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Biomedical subjects

A J Wright

Publications and source records attributed to A J Wright.

At least 37 records · Page 2Linked to original sources
PubMed2000

Meningoencephalitis due to Blastomyces dermatitidis: case report and literature review.

Infection of the central nervous system by Blastomyces dermatitidis is a rare cause of meningoencephalitis. The existence of exclusive clinical infection of the meninges in the absence of pulmonary or other foci of infection has been debated. We describe a 20-year-old man presenting with meningoencephalitis caused by B dermatitidis. Blastomycotic infection was confirmed by isolation of the organism from brain tissue obtained at biopsy. Magnetic resonance imaging demonstrated progressive enhancement of basal meninges with involvement of bilateral basal ganglia and thalami. Treatment with amphotericin B arrested further neurologic decline. However, clinical and radiographic follow-up suggested damage to diencephalic structures. The diagnosis of blastomycotic meningoencephalitis is difficult to establish because no sensitive serologic test exists, and attempts to isolate the organism in cerebrospinal fluid obtained by lumbar puncture generally fail. A biopsy specimen of brain tissue is frequently necessary for the diagnosis. Survival is possible with timely initiation of therapy.

Adult↗
PubMed2000

Erythrocyte folate analysis: saponin added during lysis of whole blood can increase apparent folate concentrations, depending on hemolysate pH.

BACKGROUND: The analysis of red cell folate (RCF) depends on complete hemolysis of erythrocytes, and it is assumed that complete hemolysis is achieved by 10-fold dilution of whole blood with hypotonic solutions of 10 g/L ascorbic acid/ascorbate. This report challenges this assumption. METHODS: The conventional method of erythrocyte lysis was modified to include saponin, a known effective hemolyzing agent. The influence of saponin was determined at various lysate pHs, using the microbiological (Lactobacillus rhamnosus) folate assay. The effect of saponin during lysate preparation was subsequently compared with either the effect of 30 s of sonication or a single 1-h freeze-thaw cycle. RESULTS: Saponin addition was found to increase assayable RCF up to ninefold, depending on lysate pH. Sonication of lysates had no effect, and freezing-thawing lysates once did not always guarantee complete hemolysis. Lysates created with 10 g/L ascorbic acid (a historically widely used diluent) without pH adjustment produced assayable folate concentrations significantly lower than optimal. CONCLUSIONS: A lysing agent should be incorporated into RCF assays to guarantee complete hemolysis. Ten-fold dilution of blood with 10 g/L ascorbic acid, without pH adjustment, produces lysates with pHs (pH 4.0) below the point (pH 4.7) at which hemoglobin can denature irreversibly. The optimum pH for hemolysates is approximately 5.0.

Blood Chemical Analysis↗
PubMed1999

TC-83 vaccine protects against airborne or subcutaneous challenge with heterologous mouse-virulent strains of Venezuelan equine encephalitis virus.

Vaccination with TC-83 virus produced solid protection against subcutaneous challenge with Venezuelan equine encephalitis (VEEV) viruses from homologous and heterologous serogroups, but breakthrough infection and disease occurred after airborne challenge. Breakthrough occurred more often with time after vaccination, and was more frequent with epizootic, homologous serogroup 1A/B viruses than with enzootic, heterologous serogroup viruses. A decrease in VEEV-specific IgA levels in the respiratory tract of vaccinated mice may explain the increased frequency of breakthrough with time after vaccination. However increased breakthrough with the highly virulent homologous serogroup 1A/B viruses (compared to less virulent viruses from heterologous serogroups) may be a consequence of their greater ability to invade the brain via the olfactory neuroepithelium and olfactory nerve.

Animals↗
PubMed1999

A case of Fournier gangrene complicating idiopathic nephrotic syndrome of childhood.

A 10-year-old boy presenting with steroid resistant nephrotic syndrome developed Fournier gangrene of the scrotum. Antimicrobial drug therapy, intravenous albumin, excision of necrotic scrotum and left orchidectomy followed by skin grafting 3 weeks later led to an excellent cosmetic and medical result. Six months later he remains nephrotic on diuretic and angiotensin converting enzyme inhibitor medication.

Amoxicillin↗
PubMed1999

Beta-carotene and lycopene, but not lutein, supplementation changes the plasma fatty acid profile of healthy male non-smokers.

Polyunsaturated fatty acids (PUFAs) are highly susceptible to free radical attack. In vitro studies of carotenoids--including beta-carotene, lycopene, and lutein--have shown them to be effective quenchers of singlet oxygen, to have good radical-trapping properties, or to be effective peroxyl radical scavengers (or to have a combination of these qualities). If carotenoids act as antioxidants in vivo, then arguably, plasma PUFA should be conserved. The objective of the current study was to answer the question "Does supplementation with beta-carotene, lycopene, or lutein, at dietarily achievable levels, over a time period known to significantly increase circulating carote concentrations, lead to an observable increase in fasting plasma PUFA?" The normal diets of human volunteers were supplemented with either 15 mg/day beta-carotene (n = 25), lycopene (n = 23), or lutein (n = 21) for 26 days in three independent double-blind, placebo-controlled supplementation studies. Supplementation with beta-carotene increased plasma linoleic acid but left the polyunsaturated:saturated (P:S) fatty acid ratio unaltered. In contrast, supplementation with lycopene reduced linoleic acid, which resulted in a large decrease in the P:S ratio. Lutein supplementation had no effect. It was concluded that neither beta-carotene, lycopene, nor lutein supplementation engender antioxidant effects that lead to the widespread general conservation of plasma PUFAs. Beta-carotene and lycopene supplementation appear to interact with the metabolism of linoleic acid, the "essential" fatty acid, resulting in either an increase (beta-carotene) or decrease (lycopene) in its plasma concentration. Alterations in plasma 18:2 or P:S ratios could ultimately lead to changes in tissue cellular membrane composition and hence to alterations in membrane fluidity and cell-surface protein expression.

Adolescent↗
PubMed1999

High performance liquid chromatography method for the determination of pyridoxal-5-phosphate in human plasma: how appropriate are cut-off values for vitamin B6 deficiency?

OBJECTIVES: Application of a HPLC (high performance liquid chromatography) method, using cyanide derivatisation, to the determination of plasma pyridoxal-5-phosphate (PLP) concentrations as an indicator of vitamin B6 adequacy. SETTING: The study was performed at the Institute of Food Research, Norwich, UK. Blood samples were taken at the Institute, at Health Centres, or in the volunteer's home. SUBJECTS: 51 adolescent, 131 adult, 68 non-institutionalized elderly and 44 aged (>73 y) volunteers were recruited from local authority schools, local Health Centres and General Practitioners. RESULTS: The mean PLP recovery was 92.8%. The intra- and inter-assay coefficients of variation were 2.8% and 5.2% respectively. Mean PLP concentrations for males and females, respectively, were: adolescents (13-14 y), 36.4 and 43.5 nM; adults (20-64 y), 39.2 and 40.0 nM; elderly (68-73 y), 34.8 and 35.3 nM; aged (>73 y), 57.8 and 49.0 nM. Percentages of subjects with PLP concentrations <34.4 nM were over 26% in all population groups. Mean vitamin B6 intakes (microg/g protein intake), as assessed by weighed dietary records, were all above reference nutrient intakes (15 microg/g protein). CONCLUSIONS: An HPLC method, using cyanide derivitisation, has been applied to the determination of plasma PLP. Comparisons of results for local population groups with current cut-off values for plasma PLP, show large numbers of volunteers at risk of vitamin B6 deficiency although this is not reflected by vitamin B6 intakes calculated from food tables. The 34.4 nM cut-off value for value for plasma PLP, indicating deficiency, is questioned.

Adolescent↗
PubMed1999

Life-threatening tamoxifen-induced hypercalcaemia.

This case report serves to emphasize two important features of metastatic breast carcinoma. First, that tamoxifen-induced flare, although a rare and self-limiting phenomenon, may be fatal and must thus be recognized and treated promptly. Secondly, those patients presenting with hypercalcaemia, as part of tamoxifen-induced tumour flare, invariably have metastatic disease but they may enjoy a durable prognosis if this is confined to the skeleton.

Aged↗
PubMed1999

Antiretrovirals.

Deaths related to the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome and the incidence of opportunistic infections have been drastically decreased in the industrialized world. These reductions are mainly due to recent advances in the management of HIV infection, including the availability of new therapies. Until November 1995, the antiretroviral drugs available and approved by the Food and Drug Administration for clinical use in the United States consisted of only four nucleoside analogue reverse transcriptase inhibitors: zidovudine, zalcitabine, didanosine, and stavudine. Since then, 2 new classes of agents and 10 new agents have been approved; thus, the number of available antiretroviral drugs has more than tripled. Additional drugs and newer classes of antiretrovirals are in various stages of development. Because of the availability of more drugs, the complexity of HIV treatment has increased. Selecting an appropriate antiretroviral therapeutic regimen involves addressing multiple interdependent issues, including patient adherence, pharmacokinetic properties of the drugs (including food effects and drug-drug interactions), drug resistance, and overlapping adverse effects.

Adolescent↗
PubMed1999

The penicillins.

The penicillin family of antibiotics remains an important part of our antimicrobial armamentarium. In general, these agents have bactericidal activity, excellent distribution throughout the body, low toxicity, and efficacy against infections caused by susceptible bacteria. The initial introduction of aqueous penicillin G for treatment of streptococcal and staphylococcal infections was an important pharmacologic landmark. The emergence of penicillinase-producing Staphylococcus aureus prompted the development of the penicillinase-resistant penicillins (for example, methicillin, oxacillin, and nafcillin), in which an acyl side chain prevented disruption of the beta-lactamase ring. Subsequently, the aminopenicillins (ampicillin, amoxicillin, and bacampicillin) were developed because of the need for gram-negative antimicrobial activity. Their spectrum initially included Escherichia coli, Proteus mirabilis, Shigella, Salmonella, Listeria, Haemophilus, and Neisseria. The search for a penicillin with additional antimicrobial activity against the Enterobacteriaceae and Pseudomonas aeruginosa led to the development of the carboxypenicillins (carbenicillin and ticarcillin) and the ureidopenicillins (mezlocillin, azlocillin, and piperacillin). Finally, the combination of a beta-lactamase inhibitor (clavulanic acid, sulbactam, or tazobactam) and an aminopenicillin, ticarcillin, or piperacillin has further extended their antibacterial spectra by inhibiting certain beta-lactamases (non-group 1) of resistant bacteria. The development of an ideal penicillin that is rapidly bactericidal, nonsensitizing, nontoxic, bioavailable, and resistant to beta-lactamases and that has a high affinity for penicillin-binding proteins remains the goal.

Humans↗
PubMed1998

Humane endpoints are an objective measure of morbidity in Venezuelan encephalomyelitis virus infection of mice.

The clinical signs are described of Venezuelan encephalomyelitis virus (VEEV) infection in mice after both airborne and subcutaneous (s.c.) challenge. Group clinical scores reflected the known pathogenesis of infection by both s.c. and airborne challenge, and with epizootic and enzootic strains of VEEV. This observation confirms the specific relationship of the observed clinical signs to VEEV infection. Within an experiment, those who are assessing the animals for clinical signs must have a common understanding of their appearance, including severity, and should be unaware of the allocation of treatments. If these conditions are met, the progress of clinical signs may be used to determine objectively the time of culling for humane endpoints.

Animals↗
PubMed1998

General principles of antimicrobial therapy.

Antimicrobial agents are appropriate treatment for acute, severe, persistent, or progressive infectious diseases. The efficacy of treatment depends on the accuracy of the diagnosis of infection and the appropriateness of the antimicrobial agent for the causative microorganism. In this symposium, the antimicrobial agents reviewed correspond with the bacterial, fungal, viral, mycobacterial, parasitic, chlamydial, and other microorganisms that cause disease in humans. Usually, the etiologic possibilities can be limited on the basis of the history and physical examination, laboratory tests, or results of treatment trials. Many of the same findings, however, can result from noninfectious, other inflammatory, or unknown mechanisms. Manifestations such as fever and organ dysfunction are nonspecific and often not caused by an infectious process. Even when infection is clinically apparent, the causative microorganism may not be identified, and empiric treatment with broad-spectrum agents is appropriate in many cases of serious disease.

Ambulatory Care↗
PubMed1998

Erythrocyte folate analysis: a cause for concern?

Neural tube defects can be prevented by adequate intake of periconceptional folate, and inverse associations between folate status and cardiovascular disease and various cancers have been noted. Thus, there is renewed interest in the analysis of red cell folate (RCF) as an indicator of folate deficiency risk. Assessment of the assumptions that underpin RCF assays indicates that many are false. Published literature suggests that increased deoxy-hemoglobin (which can bind RCF electrostatically) yields more assayable folate, and increased oxy-hemoglobin (which cannot bind RCF) yields less assayable folate. It is argued that as deoxy-hemoglobin picks up oxygen and switches quaternary structure, any bound folate must, on purely theoretical grounds, become physically "trapped". Venous blood taken for analysis is 65% to 75% saturated with oxygen, and pro-rata "trapping" will lead to serious underestimation of RCF. Hence, doubt is cast over the validity of all previous RCF values. Some strategies for accurately assessing RCF are suggested.

Erythrocytes↗