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Biomedical subjects

C Reed

Publications and source records attributed to C Reed.

At least 19 recordsLinked to original sources

Are aortic aneurysms caused by atherosclerosis?

BACKGROUND: The emerging controversy concerning the causal role of atherosclerosis in the development of aortic aneurysms was examined using the accumulated clinical and autopsy data obtained during a 20-year follow-up of a cohort of more than 8,000 men of Japanese ancestry in Hawaii. METHODS AND RESULTS: Analyses of 174 clinical incident events indicated that there were two types of aneurysmal disease, 151 aortic aneurysms and 23 aortic dissections. The baseline risk factors that predicted the clinical aortic aneurysms were the same factors that predicted aortic atherosclerosis in the same cohort, namely, high blood pressure, high serum cholesterol, and cigarette smoking. These same risk factors were also significantly associated with the occurrence of 27 aortic aneurysms among 293 autopsied men. The less common aortic dissections had an age-specific incidence pattern indicative of an innate susceptibility precipitated by an exposure to another factor. This pattern was consistent with the findings that the incidence of aortic dissections was predicted mainly by baseline high blood pressure. CONCLUSIONS: From the perspective of prevention, it appears that the risk factors for aortic atherosclerosis and probably atherosclerosis itself are necessary elements in the causal pathway for the great majority of aortic aneurysms in this cohort.

Age Factors

Dose tolerance study of fluticasone propionate aqueous nasal spray in patients with seasonal allergic rhinitis.

A multicenter, double-blind, parallel-group, dose-tolerance study was conducted to evaluate the safety of fluticasone propionate aqueous nasal spray, a potent new corticosteroid preparation. Ninety-seven adult patients with moderate to severe seasonal allergic rhinitis during the fall weed season received either placebo or fluticasone propionate in doses of 50, 200, or 800 micrograms twice daily for 4 weeks. Safety evaluations included adrenal function evaluation by morning plasma cortisol concentration, response to ACTH stimulation, and 24-hour urinary free cortisol excretion. There was no evidence of effects on adrenal function at any dose. The severity, nature, and frequency of adverse events were similar across all treatment groups, including placebo. Drug-related adverse events were consistent with local nasal irritation. The groups receiving fluticasone propionate showed greater improvement in nasal symptoms (obstruction, rhinorrhea, sneezing, and itching) than did the placebo group. The results demonstrate that fluticasone propionate aqueous nasal spray is safe in doses up to 1600 micrograms per day and effective in the treatment of seasonal allergic rhinitis.

Administration, Intranasal

Phenotypic and cytogenetic analysis of atypical multidrug resistance in human leukaemic cells selected with methotrexate at high concentration.

A series of CCRF-CEM sublines selected for extreme resistance to methotrexate has been shown previously to exhibit cross resistance to a number of agents belonging to the multidrug resistance phenotype. The mechanism(s) underlying resistance to vincristine, vinblastine and actinomycin D in the most resistant subline (CEM/MTX R3) has now been investigated. Efflux of [3H]vincristine was more rapid in CEM/MTX R3 than in either CCRF-CEM cells or a methotrexate-resistant subline not refractory to Vinca alkaloids. In addition, verapamil completely reversed resistance to vincristine, vinblastine and actinomycin D in the CEM/MTX R3 cells. While these results are suggestive of P-glycoprotein-mediated multidrug resistance, Northern analysis revealed no detectable expression of the mdr 1/gene in CEM/MTX R3 cells. Likewise, karyotypic analysis of the resistant subline, while revealing certain clonal abnormalities, provided no evidence of alteration in the mdr 1/gene locus on chromosome 7. The data suggest therefore the operation, in these cells, of a novel mechanism of resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem

Process issues in consultancy.

A piece of short term consultancy work in a school for the Mentally Handicapped is described from the perspective of both the consultants and the consultees with particular reference to the process issues involved. Reasons for the high levels of stress, experienced in the exercise are explored by an examination of the contributory factors within the school and the consultancy process itself. As well as a theoretical discussion questions of practical management are considered.

Adolescent

The value of serum cryptococcal antigen in the diagnosis of cryptococcal infection in patients infected with the human immunodeficiency virus.

Serum cryptococcal antigen titres were measured in 828 HIV-infected patients with pyrexia, 69 of whom had meningism. Serum cryptococcal antigen was positive in 17 patients of whom 16 had meningism with cryptococcus isolated from their CSF. The other patient had no meningism, had no evidence of cryptococcal infection on repeated CSF examination and remains well. A positive serum cryptococcal antigen test was therefore valuable in the diagnosis of cryptococcal meningitis, although in all 16 patients meningism was present and a diagnostic lumbar puncture was therefore carried out. In our experience routine screening for serum cryptococcal antigen did not predict patients who subsequently developed cryptococcal meningitis.

Amphotericin B

Resistance to drugs associated with the multidrug resistance phenotype following selection with high-concentration methotrexate.

To study patterns of resistance at extreme but nevertheless clinically relevant drug concentrations, we developed a series of methotrexate-selected CCRF-CEM sublines, all of which were highly resistant to this antifolate (relative resistance, 10(2)- to greater than 10(5)-fold). The least methotrexate-resistant subline was completely sensitive to drugs associated with the multidrug resistance phenotype. However, more highly methotrexate-resistant sublines were significantly cross-resistant to vincristine, vinblastine, and dactinomycin (maximum relative resistance, 40-fold). These sublines were not cross-resistant to doxorubicin, daunorubicin, and teniposide. Regression analysis indicated that relative resistance to methotrexate was correlated with relative resistance to vincristine (r = 0.96) and vinblastine (r = 0.99). Such cross-resistance in highly methotrexate-resistant cells may have important clinical implications.

Antineoplastic Agents

Haptic integration of object properties: texture, hardness, and planar contour.

Planar objects varying in shape, texture, and hardness were classified under haptic exploration. Classes were defined by values on one dimension, or redundantly, by two or three dimensions. Response times and exploratory procedures (Lederman & Klatzky, 1987) were recorded. Experiment 1 showed that a second dimension speeded responses for all combinations (redundancy gain), but a third dimension produced no further effect. In Experiments 2 and 3, classification trials began with two redundant dimensions, and subsequently one was withdrawn (held constant). When texture and hardness varied redundantly, withdrawal of either increased response time--even when subjects were initially instructed to focus on one dimension. Joint exploration for texture and hardness dominated whenever the two varied redundantly and persisted despite withdrawal. Redundancy gains (Experiment 1), but not substantial withdrawal effects (Experiments 2 and 3), were observed for combinations of texture or hardness with planar contour, indicating less integration than between substance dimensions. Compatibility of exploratory procedures appears to constrain dimensional integration.

Attention

The bacteriology of chronic venous ulcers treated with occlusive hydrocolloid dressings.

The bacterial flora of chronic venous ulcers treated with an occlusive hydrocolloid dressing were studied over a period of 8 weeks. A novel exudate sampling method was used in an attempt to isolate anaerobic bacteria. The flora was generally stable. Once a species was present, it remained with the exception of Pseudomonas, which appeared to be inhibited by the dressing. Twelve out of 20 ulcers contained anaerobic bacteria and healing did not appear to be impaired by the presence of any particular species of bacteria.

Aged

Capillary blood glucose monitor. Evaluation in a newborn nursery.

The performance of a rapid capillary blood glucose monitor, the Glucoscan 2000, was evaluated in a neonatal patient population by comparison with a reference method on 283 paired patient samples. The median glucose was 56 mg/dL (3.1 mmol/L). The slope of the regression line was .93 with a correlation coefficient r of .82. The average error in Glucoscan values at low, intermediate and high glucose ranges was 43%, 20% and 12% respectively. Precision analysis by replicate determinations also showed an increased coefficient of variation, 7.4%, at low glucose values.

Blood Chemical Analysis

Comparison of cyclophosphamide and diaziquone in a retinoblastoma xenograft model.

The benefits and optimal applications of chemotherapy in the management of retinoblastoma remain to be defined. There are major obstacles to its further study in the clinical setting. A xenograft model of human retinoblastoma heterotransplanted directly into the anterior chamber of the nude mouse eye has been adapted for evaluation of therapeutic efficacy. Cyclophosphamide, the most effective conventional drug, and diaziquone, an experimental agent, both produced documented and comparable responses in each of four xenograft cell lines. There was no evidence of rapidly emerging drug resistance or cross-resistance between two agents when sequential chemotherapy courses were given. Diaziquone is an effective chemotherapeutic agent for retinoblastoma in the xenograft model, and may have applications in clinical management.

Animals

Visceral leishmaniasis (kala azar) in a patient with AIDS.

A patient with HIV infection presented with multiple cutaneous Kaposi's sarcomata. Biopsy of one of these showed the presence of amastigotes within an otherwise typical Kaposi's sarcoma. Further investigations proved the patient to have visceral leishmaniasis (kala azar). Visceral leishmaniasis has been reported in HIV infection but it is rare and this presentation is unique. The patient made a good response to a prolonged course of treatment with sodium stibogluconate and allopurinol.

Acquired Immunodeficiency Syndrome

Increased oxidation of uroporphyrinogen by an inducible liver microsomal system. Possible relevance to drug-induced uroporphyria.

1. The hypothesis that uroporphyria-inducing drugs stimulate the oxidation of uroporphyrinogen by a microsomal NADPH-dependent mechanism was tested. 2. 3,4,3',4'-Tetrachlorobiphenyl, a very effective inducer of uroporphyria in chick-embryo hepatocyte cultures, stimulates the NADPH-dependent oxidation of uroporphyrinogen by chick-embryo microsomal fraction in vitro. 3. Two different actions of 3,4,3',4'-tetrachlorobiphenyl are apparently required for this effect: (a) induction of a microsomal system by treatment in vivo and (b) interaction with the induced microsomal fraction in vitro, producing an oxidizing species. 4. The analogue 2,4,2',4'-tetrachlorobiphenyl is relatively ineffective in both the production of porphyria in culture and the stimulation of porphyrinogen oxidation in vitro. 5. Rat hepatocytes do not develop uroporphyria when treated with polychlorinated biphenyls in culture, yet they respond to these drugs with typical induction of cytochrome P-448-dependent drug metabolism. 6. These data provide support for the hypothesis of an increased oxidation of uroporphyrinogen in drug-induced uroporphyria, but also suggest that induction of cytochrome P-448 is not the only factor involved. 7. Both I and III isomers of uroporphyrin and heptacarboxylate porphyrin accumulate when chicken hepatocytes are made uroporphyric by drugs; treatment with desferrioxamine causes a marked decrease in both isomers, suggesting that iron may be involved in the accumulation of both.

Aminolevulinic Acid

Isolation and partial characterisation of a 26 kilodalton antigen from Plasmodium falciparum recognised by an inhibitory monoclonal antibody.

A 26 kDa protein, present in trophozoites and schizonts of Plasmodium falciparum, has been identified as the target of a monoclonal antibody that weakly inhibits parasite growth in vitro. The antigen has been purified to homogeneity by immuno-affinity chromatography and electrophoresis. The sequence of 19 amino acids at the N-terminus of the protein has been determined.

Amino Acid Sequence

Non-cytocidal natural variants of human immunodeficiency virus isolated from AIDS patients with neurological disorders.

To understand the mechanism of HIV-mediated neuropathology five viral isolates were obtained from four AIDS cases with central nervous system manifestations as the primary involvement. The isolates were identified as HIVs by antigenic cross-reactivity and nucleic acid hybridizations to HIV-specific antibodies and DNA probes. The replication and cytopathic properties of these isolates were studied and compared with lymphadenopathy-associated virus (HIVLAV). All isolates had replication competence equivalent to LAV, but four isolates did not kill T4 (CD-4) cells. This isolation of non-cytocidal natural variants of HIV raises the possibility that in some AIDS cases the neurological disorders might be due to HIV variants that are non-cytocidal to T4 cells. The results also indicate that virus replication and cytotoxicity are not always concordant functions in HIV.

Acquired Immunodeficiency Syndrome