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Biomedical subjects

J M Williams

Publications and source records attributed to J M Williams.

At least 109 records · Page 6Linked to original sources

Comparison of domestic violence screening methods: a pilot study.

STUDY OBJECTIVE: Previous studies have indicated a number of barriers to screening for domestic violence (DV) in an emergency department setting. These barriers result in inconsistencies which determine who is screened as well as the content and quality of the information obtained, and if uncontrolled they are likely to affect measurements of DV incidence in ED populations. The objectives of this project were to design a screening tool that circumvented these barriers and sources of error; to assess whether such an alternative method of screening for DV was acceptable to our patients; and to determine whether the alternative and traditional methods of screening for DV would yield comparable results. Our hypotheses were that the alternative screening tool would be acceptable to our patients and that no significant differences would be found between the two methods. METHODS: The study took place in a rural, university-affiliated ED with approximately 36,000 annual patient visits. The study population consisted of 186 women older than 18 years of age who were treated by one designated physician. Approximately half of these subjects were screened for DV in a face-to-face interview. The other half listened to a tape-recorded questionnaire and recorded their responses on a coded answer sheet. RESULTS: There were 175 completed screenings. The average age of all respondents was 34 years, and 90 (51%) indicated a cumulative lifetime experience of DV of some sort. Overall, 3% of the respondents indicated they were in the ED for injuries received as a result of DV. No significant differences were found between the two methods of screening for DV on any measurement, including refusals. No problems hearing the tape or understanding the instructions were reported. CONCLUSION: These results indicate that the alternative method of employing a recorded questionnaire was no less effective than the best efforts of a designated and conscientious physician. As a means of quickly assessing the prevalence of DV in an ED setting, we find much to recommend such an approach.

Adolescent↗

Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit.

The injection of 2.0 mg chymopapain into the adolescent rabbit knee causes severe loss of articular cartilage proteoglycans (PG). Although chondrocytes attempt to restore lost PG, failure to repair ensues. Pure chondroitin 4,6-sulfate (Condrosulf, IBSA Lugano, Switzerland) has been used in clinical studies of human osteoarthritis (OA) as a slow-acting drug for OA (SYSADOA). Using our model of articular cartilage injury, we examined the effects of oral and intramuscular administration of Condrosulf after chymopapain-induced cartilage injury. In this study, animals received an injection of 2.0 mg chymopapain (Chymodiactin, Boots Pharmaceuticals) into the left knee and were sacrificed after 84 days. The contralateral right knee served as a noninjected control. Some animals received oral Condrosulf while others received intramuscular injections of Condrosulf. Serum keratan sulfate (KS) levels were monitored to ensure degradation of the cartilage PG. Those animals not exhibiting at least a 100% increase of serum KS following chymopapain injection were excluded from the study. At sacrifice, cartilage PG contents were markedly reduced in animals receiving an injection of 2.0 mg chymopapain with no further treatment. In contrast, oral administration of Condrosulf beginning 11 days prior to chymopapain injury resulted in significantly higher (P = 0.0036) cartilage PG contents. Intramuscular administration of Condrosulf resulted in higher, but less significantly so (P = 0.0457), cartilage PG contents. These results suggest that daily Condrosulf treatment prior to and continuing after chymopapain injury may have a protective effect on the damaged cartilage, allowing it to continue to re-synthesize matrix PG after the treatment is discontinued.

Administration, Oral↗

Meropenem exists in equilibrium with a carbon dioxide adduct in bicarbonate solution.

Evidence is provided for the existence of a second discrete chemical form of meropenem at clinically relevant concentrations prepared from the marketed formulation of the drug. Proton and carbon-13 NMR spectra in D2O, coupled with tandem mass spectroscopy (MS/MS) and cross polarization/magic angle spinning (CP-MAS) NMR experiments, allow structural assignment of the compound as a covalent carbon dioxide adduct of meropenem. This carbon dioxide adduct exists in equilibrium with the free drug in solution and can be observed in the solid state following lyophilization. The equilibrium constant of formation of the adduct (Keq = 20 +/- 8 M-1) was estimated in D2O at 25 degreesC.

Bicarbonates↗

Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth.

Neisseria gonorrhoeae opacity-associated (Opa) proteins are a family of outer membrane proteins involved in gonococcal adherence to and invasion of human cells. We wanted to identify additional roles for Opa in the infectious process and used the yeast two-hybrid system to identify human epithelial cell proteins that interact with Opa proteins. Although this system has been used successfully to identify many types of interacting proteins, it has not been used to screen a human cell cDNA library for binding partners of a prokaryotic outer membrane protein. Therefore, we were also interested in exploring the versatility of the yeast two-hybrid system in identifying bacteria-host interactions. Using OpaP from strain F62SF as bait, we screened a HeLa cell cDNA library for Opa-interacting proteins (OIPs). We identified five different OIPs, designated OIP1-OIP5, two of which are homologous to human proteins--thyroid hormone receptor interacting protein (TRIP6) and pyruvate kinase isoenzyme M2 (PK). In the studies presented here, we investigated the interaction between Opa proteins and PK in more depth. Opa-PK interactions were confirmed by in vitro and in vivo assays independent of the yeast two-hybrid system. Escherichia coli expressing six different Opa proteins from gonococcal strain FA1090 all bound more PK than Opa-negative E. coli in in vitro binding assays. Using anti-PK antibody and fluorescence microscopy, we showed that human epithelial cell PK co-localizes with intracellular Opa+ gonococci and E. coli expressing Opa proteins. Using a mutant of N. gonorrhoeae unable to grow on pyruvate or lactate, it appears that intracellular pyruvate is essential for gonococcal growth and survival. These results suggest a novel mechanism in bacterial pathogenesis, i.e. the requirement for direct molecular interaction with a host metabolic enzyme (PK) for the acquisition of an essential intracellular carbon source and growth substrate (pyruvate). These results demonstrate that the yeast two-hybrid system is a valuable tool for identifying biologically relevant interactions between bacteria and host proteins, providing valuable leads for further investigations into novel mechanisms of bacterial pathogenesis.

Amino Acid Sequence↗

Physicians in rural West Virginia emergency departments: residency training and board certification status.

OBJECTIVE: To describe the training and certification of physicians who staff small EDs in rural West Virginia. METHODS: A survey of rural hospital-based EDs was performed. The authors chose to study all hospitals in counties with populations of <30,000 and in which the hospital was the only one in the county. Interviews were conducted with the medical director of the ED or the hospital administrator, depending on who was available at the time of interview. Data collected describing the emergency physicians (EPs) employed at each facility included: medical school and residency training, specialty board certification, and certification in a variety of life support courses. General information about each ED, such as census and hospital resources, was also obtained. Interview data were collected on a survey form and subsequently entered into a database. Descriptive analyses were performed. RESULTS: 20 hospitals met rural criteria for inclusion in the study and all were included. The median number of full-time physicians per ED was 2 (IQR 2-4). 98 part-time doctors were identified; 28 (29%) of these were residents in training. 13/40 (33%) of full-time and 37/98 (38%) of part-time physicians were foreign medical graduates. Only 3/40 (7.5%) of full-time EPs completed residency training in emergency medicine (EM). Only 4/98 (4%) of part-time EPs were residency-trained in EM. 50% of full-time EPs were board-certified in a primary care specialty. Only 5/42 (12%) of full-time EPs were board-certified in EM. One third of full-time and the majority of part-time EPs were not board-certified in any specialty whatsoever. The majority of EPs had been certified in Advanced Cardiac Life Support, but fewer had been certified in Advanced Trauma Life Support and/or Pediatric Advanced Life Support/Advanced Pediatric Life Support. CONCLUSIONS: The majority of physicians staffing small rural EDs in West Virginia are neither residency-trained nor board-certified in EM. Further studies are warranted to determine the most efficient and effective way to maximize the skills and availability of emergency care providers in rural settings.

Certification↗

Parental autobiographical memory: is this a helpful clinical measure in behavioural child management?

OBJECTIVES: The major hypothesis was that specificity scores on the Parent-Child Autobiographical Memory Test (PCAMT; Hutchings, 1996) would differentiate between mothers of children referred to a child and adolescent mental health service for behavioural management, and those who were not referred. Within the referred sample, the objective was to examine the relationships between the PCAMT, mental health (Beck Depression Inventory; Beck, Ward, Mendelson, Mock & Erbaugh, 1961; General Health Questionnaire; Goldberg, 1972) and socio-economic deprivation (SED5; Hutchings, 1996) and measures of outcome (Eyberg Child Behavior Inventory; Eyberg, 1980). DESIGN: Pre-treatment measures on the PCAMT for the group of mothers whose children were referred were compared with measures on the PCAMT from a group of mothers of non-referred children of similar ages. Within the mothers of the referred sample, correlations of the PCAMT with other measures were examined, pre- and post-treatment. METHODS: Pre-treatment PCAMT scores from 26 mothers of children with behaviour management problems from consecutive referrals to a child and adolescent mental health service were compared with PCAMT scores from 22 mothers of children of a similar age from a local playgroup. Within the referred group, the PCAMT was administered before (N = 26) and after (N = 16) treatment. The 16 treated families received behavioural management advice. RESULTS: The PCAMT distinguished between parents of children referred for behavioural management advice and a non-clinical sample. Within the referred group it also distinguished between those who received treatment and those who did not attend treatment. CONCLUSIONS: The PCAMT is considered to have the potential of being a useful instrument for identifying referred children whose mothers may not attend for treatment and possibly for identifying those mothers who would benefit most from concentrating on attending and observation skills in child management training.

Adult↗

Sports related injuries in Scottish adolescents aged 11-15.

OBJECTIVES: To measure the age and sex distribution of self reported sports and leisure injuries in a 12 month retrospective recall period among a representative national sample of Scottish adolescents, and to examine the characteristics (gender, age, handedness, and level of sports participation) of sports related injuries in relation to injuries sustained during other activities. DESIGN/SETTING: Self completion questionnaire survey administered in schools during April-June 1994. SUBJECTS: 4710 pupils aged 11, 13, and 15 years drawn from a representative sample of 270 classes with returns from 224 classes (83% completion rate). RESULTS: 42.1% of the sample reported a medically attended injury. These were significantly more frequent among boys but there were no significant age differences in overall frequency of injury. Sport related injuries accounted for 32.2% of all medically attended injuries. As with all injuries, frequency was greater in boys than girls at all ages, and there are differences in the pattern of lesions in sports and nonsports injuries. Lower limb injuries were more frequent than upper limb injury in sports (57.6 v 23.9%), whereas there were no differences in non-sports injuries (31.5 v 31.3%). Age and handedness differences in sports injury rates were also identified. High sports participation was significantly associated with a higher risk of injury in general and sports related injury in particular. CONCLUSION: Age, gender, handedness, and level of sports participation have been shown to be implicated in differential risk of sports related injury. Reducing sports injury among adolescents should be a priority, but research into the injury profiles of different sports is needed before detailed injury prevention strategies can be developed.

Abbreviated Injury Scale↗

Measures of injury severity in childhood: a critical overview.

Many different methods for assessing injury severity have appeared in the literature. This paper discusses the commonly used measures, many of which are subjective and depend on clinical practice or sociological factors. Even if apparently objective measures are used their appropriateness for use in children is questionable. Particular problems occur with scoring or categorising events such as poisoning, choking, and near drowning. Researchers need to reach a consensus on injury severity reporting to ensure comparability between studies and programs for injury prevention.

Adult↗

A method for estimating solid organ donor potential by organ procurement region.

OBJECTIVES: This study sought to develop a methodology for estimating potential solid organ donors and measuring donation performance in a geographic region based on readily available data on the hospitals in that region. METHODS: Medical records were reviewed in a stratified random sample of 89 hospitals from 3 regions to attain a baseline of donor potential. Data on a range of hospital characteristics were collected and tested as predictors of donor potential through the use of hierarchical Poisson regression modeling. RESULTS: Five hospital characteristics predicted donor potential: hospital deaths, hospital Medicare case-mix index, total hospital staffed beds, medical school affiliation, and trauma center certification. Regional estimates were attained by aggregating individual hospital estimates. Confidence intervals for these regional estimates indicated that actual donations represented from 28% to 44% of the potential in the regions studied. CONCLUSIONS: This methodology accurately estimates organ donor potential within 3 geographic regions and lays the foundation for evaluating organ donation effectiveness nationwide. Additional research is needed to test the validity of the model in other geographic regions and to further explore organ donor potential in hospitals with fewer than 50 beds.

California↗

Interferon beta 1-b in verbal memory functioning of patients with relapsing-remitting multiple sclerosis.

The effects of interferon Beta 1-b (Betaseron) on verbal memory functioning was examined in 167 patients with relapsing-remitting multiple sclerosis and 112 matched normal controls. Subjects were administered 10 verbal memory tests from the Memory Assessment Scales and the Verbal subtests from the Wechsler Adult Intelligence Scale. Analysis showed subjects treated with Betaseron (n = 73) did not perform significantly better on measures of verbal memory or verbal ability than subjects not receiving the drug (n = 94), although the mean performance of treated subjects was higher across all verbal memory tests. Both groups of patients performed significantly worse on verbal memory subtests measuring list acquisition, delayed list recall, delayed cued recall, and the immediate and delayed recall of names and faces than control subjects. Although patients had lower performance scores across all memory tests than the control subjects, their scores were not within the impaired range. These results do not permit a clear conclusion about the effects of Betaseron on verbal memory for any effect is probably obscured by the relatively preserved cognitive functioning of this outpatient sample.

Adjuvants, Immunologic↗

Descriptive and graphical strategies for assessing change: a case study of functional status in stroke patients.

A primary focus in the current context of the health care industry is the measurement of outcomes. Outcomes research, although inclusive of the use of advanced statistical analyses, can often be conducted using more easily understood analytical techniques such as descriptive analysis and graphical display of data. The article addresses the description and analysis of patient change scores on the Functional Independence Measure (FIM) from 745 stroke rehabilitation inpatients. Display and discussion of percentiles, cross-tabulations, scatter plots, and side-by-side box plots are used in this case study of describing outcomes.

Activities of Daily Living↗

Regional differences in the rise in blood levels of antigenic keratan sulfate and hyaluronan after chymopapain induced knee joint injury.

OBJECTIVE: Results from several recent studies suggest that the levels of antigenic keratan sulfate (agKS) and hyaluronan (HA) in serum provide useful information about changes taking place in injured or diseased synovial joints. To improve our understanding of the significance of such changes, we investigated the points of entry of these molecules into the blood circulation and their subsequent clearance after experimentally induced injury to rabbit knee joint. METHODS: Chymopapain was injected into knee joints of 8 young adult rabbits to induce aggrecan degradation in articular cartilage within the injected joint. Levels of agKS and HA in serum from various blood vessels were measured before and 5 h after the injury. The statistical significance of injury related changes and differences among the different vessels were evaluated. RESULTS: After the injury, the level of agKS rose most significantly in the popliteal vein draining the injected knee joint and dropped rapidly by the time the blood reached the femoral vein. The level of agKS was similar, although lower, in other blood vessels but, in each case, it was significantly higher than before the injection. The level of HA showed a different pattern of changes after injection. While highest in the popliteal vein draining the injected knee, HA was markedly elevated in the cranial vena cava, close to the entry of lymph into the circulation, and was 50% lower in the hepatic than in the portal vein. CONCLUSION: (1) Measurement of agKS and HA in a blood vessel draining or close to an injured/diseased knee joint may provide more specific information about degradative changes taking place in that joint than measurement of levels of these markers in other blood vessels; (2) some HA molecules but no measurable amounts of agKS enter the blood circulation via the lymphatic system: and (3) HA but not agKS is very rapidly cleared from the blood by the liver.

Animals↗

Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma.

This Phase I/II radioimmunotherapy study was carried out to determine the maximum tolerated dose (MTD) and therapeutic potential of 131I-G250. Thirty-three patients with measurable metastatic renal cell carcinoma were treated. Groups of at least three patients received escalating amounts of 1311I (30, 45, 60, 75, and 90 mCi/m2) labeled to 10 mg of mouse monoclonal antibody G250, administered as a single i.v. infusion. Fifteen patients were studied at the MTD of activity. No patient had received prior significant radiotherapy; one had received prior G250. Whole-body scintigrams and single-photon emission computed tomography images were obtained in all patients. There was targeting of radioactivity to all known tumor sites that were > or =2 cm. Reversible liver function test abnormalities were observed in the majority of patients (27 of 33 patients). There was no correlation between the amount of 131I administered or hepatic absorbed radiation dose (median, 0.073 Gy/mCi) and the extent or nature of hepatic toxicity. Two of the first six patients at 90 mCi/m2 had grade > or =3 thrombocytopenia; the MTD was determined to be 90 mCi/m2 131I. Hematological toxicity was correlated with whole-body absorbed radiation dose. All patients developed human antimouse antibodies within 4 weeks posttherapy; retreatment was, therefore, not possible. Seventeen of 33 evaluable patients had stable disease. There were no major responses. On the basis of external imaging, 131I-labeled mouse monoclonal antibody G250 showed excellent localization to all tumors that were > or =2 cm. Seventeen of 33 patients had stable disease, with tumor shrinkage observed in two patients. Antibody immunogenicity restricted therapy to a single infusion. Studies with a nonimmunogenic G250 antibody are warranted.

Adult↗

Problem solving and suicidal behavior.

Research on suicidal behavior falls into two main areas: studies that aim to identify demographic and social risk factors, and studies that aim to investigate the psychological processes mediating suicidal behavior. Within the latter approach, impaired problem-solving ability has been found to be an important variable. This paper reviews recent research focusing on problem-solving deficits and their relation to suicidal behavior and considers some of the methodological problems that arise. These findings are discussed in terms of active versus passive problem solving, state or trait factors, and the psychological processes underlying problem solving. Suggestions for further research are made, focusing on the links between suicidal behavior, problem solving, and autobiographical memory.

Humans↗

Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin.

The immunosuppressant rapamycin interferes with G1-phase progression in lymphoid and other cell types by inhibiting the function of the mammalian target of rapamycin (mTOR). mTOR was determined to be a terminal kinase in a signaling pathway that couples mitogenic stimulation to the phosphorylation of the eukaryotic initiation factor (eIF)-4E-binding protein, PHAS-I. The rapamycin-sensitive protein kinase activity of mTOR was required for phosphorylation of PHAS-I in insulin-stimulated human embryonic kidney cells. mTOR phosphorylated PHAS-I on serine and threonine residues in vitro, and these modifications inhibited the binding of PHAS-I to eIF-4E. These studies define a role for mTOR in translational control and offer further insights into the mechanism whereby rapamycin inhibits G1-phase progression in mammalian cells.

Adaptor Proteins, Signal Transducing↗

Comparison of ribosome-inactivating proteins in the induction of apoptosis.

The aim of this study was to evaluate the ability of verocytotoxin-1 (VT1), VT1 B chain alone, ricin and a hybrid toxin (RASTA2) consisting of ricin A chain linked to VT1 B chain to inhibit protein synthesis and to induce apoptosis. The lethal effects of the toxins were compared using vero cells (originating from green African monkey kidney tissue). As previously described cell death occurred through apoptosis which was quantified using the diphenylamine assay. DNA fragmentation was seen with VT1 at 10 pg/ml but there was no effect with B chain alone. Fragmentation with ricin was seen at 10 ng/ml and with RASTA2 at 1 ng/ml. Protein synthesis inhibition was measured by [(35)S]methionine incorporation. VT1 had an IC50 of 0.0024 ng/ml, B chain alone was ineffective at inhibiting protein synthesis. Ricin had an IC50 of 0.39 ng/ml and RASTA2 of 1.7 ng/ml. In vero cells the B chain of these toxins does not participate in cell killing.

Animals↗

Nitric oxide synthase and arginase in cells isolated from the rat gastric mucosa.

Nitric oxide (NO) synthase activity, which converts arginine to citrulline and NO, is present in homogenates of rat gastric mucosal cells. The aims of this study were to identify the form of NO synthase expressed in gastric cells isolated from fed rats, and to investigate the metabolism of arginine by suspensions of intact mucosal cells. Antibodies directed against the neuronal form of NO synthase recognised a protein of 160 kDa on immunoblots of extracts of gastric cells, and stained isolated cells of approx. 8 microm in diameter. NO synthase was enriched in a cell fraction which banded at high-density in a Percoll gradient, and was inhibited (IC50) by N(G)-nitro-L-arginine (0.8 microM), N(G)-monomethyl-L-arginine (12.6 microM), L-canavanine (147 microM), trifluoperazine (140 microM) and by phosphorylation involving protein kinase C. Intact gastric cells converted exogenous arginine to ornithine and citrulline. Arginase was present in the cells, and was predominantly responsible for arginine metabolism because formation of ornithine and citrulline was reduced by the arginase inhibitors, N(G)-hydroxy-L-arginine and L-ornithine, but not by NO synthase inhibitors such as N(G)-nitro-L-arginine. In conclusion, NO synthase that resembles the neuronal isoform is present in gastric mucosal cells, but a pathway involving arginase seems to be largely responsible for citrulline formation from exogenous arginine in intact mucosal cells.

Animals↗