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Biomedical subjects

D A Hawkins

Publications and source records attributed to D A Hawkins.

At least 37 records · Page 2Linked to original sources
PubMed1997

A dose comparison study of a new triazole antifungal (D0870) in HIV-positive patients with oral candidiasis.

OBJECTIVE: This multicentre study evaluated the clinical efficacy and tolerability of D0870 in treating oropharyngeal candidiasis in HIV-positive patients who had no history of clinical resistance to fluconazole. METHODS: Three regimens were evaluated in two phases. In phase I a 50 mg initial dose was followed by 10 mg for 4 days (Group 1). In phase II a 100 mg initial dose was followed by 25 mg for 4 days (Group 2), or 10 mg for 5 days (Group 3). RESULTS: Clinical cure was obtained in 27 patients of a total of 35 (77%) and six other patients improved (17%). Two patients at the lowest dose failed and both had very low plasma concentration of D0870. No association was found between clinical outcome; minimum inhibitory concentration of D0870 pre-therapy for Candida albicans, maximum recorded plasma D0870 concentration, cfu of culture or CD4 cell count at entry. Overall, 37% of the patients experienced relapse during the 2 weeks post therapy. Tolerance was excellent. Mild adverse events possibly related to the study drug were recorded in five patients. CONCLUSION: D0870 demonstrates excellent efficacy at low doses in the treatment of HIV-related OPC and exhibits a favourable safety profile.

AIDS-Related Opportunistic Infections↗
PubMed1997

Biochemical assessment of pancreatic disease in human immunodeficiency virus infected men.

AIM: To determine the usefulness of measuring amylase activity as an indicator of pancreatic disease in human immunodeficiency virus (HIV) positive patients. METHODS: A prospective study of 129 ambulant HIV positive males. Total amylase, pancreatic amylase, and lipase activities were assayed using commercial test kits on an automated analyser. Samples with raised amylase were examined for the presence of macroamylasaemia using cellulose acetate electrophoresis. RESULTS: Thirty six (28%) of the subjects had raised total amylase activities compared with healthy, age matched blood donors. However, almost half of these were because of an increase of the salivary fraction. Four subjects were found to have macroamylasaemia. Pancreatic amylase and lipase assays, more specific indicators of pancreatic disease, produced significantly fewer abnormal results. There was no association between abdominal symptoms and elevated enzyme levels. CONCLUSIONS: Total amylase is a poor indicator of pancreatic disease in HIV infected outpatients. Specific assays for pancreatic amylase offer advantages over the traditional total amylase assay. The lipase assay produced the least number of abnormal results and its use could improve the biochemical identification of patients with possible pancreatic disease and allow a more selective investigation of these cases.

Adult↗
PubMed1996

Temporal aspects of ovarian follicular growth and steroidogenesis following exogenous follicle-stimulating hormone in Angus heifers.

Ultrasonography and endocrine assay techniques were used to monitor structural and hormonal alterations made by the ovary in response to the biological actions of pituitary-derived follicle-stimulating hormone (FSH-P). Angus heifers (n = 36) were allotted to receive injections (twice per day) of either FSH-P (up to a total of 28 mg over a maximum of 4 days beginning on Day 10 of a synchronized estrous cycle) or saline in order to quantify temporal relationships among follicle growth and steroid hormone profiles. Transrectal ultrasonography was utilized at 12-h intervals to monitor and record follicle growth. Plasma was collected every 12 h for the first 48 h of the experiment and then every 6 h for the remainder of the experiment. At 48 and 60 h after the onset of treatments, prostaglandin F2 alpha (PGF2 alpha; 25 mg) was administered (i.m.). FSH-treated heifers (n = 6 at each time) were terminated at 24, 48, 72 and 96 h following the onset of treatment. Saline-treated heifers were terminated at 24 and 96 h (n = 6 at each time). After ovaries were obtained, follicular number and size were recorded and follicular fluid (FF) was collected. Plasma concentration of progesterone (P) and estradiol (E2) and FF concentration of P, E2, estrone, testosterone and androstenedione were determined by radioimmunoassays. Plasma concentration of E2 increased (P < 0.05) within 36 h of initiation of FSH treatment. Plasma P decreased (P < 0.0001) by 12 h post-PGF2 alpha. Ultrasonographic examination revealed a significant decrease in the number of small follicles by 48 h, whereas the number of medium follicles increased (P < 0.05) by 60 h after the initiation of FSH treatment. The number of large follicles (LF > or = 10 mm diameter) increased (P < 0.01) over the course of the experiment. The total number of ovarian follicles (TF) 24 h after the start of FSH treatment was correlated (r = 0.99; P < 0.0001) with the number of small follicles (SF < or = 5 mm). At 72 h after the onset of FSH treatment, the number of medium follicles (i.e. 6-9 mm) was correlated with TF (r = 0.97; P < 0.0001). Estradiol was the predominant FF steroid. Follicular fluid E2 was greatest in follicles at 72 h after FSH treatment. Follicular fluid E2 and plasma E2 were positively correlated (r = 0.66; P < 0.001). Follicular aromatase activity was estimated by evaluating the ratio of FF estrogens (E) to androgens (A). Elevated aromatase activity (E:A ratio > 1.0) was detected in 196 of 206 follicles. The estrogen to progesterone ratio was used as an estimate of follicle viability. Eighty-five percent of the follicles were estimated to be viable (E:P ratio > 1.0). The peak E:A ratio in LF preceded by 24 h the peak concentration in FF E2 and plasma E2. In MF and SF the E:A ratio increased by 72 h. Enhancement of ovarian follicular growth (i.e. increased number and size of follicles; increased steroidogenesis) by exogenous, pituitary-derived FSH is characterized by (1) increased activity of aromatase, and (2) accumulation of FF E2, events which temporally preceded the increase in plasma concentration of E2. These observations will aid efforts to incorporate recombinant bovine FSH and somatotropin in an effort to develop more predictable superstimulation and ovulation induction protocols.

Animals↗
PubMed1996

Use of terbinafine in HIV-positive subjects: pilot studies in onychomycosis and oral candidiasis.

Study 1. Eighteen HIV-positive Caucasian homosexual men with initial positive fungal microscopy were recruited into this prospective, dual-centre, open-label study. They received a once-daily oral dose of 250 mg terbinafine for 12 weeks. Eight were subsequently excluded after screening cultures proved negative. The mean CD4 count of the 10 evaluable subjects was 302/mm3. All 10 positive fungal cultures were confirmed as Trichophyton rubrum. Using an intention-to-treat analysis, healthy unaffected nail growth increased from a mean of 1.6 mm at baseline to 5.2 mm after 12 weeks' treatment. Clinical response after treatment was 6.4 mm at 36 weeks and 8.0 mm at 48 weeks. Three of the 10 toenail infections were cured mycologically. This 30% cure rate was maintained over 48 weeks' follow-up, despite three patients discontinuing the study. One withdrew following a terbinafine-induced drug rash. Two others stopped treatment during HIV-related illnesses, but without terbinafine side-effects. Study 2. Ten HIV-positive subjects, nine culture-positive for Candida albicans and one for Candida albicans and Candida glabrata, were recruited into this pilot study. They received 250 mg oral terbinafine daily for 14 days. Their average CD4 count was 131/mm3. All patients remained culture-positive throughout the study. Slight improvements in signs and symptoms were seen in one or two patients but this might well have been attributable to improved oral hygiene. Oral terbinafine at this dosage was therefore not thought an effective treatment for this indication in HIV-positive patients. The drug was well tolerated and no serious treatment-related adverse events were reported.

Antifungal Agents↗
PubMed1996

Does HIV disease progression influence epidermal Langerhans cell density?

Langerhans cells (LC) are antigen-presenting CD4+ dendritic cells in the skin which may become infected by the human immunodeficiency virus (HIV). Decreased LC function could account for the cutaneous manifestations seen in HIV disease. Previous studies of epidermal LC density in HIV-infected subjects have produced conflicting results. A definitive, prospective, case-control study was performed to determine whether there is an association between epidermal LC density and HIV clinical disease stage. Skin cryosections were stained with the CD1 monoclonal antibody using a three-step immunoperoxidase method. LC were counted by light microscopy and epidermal dimensions calculated with computer-assisted planimetry. The stage of the HIV clinical disease correlated with epidermal LC densities was quantified by three different methods: mean LC numbers per mm length of basement membrane, mean LC per mm2 of epidermal area, and mean LC population per mm of epidermal surface length. Seventy-one subjects, recruited from a large out-patient HIV clinic in London, comprised 56 HIV-positive men and 15 male HIV-negative controls. Contrary to previous smaller studies, there was no detectable association between epidermal LC density (quantified by any of the three methods) and the stage of the HIV clinical disease. Given that HIV infects large numbers of CD4+ cells, we propose possible hypotheses to account for the apparent preservation of static LC numbers in the skin. Further studies of LC kinetics and function are required to elucidate their role in the natural history of HIV infection.

Adult↗
PubMed1994

A longitudinal study of the neuropsychiatric consequences of HIV-1 infection in gay men. I. Neuropsychological performance and neurological status at baseline and at 12-month follow-up.

The aim of this study was to determine whether HIV infection is associated with neurological or neuropsychological impairment in the asymptomatic and early symptomatic stages of disease. Subjects included 61 gay men (41 HIV-, 20 HIV+) who were assessed at the time of requesting their first HIV test and again 12 months later. The assessments at baseline were conducted double-blind to HIV serostatus. Measures included a neuropsychological battery, neurological examination and full psychiatric assessment. There were no differences between the asymptomatic HIV+ and HIV- groups at baseline or at follow-up in terms of mean scores on neuropsychological tests. Mean scores were within the normal range for all neuropsychological tests for both groups. Multiple regression analysis was used to predict each individual's performance at follow-up on the basis of their baseline performance, psychiatric state, neurological history and drug use for each of the neuropsychological tests. HIV+ subjects were more likely than control subjects to perform at a significantly lower level at follow-up on one or more tests than predicted on the basis of their baseline performance.

AIDS Dementia Complex↗
PubMed1994

A longitudinal study of the neuropsychiatric consequences of HIV-1 infection in gay men. II. Psychological and health status at baseline and at 12-month follow-up.

The aim of this study was to determine whether HIV infection is associated with increased psychosocial distress in the asymptomatic and early symptomatic stages of disease and to determine the factors associated with reporting health symptoms. Subjects included 61 gay men (41 HIV--, 20 HIV+) who were assessed at the time of requesting their first HIV test and again 12 months later. Measures included a detailed standardized psychiatric interview (Present State Examination, PSE), a range of psychosocial self-report measures and a physical symptom checklist. There were no differences between the HIV+ and HIV-- groups in terms of self-reported symptoms. Multiple regression analysis showed that the symptom reporting was not associated with clinical or immunological markers of disease progression but was associated with measures of psychosocial distress. Although both groups showed elevated levels of psychosocial distress at the time of HIV testing, there were no differences between serostatus groups at follow-up. Multiple regression analysis indicated that the best predictors of PSE scores at follow-up were baseline PSE score and a history of psychiatric illness. Early HIV disease is not associated with increased psychosocial distress and symptom reporting is more closely related to psychological measures than to clinical or immunological markers of disease.

AIDS Dementia Complex↗
PubMed1994

Management of pulmonary aspergillosis in AIDS: an emerging clinical problem.

AIMS: To review the clinical, radiographic, and therapeutic features of 11 cases of respiratory Aspergillus infection in patients with AIDS. METHODS: All induced sputum and bronchoalveolar lavage samples obtained from HIV seropositive patients between January 1985 and March 1993 were analysed for Aspergillus species. Additionally, where appropriate, bronchial or renal biopsy specimens, or both, were taken before treatment had started. RESULTS: In 11 patients Aspergillus fumigatus was identified in alveolar samples obtained by sputum induction. This was confirmed by bronchoalveolar lavage in eight. Three patients had Aspergillus plaques in the trachea and bronchus, while a fourth patient had an aspergilloma. Risk factors for Aspergillus infection were present in all patients, including corticosteroid treatment in three cases and neutropenia in four, three of whom had received chemotherapy for Kaposi's sarcoma. Four patients had concomitant cytomegalovirus infection. Ten patients had a CD4 count of less than 50 cells/mm3 while one patient had a disseminated T cell lymphoma with a CD4 count of 242 cells/mm3. Of the three patients with samples obtained by sputum induction who did not undergo bronchoscopy, two had a normal chest x ray picture and the third had a right lobar pneumonia complicating an aggressive lymphoma. All three were treated with itraconazole 200 mg twice a day without further investigation. Survival from the time of diagnosis of Aspergillus infection was short: seven patients died within six weeks, although only one death was directly attributed to pulmonary aspergillosis. At six monthly follow up, one patient, who initially had a positive Aspergillus culture from bronchial washings and a normal chest radiograph, developed a renal aspergilloma despite the disappearance of Aspergillus sp from the sputum. CONCLUSION: Pulmonary aspergillosis is an important clinical problem in patients with AIDS with a CD4 count of less than 50 cells/mm. Furthermore, patients with Aspergillus sp in sputum induction or bronchial washings may develop disseminated disease despite adequate treatment of the primary infection.

AIDS-Related Opportunistic Infections↗
PubMed1993

Immunohistochemical markers of uterine receptivity in the human endometrium.

The factors responsible for the initial interaction between maternal and fetal epithelium leading to the establishment of pregnancy remain poorly understood. Temporal and spatial expression of specific endometrial peptides in response to ovarian steroids is thought to contribute to the development of a period of uterine receptivity, whereby the endometrium becomes hospitable to the implanting blastocyst. The failure to establish receptivity may account for a significant percentage of the cases of infertility in the female, especially affecting women with luteal phase deficiency, leiomyomata uteri, endometriosis, habitual abortion, and unexplained infertility. In addition, despite increasing global experience with advanced reproductive technologies, the majority of In Vitro Fertilization (IVF) attempts remain unsuccessful, most likely on the basis of implantation failure. In this article, we review the concepts involved in the study of uterine receptivity in the human, highlight potential immunohistochemical (IHC) markers that have recently been discovered, and discuss how IHC assessment of the endometrium is a potentially valuable method for the evaluation of the receptive endometrial state. Using this approach we have examined several new potential markers of uterine receptivity. Endometrial progesterone receptors and one of the integrin cell adhesion molecules appear to undergo changes in expression around the time of implantation, and may be sensitive indicators of the receptive state. Further, these markers are delayed in women with infertility and luteal phase deficiency. These studies illustrate the utility of IHC diagnosis for the evaluation of endometrial function.

Animals↗
PubMed1993

Neuropsychiatric aspects of HIV-1 infection in gay men: controlled investigation of psychiatric, neuropsychological and neurological status.

The aim of this study was to determine whether HIV infection is associated with psychiatric morbidity or neuropsychological impairment in asymptomatic and early symptomatic stages of disease in gay men. The subjects were 100 gay men (68 HIV-ve, 32 HIV+ve, 6 being CDC IV). All subjects were recruited at the time of requesting their first HIV test and the assessment was double-blind to HIV serostatus. There were no differences in psychiatric status or neuropsychological performance between the HIV-ve and HIV+ve groups. Multiple regression analysis and logistic regression were used to identify factors associated with psychiatric morbidity, neuropsychological impairment and subjective reporting of memory problems and physical symptoms for all 100 subjects. Previous psychiatric history and current illegal (non-dependent) drug use were associated with psychiatric morbidity, poor education was associated with neuropsychological impairment and psychiatric status (score on HAD and PSE) was associated with subjective reporting of memory problems and physical symptoms.

AIDS Dementia Complex↗
PubMed1993

Treatment with corticosteroids--a risk factor for the development of clinical cytomegalovirus disease in AIDS.

OBJECTIVE: To assess the frequency with which HIV-seropositive patients treated with corticosteroids develop cytomegalovirus (CMV) disease. DESIGN: Retrospective case-controlled study. METHODS: All 130 patients receiving systemic corticosteroids over a 20-month period at the HIV Unit, Westminster Hospital, London, UK were reviewed for the development of clinical CMV disease within 28 days. The incidence of CMV disease in this group was compared with that in a cohort admitted during the same period, which was matched for admission diagnosis, HIV risk group, antiretroviral therapy and CD4 lymphocyte subset count (+/- 20%) at admission. RESULTS: Eleven of the 130 patients given corticosteroids developed CMV disease within 28 days, compared with two patients in the case-controlled cohort. All patients who developed CMV disease had a CD4 count < 50 x 10(6)/l on admission. CONCLUSION: The use of corticosteroids in patients with advanced immunosuppression due to HIV infection should be reviewed carefully in view of the possible increased incidence of CMV disease.

AIDS-Related Opportunistic Infections↗
PubMed1992

An activation-recruitment scheme for use in muscle modeling.

The derivation of a new activation-recruitment scheme and the results of a study designed to test its validity are presented. The activation scheme utilizes input data of processed surface EMG signals, muscle composition, muscle architecture, and experimentally determined activation coefficients. In the derivation, the relationship between muscle activation and muscle fiber recruitment was considered. In the experimental study, triceps muscle force was determined for isometric elbow extension tasks varying in intensity from 10 to 100% of a maximum voluntary contraction (MVC) using both a muscle model that incorporates the activation scheme, and inverse dynamics techniques. The forces calculated using the two methods were compared statistically. The modeled triceps force was not significantly different from the experimental results determined using inverse dynamics techniques for average activation levels greater than 25% of MVC, but was significantly different for activation levels less than 25% of MVC. These results lend support for use of the activation-recruitment scheme for moderate to large activation levels, and suggest that factors in addition to fiber recruitment play a role in force regulation at lower activation levels.

Acceleration↗
PubMed1992

Salmonella, Campylobacter and Shigella in HIV-seropositive patients.

OBJECTIVE: To study the incidence, clinical features, treatment and outcome of patients with Salmonella, Shigella or Campylobacter infection. DESIGN: Retrospective analysis. SETTING: Two dedicated HIV units within a London teaching hospital. METHODS: All patients with Salmonella, Shigella or Campylobacter infection were reviewed retrospectively by correlating the records of the gastrointestinal and microbiology departments with the computerized records of all HIV-positive patients attending the two clinics. RESULTS: Between July 1985 and June 1991, 56 episodes of Salmonella, 37 of Campylobacter and eight of Shigella infection were documented in HIV-seropositive patients. Shigella was most likely to occur early in HIV disease, whilst patients with Campylobacter or Salmonella were more likely to have had a previous AIDS diagnosis. Septicaemica was most common in patients with Salmonella and was especially likely to occur in individuals with an AIDS diagnosis. Relapse of infection was common in patients with Salmonella, especially in those with low CD4 lymphocyte counts, those with an initial septicaemic illness and those not treated with ciprofloxacin. CONCLUSIONS: Patients with Salmonella who have low CD4 lymphocytes counts and/or a septicaemic illness should be considered for life-long secondary prophylaxis with ciprofloxacin because of the high rate of relapse observed. Administration of zidovudine or cotrimoxazole as prophylaxis against Pneumocystis carinii pneumonia may prevent the development of salmonellosis: significantly fewer patients with this infection were taking these drugs than patients with Campylobacter.

AIDS-Related Opportunistic Infections↗