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Biomedical subjects

W Holmes

Publications and source records attributed to W Holmes.

At least 37 records · Page 2Linked to original sources

Influence of patients' expectations on antibiotic management of acute lower respiratory tract illness in general practice: questionnaire study.

OBJECTIVE: To assess patients' views and expectations when they consult their general practitioner with acute lower respiratory symptoms and the influence these have on management. DESIGN: General practitioners studied consecutive, previously well adults and recorded clinical data, the certainty regarding their prescribing decision, and the influence of non-clinical factors on that decision. Patients completed a questionnaire at home after the consultation. SETTING: 76 doctors from suburban, inner city, and rural practices. SUBJECTS: 1014 eligible patients entered; 787 (78%) returned the questionnaire. MAIN OUTCOME MEASURES: The views of the patient, the views of and antibiotic prescription by the doctor. RESULTS: Most patients thought that their symptoms were caused by an infection (662) and that antibiotics would help (656) and had both wanted (564) and expected (561) such a prescription. 146 requested an antibiotic, 587 received one. Of the 643 patients who thought they had an infection, 582 wanted an antibiotic and thought it would help. Severity of symptoms did not relate to wanting antibiotics. For those prescribed antibiotics, their doctor thought they were definitely indicated in only 116 cases and not indicated in 126. Patient pressure most commonly influenced the decision to prescribe even when the doctor thought antibiotics were not indicated. Doctors considered antibiotics definitely indicated in only 1% of the group in whom patient pressure influenced the prescribing decision. Patients who did not receive an antibiotic that they wanted were much more likely to express dissatisfaction. Dissatisfied patients reconsulted for the same symptoms twice as often as satisfied patients. CONCLUSION: Patients presenting with acute lower respiratory symptoms often believe that infection is the problem and antibiotics the answer. Patients' expectations have a significant influence on prescribing, even when their doctor judges that antibiotics are not indicated.

Adult↗

Phorbol esters and SDF-1 induce rapid endocytosis and down modulation of the chemokine receptor CXCR4.

The chemokine receptor CXCR4 is required, together with CD4, for entry by some isolates of HIV-1, particularly those that emerge late in infection. The use of CXCR4 by these viruses likely has profound effects on viral host range and correlates with the evolution of immunodeficiency. Stromal cell-derived factor-1 (SDF-1), the ligand for CXCR4, can inhibit infection by CXCR4-dependent viruses. To understand the mechanism of this inhibition, we used a monoclonal antibody that is specific for CXCR4 to analyze the effects of phorbol esters and SDF-1 on surface expression of CXCR4. On human T cell lines SupT1 and BC7, CXCR4 undergoes slow constitutive internalization (1.0% of the cell surface pool/min). Addition of phorbol esters increased this endocytosis rate >6-fold and reduced cell surface CXCR4 expression by 60 to 90% over 120 min. CXCR4 was internalized through coated pits and coated vesicles and subsequently localized in endosomal compartments from where it could recycle to the cell surface after removal of the phorbol ester. SDF-1 also induced the rapid down modulation (half time approximately 5 min) of CXCR4. Using mink lung epithelial cells expressing CXCR4 and a COOH-terminal deletion mutant of CXCR4, we found that an intact cytoplasmic COOH-terminal domain was required for both PMA and ligand-induced CXCR4 endocytosis. However, experiments using inhibitors of protein kinase C indicated that SDF-1 and phorbol esters trigger down modulation through different cellular mechanisms. SDF-1 inhibited HIV-1 infection of mink cells expressing CD4 and CXCR4. The inhibition of infection was less efficient for CXCR4 lacking the COOH-terminal domain, suggesting at least in part that SDF-1 inhibition of virus infection was mediated through ligand-induced internalization of CXCR4. Significantly, ligand induced internalization of CXCR4 but not CD4, suggesting that CXCR4 and CD4 do not normally physically interact on the cell surface. Together these studies indicate that endocytosis can regulate the cell-surface expression of CXCR4 and that SDF-1-mediated down regulation of cell-surface coreceptor expression contributes to chemokine-mediated inhibition of HIV infection.

Animals↗

Transarticular joint reconstruction and indirect plate osteosynthesis for complex distal supracondylar femoral fractures.

In a prospective study conducted between 1992 and 1995, displaced Müller type C2-C3 intraarticular fractures of the distal femur were treated using an indirect plate fixation technique and a lateral parapatellar arthrotomy for the direct reduction of the condylar block. There were 6 closed, and 2 open fractures (1 grade II and 1 grade IIIB). Following reconstruction of the articular block, the block was indirectly reduced and fixed to the shaft by a plate inserted by the retrograde method beneath the vastus lateralis. Transcutaneous/transmuscular screws were used to fix the plate to the shaft. Time to bone healing was 12 weeks (median range 8-17 weeks) after surgery without needing primary or secondary bone grafts. There were no infections or refractures. Except for one case which required a corrective osteotomy for 10 degrees of varus malalignment, there were no revisions. According to the Neer score, there were 6 excellent or satisfactory results, 2 unsatisfactory results, and no failures. At follow-up, there were 2 varus-valgus deformities greater than 5 degrees, 2 leg length discrepancies greater than 10 mm, and 2 rotational deformities of 15 degrees. The treatment results for complex supracondylar/intracondylar fractures of the distal femur obtained with this technique compare favourably with other reported series using different techniques without the added morbidity associated with autogenous bone grafting. However, the surgical technique is demanding and special care must be taken to ensure correct axial alignment.

Adult↗

Contemporary use of antibiotics in 1089 adults presenting with acute lower respiratory tract illness in general practice in the U.K.: implications for developing management guidelines.

Respiratory symptoms are the most common cause of general practitioner (GP) consultation, and hospital-based specialists are often called on to provide management guidelines, particularly in the area of antibiotic prescribing. The present authors have assessed factors associated with antibiotic use by 115 GPs when managing 1089 adults with an acute lower respiratory tract illness, including cough. They prescribed antibiotics to three-quarters of patients, but felt antibiotics to be definitely indicated in less than one-third of these cases and not needed in one-fifth. Univariate analysis revealed that antibiotics were prescribed more frequently by older GPs for older patients in the presence of underlying disease, discoloured sputum, shortness of breath, wheeze, fever, signs on chest examination, and 'other factors'. Multivariate logistic regression confirmed an independent effect for all these findings except for the presence of underlying disease, shortness of breath and wheeze. 'Other factors' included patient 'pressure' and social factors, and GP work pressure or prior experience with the patient. These factors were an important influence on prescribing, especially if the GP felt an antibiotic was not indicated. Amoxycillin was the first choice (58% of total) except where the patient had recently received antibiotics for the same illness. Broader spectrum antibiotics were used more commonly in patients with chronic lung disease, discoloured sputum, chest signs on examination and where the GP felt antibiotics were indicated. However, these antibiotics were also prescribed to 14% of previously well patients. General practitioners used a wide variety of terms to describe the illness with little consistency or structure. The decision concerning the use and choice of antibiotics and the confidence with which the GP makes that decision is a complex interaction between patient, doctor and disease, being affected not only by clinical features but also by the social and psychological elements of the presenting problem. Such issues need to be appreciated by hospital specialists when called on to advise on developing relevant guidelines for primary care.

Acute Disease↗

Initiation rate and duration of breast-feeding in the Melbourne aboriginal community.

Breast-feeding is important for child health and helps to protect the child against infections. The objective of this study was to determine baseline breast-feeding rates in the Melbourne Aboriginal community prior to a breast-feeding promotion project. A brief questionnaire was administered to 116 mothers of infants up to two years of age with a Melbourne metropolitan address. During their pregnancies, 99 (85.3 per cent) of the women had planned to breast-feed, and 98 (84.5 per cent, 95 per cent confidence interval (CI) 77.9 to 91.1 per cent) initiated breast-feeding. However, 10 (8.6 per cent) stopped within the first week, and seven (6 per cent) more stopped within the first four weeks. Only 50 per cent of the babies (CI 40.9 to 59.1 per cent) were still being breast-fed at three months of age and 32 per cent were still being breast-fed at six months of age (CI 23.5 to 40.5 per cent). Younger mothers were less likely to choose to breast-feed (73 per cent) than women 20 years and over (87 per cent) and were also more likely to stop breast-feeding within three months. A total of 45 (51.1 per cent) of the babies received food other than breast milk or formula earlier than the recommended minimum age of four months. These results are similar to those for the general Victorian population. They show that while most Aboriginal women choose to breast-feed, many cease breast-feeding before they had intended.

Adult↗

Influences on infant-feeding beliefs and practices in an urban aboriginal community.

The Victorian Aboriginal Health Service initiated a project to increase breast-feeding rates in the Melbourne Aboriginal community. The results of focus-group discussions on infant-feeding experiences and beliefs provided a wealth of information for the design of appropriate interventions. Most women wanted and expected to breast-feed. Some chose artificial feeding because of embarrassment, a belief that it is as good as breast-feeding, or perceptions that breast-feeding is painful and inconvenient. The most common reasons that women stopped breast-feeding were sore nipples, worries about their supply of milk and tiredness. Lack of knowledge, hospital practices, lack of support and appropriate advice, and lack of confidence and self-esteem contributed to these problems. Disruption of the passing on of knowledge of healthy infant-feeding practices between generations is another cultural loss suffered by Aboriginal communities. Efforts to restore traditional rates of breast-feeding need to be under Aboriginal control and to take account of these influences.

Adolescent↗

Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1.

The 2.6 Angstrom crystal structure for human cyclin-dependent kinase 2(CDK2) in complex with CksHs1, a human homolog of essential yeast cell cycle-regulatory proteins suc1 and Cks1, reveals that CksHs1 binds via all four beta strands to the kinase C-terminal lobe. This interface is biologically critical, based upon mutational analysis, but far from the CDK2 N-terminal lobe, cyclin, and regulatory phosphorylation sites. CDK2 binds the Cks single domain conformation and interacts with conserved hydrophobic residues plus His-60 and Glu-63 in their closed beta-hinge motif conformation. The beta hinge opening to form the Cks beta-interchanged dimer sterically precludes CDK2 binding, providing a possible mechanism regulating CDK2-Cks interactions. One face of the complex exposes the sequence-conserved phosphate-binding region on Cks and the ATP-binding site on CDK2, suggesting that CKs may target CDK2 to other phosphoproteins during the cell cycle.

Base Sequence↗

SF-20 score and item distributions in a human immunodeficiency virus-seropositive sample.

The question of whether the full range of possible health states is measured by the Medical Outcomes Study (MOS) 20-Item Short-Form Health Survey (SF-20) in human immunodeficiency virus (HIV)-seropositive individuals is examined in this article. Ninety-five HIV-seropositive men (37 with asymptomatic infection, 58 with symptomatic infection) from two primary care practices were enrolled. Patients completed the SF-20 evaluating six dimensions of health status. Asymptomatic patients reveal substantial skew in score distributions for the dimensions of physical (-1.60), role (-1.19), and social (-1.13) functioning; no substantial skew is exhibited by symptomatic patients. Both subgroups reveal ceiling effects for physical, role, and social functioning, and pain dimensions; asymptomatic patients' ceiling effects are higher (physical functioning: 65% versus 31%; role functioning: 73% versus 41%; social functioning: 54% versus 43%; and pain: 41% versus 24%). Patients from both subgroups reveal floor effects for the role functioning dimension (asymptomatic patients, 22%; symptomatic patients, 34%). When looking at items rather than scales, asymptomatic patients' item distributions for the physical, role, and social functioning, and pain dimensions reveal clustering toward positive health states in most items; distributions of symptomatic patients are similar. Because this HIV-seropositive sample exhibits substantial ceiling effects in four of six SF-20 dimensions, effects that particularly are notable for asymptomatic patients, these dimensions should be revised for use in HIV-seropositive individuals or a disease-specific quality of life instrument should be constructed.

Activities of Daily Living↗

Employee injuries and convenience store robberies in selected metropolitan areas.

The number of robberies and robbery-related injuries to employees in convenience stores (C-stores) during 1992 or 1993 were estimated for selected metropolitan areas around Miami and Tampa, Florida; Atlanta, Georgia; Chicago, Illinois; Baltimore, Maryland; Boston, Massachusetts; Detroit, Michigan; Pittsburgh and Philadelphia, Pennsylvania; Charleston, Columbia, Greenville, and Spartanburg, South Carolina; and Arlington, Chesterfield, and Henrico counties, Virginia. Of the 1835 C-store robberies that occurred during 1992 or 1993 in all selected areas (excluding Atlanta and Chicago), there were 12 homicides of C-store employees; 219 nonfatal injuries of C-store employees; 1071 robberies in which there were no injuries but a weapon was used, displayed, or implied toward a C-store employee; and 132 robberies in which there was no injury and no weapon used, but an employee was struck, pushed, or shoved. Corresponding figures for the 238 robberies that occurred in Chicago during January to June 1993, and for which victim employment status was unknown (customer or employee) were three homicides, 53 nonfatal injuries, 120 attacks in which a weapon was used but there was no injury, and 57 attacks in which a person was struck, pushed, or shoved but there was no injury. The proportion of robberies that resulted in a homicide or injury to an employee varied among selected areas from .03 to .25. The proportion of homicides and injuries to an employee was. 14 or higher for target areas in Baltimore (.24), Detroit (.25), and Virginia (.14); the proportion to an employee or customer was .24 in Chicago. The conclusions from these data are that the risk of employee injury in C-store robberies was high in selected metropolitan areas. This underscores the need for effective robbery prevention programs to reduce injury. In addition, further research is needed to determine the effectiveness of prevention programs in the C-store industry and the application of these programs to other retail industries.

Commerce↗

Ambulatory elderly patients of primary care physicians: functional, psychosocial and environmental predictors of need for social work care management.

With increasing numbers of elderly people, and the escalating costs of health care, screening becomes increasingly important for identifying those older people with social health care needs who appear in their primary care physicians' offices. Many people are not aware of available social services. Families with serious social problems are not finding the help they need. The aim of this study was to develop and refine a questionnaire as a screening tool to identify elderly outpatients in primary care settings who are at high risk for psychological, social or environmental needs. This study identified those ten factors at each site which were most indicative that further intervention was needed. There were consistencies among the coordinators across sites in terms of what factors triggered intervention. Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs) were more likely to be predictive of the coordinator's intervention than were other factors.

Activities of Daily Living↗

Relationship between psychiatric disease and neuropsychological impairment in HIV seropositive individuals.

Neuropsychological impairment and DSM-III-R Axis I psychiatric diagnoses were evaluated in a heterogenous group of HIV seropositive individuals and seronegative individuals with similar risk factors for HIV infection. Neuropsychological and psychiatric disorders were common in the HIV seropositive group, but there were no relationships between these two aspects of neuropsychiatric dysfunction in seropositive patients. Results indicate that psychiatric disorders in HIV seropositive individuals tend to predate infection and decrease over time following knowledge of seroconversion, suggesting that they are primarily a function of psychosocial factors. Neuropsychological disorders are specific to HIV seropositive patients and tend to increase over time following seroconversion, suggesting that they are due to neurological effects of HIV-infection.

AIDS Dementia Complex↗

Preliminary results from the third flight of the Millimeter Anisotropy Experiment (MAX).

Preliminary results from the June 1991 flight of MAX are presented. Simultaneous observations were made in bands centered at 6, 9, and 12 cm-1 with a bolometric receiver operating at 300 mK. The experimental sensitivities are the highest reported at angular scales of 0.3 degrees to 1.0 degrees. Interstellar dust is observed to have an emissivity [symbol, see text] nu 1.4+/-0.3 and to correlate with the Infrared Astronomical Satellite (IRAS) 100- map. After removal of emission from interstellar dust, 1.3 hr of integration on a 6 degrees scan yields an upper limit of temperature difference Delta T/T < 2.6 x 10(-5) at a Gaussian autocorrelation function centered at 0.5 degrees. The experiment and data analysis are described.

Journal Article↗

Documentation of neurotoxicity resulting from high-dose cytosine arabinoside.

High-dose cytosine arabinoside or ARA-C (HDAC) has been shown to be an effective regimen in patients who are refractory to conventional doses. Neurotoxicity, a side effect associated with HDAC, has been reported in 7%-28% of patients. Both cerebellar and cerebral dysfunction have been reported. Neurotoxicity cannot be completely prevented, but a nurse's early detection of subtle changes can decrease toxicity severity. Assessment includes evaluating the patient's level of consciousness, speech patterns, vision, ocular movements, and coordination of upper and lower extremities. Early detection and intervention can lead to improved patient outcomes and enhanced quality of life. A neurotoxicity assessment tool and implications for its use are presented.

Brain Diseases↗