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Biomedical subjects

T Williams

Publications and source records attributed to T Williams.

At least 163 records · Page 9Linked to original sources

Terbinafine in onychomycosis of the toenail: a novel treatment protocol.

BACKGROUND: Current treatment of onychomycosis of the toenail is poor and relapse is common. OBJECTIVE: Our purpose was to assess the efficacy and safety of oral terbinafine and placebo in onychomycosis of the toenail with the use of a novel treatment protocol. METHODS: This was a randomized, double-blind, 48-week study. Twelve weeks of terbinafine (250 mg daily) or placebo was followed by 12 weeks of observation. Responders received no further treatment and nonresponders were offered 12 weeks of terbinafine (250 mg daily) from week 28. RESULTS: Of 111 evaluable patients, 88% (49 of 56) of the patients given terbinafine and 29% (16 of 55) of the patients given placebo had a negative mycologic culture at week 24 (p < 0.001), 57% (32 of 56) of the terbinafine group and 6% (3 of 55) of the placebo group were responders (p < 0.001). By week 48, after the terbinafine nonresponders were given a second 12-week course of terbinafine, the overall mycologic cure rate for the patients given terbinafine was 94%. CONCLUSION: High mycologic cure rates in onychomycosis of the toenail can be achieved by terbinafine by this novel treatment regimen.

Adolescent↗

Sports injuries in athletes with disabilities: wheelchair racing.

This study investigates the incidence of sports injuries in athletes who participate in wheelchair racing in the UK. Wheelchair racing has been identified as one of the top 'injury risk' sports but little information is available as to the incidence or type of injury sustained by British athletes. A questionnaire was used to collect information about injuries sustained in the last 12 months. Members of the British Wheelchair Racing Association (BWRA) were sent questionnaires. Most subjects (72%) reported having at least one injury within the previous 12 months. Training variables such as the distance pushed per week (Mann-Whitney U = 61, P > 0.05), the amount of speed training (Mann-Whitney U = 110, P > 0.05), the number of weight training sessions (Mann-Whitney U = 26, P > 0.05) or the length of time the athlete had been involved in wheelchair racing (Mann-Whitney U = 103, P > 0.05) were not associated with the occurrence of an injury. Overuse injuries were common and recurred more often than other types of injuries (chi 2 = 3.95, P < 0.05). Those athletes with recurring injuries also tended to be those who restarted training before they were pain-free from their injury (chi 2 = 5.31, P < 0.05). There appears to be a link between overuse injuries, the presence of pain during training and the recurrence of injuries. A lack of knowledge about sports injuries, what causes them and what to do following an injury may contribute to the high incidence of overuse injuries in this group of athletes.

Adult↗

The absence of evidence of staphylococcal toxin involvement in the pathogenesis of Kawasaki disease.

To detect a causative superantigen and to clarify a possible role for staphylococci in Kawasaki disease (KD), culture supernatants of individual bacterial isolates from 11 acute-stage patients were studied. Toxic shock syndrome toxin-1 (TSST-1) and antibody to TSST-1 and enterotoxins A (SEA), B (SEB), and C (SEC) in acute (mean, day 7) and late convalescent (mean, month 15) sera from 26 patients (12 with coronary artery aneurysms) and 22 age-matched controls were measured. Only 1 of 60 supernatants was mitogenic for human lymphocytes; it was 1 of the 4 Staphylococcus aureus isolates. Mitogenicity was neutralized by sera obtained after administration of intravenous gamma globulin (mean, week 4) but not by late convalescent sera. TSST-1 was detectable in 2 of 26 acute sera and 1 of 22 control sera. No KD but 1 control serum had IgM to TSST-1. IgG seroconversion rates to TSST-1, SEA, SEB, and SEC were 10%, 15%, 21% and 16%, respectively. These data do not support the involvement of toxin-producing staphylococci in KD.

Antibodies, Bacterial↗

Variability in lesion depth on prone and supine CT scans of the chest: implications for the accuracy of transthoracic needle aspiration biopsy.

Transthoracic needle biopsy of the lung is often performed fluoroscopically in the prone position; nodule depth measurements are made from accompanying computed tomographic (CT) scans performed supine. We evaluated the effect of prone and supine positioning on the effect of nodule depth as measured from the skin surface. Twenty consecutive patients having CT-guided biopsy performed in the prone position were assessed. Nodule depth from posterior skin surface to nodule was compared with prebiopsy supine CT scan. Nodules above the carina showed minimal change in depth. Those below the carina showed considerable variability, with depth changes < or = 4.0 cm. Awareness of the magnitude of the potential effect of patient position on lesion depth should be helpful in reducing the likelihood of false negative results in fluoroscopically guided biopsy.

Biopsy, Needle↗

Sibling interaction of children with learning disabilities: a comparison of autism and Down's syndrome.

Two potentially contrasting hypotheses can be generated about sibling interactions involving a child with Down's syndrome or autism. Research on siblings would predict that learning disabled children adopt responsive roles. Studies of children with autism would predict impoverished interactions. Home observations were conducted on 30 sibling pairs involving children with autism or Down's syndrome. Both hypotheses were partially supported. All learning disabled children engaged in frequent bouts of interaction, usually directed by their sibling. While children with autism engaged in fewer bouts and imitated less, they did reciprocate their siblings' initiations. Sibling encounters provide a unique opportunity for such children to learn about social relationships.

Autistic Disorder↗

Evaluation and validation of a monoclonal immunofluorescent reagent for direct detection of Bordetella pertussis.

An outbreak of pertussis in Manitoba, Canada, provided an opportunity to evaluate the recently developed monoclonal antibody (MAb) BL-5 for the direct detection of Bordetella pertussis. The MAb recognizes a lipooligosaccharide epitope. A total of 1,507 consecutive nasopharyngeal swabs for culture and companion smears for direct fluorescent-antibody (DFA) detection were evaluated at Cadham Provincial Laboratory between September and November 1994. The cutoff for DFA positivity was four fluorescing organisms with morphology characteristic of B. pertussis. PCR analysis for B. pertussis DNA was performed on a subset of 100 smears by eluting material from the slides after DFA examination. In comparison with culture, the sensitivity, specificity, and positive and negative predictive values of BL-5 were 65.1% (41 of 63 samples), 99.6% (1,438 of 1,444 samples), 87.2% (41 of 47 samples), and 98.5% (1,438 of 1,460 samples), respectively. The sensitivity of culture compared with PCR was 45.5% (10 of 22 samples) for the subset of 100 specimens tested by both procedures. An expanded "gold standard" of positivity by culture or PCR for these 100 specimens resulted in DFA sensitivity, specificity, and positive and negative predictive values of 32.3, 97.1, 83.3, and 76.1%, respectively. The utility of MAb BL-5 for direct detection of B. pertussis in a clinical laboratory setting has been demonstrated by this investigation.

Adult↗

Detection of penicillin-resistant Streptococcus pneumoniae with commercially available broth microdilution panels.

We compared penicillin MICs obtained with three different commercially available broth microdilution panels (MicroScan, Sensititre, and Pasco) with MICs obtained with reference microdilution panels for 20 well-characterized pneumococci with decreased susceptibilities to penicillin (7 resistant and 13 intermediate). All panels were supplemented with 2 to 5% lysed horse blood (LHB) prepared in-house. Additional supplements included fastidious inoculum broth (FIB) for MicroScan panels and commercially prepared LHB (Difco) for Pasco panels. The percentages of penicillin-resistant strains (MIC 2 micrograms/ml) detected by the different methods follow: MicroScan-FIB, 0; MicroScan-LHB 0; Pasco in-house LHB, 71; and Sensititre-LHB, 100. The percentages of intermediate strains (MIC = 0.1 to 1.0 micrograms/ml) detected by the different methods follow: MicroScan-FIB, 31; MicroScan-LHB 23; Pasco in-house LHB, 46; and Sensititre-LHB, 85. Difco LHB supplement failed to support the growth of 86% of the strains in the Pasco panels. Of the commercially available panels evaluated, only Sensititre, supplemented with LHB prepared in-house could reliably detect penicillin-resistant pneumococci.

Culture Media↗

The 5' enhancer of the mouse mammary tumor virus long terminal repeat contains a functional AP-2 element.

The mouse mammary tumor virus (MMTV) retrovirus causes mammary adenocarcinomas in mice by proviral insertion near members of the wnt family of proto-oncogenes, leading to their deregulation and cellular transformation. The 5' end of the MMTV long terminal repeat (LTR) has been implicated in tissue-specific activation of these genes. In this study, we characterize an enhancer element (Ban2; -1075 to -978) at the 5' end of the MMTV LTR. We show that this enhancer is 5-fold more active in a murine mammary carcinoma cell line (34i) than in a fibroblast cell line (NIH3T3), and is inactive in the liver carcinoma cell line HepG2. Mutagenesis of the enhancer reveals four cis-acting elements that are required for maximal activity. DNA-binding proteins that interact with each of the four elements have been identified. One of these factors, designated mp5, is either identical to, or closely related to, the transcription factor AP-2. The mp5/AP-2 DNA binding activity co-migrates with recombinant AP-2 and is supershifted by anti-AP-2 antibodies. We also show that the lack of enhancer activity in HepG2 cells results from the absence of AP-2 protein in these cells. Co-transfection of an AP-2 expression vector restores the activity of this enhancer in HepG2 cells, and requires an intact mp5-binding site.

Animals↗

Phosphorylation of an inhibitory subunit of cGMP phosphodiesterase in Rana catesbeiana rod photoreceptors. I. Characterization of the phosphorylation.

Interaction between the inhibitory subunit (P gamma) and catalytic subunits of cGMP phosphodiesterase is essential for the regulation of cGMP phosphodiesterase in vertebrate rod photoreceptors. P gamma phosphorylation in vitro has been studied using a kinase which is extracted from amphibian rod outer segments. Various chromatographies of the kinase preparation using ionic exchange, gel filtration, and heparin-Sepharose columns indicate that a kinase with M(r) 70,000 is responsible for the P gamma phosphorylation. The kinase does not require any of the known activators for protein kinases but is inhibited by cGMP in a concentration-dependent manner. Together with analysis by laser-desorption mass spectrometry, measurement of 32P radioactivity in phosphorylated P gamma indicates that P gamma extracted with GTP-bound transducin alpha subunit is not phosphorylated and that a phosphate is incorporated into more than 80% of the P gamma by the kinase. Phosphoamino acid analysis, sequencing of phosphorylated peptides derived from phosphorylated P gamma, and phosphorylation of synthetic peptides indicate threonine 22 in P gamma is phosphorylated by the kinase. Phosphorylated P gamma has a higher inhibitory activity for active cGMP phosphodiesterase than non-phosphorylated P gamma. These data suggest that threonine 22 in P gamma is phosphorylated by a specific kinase and that the P gamma phosphorylation governs the interaction between P gamma and catalytic subunits of cGMP phosphodiesterase in vertebrate rod photoreceptors.

3',5'-Cyclic-GMP Phosphodiesterases↗

Purification and characterization of a collagen-degrading protease from Porphyromonas gingivalis.

A trypsin-like protease was purified from spent culture medium of oral pathogen Porphyromonas gingivalis by chromatography on columns of DEAE-Sepharose, gel filtration on Sephadex G-100, and chromatofocusing on PBE-94. Purified enzyme showed a single band on SDS-polyacrylamide gel electrophoresis with an estimated molecular weight of 55,000. Purified protease hydrolyzed type I, III, IV, and V collagen from human placenta, and type I collagen from rat tail and calf skin, but did not hydrolyze type II collagen from chicken sternal cartilage. The purified enzyme also hydrolyzed the C3 component of complement, fibrinogen, fibronectin, alpha 1-antitrypsin, alpha 2-macroglobulin, apotransferrin, and human serum albumin. The hydrolytic activity of the purified enzyme on chromogenic substrates was limited to substrates with arginine in the P-1 position, although synthetic peptides were also cleaved at Lys-X linkage. The enzyme was activated by reducing agents dithiothreitol, L-cysteine, and glutathione and inhibited by cysteine protease inhibitors N-ethylmaleimide, iodoacetic acid, and iodoacetamide. The enzyme was also inhibited by trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64), leupeptin, antipain, salivary histidine-rich protein (HRP-5), soybean trypsin inhibitor, and EDTA. Since the protease is able to degrade the connective tissue components of periodontal tissue as well as components of host defense mechanism, this enzyme may be a potent virulence factor of P. gingivalis involved in invasion and tissue destruction.

Amino Acid Sequence↗

Characterization of cladribine and its related compounds by high-performance liquid chromatography/mass spectrometry.

High-performance liquid chromatography/mass spectrometer (HPLC/MS) was used to identify and structurally characterize the modified nucleoside cladribine (2-chloro-2'-deoxy-beta-adenosine) and 13 synthesis-related byproducts in bulk drug. Confirmation of compound identity was accomplished by spectral analysis (1H and 13C NMR spectroscopy, mass spectrometry, and UV absorption spectroscopy) of the related compounds as isolated from crude mixtures of the drug substance and by spiking experiments with authentic standards. The use of on-line mass spectrometric analysis (i.e., LC/MS) to augment UV absorption spectra permitted rapid identification of many of the compounds of interest.

Chromatography, High Pressure Liquid↗

Use of polypentapeptides of elastin to prevent postoperative adhesions: efficacy in a contaminated peritoneal model.

We investigated the use of a sheet of polypentapeptide of elastin as a physical barrier to adhesion formation in a contaminated peritoneal wound model. A total of 88 rats were studied with random assignment of animals to three study groups; control (29), polypentapeptide steam sterilized (30), and polypentapeptide gas sterilized (29). Animals were anesthetized and a laparotomy was conducted to reveal the cranial portion of the ileum. The abdominal wall muscle peritoneum was excoriated until hemorrhage was noted. In sham animals, there was no physical barrier placed between bowel loop and the abdominal wall. In two of the study groups, the polypentapeptide sheet was placed directly over the excoriated area. The intestinal loop was then loosely secured to excoriated area with 2-O nylon (stay suture) which was tied subcutaneously in all groups. Four puncture wounds were made with a 20-gauge hypodermic needle in the bowel that was apposed to the excoriated peritoneal musculature which allowed leakage of intestinal contents and contamination. On Day 7 postsurgery, the animals were anesthetized and the stay suture was removed. On Day 14, all animals were sacrificed and adhesions were graded. The incidence of significant adhesions was 28% for the barrier group versus 90% for control animals (P < 0.05). The results of this study indicate that the polypentapeptide of elastin sheet is an effective physical barrier in this surgically induced contaminated wound model.

Animals↗

The use of local and systemic antibiotics in rat fecal peritonitis.

Treatment of fecal peritonitis includes administration of antibiotics, physical removal of contaminants, and restoration of gastrointestinal integrity. The temporal relationship of parenteral antibiotics and peritoneal irrigation with varied antibiotic solutions was studied in a peritonitis model. Antibiotics in high concentrations may actually inhibit host immune cells; therefore, dilute solutions used were MIC (minimum inhibitory concentration) (micrograms per millimeter) equivalent to usually achieved standard therapeutic blood levels. Sprague-Dawley rats were given a quantitative intraperitoneal challenge of 2 x 10(10) CFU/kg Escherichia coli and 10 mg autoclaved rat feces. Rats were randomized to receive 30 mg/kg intramuscular ceftriaxone (CTRX) either at the time of challenge (T = 0) or 2 hr later (T = 2). Two hours after peritonitis, rats received peritoneal irrigation with 30 cc of (1) normal saline, (2) dilute (10 mg/liter) CTRX solution, or (3) concentrated (1000 mg/liter) CTRX solution or (4) no irrigation. Survival and intraperitoneal pathology were then assessed. Parenteral CTRX given concurrently with peritoneal contamination improved survival (67%) compared with parenteral administration given 2 hr later (33%) (P < 0.05). Intraperitoneal CTRX irrigation improved survival (100%) in animals that received parenteral CTRX concurrently with contamination; this beneficial effect was present with both dilute and concentrated solutions and was significantly better than saline irrigation alone. Parenteral antibiotics given early after contamination of the peritoneum associated later with peritoneal lavage with antibiotic solutions improved survival.

Abscess↗

Daily variability in exercise ventilation.

The purpose of this study was to quantify daily variability in ventilation (VE) during submaximal exercise and establish the number of testing sessions required to produce stable exercise ventilation measures. Following 60 min of treadmill accommodation, four male (M) and four female (F) distance runners completed 5 weeks of daily treadmill testing at the same time of day while engaged in a normal routine of training and racing. During each test session, subjects completed three 6-min level treadmill runs at either 3.13, 3.57, and 4.02 m.sec-1 for F or 3.57, 4.02, and 4.47 m.sec-1 for M. Measures of VE were obtained during the last 2 min of each 6-min run. Results indicated that the mean coefficient of variation (CV) for VE across speeds was 4.33%. Reliability analyses examining all possible combinations of testing days over the 5-week period revealed that 97% of the variation in mean VE was accounted for in either 2 consecutive or non-consecutive days, while 98% of the variation in mean VE was accounted for in 5 consecutive days. These data suggest that when treadmill exposure and circadian variation are controlled, intraindividual differences in exercise VE are relatively small in male and female subjects following an unrestricted program of training and competitive racing. Additionally, acceptably stable VE values in this cohort can be derived by averaging duplicate measures obtained from consecutive or non-consecutive testing sessions.

Adult↗

Comparative studies of iridoviruses: further support for a new classification.

Changes in the classification of invertebrate iridoviruses (IVs) (Iridoviridae) have recently been proposed (Williams and Cory, 1994). The previous system of naming isolates according to the host and sequence of discovery (IV type 1, IV2, IV3, etc.) is not adequate for the purposes of taxonomy, since iridovirus isolates may infect many species, including hosts from diverse invertebrate orders. The new system of invertebrate iridovirus nomenclature, as with several other virus families, is based on geographical origin. Proposals have been made, based on DNA hybridization and other characteristics, by which invertebrate iridovirus isolates can be assigned to one of four recognized complexes, or considered as candidates for alternative assignations. This study reports comparative data on the DNA of 14 invertebrate iridovirus isolates used in the Williams and Cory study plus the two type vertebrate iridoviruses, frog virus 3 and flounder lymphocystis disease virus. DNA studies support the validity of assigning several isolates a common name and of grouping the known isolates into four complexes. The detection of such complexes is in broad agreement with previous serological studies. A previously undescribed isolate (San Miguel IV) obtained from the lepidopteran pest Anticarsia gemmatalis (Lep.: Noctuidae) has been initially characterized following the procedures recommended by Williams and Cory. DNA hybridization and Southern blot analysis identified this isolate as a new member of the Polyiridovirus complex. The San Miguel IV MSP gene was identified and a central fragment of ca. 719 bp was recovered by PCR amplification. The restriction endonuclease profiles (5 enzymes) of this isolate were distinct from others previously described.

Animals↗