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Biomedical subjects

D J Ward

Publications and source records attributed to D J Ward.

At least 37 records · Page 2Linked to original sources
PubMed1998

Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata.

Sequential Candida glabrata isolates were obtained from the mouth of a patient infected with human immunodeficiency virus type 1 who was receiving high doses of fluconazole for oropharyngeal thrush. Fluconazole-susceptible colonies were replaced by resistant colonies that exhibited both increased fluconazole efflux and increased transcripts of a gene which codes for a protein with 72.5% identity to Pdr5p, an ABC multidrug transporter in Saccharomyces cerevisiae. The deduced protein had a molecular mass of 175 kDa and was composed of two homologous halves, each with six putative transmembrane domains and highly conserved sequences of ATP-binding domains. When the earliest and most azole-susceptible isolate of C. glabrata from this patient was exposed to fluconazole, increased transcripts of the PDR5 homolog appeared, linking azole exposure to regulation of this gene.

AIDS-Related Opportunistic Infections↗
PubMed1997

Sleep deprivation increases brain serotonin turnover in the rat.

IN order to study possible time-dependent changes in serotonin metabolism in rat brain, male Wistar rats were subjected to 3, 6 or 12 h total sleep deprivation (SD) by gentle handling. In addition two groups of rats subjected first to 6 h SD were allowed 2 or 4 h rebound sleep. Tissue concentrations of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured from several brain areas using HPLC/ECD. SD significantly increased the 5-HIAA/5-HT ratio in frontal cortex, hippocampus, hypothalamus and brain stem, indicating increased 5-HT turnover in those areas. After 2 and 4 h rebound sleep, the 5-HIAA/5-HT ratio was similar to that in controls. We conclude that a short SD increases 5-HT turnover in the rat brain for the duration of SD only.

Animals↗
PubMed1993

Long-term gastrointestinal problems in burns patients.

Paralytic ileus occurs commonly in patients with over 20 per cent TBSA burns in the first few days after the burn. In the absence of sepsis, it is unusual for abdominal problems to develop later. We present an example of acute abdominal pseudo-obstruction occurring 5 weeks after a burn and review the management of this condition.

Acute Disease↗
PubMed1992

Visual field testing in the management of cytomegalovirus retinitis.

BACKGROUND: Sequential visual field testing is an extremely helpful adjunct to ophthalmoscopy and fundus photography in the management of cytomegalovirus (CMV) retinitis with the antiviral agents ganciclovir or foscarnet in patients with the acquired immune deficiency syndrome (AIDS). The authors studied the visual field defects found in a series of 110 patients with AIDS and CMV retinitis. METHODS: Ophthalmoscopy and fundus photography were performed on all patients. Visual field analysis was performed with either tangent screen, Goldmann kinetic, or Humphrey automated static perimetry. RESULTS: Of 166 eyes in 110 patients with CMV retinitis, visual field defects were present initially in 92 (55%) eyes of 78 (70%) patients, and ultimately in 97 (53%) eyes of 90 patients in whom follow-up was available. Stabilization of visual field defects was indicative of controlled retinitis. CONCLUSION: Sequential visual field testing will confirm ophthalmoscopic evidence of successful antiviral treatment of CMV retinitis and will corroborate very early progression of previously controlled retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1991

Development and testing of protocols for computer-aided design of peptide drugs, using oxytocin.

Considerable clinical interest in neuropeptides and peptide hormones has stimulated recent research and development of peptide-based drugs. This process differs from most classical drug discovery procedures because peptide molecules have considerable inherent flexibility. In the present paper, to identify lowest energy and metastable conformers for drug design, and to develop protocols for such studies, conformational search algorithms, incorporating empirical energy calculations, have been applied in the analysis of the peptide oxytocin. Energy minimization in torsion angle space was carried out from a variety of starting conformations, including published structures, in all-atom mode and all with distance constraints for disulphide bond formation. The energy-minimized conformations have been further optimized by a mapping method. Complementary simulations have been performed in united-atom mode and a model representing the effects of water using dummy sites has been developed and tested for this representation. Several of the preferred conformers together with de novo conformations have been used as starting points in molecular dynamics simulations; 28 low potential energy conformations were located at a temperature of 4 K. Conformations are analysed to identify hydrogen bonds, phi-psi angle distributions and the RMS values relative to the X-ray structure of deamino-oxytocin. The modelled structure of lowest energy in the molecular mechanics calculations was also that of least RMS deviation from the crystal structure; whilst structures of lower energy but larger deviation were identified by molecular dynamics techniques. A metastable structure has been identified which satisfies existing criteria for the "active form", and this model is tested by a theoretical residue-substitution technique, to provide clues on the agonist/antagonist relationship at the atomic level.

Computers↗
PubMed1991

Immunity to onchocerciasis: recognition of larval antigens by humans putatively immune to Onchocerca volvulus infection.

Immunoblot analyses were done using sera from 12 individuals without evidence of onchocerciasis and 16 with active infection from an area of Guatemala holoendemic for onchocerciasis. For adult antigens from Onchocerca volvulus, no differences in antigen recognition could be identified between the two groups. In contrast, when infective larval (L3) antigen preparations derived from the related animal parasite Onchocerca lienalis were used, IgG from the "immune" individuals preferentially recognized a 45- to 50-kDa triplet and a 22-kDa L3 antigen. When L3 antigens of Brugia malayi were used, sera from putatively immune individuals identified a high-molecular-weight triplet/quadruplet plus several additional antigens of lower molecular weights that were recognized by sera from few (or none) of the infected patients. These findings define some differences in antibody specificity in onchocerciasis patients and therefore might define potential target antigens of humoral host defense. The exact nature of such defenses is unknown.

Adolescent↗
PubMed1991

Typing of normal and variant red cells with ABO, Rh, and Kell typing reagents using a gel typing system.

In 1989 Lapierre et al. described a novel method of detecting agglutination reactions by the use of a Sephadex (DiaMed ID Typing System) gel held in a microtube. This report examines the use of gels containing ABO, Rh, and Kell system specific antibodies. The anti-A and -B were monoclonal reagents; anti-A,B, and those for the Rh and Kell systems were polyclonal. Five hundred and fifty-one tests performed for the ABO system detected all but the most weakly reacting variants, a detection rate superior to most commercially available reagents. Five hundred and thirty samples were typed for Rh antigens. One hundred and twenty-seven of these were of various D category III through VII types (Dcats) and 154 were Du>s. The gel system detected all but seven DVI variants and seven Dus. The seven DVI variants, from individuals with no anti-D in their sera, gave reactions identical to the seven Dus when tested against a panel of over 50 monoclonal IgG and IgM anti-Ds. The 554 samples tested for the K1 antigen gave correct results.

Journal Article↗
PubMed1990

Cessation of Cryptosporidium-associated diarrhea in an acquired immunodeficiency syndrome patient after treatment with hyperimmune bovine colostrum.

Cryptosporidium is a parasite of the human gastrointestinal tract that can cause life-threatening diarrhea in immunodeficient patients. Although more than 80 agents have been tried with occasional anecdotal success, treatment remains primarily limited to hydration. A 38-yr-old homosexual man with antibody to human immunodeficiency virus and Cryptosporidium-related diarrhea is described. The patient excreted 6-12 L of stool per day for at least 3 mo, 2 of them spent in the hospital. Trials with more than 6 antidiarrheal medications were ineffective. The patient received bovine colostrum hyperimmune to Cryptosporidium by direct duodenal infusion. During infusion, the patient's fecal output decreased to less than 2 L per day, and 48 h after treatment, stools were formed and oocysts to Cryptosporidium were absent. The patient remained asymptomatic for 3 mo. Hyperimmune bovine colostrum offers an exciting new therapy for cryptosporidiosis; controlled trials to establish efficacy should be undertaken and the active factor(s) characterized.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Treatment of toxic epidermal necrolysis and a review of six cases.

Six cases of drug-induced toxic epidermal necrolysis treated in a burns unit are presented. The mean skin loss was 67.3 per cent of the total body surface area. Two patients developed renal failure and two had ocular symptoms. The mortality rate was 50 per cent, with two patients dying from septicaemia and one from respiratory and renal failure. The diagnosis of toxic epidermal necrolysis can be confirmed by skin biopsy. We recommend that this disease is treated in a burns unit so that both adequate wound care and essential intensive supportive treatment can be given. Antibiotics are indicated only for specific infections such as septicaemia or pneumonia. Steroids have been shown to increase greatly the mortality from septic complications and are not recommended. The mortality ranges from 10 per cent to 70 per cent and bad prognostic factors include increasing age, greater than 50 per cent of body surface skin loss and neutropenia.

Adolescent↗
PubMed1990

Spontaneous pneumothorax in patients with acquired immunodeficiency syndrome treated with prophylactic aerosolized pentamidine.

Spontaneous pneumothorax is a known complication of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. To evaluate the possible pathogenesis and natural history of pneumothorax in patients receiving aerosolized pentamidine prophylaxis, we retrospectively reviewed 327 outpatients positive for human immunodeficiency virus receiving aerosolized pentamidine. There were 12 spontaneous pneumothoraces in this group of patients. Seventy-five percent of patients with pneumothorax had roentgenographic evidence of fibrocystic lung parenchyma and clinical evidence of active Pneumocystis pneumonia. The majority (83%) required chest tube evacuation. There was a 50% mortality rate associated with this complication. These findings suggest that spontaneous pneumothorax in patients treated with aerosolized pentamidine most commonly represents a prophylaxis failure associated with a high mortality rate.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The healing of chronic venous leg ulcers with prepared human amnion.

Forty chronic venous leg ulcers were treated, before split skin grafting, with human amnion prepared in one of the four following ways: tissue-culture-maintained, frozen, fresh or lyophilised. Although there was no significant statistical difference in the results obtained with the different preparations of amnion, we found that lyophilised amnion was at least as good as the other preparations in promoting a good take of the skin grafts and was the simplest to store and use. It also produced the shortest healing times. Frozen and fresh amnion were easier to prepare than lyophilised amnion but gave a lower graft take and a longer healing time. Tissue-culture-maintained amnion was the most difficult to prepare and gave the poorest results. Its use was abandoned during the trial because of technical difficulties and a high infection rate.

Aged↗
PubMed1989

Abdominal reduction following jejunoileal bypass for morbid obesity.

We present six patients who underwent abdominal reduction after successfully losing weight following jejunoileal bypass. Three patients needed more than one operation to achieve a good cosmetic result. There were no serious complications. After reviewing these patients and the few previously reported cases we make the following suggestions: 2 years should elapse after a stable weight is attained before surgery. Preoperative metabolic screening is essential. Preoperative marking of the lines of excision, prophylactic antibiotics and drainage of the wounds are strongly recommended. Lower abdominal aprons may be safely removed by a low transverse incision extended laterally up to the iliac crests and superiorly as far as the umbilicus. The umbilicus can be resited without risk of necrosis. High abdominal aprons should be excised as a transverse or vertical "melon-slice" ellipse without undermining.

Abdomen↗
PubMed1988

Beau's lines following hand trauma.

Six cases are described of Beau's lines (transverse grooves in the fingernails) developing after injuries to the hand involving damage to nerves and flexor tendons. The literature is reviewed.

Adolescent↗
PubMed1988

Onchocerciasis and immunity in humans: enhanced T cell responsiveness to parasite antigen in putatively immune individuals.

To identify possible immune mechanisms in human onchocerciasis, we compared a group of 12 individuals who had no clinical or parasitological evidence of infection, despite ongoing exposure to the parasite, with a group of 16 individuals from the same area who had active Onchocerca volvulus infection. Despite having less parasite-specific serum antibody, the infection-free ("putatively immune") individuals showed greater lymphocyte responsiveness, especially interleukin-2 (IL-2) production, to O. volvulus antigen (OVA) than did the infected subjects; lymphocyte responses (including IL-2 production) to mitogens and nonparasite antigen in both study groups were equivalent and normal. Our findings define differences in parasite-specific T cell subpopulations between infected and putatively immune subjects that could be a central element in developing or maintaining protective immunity to O. volvulus infection.

Adolescent↗
PubMed1988

Quality control system promotes accountability.

Catholic Health Corporation's (CHC) comprehensive quality control system is an integrated network of review and feedback mechanisms. The mechanisms apply to many facilities and may help them to enhance services and to follow more closely in the Church's tradition of teaching through example. The operational model adapted for use here suggests a system of checks and balances of the following planning, management, and governance functions: Selecting a CEO. Updating strategic plan. Updating mission and philosophy statements. Setting CEO performance objectives. Developing value-based administrative policies. Budgeting. Monitoring operational trends. Problem solving. Planning a major capital investment. Approving board appointments. Evaluating CEO performance. Providing stewardship accountability to the sponsor. Managers, trustees, and sponsors may use information from the system to improve performance, shift strategy or revise major policies, and ensure continuity with the mission, philosophy, and traditions of the religious institute.

Aged↗