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Biomedical subjects

G Watt

Publications and source records attributed to G Watt.

At least 55 records · Page 3Linked to original sources
PubMed1997

Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian soldiers. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Mefloquine and doxycycline are the two drugs recommended for prophylaxis of malaria for visitors to areas where Plasmodium falciparum is resistant to chloroquine. OBJECTIVE: To compare the efficacy and tolerability of mefloquine with those of doxycycline as prophylaxis for malaria. DESIGN: Randomized, double-blind, placebo-controlled field trial of chemoprophylaxis of malaria. SETTING: Northeastern Irian Jaya, Indonesia. PARTICIPANTS: 204 Indonesian soldiers. INTERVENTION: After radical curative treatment, participants were randomly assigned to receive 100 mg of doxycycline per day and mefloquine placebo; 250 mg of mefloquine per week (preceded by a loading dose of 250 mg/d for 3 days) and doxycycline placebo; or placebos for both drugs. Prophylaxis lasted approximately 13 weeks. MEASUREMENTS: The primary end point for efficacy was the first occurrence of malaria, as documented by a positive malaria smear. Malaria smears were obtained weekly and when patients had symptoms suggesting malaria. Reported symptoms were recorded daily, and an exit study questionnaire was conducted. RESULTS: In the placebo group, 53 of 69 soldiers developed malaria (9.1 person-years), resulting in an attack rate of 5.8 cases per person-year (95% CI, 4.3 to 7.7 cases per person-year). Plasmodium falciparum accounted for 57% of cases, and P. vivax accounted for 43% of cases. No malaria occurred in the 68 soldiers (16.9 person-years) in the mefloquine group; thus, the protective efficacy of mefloquine was 100% (CI, 96% to 100%). In the doxycycline group, P. falciparum malaria occurred in 1 of 67 soldiers (16.0 person-years), yielding a protective efficacy of 99% (CI, 94% to 100%). Both drugs were very well tolerated. CONCLUSIONS: Mefloquine and doxycycline were both highly efficacious and well tolerated as prophylaxis of malaria in Indonesian soldiers.

Adult↗
PubMed1997

Successful use of ivermectin in the treatment of endemic scabies in a nursing home.

Ivermectin, an antiparasitic agent, was successfully used as a sole agent to combat endemic scabies in a closed 33-bed ward of a rural nursing home. Previous topical therapies, including multiple applications of permethrin, gamma-benzene hexachloride, benzyl benzoate and precipitated sulfur in white soft paraffin, had failed. Several patients exhibited hyperkeratotic crusted scabies with head and neck involvement and all residents except one recently arrived resident had evidence of active infestation. All residents were treated with 200 micrograms/kg of ivermectin and this dose was repeated 2 weeks later in all subjects. Four weeks after the first dose of ivermectin there was no evidence of active scabies and all rashes were totally resolved by 6 weeks. The action of ivermectin, its safety and its indications are discussed.

Administration, Oral↗
PubMed1997

Has regional variation in mortality rates declined since 1931, and in all age groups, in Britain? A re-analysis using formal statistical modelling.

STUDY OBJECTIVE: To examine changes in regional variance in all cause mortality rates in Great Britain from 1931-91 using formal statistical modelling procedures, and to follow up the suggestion by Illsley and Le Grand that there has been a reduction over time in the regional variance in younger but not older age groups. DESIGN, SETTING, AND PARTICIPANTS: Data were the age and sex specific death rates around each census from 1931-91 for the British regions, reconstructed to make them comparable with the 1981 regional definitions. Regional variance was modelled using bootstrap simulation tests and by age-period and age-cohort models. MEASUREMENTS AND MAIN RESULTS: While there was some evidence of a decline and levelling off of the regional variance over time in older age groups (over 35), the decline in younger age groups was more marked. This broadly confirms previous findings. Parametrising the period effect into linear and quadratic components, with allowance for an increase in regional variance in the war years, gave broadly comparable fit to the data as a model with period as a factor. Models for the changes in regional variance which were based on period effects seemed to provide a better description of the observed variances than those based on birth cohort effects. In the younger (but not older) groups there was evidence of a rise in the regional variance between 1981 and 1991. CONCLUSIONS: The decline in regional variance is larger in younger than in older age groups when allowance is made for the increase in regional variance over the war years. Statistical modelling can provide insights into the data which are not always detected by descriptive analyses. Moreover, they provide a capacity for generalisation beyond the particular data; relationships found can form the basis for studies of replicability, for example, in other countries.

Adolescent↗
PubMed1996

Scrub typhus infections poorly responsive to antibiotics in northern Thailand.

BACKGROUND: Rickettsia tsutsugamushi, the aetiological agent of scrub typhus, is common in Asia and readily infects visitors to areas where disease transmission occurs. Rapid defervescence after antibiotic treatment is so characteristic that it is used as a diagnostic test for R tsutsugamushi infection. Reports from local physicians that patients with scrub typhus in Chiangrai, northern Thailand responded badly to appropriate antibiotic therapy prompted us to do a prospective clinical evaluation and antibiotic susceptibility testing of human rickettsial isolates. METHODS: The clinical response to doxycycline treatment in patients with early, mild scrub typhus in northern Thailand was compared with the results of treatment in Mae Sod, western Thailand. Prototype and naturally occurring strains of R tsutsugamushi were tested for susceptibility to chloramphenicol and doxycycline in mice and in cell culture. FINDINGS: By the third day of treatment, fever had cleared in all seven patients from Mae Sod, but in only five of the 12 (40%) from Chiangrai (p < 0.01). Median fever clearance time in Chiangrai (80 h; range 15-190) was significantly longer than in Mae Sod (30 h; range 4-58; p < 0.005). Conjunctival suffusion resolved significantly more slowly in Chiangrai (p < 0.05). Antibiotics prevented death in mice infected by Chiangrai strains of R tsutsugamushi less often than after infection by the prototype strain (p < 0.05). Only one of three Chiangrai strains tested in cell culture was fully susceptible to doxycycline. INTERPRETATION: Chloramphenicol-resistant and doxycycline-resistant strains of R tsutsugamushi occur in Chiangrai, Thailand. This is the first evidence of naturally occurring antimicrobial resistance in the genus Rickettsia.

Administration, Oral↗
PubMed1996

Sex differences in myocardial infarction and coronary deaths in the Scottish MONICA population of Glasgow 1985 to 1991. Presentation, diagnosis, treatment, and 28-day case fatality of 3991 events in men and 1551 events in women.

BACKGROUND: Scottish MONICA used medical and medico-legal records and World Health Organization MONICA Project criteria to register coronary events in 25- to 64-year-old residents of the high-incidence area of north Glasgow from 1985 to 1991. METHODS AND RESULTS: Age-standardized data from 3991 episodes of nonfatal definite myocardial infarction and coronary deaths in men (mean age, 55.5 years) were compared with 1551 in women (57.0 years). Many results, such as the overall 28-day fatality rates of 49.8% in men and 48.5% in women, showed insignificant differences. However, 74.3% of deaths in men occurred out of hospital versus 67.8% in women (P = .0004). After admission to hospital, fatality rates in women were 14% higher (P = .07) and after admission to coronary care, 22% higher (P = .04). Women were more often widowed. Fewer had a history of previous myocardial infarction, but the prevalence of angina pectoris, of smoking, and of chest pain in the attack was the same as in men; more had shock, syncope, and breathlessness. More consulted a doctor before admission to hospital, which delayed their coming under care. More men had ECG Q-wave progression, and more women had smaller ECG changes. This, and marginally reduced chances of direct admission to coronary care, of thrombolysis, of aspirin, and of beta-blockers, did not explain women's excess hospital fatality. CONCLUSIONS: Acute coronary events appear to be recognized and treated fairly equally in men and women 25 to 64 years old in Glasgow, so differences are small but subtle. More men die suddenly out of hospital; the reason why more women die after arrival may be because the equivalent number of men have already died outside.

Acute Disease↗
PubMed1996

Enhanced detection of Plasmodium vivax liver stages by cytocentrifugation.

Malaria parasites circulating in the blood or developing in the mosquito host can easily be seen and studied. We know much less about malaria parasites in the liver not only because of their location, but also because there are so few of them. Hepatic parasites are most often grown within hepatoma cells in culture, stained and visualized on slides under direct microscopy. In this report, Chitraporn Karnasuta and George Watt investigate the potential of cytocentrifugation as a tool for improving the detection of liver-stage malaria parasites.

Journal Article↗
PubMed1996

Infection with human immunodeficiency virus does not influence the clinical severity of scrub typhus.

Infection by Orientia (formerly Rickettsia) tsutsugamushi causes scrub typhus, a severe febrile disease common in Asia. Both scrub typhus and AIDS are prevalent in northern Thailand. Therefore, we prospectively investigated the impact of infection due to human immunodeficiency virus (HIV) on the severity of the clinical syndrome produced by O. tsutsugamushi. The severity of scrub typhus was objectively graded on admission of patients to the hospital, and serologies for antibodies to HIV were performed. Fourteen (16%) of 86 patients with scrub typhus were infected with HIV; the median T helper cell count was 70/mm3. There were no significant differences between HIV-infected patients and non-HIV-infected patients in severity scores or other admission characteristics. O. tsutsugamushi was isolated in blood samples from 48.6% of patients without HIV infection and in blood samples from 14.3% of HIV-infected patients (P < .05 x 2 test). The clinical manifestations of O. tsutsugamushi infection, unlike those due to some other intracellular pathogens, are not unusually severe in immunocompromised patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1995

Pharmacokinetics of an extended-dose halofantrine regimen in patients with malaria and in healthy volunteers.

The pharmacokinetics and tolerance of a 4.5 gm 7-day halofantrine loading dose regimen were evaluated in 10 Thai patients with malaria and in 10 noninfected volunteers. Halofantrine peak plasma concentrations and bioavailability on the first day of treatment were significantly lower in patients with malaria than in healthy volunteers. Halofantrine elimination half-life was significantly shorter in patients with malaria than healthy control subjects (9.5 versus 15.8 days). These data show a distinct effect of acute malaria on the absorption and elimination of the drug. In addition, marked intersubject and intrasubject variability in peak and trough halofantrine levels was observed, indicating variable drug absorption. This dosing regimen was effective and well tolerated, with mild transient diarrhea during the first few days of treatment in both groups. To produce consistently effective drug levels, the currently recommended dosing regimens may be suboptimal. Slow halofantrine elimination raises concern for induction of parasite resistance when the drug is used in endemic areas of the world.

Administration, Oral↗
PubMed1995

Prospective comparison of methods for the early prediction of treatment failure in patients with falciparum malaria.

The prompt identification of patients with falciparum malaria who are at risk of late therapeutic failure could help clinicians avoid the dangers of missed or delayed retreatment. Different methods for predicting late recrudescence were compared for 52 patients whose parasitemia initially cleared after treatment with either halofantrine or quinine. Parasites reappeared in the peripheral circulation of six individuals 17 to 28 days after the initiation of therapy. Transient rises in parasite counts on thick blood films were accurate (91% specific and 100% sensitive) and prompt indicators of eventual recrudescence. All six therapeutic failures had been predicted by the third day (mean time [+/- SEM], 51.5 +/- 3.6 hours) after initiation of treatment. Parasite clearance time, fever clearance time, rRNA probe, and the polymerase chain reaction had less practical prognostic value. Serial thick-film parasite counts are a simple, cheap, rapid, and reliable method for identifying patients at high risk of recrudescence.

Adult↗
PubMed1995

Complete development of the liver stage of Plasmodium falciparum in a human hepatoma cell line.

Plasmodium falciparum parasites develop in the liver before being released into the bloodstream, where they exert the potentially lethal effects characteristic of malaria. Our understanding of the hepatic phase of the life cycle is limited by the parasite's requirement for fresh human liver cells in which to mature. In this work, liver parasites completed their development within a Thai human hepatoma cell line (HHS-102), and the presence of ring-form parasites in erythrocytes overlying the liver cell culture confirmed that an entire liver cycle was completed, culminating in the production of viable blood-stage parasites. The HHS-102 cell line allows investigation of the undefined liver stage of falciparum malaria previously unavailable in the laboratory.

Animals↗
PubMed1994

Purification and characterization of a FeMo cofactor-deficient MoFe protein.

Previous studies have shown that the nifH gene product is required for FeMo cofactor biosynthesis and insertion and that a delta nifH strain of Azotobacter vinelandii designated DJ54 accumulates a FeMo cofactor-deficient MoFe protein that is distinct from the FeMo cofactor-deficient protein synthesis by Nif B-, N-, or E- strains [Tal, S., Chun, T., Gavini, N., & Burgess, B. K. (1991) J. Biol. Chem. 266, 10654-10657]. Here we report the purification and activation of the MoFe protein from DJ54. The purified protein is an alpha 2 beta 2 tetramer that is indistinguishable from the wild-type MoFe protein by the criteria of SDS-polyacrylamide gel electrophoresis, native gel electrophoresis, and two-dimensional gel electrophoresis. It binds normally to its redox partner, the Fe protein, by the criterion of chemical cross-linking. It does not contain FeMo cofactor and does not catalyze significant C2H2 reduction or reduction-independent MgATP hydrolysis. It can, however, be activated with FeMo cofactor following the addition of the Fe protein and MgATP when an additional required component(s) is supplied by cell-free extracts from a delta nifD strain of A. vinelandii. The purified DJ54 MoFe protein does contain P-clusters by the criteria of metal analysis, CD spectroscopy, cluster extrusion, and electrochemical reduction of the POX state. In the presence of dithionite it exhibits an axial S = 1/2 EPR signal that integrates to 0.1-0.3 spin per alpha 2 beta 2 tetramer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

Life-threatening scrub typhus in a traveler returning from Thailand.

Scrub typhus is not one of the more commonly encountered diseases in travelers returning from Asia, but it deserves more consideration in view of its severity and the availability of specific chemotherapy and chemoprophylaxis. We describe a case of scrub typhus that was associated with coma and multiorgan failure in a traveler returning to the United States from Thailand. The diagnosis was made only retrospectively despite a travel history and clinical signs that suggested infection with Rickettsia tsutsugamushi. No specific therapy was given, and marked neurological impairment persisted 6 months after the beginning of the illness. An increased awareness of scrub typhus is a prerequisite for recommending prophylaxis and instituting prompt therapy.

Coma↗
PubMed1994

Efficacy and tolerance of extended-dose halofantrine for drug-resistant falciparum malaria in Thailand.

New treatments for malaria are urgently needed in areas such as Thailand where highly drug-resistant strains of Plasmodium falciparum are prevalent. Mefloquine is rapidly losing efficacy and conventional doses of halofantrine are infective. We therefore used pharmacokinetic stimulation to design an extended-dose halofantrine regimen and tested it in 26 soldiers stationed along the Thai-Cambodian border. Halofantrine was given after meals as three doses of 500 mg each at 4-hr intervals on the first day, followed by 500 mg a day for six days (total dose 4.5 g). Twenty-six soldiers treated with quinine-tetracycline for seven days (Q7T7) served as controls. There were no significant differences in efficacy between halofantrine and Q7T7 (P > 0.1) as assessed by cure rate (92% versus 85%), mean parasite clearance time (82 hr versus 81 hr), or mean fever clearance time (93 hr versus 99 hr). Halofantrine was better tolerated than Q7T7. The side effects score was lower (2 versus 11; P < 0.001), there were less days on which side effects occurred (2.0 days versus 5.5 days; P < 0.001), and fewer patients had adverse effects on every treatment day (4% versus 42%; P < 0.01). High-dose halofantrine is as effective and better tolerated than quinine-tetracycline for multidrug-resistant falciparum malaria.

Adult↗