Poor world health and rich world wealth.
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Anti-HIV Agents↗
Biomedical subjects
D Taylor
Publications and source records attributed to D Taylor.
Low pressure cardiac tamponade.
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Adenocarcinoma↗
Tracking the response of Xid B cells in vivo: TI-2 antigen induces migration and proliferation but Btk is essential for terminal differentiation.
X-linked immunodeficient (Xid) mice carry a Bruton's tyrosine kinase (Btk) mutation and exhibit a selective failure to produce antibodies against bacterial capsular polysaccharides. Studies in vitro point to a fundamental survival defect of Xid B cells after receptor cross-linking by thymus-independent type-2 (TI-2) antigen because B cells undergo apoptosis without proliferating. We describe results from a novel model, which we have used to investigate the impact of the Xid mutation on migration, proliferation and differentiation of B cells after polysaccharide immunization in vivo. Immunoglobulin knock-in mice, in which a large proportion of B cells express transgene-encoded receptors specific for (4-hydroxy-3-nitrophenyl)-acetyl (NP), were crossed with CBA/N mice. The male progeny contain NP-specific Xid B cells, while the female progeny contain NP-specific B cells with normal Btk. After immunization with the TI-2 antigen NP-Ficoll, NP-specific Xid B cells migrate to the T zones and proliferate. Despite transient up-regulation of blimp-1 and survival beyond the time when terminal differentiation is normally underway, Btk-defective B cells fail to differentiate to plasmablasts or germinal center cells. CD40 ligation partially restores their ability to form plasma cells in response to TI-2 antigen.
Agammaglobulinaemia Tyrosine Kinase↗
The value of the chloride: sodium ratio in differentiating the aetiology of metabolic acidosis.
OBJECTIVE: Stewart's physicochemical approach to acid-base balance defines the aetiology of a metabolic acidosis by quantifying anions of tissue acids (TA), which consist of unmeasured anions (UMA) and/or lactate. We hypothesised that an increase in TA during metabolic acidosis would lead to a compensatory fall in the plasma chloride (Cl) relative to sodium (Cl:Na ratio) in order to preserve electro-neutrality. Thus, the Cl:Na ratio could be used as a simple alternative to the anion gap in identifying raised TA. PATIENTS: Two hundred and eighty two consecutive patients who were admitted to our Paediatric Intensive Care were enrolled in the study. INTERVENTIONS: We obtained 540 samples (admission n = 282, 24 h n = 258) for analysis of blood chemistry, lactate and quantification of TA and UMA. Samples were subgrouped into those with metabolic acidosis (standard bicarbonate < 22 mmol/l) either with or without increased UMA (> 3 mEq/l). MEASUREMENTS AND RESULTS: Metabolic acidosis occurred in 46% of samples, of which 52.3% (120/230) had increased UMA. The dominant component of TA was UMA rather than lactate, and these two components did not always rise in tandem. Our hypothesis of relative hypochloraemia was supported by a lower Cl:Na ratio (P < 0.0001) but not a lower absolute Cl (P = 0.5) in the acidotic subgroup with raised UMA, and by the inverse relationship between TA and the Cl:Na ratio. (coefficient of determination (r2) = 0.37, P < 0.0001). The best discriminator for the presence of raised TA was the albumin-corrected anion gap (AGcorr), however, this could not track changes in TA with clinical accuracy. The Cl:Na ratio discriminated reasonably well, a ratio of < 0.75 identified TA (positive predictive value (PPV) 88%) with a likelihood ratio (LR) similar to the AG (7.8 vs7.4). Conversely, a high ratio (> 0.79) excluded TA (PPV 81%, LR 4.5). Base deficit (BD) and lactate performed poorly. CONCLUSION: In metabolic acidosis due to TA, plasma Cl concentration decreases relative to sodium. The Cl:Na ratio is a simple alternative to the AG for detecting TA in this setting.
Acidosis↗
Effects of procyclidine on prepulse inhibition of the acoustic startle response in healthy human volunteers.
RATIONALE: Prepulse inhibition (PPI) of the startle response refers to an attenuation in response to a strong stimulus (pulse) if this is preceded shortly by a weak non-startling stimulus (prepulse). Patients with schizophrenia have repeatedly been found to show reduced PPI when compared to healthy people. Anticholinergic drugs are often used to control extrapyramidal symptoms induced by antipsychotic medication in schizophrenic patients. Antipsychotic medication, in particular with atypical drugs, has been shown to improve a range of cognitive functions and normalize PPI deficits in schizophrenia, whereas anticholinergic drugs disrupt cognitive functions in both normal and schizophrenic populations and also impair PPI in experimental animals. No previous study has investigated the effects of anticholinergic drugs on human PPI. OBJECTIVES: This study determined the effects of procyclidine, an anticholinergic drug, on PPI in healthy male volunteers, employing a double-blind placebo-controlled cross-over design. METHODS: Subjects underwent testing for PPI on two occasions: once after the oral administration of a placebo and once after the oral administration of procyclidine in two separate experiments. Experiment 1 examined the effects of 10 mg procyclidine, whereas experiment 2 examined the effects of 15 mg procyclidine. RESULTS: Procyclidine at a 10 mg dose, as compared to placebo, had no effect on PPI, but caused impairments at a 15 mg dose. In both experiments, procyclidine reduced response amplitude over the pulse-alone trials and heart rate 1-2 h post-administration. CONCLUSIONS: PPI of the human acoustic startle response is modulated by procyclidine. The use of anticholinergics needs to be considered in PPI studies in schizophrenia.
Acoustic Stimulation↗
Randomized crossover trial comparing the eZ.on plastic condom and a latex condom.
This randomized crossover trial compared the breakage and slippage rates, safety, and acceptability of the recently developed polyurethane bi-directional eZ.on condom with a marketed latex condom. Three hundred sixty couples were asked to use 4 eZ.on condoms and 4 latex condoms. Like several other non-latex condoms tested to date, the eZ.on condom had a higher clinical breakage rate than its latex comparator, while the slippage rates were similar. The clinical breakage rate for the eZ.on condom was 5.6%, compared with 0.9% for the latex condom (difference = 4.76%, with upper 95% confidence bound on the difference = 6.26%). Thus, based on an a priori definition of a 2% clinically acceptable difference, the study failed to conclude equivalence relative to clinical breakage. The complete slippage rate for eZ.on was 1.6%; compared to 0.7% for latex (difference = 0.87%, with upper 95% confidence bound = 1.55%). Thus, based on an a priori definition of a 2% difference we concluded equivalence relative to complete slippage. The safety profile of the eZ.on condom was good and similar to the latex condom. The eZ.on was also found to be easier to don and remove than the latex condom. Although no overall preference existed for either condom, nearly 30%women and men strongly preferred the eZ.on condom to the latex condom. The eZ.on condom may be an acceptable alternative for couples unable or unwilling to use latex condoms.
Adult↗
Gulfwatch: monitoring spatial and temporal patterns of trace metal and organic contaminants in the Gulf of Maine (1991-1997) with the blue mussel, Mytilus edulis L.
Gulfwatch, established in 1991, is an international contaminant monitoring program in which the blue mussel, Mytilus edulis, is used as an indicator of the level and extent of contamination in the Gulf of Maine. Since 1991, trace metals, PAHs, PCBs, and OC pesticides have been measured in mussel tissues at 56 sites. The distribution of most metals was relatively uniform throughout the Gulf with the exception of Ag, Pb and Cr. However, the concentration of organic contaminants increased in a north-to-south direction. High concentrations of contaminants were correlated with large human population density and proximity to large rivers. Temporal analysis of five sites revealed that the majority of contaminant concentrations were either unchanged or decreasing. The concentrations of most contaminants were lower than the median of the National Status and Trends (NS & T) Mussel Watch with the exceptions of Cr, Hg, Pb and sigma PCB24. Hg concentrations at > 80% of the Gulfwatch sites exceeded the NS & T median +1 SD. Gulfwatch continues as a primary contaminant monitoring program in the Gulf of Maine.
Animals↗
The prediction of stress fractures using a 'stressed volume' concept.
This paper addresses an anomaly which exists in the current literature regarding stress fractures. Analysis of the data on fatigue strength of bone samples in vitro would conclude that these fractures should never occur at the strain levels known to occur in vivo. This anomaly can be resolved by including in the analysis the effect of stressed volume, whereby larger volumes of material are expected to have worse fatigue properties. A Weibull analysis was used to predict the probability of failure, Pf; this was an upper-bound prediction because it did not include the effects of remodelling and adaptation. Combining this analysis with a finite element model of the human tibia, we predicted a Pf value of 21% after five weeks of strenuous exercise, which is comparable with reported incidences in military personnel. The high incidence of stress fractures in the cannon bone of racehorses could also be predicted (Pf = 62%, compared to 70% experimentally). The approach can be used to investigate the effect of variables in the exercise regime such as the distance run per day and the use of improved footwear. It can also predict the increased risk of stress fractures in elderly people. The results suggest certain simple rules which may be of clinical value in designing exercise regimes and in understanding the risk factors for this type of injury.
Animals↗
Retrospective vs. prospective coital frequency and menstrual cycle length in a contraceptive effectiveness trial.
PURPOSE: To determine how well information at enrollment would predict coital frequency and menstrual segment length during a prospective contraceptive effectiveness trial. METHODS: We compared retrospective reports of monthly coital frequency and menstrual segment (cycle) length with prospective information for women participating in a contraceptive trial of the Reality((R)) female condom. RESULTS: Participants reported slightly higher mean monthly coital frequency and slightly longer menstrual segments prior to the study than during the study (12.6 acts vs. 12.0 acts per month and 30.8 days vs. 28.4 days). We examined the actual distribution of differences between the retrospective and prospective measures and found considerable variability. Among the 195 participants studied, parous women were less likely to predict accurately menstrual segment length (OR 0.4; 95% CI 0.3--0.9), while older women were more likely to predict accurately coital frequency (OR 1.9; 95% CI 0.9--3.3). CONCLUSIONS: Coital frequency and menstrual segment length vary considerably over time. Hence, prospective data collection is essential to accurately characterize these variations and to properly interpret results from contraceptive trials and other studies concerned with fecundability and hazards of reproduction.
Adult↗
Diagnosing children presenting with asymmetric pendular nystagmus.
Horizontal asymmetric nystagmus usually occurs in one of three situations: secondary to an intracranial lesion, with monocular visual loss, or as part of the triad that constitutes the diagnosis of spasmus nutans (asymmetric nystagmus, abnormal head posture, head shake). Clinical records of 277 children, presenting with congenital nystagmus over an 8-year period were reviewed. Nystagmus was asymmetric in 24 of 277 cases. Seven of these patients were diagnosed with spasmus nutans. This is a rare condition that is only diagnosed retrospectively based on the absence of any abnormal neuroimaging or electrophysiological findings. Twelve of 24 patients had intracranial pathology and all had abnormal visual evoked potentials (VEPs). Five patients were diagnosed with congenital sensory defect nystagmus including one with albinism, three with congenital cone dysfunction, and one with cone-rod dystrophy. This paper stresses that although neuroimaging is necessary in all patients presenting with asymmetric nystagmus, such nystagmus can also occur with retinal disease or albinism and indicates the importance of non-invasive VEP/ERG testing in all forms of nystagmus.
Albinism↗
Surveillance of antimicrobial resistance--what, how and whither?
OBJECTIVE: To express the views of a working party held to consider antibiotic resistance surveillance systems, their strengths and weaknesses, and their current and future applications. METHODS: The participants, all of whom were experienced in this field, discussed the development of surveillance systems in relation to the increasing prevalence of resistance to antibacterial agents and the current interest in surveillance systems shown by many official bodies, in both the human and veterinary fields. The problems inherent in surveillance systems were considered together with the applications of different systems. RESULTS: The properties of good antibiotic resistance surveillance systems were defined. Surveillance systems vary widely from those with a narrow base, focusing on few organisms in one disease area, to those covering many diseases, many organisms (including normal flora) and many compounds. Whatever their design, they should be able to detect significant differences and shifts in susceptibility to various antibacterial agents, and the information derived from them should reach as many interested parties as possible in a timely manner. In using this information to decide strategies, criteria for action need to be determined by pragmatic consensus. Funding remains a major problem, with few large studies being supported by official bodies in spite of their professed enthusiasm for surveillance. In consequence, many current systems are funded by the pharmaceutical industry and are of necessity restricted in their focus. CONCLUSIONS: Antibiotic resistance surveillance studies should and can be well planned and well executed. Many current systems suffer from well-recognized but uncorrected biases. Consortium funding will be necessary for large schemes to be successful. There is no "ideal" surveillance system.
Animals↗
Bowen's disease, solar keratoses and superficial basal cell carcinomas treated by photodynamic therapy using a large-field incoherent light source.
BACKGROUND: Photodynamic therapy (PDT) has not yet been demonstrated to be superior to conventional treatment in the treatment of superficial skin cancers and premalignant skin conditions. A limitation for PDT is the absence to date of a light source suitable for the treatment of larger lesions or 'field changes' where several lesions are present on one anatomical site. OBJECTIVES: To investigate the safety and efficacy of a large field light source, the Waldmann PDT 1200, in the treatment of Bowen's disease (BD), superficial basal cell carcinomas (BCCs) and solar keratoses (SKs). METHODS: After application of 5-aminolaevulinic acid for 4-6 h, each lesion was irradiated with 105 J cm-2 of incoherent red light centred on 640 nm. Eighty-eight patients with 239 lesions were recruited. RESULTS: Within two treatments, 88% of BD lesions, 95% of BCCs and 99% of SKs showed complete clinical clearance. At 12 months the complete response rates were 69% for BD, 82% for BCC and 72% for SK. CONCLUSIONS: This study confirms that PDT is a useful treatment and that selected superficial BCCs and SKs respond well to PDT. The PDT 1200 light source proved capable of treating multiple lesions amounting to a 'field change' and also lesions up to 10 cm in diameter within an acceptable treatment time. Thus far, PDT has failed to become established as a routine treatment for small premalignant and malignant skin lesions as it has not proved superior to simple cheaper conventional therapies such as cryotherapy, curettage and cautery, topical chemotherapy with 5-fluorouracil, or surgery. However, PDT has become established as a treatment for selected cases in some centres. This study suggests a role for PDT in the treatment of large premalignancies, superficial BCCs and field change where existing treatments may be problematic.
Adult↗
Advancing the science of symptom management.
UNLABELLED: Since the publication of the original Symptom Management Model (Larson et al. 1994), faculty and students at the University of California, San Francisco (UCSF) School of Nursing Centre for System Management have tested this model in research studies and expanded the model through collegial discussions and seminars. AIM: In this paper, we describe the evidence-based revised conceptual model, the three dimensions of the model, and the areas where further research is needed. BACKGROUND/RATIONALE: The experience of symptoms, minor to severe, prompts millions of patients to visit their healthcare providers each year. Symptoms not only create distress, but also disrupt social functioning. The management of symptoms and their resulting outcomes often become the responsibility of the patient and his or her family members. Healthcare providers have difficulty developing symptom management strategies that can be applied across acute and home-care settings because few models of symptom management have been tested empirically. To date, the majority of research on symptoms was directed toward studying a single symptom, such as pain or fatigue, or toward evaluating associated symptoms, such as depression and sleep disturbance. While this approach has advanced our understanding of some symptoms, we offer a generic symptom management model to provide direction for selecting clinical interventions, informing research, and bridging an array of symptoms associated with a variety of diseases and conditions. Finally, a broadly-based symptom management model allows the integration of science from other fields.
Holistic Nursing↗
Antiretroviral therapy for HIV-2 infected patients.
OBJECTIVES: To evaluate clinical and RNA load response to antiretroviral therapy amongst patients infected with HIV-2 and to study the development of drug resistance. METHODS: Seven HIV-2 seropositive patients were monitored with clinical examination, CD4 cell count and HIV-2 viral RNA load. Viruses from four subjects were genotyped and in vitro recovery of virus by co-cultivation with PBMCs and HVS T-cells was attempted. Viruses isolated from two subjects were assayed for phenotypic antiviral resistance. The main outcome measures were the relationship between disease stage, viral load, CD4 cell count, viral subtype and the clinical course of HIV-2 infection and the effect of combination antiretroviral therapy on disease progression, CD4 cell count, HIV-2 RNA viral load and drug resistance. RESULTS: The median time of follow-up was 3 years (range 0-8 years). Three patients had AIDS, and one had symptomatic disease. Of the four patients genotyped, three were infected with HIV-2 subtype B and one with subtype A. Viraemia was detectable only at CD4 counts of less than 300 x 10(6)/ml. Two patients with high viral loads failed to respond to antiretroviral therapy although their treatment may not have been optimal. One developed in vitro phenotypic antiviral resistance. The genotype of this patient's viral reverse transcriptase is being analysed. CONCLUSIONS: In contrast to HIV-1, HIV-2 RNA levels were often undetectable despite advanced disease and low CD4 cell counts. However, HIV-2 was clearly capable of causing CD4 cell depletion resulting in symptomatic disease. The principles of highly active antiretroviral therapy seem to apply to HIV-2 and suboptimal therapy may lead to drug resistance. The timing of therapy initiation, monitoring of response and the measurement of resistance remain unresolved issues and conclusions cannot be extrapolated from HIV-1.
Acquired Immunodeficiency Syndrome↗
A critical review of rural medical workforce retention in Australia.
The problem of how best to recruit and retain doctors in rural and remote communities has led governments to adopt a range of medical workforce incentives, including retention grants. A comprehensive literature survey suggests that medical workforce retention has been poorly distinguished from other supply issues such as recruitment, and that its determinants and the process leading to retention are poorly understood. Such a knowledge gap is likely to limit the effectiveness of retention incentives. This article reports the results of this literature review, and advances a conceptual framework as the basis for ongoing research and evaluating how best to deliver effective retention interventions.
Australia↗
Cryoglobulinaemic vasculitis caused by intravenous immunoglobulin treatment.
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Cryoglobulinemia↗
Atypical antipsychotics and hyperglycaemia.
Hyperglycaemia is known occasionally to occur with conventional neuroleptics, but has more recently been associated with atypical antipsychotics especially clozapine and olanzapine. This article examines more closely this association. A review of relevant published literature from 1970 to date was undertaken following Medline and Embase searches in June 2000. Hyperglycaemia with clozapine was widely reported: spontaneous reports of either hyperglycaemia or ketoacidosis were described in a total of 17 people. In a five-year naturalistic study, 30.5% of patients taking clozapine were eventually diagnosed with Type 2 diabetes. With olanzapine, a total of 10 cases of hyperglycaemia and 5 cases of ketoacidosis have been published. Reports of hyperglycaemia with other atypicals are relatively scarce. The association of hyperglycaemia or ketoacidosis with clozapine and olanzapine appears to be a true drug-induced effect. Risk factors may include male gender, age of around 40 years and being non-Caucasian. The management of hyperglycaemia depends on the causative agent. With clozapine, treatment with oral hypoglycaemics has been successful. With olanzapine, other atypical antipsychotics may be considered. Blood glucose monitoring is essential for all patients starting clozapine or olanzapine.
Adult↗