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Biomedical subjects

G McDonald

Publications and source records attributed to G McDonald.

At least 37 records · Page 2Linked to original sources

The prevalence of learning disability in a Health and Social Services Board in Northern Ireland.

The Southern Health and Social Services Board is one of four in the province and encompasses three administrative areas. The survey included ascertained mild cases of learning disability, and both ascertained and unascertained individuals functioning at levels below IQ 50. The prevalence of mild learning disability is within the limits reported in the literature and is discussed in the context of the 'new morbidity'. However, the rates of severe learning disability (IQ < 50) in all three areas are high--between 7.9 and 10.2 per 1000 in the 15-19-years-old age group--and confirm the findings of an earlier survey. Half of all cases live at home in 'intact' families. In families with a sole carer, the mother is seven times more likely to fill the role than the father.

Adolescent↗

Apoptosis of gamma/delta T cells in human ehrlichiosis.

Expansion of activated T cells expressing the T-cell receptor (TCR) gamma/delta, CD45RO, and HLA-DR antigens is a prominent feature of acute infection with Ehrlichia chaffeensis in humans. The fate of these activated cells and the resolution of the gamma/delta T-cell response with return to the usual alpha/beta T-cell populations in this disease are not clearly understood. At a morphologic level, apoptotic cells are present in the peripheral blood during the acute and resolution phases of the infection. Simple culture of density gradient-separated lymphocytes from the blood of patients with acute ehrlichiosis produced cell death rapidly in the media compared to alpha/beta T cells. This loss of viability after incubation was apparently mediated by apoptosis, based on flow cytometric and morphologic analyses. The results suggest that most primed (CD45RO+) and activated (HLA-DR+) gamma/delta T cells in acute ehrlichiosis might be subject to removal from the body by programmed or apoptotic cell death.

Apoptosis↗

Central nervous system manifestations of human ehrlichiosis.

Since 1989, we have confirmed the diagnosis of human ehrlichiosis in 57 patients. Although routine radiological studies of the central nervous system (CNS) or analyses of cerebrospinal fluid (CSF) samples were not done for these patients, primary care physicians detected symptoms or signs that prompted them to perform such studies. CSF samples were examined for 15 of the 57 patients. Findings in eight of the 15 CSF samples were abnormal, and the most common abnormalities were lymphocytic pleocytosis and elevated protein levels. A search of the English-language literature revealed 21 additional cases in which CSF examinations were performed; in 13 of these cases, CSF findings were abnormal. The most common clinical finding that predicted CSF abnormalities was a change in mental status. A total of 14 patients underwent computerized tomographic studies, and none of these studies showed abnormalities. Four (19%) of the 21 patients with CNS manifestations of ehrlichiosis and abnormal CSF findings died.

Adult↗

Heat-related deaths in Philadelphia--1993.

A study of heat-related deaths associated with the 1993 heat wave in Philadelphia, Pennsylvania, was conducted. Most of these deaths were in the susceptible elderly with preexisting natural diseases who lived alone without air conditioning in upstairs bedrooms with windows shut, thus creating an even hotter environment. These excessive deaths under such conditions did not meet the standard clinical criteria for hyperthermia because of varying postmortem intervals. Therefore, the authors stress the utility of a postmortem definition of heat-related death to better define the magnitude of health risk posed by hot weather and warn public health and other agencies to take preventative measures.

Adult↗

Prevalence of allergic bronchopulmonary aspergillosis and atopy in adult patients with cystic fibrosis.

BACKGROUND: Underestimation of allergic bronchopulmonary aspergillosis (ABPA) prevalence in the cystic fibrosis (CF) population is suspected due to nonuniform diagnostic criteria, nonspecific signs and symptoms, assessment during asymptomatic intervals, and physician nonaggressiveness in making the diagnosis. OBJECTIVE: To define the prevalence of ABPA in adult patients with CF, as the increased duration of bronchiectasis may increase the probability of Aspergillus fumigatus (Af) colonization. We also sought to determine whether atopy increases the prevalence of ABPA in adults with CF. METHODS: We examined a cross-sectional population of adult patients with CF at the University of Washington for 1 year. RESULTS: Information was collected on 53 of 65 (82%) patients. Fifteen of 51 (29%) had an immediate skin test reaction to Af, and 30 of 51 (59%) had at least one positive skin test. Increased total serum IgE (>450 IU/mL) was present in 0 of 53; increased IgE-Af and IgG-Af were found in 12 of 53 (23%) and 9 of 53 (17%), respectively; 24 of 53 (45%) had Af-precipitins. Peripheral blood eosinophilia was present in one patient. Eight of 49 (16%) patients' sputum cultures grew Af. ABPA-CB (ABPA-central bronchiectasis) was present in one patient and ABPA-S (ABPA-seropositive) in no patients. Atopy was present in 20 of 51 (39%). CONCLUSION: There was a low prevalence of ABPA in the adult CF population despite frequent immunologic responses to Af. The prevalence of ABPA was too small to determine an association with atopy.

Adult↗

Investigation of the prebiotic synthesis of amino acids and RNA bases from CO2 using FeS/H2S as a reducing agent.

An autotrophic theory of the origin of metabolism and life has been proposed in which carbon dioxide is reduced by ferrous sulfide and hydrogen sulfide by means of a reversed citric acid cycle, leading to the production of amino acids. Similar processes have been proposed for purine synthesis. Ferrous sulfide is a strong reducing agent in the presence of hydrogen sulfide and can produce hydrogen as well as reduce alkenes, alkynes, and thiols to saturated hydrocarbons and reduce ketones to thiols. However, the reduction of carbon dioxide has not been demonstrated. We show here that no amino acids, purines, or pyrimidines are produced from carbon dioxide with the ferrous sulfide and hydrogen sulfide system. Furthermore, this system does not produce amino acids from carboxylic acids by reductive amination and carboxylation. Thus, the proposed autotrophic theory, using carbon dioxide, ferrous sulfide, and hydrogen sulfide, lacks the robustness needed to be a geological process and is, therefore, unlikely to have played a role in the origin of metabolism or the origin of life.

Amino Acids↗

Lymphocytosis of gamma/delta T cells in human ehrlichiosis.

The majority of T cells in peripheral blood express a T-cell receptor (TCR) comprised of alpha and beta chains. An alternate form of the TCR is comprised of gamma and delta chains. These gamma/delta T cells are associated with certain infectious lesions, and modestly elevated in peripheral blood in certain disease states. Human ehrlichiosis is characterized by hematologic abnormalities including multi-lineage cytopenias. In most cases reported, a lymphocytopenia has been present either at diagnosis, or at some time during the illness. Early in the course of antibiotic treatment (48-72 hours), the lymphocytopenia corrects itself and is rapidly followed by a lymphocytosis of T cells that express CD3, but are negative for CD4 and CD8, as well as the major form of the TCR formed by the alpha/beta heterodimer. Instead, these CD3+4-8- T cells express the gamma/delta heterodimer associated with V gamma 9 and V delta 2 chains, a population of cells usually the distinctive minority of peripheral blood T cells, but constituting the major phenotype of peripheral gamma/delta T cells.

Ehrlichiosis↗

Ehrlichiosis--a cause of prolonged fever.

Human ehrlichiosis is a recently described illness that is thought to be tick-borne. Most recognized cases of human ehrlichiosis manifest as an acute nonspecific febrile illness. The natural history of untreated symptomatic disease is largely unknown. Over a 4-year period, we identified 41 cases of human ehrlichiosis by serological testing, polymerase chain reaction analysis, or both methods. The principal finding for six of the patients was protracted fever. The duration of their fevers ranged from 17 to 51 days. At the time of presentation, all six patients had clinical features, laboratory features, or both consistent with a diagnosis of ehrlichiosis. Polymerase chain reaction analysis helped to rapidly confirm the diagnosis for four of five patients tested. The diagnosis of human ehrlichiosis should be considered for patients with prolonged fever who live in an area of endemicity.

Adult↗

Human ehrlichiosis in adults after tick exposure. Diagnosis using polymerase chain reaction.

OBJECTIVE: To identify and prospectively follow patients with suspected human ehrlichiosis regarding clinical manifestations, laboratory variables, methods for confirming the diagnosis, and complications. DESIGN: Prospective case study. SETTING: University and Veterans Affairs hospital and clinics. PATIENTS: Observations in 30 adult patients with acute febrile illness or with unexplained fevers and cytopenias or abnormal liver profiles or both. MEASUREMENTS: Serial clinical examinations, hematologic profiles, liver profiles, electrolyte determinations, chest radiographs, and response to therapy; other studies appropriate for patient care. INTERVENTION: Therapy with doxycycline. RESULTS: Thirty cases of ehrlichiosis were identified between 1989 and 1992. Tick exposure was strongly associated with the illness (P = 0.0001). Symptoms were nonspecific; fever, chills, and headache predominated but many other symptoms also occurred. Fever and skin rashes with various morphologic characteristics were the most common physical findings. Laboratory investigations indicate that the hematologic, hepatic, and central nervous systems are commonly involved in human ehrlichiosis. Twenty of 23 patients (87%) tested by the polymerase chain reaction using Ehrlichia chaffeensis sequences and whole blood samples were positive for E. chaffeensis. CONCLUSIONS: The syndrome of human ehrlichiosis is not commonly recognized by physicians. Ehrlichiosis should be considered in the differential diagnosis of patients with febrile illness after known or possible tick exposure, particularly if accompanying cytopenias or abnormal liver profiles or both are present. The therapeutic response to doxycycline is prompt, and complications are uncommon in promptly treated patients. The polymerase chain reaction applied to whole blood samples is a promising test for rapid confirmation of the diagnosis within 24 to 48 hours.

Adult↗

Selective serotonin reuptake inhibitors: meta-analysis of discontinuation rates.

A meta-analysis was carried out of 42 published randomized controlled studies comparing the selective serotonin reuptake inhibitors (SSRIs) with the tricyclic antidepressants (TCAs) that measured discontinuation rates for side effects and lack of efficacy by treatment group in order to compare the discontinuation rates for side effects and lack of efficacy. These discontinuation rates were pooled to produce the main outcome measure. Seven studies were placebo controlled and the discontinuation rates in these studies were also pooled in a separate analysis. Significantly fewer patients receiving SSRIs discontinued treatment because of side effects (14.9%) compared with those receiving TCAs (19%) (p < 0.01). There was also a significant difference in discontinuation rates due to side effects in the placebo- and TCA-controlled studies analysed separately, SSRIs (19%) compared with TCAs (27%) (p < 0.01). In both analyses a similar proportion of patients discontinued for lack of efficacy on SSRIs and TCAs. There is a significant and clinically important advantage for the SSRIs compared with the TCAs in the acceptability of treatment measured by the number of discontinuations due to side effects reported in published studies. The risk-benefit calculation favours the SSRIs since there were similar levels of efficacy but more discontinuations with the TCAs. The selection of an antidepressant for first-line treatment requires critical evaluation of the full risk-benefit equation.

Antidepressive Agents, Tricyclic↗

Reducing the economic burden of depression.

Depressive illness places an enormous economic burden on health services, the community and the individual patient. It is a serious medical disorder associated with high levels of social and physical disability. Antidepressant drug therapy can produce significant improvement in the majority of patients. However, despite its high prevalence depressive illness is frequently undetected, misdiagnosed or inappropriately treated. The selection of a cost-effective antidepressant requires a broad evaluation of the risks, costs and benefits. A choice should not be made on prescription drug costs alone but on the basis of the overall value a treatment option offers in the management of illness. Benefits, such as improved treatment compliance, reduced toxicity in overdose, long-term safety and efficacy in the prevention of relapse and recurrence of depression, improved patient quality of life and decreased accident liability all have cost implications which must be considered when determining the relative cost of medication.

Antidepressive Agents↗

Immunohistochemical identification of leucocyte populations in normal tissue and inflamed synovium of the rabbit.

A panel of monoclonal antibodies which recognizes well-defined markers of rabbit leucocytes has been used in an immunohistochemical survey of normal rabbit spleen, thymus, and liver, and of inflamed synovial tissue. The results demonstrate that these antibodies are well suited for the identification of leucocytes in frozen sections of rabbit tissues and that T lymphocytes, macrophages, and neutrophils can be readily distinguished. Antibodies to CD44 differentiate between medullary and cortical thymocytes, with the cortical cells being almost entirely negative for this marker. Antibodies to RLA class II show that periportal lymphocytes in the liver express RLA-DR but not RLA-DQ. The type A cells of the synovial lining from inflamed joint tissue are stained by antibodies that recognize macrophages in a manner similar to that found in the human synovial lining.

Animals↗

Factors determining the decision to institutionalize dementing individuals: a prospective study.

This longitudinal study of 196 caregiver/care receiver dyads was undertaken to determine the variables predictive of caregiver decision to institutionalize a dependent with dementia. Seven variables (use of services, enjoyment of caregiving, caregiver burden and health, caregiver rating and reaction to care receiver behavior and memory problems, and presence of troublesome behaviors) predicted the decision to institutionalize. Six variables (caregiver health and burden, use of services, care receiver cognitive function and troublesome behaviors, and caregiver reaction to behaviors) predicted actual institutionalization at 18 months.

Aged↗

Nontuberculous mycobacterial disease in adult cystic fibrosis patients.

This study was conducted to determine the prevalence of mycobacterial disease in an adult cystic fibrosis (CF) population and to determine if there were any patients at higher risk for this disease within the group. Sixty-four patients (28 women, 36 men), ranging in age from 17 to 50 years were screened. One-step purified protein derivative skin testing with controls was performed and sputum was taken for examination. Eight of 64 had positive sputum culture for nontuberculous Mycobacterium. The CF patients with positive mycobacterial sputum cultures tended to be older and to have lower clinical scores than those who did not have Mycobacterium organisms in sputum. Guidelines to determine whether mycobacterial disease or colonization is present should be pursued for the CF population.

Adolescent↗

Defective chemotaxis and calcium response in localized juvenile periodontitis neutrophils.

Localized juvenile periodontitis (ljp) is an early onset form of periodontal disease characterized by unique localization to first molars and incisors and a high prevalence of neutrophil abnormalities, particularly chemotaxis. The intracellular transduction mechanisms that follow receptor-ligand coupling on the neutrophil surface and lead to chemotaxis are not clearly established. Chemotaxis and phagocytosis are modulated by a variety of receptors and involve several activation pathways; the role of intracellular calcium as a presumptive second messenger and mediator of these events is well established. The putative effector mechanisms for the chemotactic receptor of neutrophils also include the possible activation of a phospholipase, protein kinase C, methyltransferase, or adenylate cyclase. In normal neutrophils, a phosphoinositide pathway initiated by phospholipase C, which results in the activation of protein kinase C via diacylglycerol and the generation of IP3, has been implicated. In order to better understand the stages of neutrophil transduction, fluorescent probes were used to monitor neutrophil calcium changes. Chlorotetracycline (CTC) was used as an indirect probe of intracellular membrane-bound pool of calcium stores, and Quin-2 was used to monitor cytosolic free calcium levels of FMLP stimulated normal and LJP neutrophils. The results indicate that the early phase of the calcium response affiliated with the release of intracellularly sequestered calcium appears intact in LJP neutrophils, as the CTC fluorescence changes were similar to control values. The second phase of the calcium response, associated with membrane channel activation and an influx of extracellular calcium, appeared compromised in the neutrophils of the LJP population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗