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Biomedical subjects

A Hay

Publications and source records attributed to A Hay.

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

Molecular basis of a bacterial consortium: interspecies catabolism of atrazine.

Pseudomonas sp. strain ADP contains the genes, atzA, -B, and -C, that encode three enzymes which metabolize atrazine to cyanuric acid. Atrazine-catabolizing pure cultures isolated from around the world contain genes homologous to atzA, -B, and -C. The present study was conducted to determine whether the same genes are present in an atrazine-catabolizing bacterial consortium and how the genes and metabolism are subdivided among member species. The consortium contained four or more bacterial species, but two members, Clavibacter michiganese ATZ1 and Pseudomonas sp. strain CN1, collectively mineralized atrazine. C. michiganese ATZ1 released chloride from atrazine, produced hydroxyatrazine, and contained a homolog to the atzA gene that encoded atrazine chlorohydrolase. C. michiganese ATZ1 stoichiometrically metabolized hydroxyatrazine to N-ethylammelide and contained genes homologous to atzB and atzC, suggesting that either a functional AtzB or -C catalyzed N-isopropylamine release from hydroxyatrazine. C. michiganese ATZ1 grew on isopropylamine as its sole carbon and nitrogen source, explaining the ability of the consortium to use atrazine as the sole carbon and nitrogen source. A second consortium member, Pseudomonas sp. strain CN1, metabolized the N-ethylammelide produced by C. michiganese ATZ1 to transiently form cyanuric acid, a reaction catalyzed by AtzC. A gene homologous to the atzC gene of Pseudomonas sp. strain ADP was present, as demonstrated by Southern hybridization and PCR. Pseudomonas sp. strain CN1, but not C. michiganese, metabolized cyanuric acid. The consortium metabolized atrazine faster than did C. michiganese individually. Additionally, the consortium metabolized a much broader set of triazine ring compounds than did previously described pure cultures in which the atzABC genes had been identified. These data begin to elucidate the genetic and metabolic bases of catabolism by multimember consortia.

Journal Article↗
PubMed1998

The effect of drug packaging on patients' compliance with treatment for Plasmodium vivax malaria in China.

A study conducted in 1994 showed that the use of blister packs containing antimalarial drugs significantly increased patients' compliance, compared with traditional means of dispensing drugs in a paper envelope. The present study assessed patients' compliance and compared the difference between 3-day chloroquine and 8-day primaquine courses of treatment for vivax malaria. The level of real compliance was determined by making the drugs with phenobarbital, and measuring its level in the blood following treatment. The results show that blister packaging significantly improved patients' compliance (p < 0.001) over traditional means of dispensing antimalarial drugs; there was no difference in treatment compliance between 3-day and 8-day courses when the drugs were in blister packs. However, with ordinary packaging the treatment compliance rate for an 8-day course was significantly less than for a 3-day course (P < 0.05).

Adolescent↗
PubMed1998

Initial evaluation of low-dose phenobarbital as an indicator of compliance with antimalarial drug treatment.

Since poor compliance with antimalarial therapy is often suspected but difficult to prove, this study attempted to establish a model for predicting the plasma concentration of phenobarbital (given in low doses in conjunction with the drug) as an indicator of compliance. Phenobarbital was chosen because its value had been demonstrated as a marker of compliance in long-course therapies, any significant departure from steady-state concentrations (achieved with full compliance) indicating one or more missed doses. Therapy for uncomplicated malaria varies from 5 days with artesunate to 7 days with quinine + tetracycline. Volunteers with confirmed falciparum malaria were randomized into 5 groups and given malaria therapy as well as phenobarbital daily for 3-7 days. Plasma samples for determination of phenobarbital concentrations were taken just prior to the daily dose of phenobarbital. Although there was a clear and predictable individual pattern of blood concentrations following each dose of phenobarbital, inter-individual variation in blood levels was significant and reduced their predictive value beyond the second day's dose. The cause of the variations is not clear; it could be attributable to different sources of the drug, previous intake of phenobarbital by the patient, or differences in drug absorption and disposition in malaria patients. Results for the 5-day artesunate regimen suggest that phenobarbital may be useful as a marker of compliance if the patient stops medication after 3 days; clear differences were evident at the end of the course of treatment between plasma phenobarbital concentrations in individuals completing the 5-day course and those who stopped after 3 days. For the quinine-tetracycline regimen, results suggest that it may be possible to discriminate between subjects where there is a 3-day difference in treatment. Phenobarbital is a better discriminant when dosing is every 24 hours as with artesunate, rather than the 8-hourly regimen for quinine-tetracycline. When measuring compliance for malaria treatment, if it is important to know what proportion of patients reach 3, 5 or 7 days of compliance, then phenobarbital might have a role to play in this assessment, but further investigations in more patients would be required. Alternatively, different markers could be used for the doses to be given on these days and, as long as the patient does not mix the doses for the different days, sequential doses and determination of compliance could be based on an "all or none" detection of the marker rather than on drug levels.

Adolescent↗
PubMed1997

Mortality of power workers exposed to phenoxy herbicides and polychlorinated biphenyls in waste transformer oil.

Herbicide spray crews employed by a Canadian power company between 1950 and 1967 had a higher than expected death rate, with a standardized mortality ratio of 157% (CI 130%-194%). In 1991, the cohort consisted of 225 former sprayers of whom 127 were still alive and 98 had died. Eligibility for inclusion in the cohort was based on employer records; and a history of spraying for 30 days or more in at least one spray season. Deaths expected were based on age-specific population mortality rates for New Brunswick. The all-age SMR for the total cohort was 159%. After 1958, however, waste transformer oil was added to the phenoxy-herbicide spray mixture, the oil representing 10% of the final mixture. Spray crews wore no protective clothing. Subdividing the cohort into spray years 1950-1958 and 1959-1967 yielded SMRs of 146% (CI 115%-184%); and 215% (CI 139%-318%), respectively. The transformer oil was used during the period 1959-1967. Most excess deaths were due to cardiovascular disease.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1997

Methadone maintenance and drug-related crime.

Using data from an evaluation of methadone maintenance treatment, this study investigated factors associated with continued involvement in crime during treatment, and in particular whether there appeared to be differences in effectiveness of treatment between different methadone clinics. The methodology was an observational study, in which 304 patients attending three low-intervention, private methadone clinics in Sydney were interviewed on three occasions over a twelve month period. Outcome measures were self-reported criminal activity and police department records of convictions. By self-report, crime dropped promptly and substantially on entry to treatment, to a level of acquisitive crime about one-eighth that reported during the last addiction period. Analysis of official records indicated that rates of acquisitive convictions were significantly lower in the in-treatment period compared to prior to entry to treatment, corroborating the changes suggested by self-report. Persisting involvement in crime in treatment was predicted by two factors: the cost of persisting use of illicit drugs, particularly cannabis, and ASPD symptom count. Treatment factors also were independently predictive of continued involvement in crime. By both self-report and official records, and adjusting for subject factors, treatment at one clinic was associated with greater involvement in crime. This clinic operated in a chaotic and poorly organized way. It is concluded that crime during methadone treatment is substantially lower than during street addiction, although the extent of reduction depends on the quality of treatment being delivered.

Adult↗
PubMed1995

Follow up of an immunocompromised contact group of a case of open pulmonary tuberculosis on a renal unit.

BACKGROUND: The organisation, management, outcome and cost of follow up of a large group of mainly immunocompromised patients and healthcare workers who were exposed to a staff member of a London renal unit with smear positive pulmonary tuberculosis are described. METHODS: Following British Thoracic Society (BTS) guidelines, 576 close contacts were identified and divided into three groups: (1) 303 renal patients including 61 with renal transplants; (2) 90 surgical patients; and (3) 183 staff members. Screened contacts were interviewed, completed a symptoms questionnaire, and were offered a chest radiograph and Heaf or Mantoux test if appropriate with referral to a chest physician if required. RESULTS: Overall, 524 (85%) living contacts have been screened: 243 (97%) renal (first screening), 63 (70%) surgical, and 135 (74%) staff contacts. Thirty one transplant patients were prescribed isoniazid chemoprophylaxis. Fifty two renal patients had died before screening and 11 deaths occurred after first interview. One case of tuberculosis epidemiologically related to the index case was diagnosed on clinical criteria. A review of the case records and/or death certificates and entries on to tuberculosis registers indicated no further cases. The cost of the investigation was estimated to be approximately franc25 000, or franc44 per contact screened, with staff costs comprising 79% of the total. CONCLUSIONS: Undiagnosed tuberculosis in healthcare workers working with immunosuppressed patients can lead to large and expensive follow up studies. The applicability of the 1990 and 1994 BTS guidelines to the investigation of tuberculosis in an immunocompromised nosocomial group, and the role of the infection control doctor and the consultant in Communicable Disease Control in overlapping nosocomial and community incidents, are discussed.

Adolescent↗
PubMed1994

Anti-HIV-1 activity of chemically modified heparins: correlation between binding to the V3 loop of gp120 and inhibition of cellular HIV-1 infection in vitro.

Chemically modified heparins were tested for their activities in (i) inhibiting HIV-1 replication in vitro and (ii) inhibiting the binding to recombinant HIV-1 gp120 of monoclonal antibodies specific for the V3 loop. The results reveal that N-desulfation reduces activity, although this is largely restored on N-acetylation. Selective O-desulfation also markedly reduces activity, whereas carboxyl reduction has little effect. Overall these results show that the anti-HIV-1 activity of heparin does not depend simply on negative density, and indicate instead that particular structures, notably O-sulfates, are involved. Our studies reveal that for chemically modified heparins and heparin-derived fragments there is a striking correlation between anti-HIV-1 activity in vitro and binding to the V3 loop of gp120 in solid phase ELISA. This strongly suggests that the heparin exerts its anti-HIV-1 activity by binding to the V3 loop of gp120.

Acetylation↗
PubMed1994

Fibrinolytic-assisted removal of experimental subretinal hemorrhage within seven days reduces outer retinal degeneration.

PURPOSE: To better determine the surgical window for removing experimental subretinal hemorrhages in the cat model and to compare the histopathologic effect of such removal with the natural history of untreated subretinal hemorrhages. METHODS: Twenty-three large experimental subretinal hemorrhages were created with a neodymium:YAG laser focused through a performed retinal bleb in a cohort of cats. Fourteen subretinal hemorrhages were observed without treatment, six were removed at 7 days through a micropipette after injecting 10 micrograms/ml of human recombinant tissue plasminogen activator (rt-PA) into the subretinal space, and three were removed through an access retinotomy without the use of rt-PA. The tissues from these eyes were examined with light and electron microscopy 14 to 28 days after creation of the subretinal hemorrhages. RESULTS: Severe outer retinal degeneration was evident by day 14 in all of the untreated subretinal hemorrhages 3 disc diameters or greater in size. In contrast, the outer retinal architecture was better preserved in the eyes that underwent rt-PA-assisted removal of their subretinal hemorrhage that was 3 disc diameters or greater on day 7. In these eyes, mild abnormalities such as abnormally short and misaligned photoreceptor outer segments with vacuolization were present within the retina that was formerly located over the hemorrhage center. The eyes that underwent subretinal hemorrhage removal through an access retinotomy without rt-PA on day 7 had a low-lying retinal detachment and outer retinal degeneration. CONCLUSION: Removing experimental subretinal hemorrhages within 7 days of their occurrence with the assistance of rt-PA and an ultramicrosurgical approach may reduce outer retinal degeneration in the cat model.

Animals↗
PubMed1993

Gastric intramural pH as a predictor of success or failure in weaning patients from mechanical ventilation.

OBJECTIVE: To determine whether gastric intramural pH (pHi), an indirect measure of gastric mucosal ischemia, can be used to predict the success of weaning from mechanical ventilation. Gastric mucosal ischemia (and, therefore, acidosis) may develop in patients during unsuccessful attempts to wean them from mechanical ventilation because blood flow from nonvital areas (for example, splanchnic bed) is diverted to meet the increased demands of respiratory muscles. DESIGN: Cohort study. SETTING: Intensive care unit. PATIENTS: Twenty-nine patients receiving assisted mechanical ventilation for respiratory failure who were thought by their physicians to be weanable from mechanical ventilation. MEASUREMENTS: Simultaneous samples of arterial blood and gastric juice were obtained from patients during assisted mechanical ventilation, as well as during weaning trials. The predictor variable, pHi, was calculated using the following equation: 6.1 + log HCO3/(gastric PCO2 x 0.0307). The outcome was success or failure of weaning, decided by physicians blinded to the study. RESULTS: Patients who could not be weaned from mechanical ventilation had a substantially reduced gastric pHi (7.36 during mechanical ventilation compared with 7.09 during weaning [difference, 0.27; 95% Cl, 0.12 to 0.42; P < 0.01]). Patients who were successfully weaned from mechanical ventilation showed no change in pHi (7.45 during mechanical ventilation compared with 7.46 during weaning [difference, 0.01; Cl, -0.01 to 0.03; P = 0.29]). The sensitivity and specificity of pHi in predicting weaning success or failure were both 100% (Cl, 81 to 100 and 72 to 100, respectively). CONCLUSION: Gastrointestinal acidosis may be an early sign of weaning failure. Measurement of pHi, which is simple and rapid, may be of practical value in predicting the likelihood of weaning success or failure during weaning trials.

Acidosis↗
PubMed1993

A comparison of argon and diode photocoagulation combined with supplemental oxygen for the treatment of retinopathy of prematurity.

The efficacy of argon and diode laser photocoagulation of the avascular peripheral retina for threshold retinopathy of prematurity (ROP) was compared in a prospective trial. The study group included 9 premature infants (17 eyes). In each infant, one eye was treated with the diode laser indirect ophthalmoscope (LIO), and the fellow eye was treated with the argon LIO. Supplemental oxygen therapy was administered after laser treatment to all nine infants. The mean duration of the follow-up period was 9.7 +/- 2.6 months. All 17 eyes (100%) had complete regression of ROP and favorable outcomes. The diode and argon LIO appear to be equally effective in treating threshold ROP. Two patients sustained burns of the tunica vasculosa lentis and anterior lens capsule in the argon laser treated eye but not in the fellow diode treated eye. Photocoagulation with either the diode or argon LIO, combined with supplemental oxygen treatment, appears to be a promising treatment for retinopathy of prematurity.

Combined Modality Therapy↗
PubMed1993

Expression of the terminal protein of hepatitis B virus is associated with failure to respond to interferon therapy.

The terminal protein domain of the hepatitis B viral polymerase can inhibit the cellular response to interferon. To clarify the clinical relevance of this inhibitory effect, we examined the expression of terminal protein in liver biopsy specimens from patients with chronic hepatitis B infection. We found that expression of terminal protein is associated with a failure of hepatocytes to respond to interferon, as assessed by expression of the interferon-inducible protein beta 2-microglobulin. Patients whose liver specimens contained large numbers of cells expressing terminal protein tended not to respond to treatment. During interferon therapy the percentage of cells expressing terminal protein remained constant, but treatment significantly reduced the number of cells that expressed the hepatitis B nucleocapsid protein. Hence expression of terminal protein in a cell may prevent elimination of the virus by interferon therapy.

Adult↗