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T Butler

Publications and source records attributed to T Butler.

At least 19 recordsLinked to original sources

Cross-species color banding in ten cases of myeloid malignancies with complex karyotypes.

Cross-species color banding is a multiple-color fluorescence in situ hybridization (FISH) technique using probes developed from other animal species. Hybridization to human metaphases produces color banding patterns specific for each homologous chromosome pair. The technique has been evaluated in a complementary manner with G-banding and chromosome painting in a series of 10 myeloid malignancies with complex or unresolved karyotypes. Color banding detected the majority of chromosomal abnormalities, which had been identified by G-banding and in each case revealed chromosomal changes that G-banding had not identified. Painting was necessary to confirm these abnormalities due to the limitation of only seven colors in the color-banded karyotype. At the same time, painting fortuitously uncovered cryptic abnormalities in 6 of 10 cases that had not been detected by color banding. Insertions were visible by painting only. This study has demonstrated that in the analysis of complex karyotypes, the application of color banding revealed the involvement of the long arm of chromosome 3, indicating a poor risk, in two cases not identified by G-banding. Therefore, these techniques applied together have revealed cryptic chromosomal abnormalities with prognostic significance, which in some cases may have implications for patient management.

Adolescent↗

New developments in the understanding of cholera.

Recent advances in prevention and treatment of cholera have occurred in the areas of vaccine testing, modifications of oral-rehydration solutions (ORS), and antimicrobial treatment. Oral vaccines consisting of killed whole bacterial cells (WC) with and without the B-subunit of cholera toxin (BS) were shown to be effective in large trials in Bangladesh, Peru, and Vietnam. However, the trials did not resolve whether two or three doses of vaccine are required and whether BS adds significantly to the immune protection of WC. Live, attenuated bacterial vaccines that are immunogenic and have been shown protective in human volunteer studies are candidates for future field trials. Rehydration of patients is a life- saving effort. The best ORS contains rice powder in place of glucose, and solutions with reduced osmolarity (245 mOsm/L, sodium 75 mEq/L) are as effective as standard ORS. Ciprofloxacin in a single dose is effective in adults, and erythromycin or ampicillin in multiple doses is effective in children.

Cholera↗

Mortality among homeless people with schizophrenia in Sydney, Australia: a 10-year follow-up.

OBJECTIVE: The aims were first, to describe deaths in a cohort of homeless people compared to the general population and secondly, to compare deaths among the individuals with schizophrenia to those without schizophrenia. METHOD: Mortality was assessed in a cohort of 708 homeless subjects, 506 with schizophrenia who were referred 10 years previously to psychiatric outreach clinics. Standardized mortality ratios (SMRs) were calculated. RESULTS: Eighty-three people (12%) had died, 19 from suicide. The SMR was 3.76 for homeless men and 3.14 for homeless women. There was a non-significant trend for higher excess mortality among men without schizophrenia compared to men with schizophrenia. SMRs for suicide were significantly elevated among homeless men. CONCLUSION: Homeless people in inner Sydney have death rates three to four times higher than people in the general population of New South Wales. Excess mortality was greatest for younger age groups.

Adult↗

Acute myeloblastic leukaemias of FAB types M6 and M4, with cryptic PML/RARalpha fusion gene formation, relapsing as acute promyelocytic leukaemia M3.

Demonstration of either the translocation t(15;17)(q22;q21) or the fusion of PML and RARalpha genes is regarded as diagnostic for acute myeloid leukaemia (AML) of FAB type M3, but has occasionally been seen in other FAB types. We present two such cases. Case 1 presented with FAB type M6 and a complex karyotype involving chromosomes 1, 2, 11 and 17. Bone marrow relapse of FAB type M3 followed autologous bone marrow transplantation. Subsequent marrow dysplasia and an M6 relapse were accompanied by a new cytogenetic clone involving chromosomes X, 2, 4, 6, 7 and 16. Fluorescence in situ hybridization (FISH) of metaphase chromosomes at diagnosis showed insertion of material from chromosome 17 into a 'normal' 15 with juxtaposition of PML and RARalpha. Case 2 presented as AML M4 and relapsed as M3. Cytogenetic analysis at diagnosis and in relapse showed 46,XY,t(15;17)(q22;q11),del(16)(q22). FISH analysis showed this to be a three-way translocation involving chromosomes 15, 16 and 17 again with juxtaposition of PML and RARalpha. Reverse transcription-polymerase chain reaction (RT-PCR) revealed PML/RARalpha fusion at diagnosis, in remission and in first relapse. These examples strengthen the case for RT-PCR screening of all AML patients for these fusion genes.

Adult↗

In vitro effects of azithromycin on Salmonella typhi: early inhibition by concentrations less than the MIC and reduction of MIC by alkaline pH and small inocula.

To explain good clinical results of azithromycin in patients with typhoid fever, 10 strains of Salmonella typhi were grown in cation-adjusted Mueller-Hinton broth. MICs of azithromycin were 4-16 mg/L. At a sub-MIC of 2 mg/L, early inhibition of growth was shown at 2, 4 and 8 h of incubation, but at 24 and 48 h growth to turbidity occurred. At 4 mg/L, inhibition occurred up to 8 h, after which growth towards turbidity followed. Elongated curved bacilli formed in broth containing 4 mg/L after 24-48 h. Adjusting the pH of the broth with phosphate-citrate buffer to 7.5 and 8.0 caused reductions in MICs to 0.25-0.5 mg/L. Large inocula of 10(6) cfu/mL resulted in median MICs four- to six-fold greater than with inocula of 10(1)-10(3) cfu/mL. An inoculum of 10 bacteria per mL in broth at pH 7.5 resulted in an MIC of 0.13 mg/L. Clinical benefits in patients may occur because of early inhibition by sub-MIC concentrations of azithromycin, and due to lower MICs at alkaline pH and lower MICs with small inocula that may correspond to the low-grade bacteraemia in typhoid fever.

Anti-Bacterial Agents↗

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients.

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.

APACHE↗

Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: a multicenter, randomized, placebo-controlled, single-blind, dose escalation study.

OBJECTIVE: To identify a safe and potentially effective recombinant tissue factor pathway inhibitor (rTFPI) dose for further clinical evaluation in patients with severe sepsis. DESIGN: Prospective, randomized, single-blind, placebo-controlled, dose escalation, multicenter, multinational phase II clinical trial. SETTING: Thirty-eight intensive care units in the United States and Europe. PATIENTS: Two hundred and ten subjects with severe sepsis who received standard supportive care and antimicrobial therapy. INTERVENTIONS: Subjects received a continuous intravenous infusion of placebo or rTFPI at 0.025 or 0.05 mg/kg/hr for 4 days (96 hrs). MEASUREMENTS AND MAIN RESULTS: There were no significant imbalances in demographics, severity of illness, or source of infection in patients randomized to placebo or either dose of rTFPI. A 20% relative reduction in 28-day all-cause mortality was observed when all rTFPI-treated patients were compared with all placebo patients. An improvement in pulmonary organ dysfunction score and in a composite intensive care unit score (pulmonary, cardiovascular, and coagulation) were also noted in the rTFPI-treated patients. Logistic regression modeling indicated a substantial treatment by baseline laboratory international normalized ratio (INR) interaction effect when only treatment and INR were in the model (p =.037) and when baseline Acute Physiology and Chronic Health Evaluation (APACHE II) and log10 interleukin 6 were adjusted for (p =.026). This interaction effect indicates that higher baseline INR is associated with a more pronounced beneficial rTFPI effect. There was no increase in mortality in subjects treated with either dose of rTFPI compared with placebo. Biological activity, as detected by a statistically significant reduction in thrombin-antithrombin complexes (TATc), was noted in the all rTFPI-treated patients compared with those receiving placebo. There were no major imbalances across all treatment groups with respect to safety. The frequency of adverse events (AEs) and severe adverse events (SAEs) was similar among the treatment groups, with a slight increase in SAEs and SAEs involving bleeding in the 0.05 mg/kg/hr rTFPI group. The overall incidence of AEs involving bleeding was 28% of patients in the all placebo group and 23% of patients in the all rTFPI-treated group; a slight but statistically insignificant increase in incidence of SAEs involving bleeding was observed in the all rTFPI group (9%) as compared with the all placebo group (6%; p =.39). CONCLUSIONS: Although the trial was not powered to show efficacy, a trend toward reduction in 28-day all-cause mortality was observed in the all rTFPI group compared with all placebo. This study demonstrates that rTFPI doses of 0.025 and 0.05 mg/kg/hr could be safely administered to severe sepsis patients. Additionally, rTFPI demonstrated bioactivity, as shown by reduction in TATc complexes and interleukin-6 levels. These findings warrant further evaluation of rTFPI in an adequately powered, placebo controlled, randomized trial for the treatment of severe sepsis.

APACHE↗

Syphilis in New South Wales (Australia) prisons.

This paper describes the prevalence of, and risk factors for, exposure to syphilis in a random sample of male and female prisoners. We found that only 2% of male and 1% of female prison inmates in New South Wales (NSW) had confirmed evidence of untreated syphilis, and none appeared to be in an infectious phase. In the multivariate analysis, indigenous ethnicity remained the most potent predictor for confirmed syphilis (either past or present). There was some evidence to suggest that syphilis among indigenous prisoners may be associated with limited access to health services outside prison. The epidemiology of syphilis reflects that of the general community suggesting that prisons could be used as sentinel sites to help evaluate the effectiveness of STD prevention and control strategies.

Adult↗

Multiplex fluorescence in situ hybridization and cross species color banding of a case of chronic myeloid leukemia in blastic crisis with a complex Philadelphia translocation.

Exciting new techniques in molecular cytogenetics--namely, spectral karyotyping, multiplex fluorescence in situ hybridization (M-FISH), and cross species color banding--have been recently developed. An increasing number of reports demonstrate the success of these procedures in providing additional cytogenetic information--identifying marker chromosomes and revealing the presence of previously undetected chromosomal changes. However, these procedures have their limitations, and their absolute sensitivity in the accurate identification of subtle chromosomal abnormalities remains to be established. M-FISH and color banding have been applied to a case of chronic myeloid leukemia with a complex Philadelphia translocation involving chromosomes 9, 17, and 22, which had initially been identified from G-banded chromosome analysis. The abnormalities were confirmed by chromosome "painting" and specific probes. Although M-FISH and color banding revealed no additional cryptic chromosomal changes, this study has clearly demonstrated the success of these multiple color FISH approaches in the accurate characterization of a complex rearrangement with subtle abnormalities.

Adolescent↗

Matching resources to care: the acceptability, validity and inter-rater reliability of a new instrument to assess severe mental illness (MARC-1).

BACKGROUND: Most definitions of severe mental illness (SMI) are categorical and assign the patient to either SMI or not-SMI status. While this is useful for some purposes, it is a rather limited approach. The purpose of the present study is to develop a new method of addressing the issue of 'severity', and to develop a dimensional rather than a categorical approach. The paper reports on the acceptability, reliability and validity of a method developed to collect a standard set of data covering the majority of items specified in the academic and policy literature as characterising SMI. METHOD: A single page form, Matching Resources to Care (MARC-1), containing most of the items used in definitions of SMI was used to collect data from community mental health staff about their current open caseload, in four co-terminous health and social services settings during a census week (n = 2139). In addition to the data from the four pilot sites, we conducted a substudy (n = 91), in which two raters rated the same cases during the same week. RESULTS: The MARC-1 scores were able to distinguish between patients in receipt, and those not in receipt, of specific types of community care (level of care, eligibility for care and statutory aftercare) (P < 0.001). The MARC-1 score was modestly but significantly correlated (r = 0.28) with the Global Assessment Scale (P < 0.001). The mean percentage inter-rater agreement for the MARC-1 score items was 87%. CONCLUSION: It is possible to use a simple census form in both health and social services agencies. The completion rates were good in both services. The levels of reliability were good, and concurrent validity was established with specific types of care in the community.

Adolescent↗

Prescribing patterns for asthma by general practitioners in six European countries.

To assess the level of concordance with international consensus on asthma management, we compared primary care prescribing patterns for asthma in different European countries. A prospective study of prescription items with an associated diagnostic label of asthma in patient consultations with a total of 235 general practitioners (GPs) from Belgium, England, Ireland, Italy, Northern Ireland, Portugal, Scotland and Spain was performed. A total of 101,544 consecutive consultations were recorded in autumns 1994 and 1995 of which 3595 (3.5%) were for patients with asthma and 3243 (3.2%) were for patients receiving a prescription for asthma. Overall, asthma consultations varied from 1.8% in Italy to 5.8% in Ireland (mean 3.4%, SD 1.6). Prescribed inhaled medications for children varied from 72% of the total asthma prescriptions in Ireland and Portugal to 82% in Northern Ireland (mean 79%, SD 8.1) and for adults 55% in Italy to 85% in Spain (mean 70%, SD 10). Inhaled corticosteroid usage for adults varied from 14% in Italy to 31% in Northern Ireland (mean 24%, SD 6.4). For children, beta2-agonist use varied from 24% in Italy to 67% in Spain (mean 45%, SD 13). Despite publication of international guidelines for the management of asthma, inter-country prescribing practices vary considerably and could be improved. The frequency of use of asthma as a diagnostic label also varies markedly.

Administration, Inhalation↗

Herpes simplex virus type 2 in prisoners, New South Wales, Australia.

Our objectives were to determine the prevalence of, and risk factors for, herpes simplex virus type 2 (HSV-2) antibodies in male and female prisoners. A cross-sectional random sample was used consisting of 789 prisoners (657 males and 132 females) from 27 correctional centres across New South Wales (NSW), stratified by sex, age and Aboriginality. Participants were questioned about demographics and behavioural risk factors and were screened for serum antibody to HSV-2. The overall prevalence of HSV-2 antibodies was higher in females (58%) than males (21%), and in Aborigines (34%) compared with non-Aborigines (24%). HSV-2 prevalence increased with the number of sexual partners. Few prisoners (1%) reported a previous diagnosis of genital herpes. Independent risk factors for the presence of HSV-2 antibodies were increasing age and Aboriginality for men, and higher reported number of lifetime sexual partners and the presence of hepatitis C antibodies for women. HSV-2 infection is common in prison inmates. There is a need to incorporate information about STDs, including HSV-2, into education programmes for inmates.

Adult↗

Individual traits and family contexts predict sons' externalizing behavior and preliminary relative risk ratios for conduct disorder and substance use disorder outcomes.

An ontogenetic framework for elucidating the etiology of substance use disorders (SUD) requires identifying how individual traits and family contexts combine to increase risk for SUD outcomes. In this study, we examine individual traits in family context to identify processes that account for the relationship between fathers' SUD + status and sons' externalizing behaviors. Results obtained from SUD + (n = 89) and SUD - (n = 139) families show that fathers' abusive propensities toward their sons mediated the relationship between fathers' SUD + status and sons' externalizing behavior scale (EBS) scores 2 years later. Moreover, individual traits, family contextual variables and deviant peer affiliations accounted for 58% of the variance on sons' EBS scores. Also, high risk cluster (HRC) and low risk cluster (LRC) memberships were derived from cluster analyses of the continuous risk factor scores that predicted sons' EBS scores. Preliminary relative risk ratios show that sons classified into the HRC at age 10-12 were at greater risk for DSM-III-R conduct disorder and SUD outcomes at age 16 than sons assigned to the LRC, SUD + or SUD - groups. Implications for selected family-based prevention initiatives are presented.

Adolescent↗

Cyanocobalamin (vitamin B-12) status in Seventh-day Adventist ministers in Australia.

As part of the Adventist Ministers' Health Study, a series of cross-sectional surveys conducted in 1992, 1994, and 1997, the serum vitamin B-12 status of 340 Australian Seventh-day Adventist ministers was assessed in 1997. The ministers in the study participated voluntarily. Of this group, 245 were either lactoovovegetarians or vegans who were not taking vitamin B-12 supplements. Their mean vitamin B-12 concentration was 199 pmol/L (range: 58-538 pmol/L), 53% of whom had values below the reference range for the method used (171-850 pmol/L) and 73% of whom had values <221 pmol/L, the lower limit recommended by Herbert. Dual-isotope Schillings test results in 36 lactoovovegetarians with abnormally low vitamin B-12 concentrations indicated that dietary deficiency was the cause in 70% of cases. Data from the dietary questionnaires supported dietary deficiency as the cause of low serum vitamin B-12 in this population of lactoovovegetarians and vegans, 56 (23%) of whom consumed sufficient servings of vitamin B-12-containing foods to obtain the minimum daily maintenance allowance of the vitamin (1 microg).

Adult↗

Treatment of typhoid fever with azithromycin versus chloramphenicol in a randomized multicentre trial in India.

To compare the clinical and bacteriological efficacies of azithromycin and chloramphenicol for treatment of typhoid fever, 77 bacteriologically evaluable adults, with blood cultures positive for Salmonella typhi or Salmonella paratyphi A susceptible to their assigned drugs, were entered into a randomized open trial at four hospitals in India. Forty-two patients were randomized to receive azithromycin 500 mg p.o. od for 7 days and 35 to receive chloramphenicol 2-3 g p.o. od in four divided doses for 14 days. Thirty-seven patients (88%) in the azithromycin group responded with clinical cure or improvement within 8 days and 30 patients (86%) in the chloramphenicol group responded with cure or improvement. By day 14 after the start of treatment, all patients treated with azithromycin and all except two of the patients treated with chloramphenicol (94%) were cured or improved. Blood cultures repeated on day 8 after start of therapy showed eradication of organisms in 100% of patients in the azithromycin group and 94% of patients in the chloramphenicol group. By day 14 the eradication rate in the chloramphenicol group had increased to 97%. Stool cultures on days 21 and 35 after start of treatment showed no prolonged faecal carriage of Salmonella spp. in either group. These results indicate that azithromycin given once daily for 7 days was effective therapy for typhoid fever in a region endemic with chloramphenicol-resistant S. typhi infection and was equivalent in effectiveness to chloramphenicol given to patients with chloramphenicol-susceptible infections.

Adolescent↗

Mantoux positivity among prison inmates--New South Wales, 1996.

OBJECTIVES: To determine the prevalence of Mantoux positivity in a prison population; identify risk factors associated with tuberculosis infection; and assess the risk of tuberculosis transmission in a correctional system. METHOD: Cross sectional random sample (between May and August 1996) of inmates stratified by sex, age and Aboriginality. Participants were 789 adult inmates (657 male and 132 female) from 27 New South Wales (NSW) correctional centres (24 male and 3 female). RESULTS: Of the 789 inmates (657 male and 132 female) included in the survey, 639 were given a Tuberculin skin test (Mantoux). Eighty-four (13%) were Mantoux positive. A higher proportion of male inmates were Mantoux positive compared with females (14% vs. 8%, p = 0.08). Significant independent predictors of Mantoux positivity were: being male, aged over 25 years, Aboriginal, born overseas and resident at a jail where there had been a recent tuberculosis outbreak. CONCLUSION: Screening of inmates in NSW prisons based on the principle of risk stratification is appropriate. IMPLICATIONS: While the risk of tuberculosis transmission in NSW jails is currently considered low, continued surveillance is recommended.

Adolescent↗