture. In CBA a blind-ending bronchus may be revealed, although FOB is often normal. Bronchographic examination is generally abnormal but the appearances may be confusing and is rarely performed. Pathologically, CBA is characterized by a blind-ending bronchus associated with dilated distal bronchi containing impacted mucus. The surrounding lung parenchyma is hyperinflated due to collateral air drift. CBA can be identified accurately by imaging techniques which may make surgery unnecessary in asymptomatic cases.

Adolescent↗
PubMed1999

Blockade of kit signaling induces transdifferentiation of interstitial cells of cajal to a smooth muscle phenotype.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) serve as pacemaker cells and mediators of neurotransmission from the enteric nervous system to gastrointestinal muscles. ICC develop from mesenchymal cells that express c-Kit, and signaling via Kit receptors is necessary for normal development of ICC. We studied the fate of functionally developed ICC after blockade of Kit receptors to determine whether ICC undergo cell death or whether the phenotype of the cells is modified. The fate of undeveloped ICC was also investigated. METHODS: Neutralizing, anti-Kit monoclonal antibody (ACK2) was administered to mice for 8 days after birth. ICC in the small intestine were examined by immunohistochemistry and electron microscopy. Occurrence of apoptosis was also assayed. RESULTS: When Kit receptors were blocked, ICC nearly disappeared from the small intestine. Apoptosis was not detected in regions where ICC are normally distributed. Remaining Kit-immunopositive cells in the pacemaker region of the small intestine developed ultrastructural features similar to smooth muscle cells, including prominent filament bundles and expression of the muscle-specific intermediate filament protein, desmin, and smooth muscle myosin. ICC of the deep muscular plexus normally develop after birth in the mouse. Precursors of these cells remained in an undifferentiated state when Kit was blocked. CONCLUSIONS: These data, along with previous studies showing that ICC in the pacemaker region of the small intestine and longitudinal muscle cells develop from the same Kit-immunopositive precursor cells, suggest inherent plasticity between the ICC and smooth muscle cells that is regulated by Kit-dependent cell signaling.

Animals↗
PubMed1999

Intracytoplasmic sperm injection after follicle stimulation with highly purified human follicle-stimulating hormone compared with human menopausal gonadotropin.

PURPOSE: Our purpose was to compare oocyte nuclear maturation and embryo quality after pituitary down-regulation and ovarian stimulation with highly purified follicle-stimulating hormone (FSH) or human menopausal gonadotropin (HMG). METHODS: Fifty-five patients 37 years of age or younger who were undergoing in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) were evaluated retrospectively. In all cases, male factor was the only indication for treatment, with no female-related factors identified. Following pituitary down-regulation, patients were stimulated with hMG (n = 20) or highly purified FSH (n = 35). Main outcome measures included ovarian response to stimulation, oocyte maturity, and ICSI fertilization results. Secondary outcome measures included pregnancy rates and outcome. RESULTS: The ovarian response to stimulation was similar for the two groups, as were the percentage of metaphase II oocytes, fertilization and cleavage rates, and number and quality of transferred and cryopreserved embryos. Cycle outcome was comparable. CONCLUSIONS: In normogonadotropic subjects, monocomponent therapy with highly purified FSH is as effective as hMG in stimulating ovarian follicular development, synchronization of oocyte maturation, and IVF-ICSI outcome. Our findings support the conclusion that the luteinizing hormone component in the stimulation protocol is unnecessary.

Adolescent↗
PubMed1999

spe-12 encodes a sperm cell surface protein that promotes spermiogenesis in Caenorhabditis elegans.

During spermiogenesis, Caenorhabditis elegans spermatids activate and mature into crawling spermatozoa without synthesizing new proteins. Mutations in the spe-12 gene block spermatid activation, rendering normally self-fertile hermaphrodites sterile. Mutant males, however, are fertile. Surprisingly, when mutant hermaphrodites mate with a male, their self-spermatids activate and form functional spermatozoa, presumably due to contact with male seminal fluid. Here we show that, in addition to its essential role in normal activation of hermaphrodite-derived spermatids, SPE-12 also plays a supplementary but nonessential role in mating-induced activation. We have identified the spe-12 gene, which encodes a novel protein containing a single transmembrane domain. spe-12 mRNA is expressed in the sperm-producing germ line and the protein localizes to the spermatid cell surface. We propose that SPE-12 functions downstream of both hermaphrodite- and male-derived activation signals in a spermatid signaling pathway that initiates spermiogenesis.

Alleles↗
PubMed1999

Outcome of twin pregnancies complicated by single intrauterine death in relation to vascular anatomy of the monochorionic placenta.

The objective of this study was to determine the relationship between the type of placentation, vascular anatomy of the monochorionic (MC) placenta and the perinatal outcome of the surviving twin following a single intrauterine fetal death (IUFD). In this retrospective study, 92 twin pregnancies complicated by a single intrauterine death were identified from three tertiary referral centres [50 MC and 42 dichorionic (DC)]. Antenatal and neonatal data as well as information on the chorionicity, vascular anastomoses, and autopsy findings were also obtained. The percentage risk of IUFD (26 versus 2.4; P < 0.001), anaemia (51.4 versus 0; P < 0.001) and intracranial lesions at birth (46 versus 0; P < 0.001) was greater in MC than in DC twins. In MC twins without twin-twin transfusion syndrome (TTTS), perinatal mortality was higher in the group with superficial arterioarterial (AA)/venovenous (VV) channels than those with only multiple bidirectional arteriovenous (AV) anastomoses (12/15 versus 0/8; P < 0.001). However, in the TTTS pregnancies (n = 26), perinatal outcome of the surviving twin was dependent on whether the recipient (n = 16) or the donor twin (n = 10) died first. Incidence of IUFD (9/16 versus 0/10; P < 0.001), severe anaemia (7/7 versus 1/10; P < 0.001) and intracranial lesions at birth (6/7 versus 2/10; P < 0.001) was common in pregnancies where the recipient twin died first. In the TTTS group, unidirectional AV anastomotic channels were found in all but two placentae. In conclusion, this study suggests that the outcome of twin pregnancies complicated by IUFD is dependent on the type of vascular anastomoses and TTTS.

Female↗
PubMed1999

Rapid absorption and clinical effectiveness of intragastric mefloquine in the treatment of cerebral malaria in African children.

To obviate the lack of injectable quinine in a hospital in rural Burundi, mefloquine, only available as an oral formulation, was administered (25 mg/kg bodyweight) as a single dose by nasogastric tube to four small children with cerebral malaria. All patients recovered uneventfully after a mean coma duration of 20.5 h. Mefloquine was rapidly absorbed and therapeutic serum concentrations were achieved within a few hours in all subjects, with parasite reduction ratios after 48 h within the expected range for drug-sensitive parasites. These findings suggest that intragastric mefloquine deserves consideration whenever parenteral drugs are not available for the treatment of cerebral malaria.

Absorption↗
PubMed1999

The influence of access to a private attending physician on the withdrawal of life-sustaining therapies in the intensive care unit.

OBJECTIVE: To assess the influence of patient access to a private attending physician on the withdrawal of life-sustaining therapies in a medical intensive care unit (ICU). DESIGN: Prospective cohort study. SETTING: A university-affiliated teaching hospital. PATIENTS: A total of 501 consecutive patients admitted to the medical ICU during a 5-month period. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Among patients dying in the medical ICU, those without a private attending physician (n = 26) were statistically more likely to undergo the active withdrawal of life-sustaining therapies than patients with a private attending physician (n = 87) (80.8% vs. 29.9%; relative risk = 2.70; 95% confidence interval = 1.86-3.92; p < .001). Despite having similar predicted mortality rates by Acute Physiology and Chronic Health Evaluation II score (60.5% +/- 27.0% vs. 66.1% +/- 21.3%; p = .280), patients dying in the medical ICU without a private attending physician had statistically shorter hospital and ICU lengths of stay, a shorter duration of mechanical ventilation, and fewer total hospital costs and charges compared with patients with access to a private attending physician. Multiple logistic regression analysis, controlling for severity of illness, demographic characteristics, and patient diagnoses, demonstrated that lack of access to a private attending physician (adjusted odds ratio = 23.10; 95% confidence interval = 9.10-58.57; p < .001) and the presence of a do-not-resuscitate order while in the ICU (adjusted odds ratio = 7.33; 95% confidence interval = 3.69-14.54; p = .004) were the only variables independently associated with the withdrawal of life-sustaining therapies before death. CONCLUSIONS: Patients dying in a medical ICU setting without access to a private attending physician are more likely to undergo the active withdrawal of life-sustaining therapies before death than patients with a private attending physician. Health care providers should be aware of possible variations in the practice of withdrawal of life-sustaining therapies in their ICUs based on this patient characteristic.

Adolescent↗
PubMed1999

Heat transfer from starlings sturnus vulgaris during flight

Infrared thermography was used to measure heat transfer by radiation and the surface temperature of starlings (Sturnus vulgaris) (N=4) flying in a wind tunnel at 6-14 m s-1 and at 15-25 degrees C. Heat transfer by forced convection was calculated from bird surface temperature and biophysical modelling of convective heat transfer coefficients. The legs, head and ventral brachial areas (under the wings) were the hottest parts of the bird (mean values 6.8, 6.0 and 5.3 degrees C, respectively, above air temperature). Thermal gradients between the bird surface and the air decreased at higher air temperatures or during slow flight. The legs were trailed in the air stream during slow flight and when air temperature was high; this could increase heat transfer from the legs from 1 to 12 % of heat transfer by convection, radiation and evaporation (overall heat loss). Overall heat loss at a flight speed of 10.2 m s-1 averaged 11. 3 W, of which radiation accounted for 8 % and convection for 81 %. Convection from the ventral brachial areas was the most important route of heat transfer (19 % of overall heat loss). Of the overall heat loss, 55 % occurred by convection and radiation from the wings, although the primaries and secondaries were the coolest parts of the bird (2.2-2.5 degrees C above air temperature). Calculated heat transfer from flying starlings was most sensitive to accurate measurement of air temperature and convective heat transfer coefficients.

Journal Article↗
PubMed1999

Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients.

STUDY OBJECTIVE: To evaluate the relationship between inadequate antimicrobial treatment of infections (both community-acquired and nosocomial infections) and hospital mortality for patients requiring ICU admission. DESIGN: Prospective cohort study. SETTING: Barnes-Jewish Hospital, a university-affiliated urban teaching hospital. PATIENTS: Two thousand consecutive patients requiring admission to the medical or surgical ICU. INTERVENTIONS: Prospective patient surveillance and data collection. MEASUREMENTS AND RESULTS: One hundred sixty-nine (8.5%) infected patients received inadequate antimicrobial treatment of their infections. This represented 25.8% of the 655 patients assessed to have either community-acquired or nosocomial infections. The occurrence of inadequate antimicrobial treatment of infection was most common among patients with nosocomial infections, which developed after treatment of a community-acquired infection (45.2%), followed by patients with nosocomial infections alone (34.3%) and patients with community-acquired infections alone (17.1%) (p < 0.001). Multiple logistic regression analysis, using only the cohort of infected patients (n = 655), demonstrated that the prior administration of antibiotics (adjusted odds ratio [OR], 3.39; 95% confidence interval [CI], 2.88 to 4.23; p < 0.001), presence of a bloodstream infection (adjusted OR, 1.88; 95% CI, 1.52 to 2.32; p = 0.003), increasing acute physiology and chronic health evaluation (APACHE) II scores (adjusted OR, 1.04; 95% CI, 1.03 to 1.05; p = 0.002), and decreasing patient age (adjusted OR, 1.01; 95% CI, 1.01 to 1.02; p = 0.012) were independently associated with the administration of inadequate antimicrobial treatment. The hospital mortality rate of infected patients receiving inadequate antimicrobial treatment (52.1%) was statistically greater than the hospital mortality rate of the remaining patients in the cohort (n = 1,831) without this risk factor (12.2%) (relative risk [RR], 4.26; 95% CI, 3.52 to 5.15; p < 0.001). Similarly, the infection-related mortality rate for infected patients receiving inadequate antimicrobial treatment (42.0%) was significantly greater than the infection-related mortality rate of infected patients receiving adequate antimicrobial treatment (17.7%) (RR, 2.37; 95% CI, 1.83 to 3.08; p < 0.001). Using a logistic regression model, inadequate antimicrobial treatment of infection was found to be the most important independent determinant of hospital mortality for the entire patient cohort (adjusted OR, 4.27; 95% CI, 3.35 to 5.44; p < 0.001). The other identified independent determinants of hospital mortality included the number of acquired organ system derangements, use of vasopressor agents, the presence of an underlying malignancy, increasing APACHE II scores, increasing age, and having a nonsurgical diagnosis at the time of ICU admission. CONCLUSIONS: Inadequate treatment of infections among patients requiring ICU admission appears to be an important determinant of hospital mortality. These data suggest that clinical efforts aimed at reducing the occurrence of inadequate antimicrobial treatment could improve the outcomes of critically ill patients. Additionally, prior antimicrobial therapy should be recognized as an important risk factor for the administration of inadequate antimicrobial treatment among ICU patients with clinically suspected infections.

APACHE↗
PubMed1999

Accuracy of CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients.

OBJECTIVE: The purpose of this study was to assess the accuracy of high-resolution CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients. MATERIALS AND METHODS: The high-resolution CT scans of 44 asthmatic patients with allergic bronchopulmonary aspergillosis and 38 asthmatic patients without allergic bronchopulmonary aspergillosis were analyzed retrospectively and randomly by two independent observers for these features: bronchial wall thickening, bronchiectasis, centrilobular nodules, mucoid impaction, mosaic perfusion, atelectasis, and consolidation. Each observer made a final diagnosis with a stated degree of confidence. The results are expressed as the average number of observations by the two observers. RESULTS: Findings seen more commonly in patients with allergic bronchopulmonary aspergillosis than in patients with asthma alone included bronchiectasis, centrilobular nodules, and mucoid impaction (p < .01, chi-square test). Bronchiectasis was present in 42 (95%) of 44 patients with allergic bronchopulmonary aspergillosis, centrilobular nodules in 41 (93%), and mucoid impaction in 29.5 (67%) (average of two observers). In the asthmatic control group, bronchiectasis was detected in 11 (29%) of 38 patients, centrilobular nodules in 10.5 (28%), and mucoid impaction in 4%. Bronchiectasis was seen in 184 (70%) of 264 lobes of patients with allergic bronchopulmonary aspergillosis compared with 19.5 (9%) of 228 lobes in asthmatic controls (p < .001, chi-square test). CONCLUSION: In asthmatic patients, bronchiectasis affecting three or more lobes, centrilobular nodules, and mucoid impaction are findings on high-resolution CT that are highly suggestive of allergic bronchopulmonary aspergillosis.

Adult↗