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Biomedical subjects

A Beveridge

Publications and source records attributed to A Beveridge.

12 recordsLinked to original sources
PubMed1998

Treatment response and durability of a double protease inhibitor therapy with saquinavir and ritonavir in an observational cohort of HIV-1-infected individuals.

OBJECTIVE: To evaluate treatment response, durability and tolerance of a four-drug regimen including saquinavir and ritonavir in combination with either zidovudine/lamivudine or stavudine/lamivudine. DESIGN: Observational cohort of HIV-positive individuals. METHODS: Viral load, CD4+ and CD8+ T lymphocyte counts were assessed at intervals of 1-3 months in subjects commencing therapy between July 1996 and November 1996. Adverse events were evaluated as well as risk factors for therapeutic failures. RESULTS: A group of 56 male patients were included and followed for 48 weeks. Of these, 66% had already taken a protease inhibitor. Viral load dropped by a median 1.98 log10 HIV RNA copies/ml from baseline (interquartile range: 1.49-2.46) and became undetectable (< 400 copies/ml) in 68% of patients. Response varied: 9% were non-responders (HIV RNA reduction < 0.5 log10 copies/ml) and 23% were incomplete responders (nadir of HIV RNA > 400 copies/ml). After 48 weeks, viral load remained undetectable in 49%. Median CD4+ T lymphocyte count increased from 191 x 10(6) to 418 x 10(6) cells/l (range, 241-537 x 10(6) cells/l). Although protease inhibitor and nucleoside pretreatment selected for drug-resistant viral mutants, only the protease inhibitor experience was identified as a risk factor for therapeutic failure. Adverse events occurred in 73% of patients and led to a change of therapy in 9%. CONCLUSION: Despite advanced HIV disease and pretreatment with multiple antiretroviral drugs, a strong initial treatment response to this drug regimen was observed. However, virological failure occurred in 51% of patients after 48 weeks and frequent adverse events complicated therapy.

Adult↗
PubMed1997

Voices of the mad: patients' letters from the Royal Edinburgh Asylum, 1873-1908.

BACKGROUND: This paper is based on a rich archive of 1151 letters by patients, who were admitted to the Royal Edinburgh Asylum during the reign of Thomas Clouston (1873-1908). METHODS: All letters were examined for evidence of psychopathology, and the material obtained was organized under the various psychopathological categories, such as delusions or hallucinations, as defined by Sims (1988). RESULTS: A descriptive account of patient symptomatology is given. It is found that nineteenth century psychopathology is very similar to that of the modern day, and that most forms of morbid mental phenomena can be found in the patients' letters. More specifically, most of the cardinal symptoms of schizophrenia were described in the patients' correspondence. The letters also illustrate how mental symptoms reflect the cultural and scientific concerns of their time. CONCLUSIONS: The evidence in the patients' letters argues for the unchanging nature of mental illness across time, at least for the last 120 years. It also demonstrates that patients admitted to the Royal Edinburgh Asylum suffered from serious mental illness, and it undermines the view that the Asylum was simply a dumping ground for society's disaffected.

Correspondence as Topic↗
PubMed1997

Transmission of human immunodeficiency virus type 1 resistant to nevirapine and zidovudine. Sydney Primary HIV Infection Study Group.

Human immunodeficiency virus type 1 (HIV-1) resistant to the nonnucleoside reverse transcriptase inhibitor nevirapine and to the nucleoside analogue zidovudine was transmitted from a homosexual man to his sex partner. The virus source patient had commenced combination zidovudine and nevirapine therapy 2.5 years prior to his partner's primary HIV infection. He received both therapies for 7 months, then discontinued nevirapine treatment, continuing to receive zidovudine monotherapy for a further 16 months. He had ceased zidovudine therapy 6 months before the time of his partner's seroconversion. Analysis of major and minor isolates obtained from both patients soon after onset of the recipient's primary HIV infection illness confirmed that an HIV-1 variant mutant at codons 70, 98, and 181 of the viral reverse transcriptase was transmitted. This is the first documented case of transmission of HIV-1 resistant to two antiretroviral compounds.

Adolescent↗
PubMed1996

A theoretical study of torsional flexibility in the active site of aspartic proteinases: implications for catalysis.

We have performed ab initio Hartree-Fock self-consistent field calculations on the active site of endothiapepsin. The active site was modeled as a formic acid/formate anion moiety (representing the catalytic aspartates, Asp-32 and -215) and a bound water molecule. Residues Gly-34, Ser-35, Gly-217, and Thr-218, which all form hydrogen bonds to the active site, were modeled using formamide and methanol molecules. The water molecule, which is generally believed to function as the attacking nucleophile in catalysis, was allowed to bind to the active site in four distinct configurations. The geometry of each configuration was optimized using two basis sets (4-31G and 4-31G*). The results indicate that in the native enzyme the nucleophilic water is bound in a catalytically inert configuration. However, by rotating the carboxyl group of Asp-32 by about 90 degrees the water molecule can be reorientated to attack the scissile bond of the substrate. A model of the bound enzyme-substrate complex was constructed from the crystal structure of a difluorostatone inhibitor complexed with endothiapepsin. This model suggests that the substrate itself initiates the reorientation of the nucleophilic water immediately prior to catalysis by forcing the carboxyl group of Asp-32 to rotate. The theoretical results predict that the active site of endothiapepsin undergoes a large distortion during substrate binding and this observation has been used to explain some of the kinetics results which have been reported for mutant aspartic proteinases.

Aspartic Acid Endopeptidases↗
PubMed1996

Poor and mad: a study of patients admitted to the Fife and Kinross District Asylum between 1874 and 1899.

This is the first detailed study of patients admitted to a Scottish pauper asylum. A one in four sample of patients admitted to the Fife and Kinross District Asylum between 1874 and 1899 was undertaken and yielded 262 males and 266 females. Each patient's case-notes were studied from admission to the time of discharge and a wide range of information relating to sociodemographic and clinical features was extracted and subsequently analysed. The study found that while the Fife and Kinross Asylum shared many of the features of its English counterparts, the general picture was less bleak: the Asylum population did not grow to such large numbers; the recovery rate did not fall so precipitately and even rose towards the end of the century and cases of general paralysis were less frequent. In the discussion, these findings are related to other asylum studies.

Cause of Death↗
PubMed1993

The management of spinal cord compression in patients with advanced malignancy.

We retrospectively evaluated the medical records of 17 hospice patients who developed spinal cord or cauda equina compression due to metastatic epidural tumor to ascertain the nature and outcome of the disorder in this setting. Epidural compression occurred following admission to the hospice in five cases and prior to admission in 12 cases. Six patients were ambulatory following treatment, and this favorable outcome occurred only in those who were ambulatory at diagnosis. In the group of patients who were paraplegic after treatment, problems related to pain, decubitus ulcers, and constipation were most challenging. This experience highlights the need for a more vigilant approach to back pain in patients at risk of epidural compression in the hospice setting. Further studies are necessary to establish the appropriate management of these patients.

Adrenal Cortex Hormones↗
PubMed1992

Screening for patients at risk of alcohol related problems: the results of the York District Hospital Alcohol Study.

This study examined the feasibility of training medical and nursing staff in the use of a brief Alcohol Screening Questionnaire, which assists the early identification of patients who drink to excess. Over a two-year period 7,217 questionnaires were completed on patients admitted to York District General Hospital. Analysis showed the screening questionnaire to be a quick and reliable instrument, although the characteristics of the screener influenced its effectiveness. The results suggest that hospital staff require little training before they can effectively identify patients who drink to excess.

Alcoholism↗
PubMed1987

Conformational properties of 3'-azido-3'deoxy-thymidine (AZT), an inhibitor of HIV reverse transcriptase.

The low-energy conformations of 3'-azido-3'-deoxy-thymidine, (AZT), an inhibitor of retroviral reverse transcriptase, have been studied by molecular mechanics techniques. A force-field has been developed for the azido group by quantum-mechanical methods, and used in the analysis. The global low-energy structure of AZT has C3'-endo sugar pucker, an anti glycosidic angle, and a g+ C4'-C5' conformation. It is concluded that the AZT molecule has conformational properties that are very similar to those of standard deoxypyrimidines.

Antiviral Agents↗