Empirical cephalosporin treatment of melioidosis.
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Adult↗
Biomedical subjects
A J Simpson
Publications and source records attributed to A J Simpson.
A comparison of chloramphenicol, trimethoprim-sulfamethoxazole, and doxycycline with doxycycline alone as maintenance therapy for melioidosis.
A prospective, open, randomized, comparative treatment trial was conducted to compare the therapeutic efficacy of the conventional four-drug combination (chloramphenicol, trimethoprim-sulfamethoxazole, and doxycycline) with that of doxycycline alone in oral maintenance treatment of melioidosis. Adult Thai patients with culture-confirmed melioidosis were randomized to receive treatment with either regimen for a minimum of 12 weeks, usually following intravenous treatment of severe disease. The main outcome measure was culture-confirmed relapse. One hundred sixteen patients were enrolled; 109 had culture-confirmed melioidosis, and 87 were considered evaluable (43 had received doxycycline). Culture-confirmed relapse occurred in one patient randomized to the conventional regimen and in 11 (25.6%) randomized to the doxycycline regimen (P = .009), and treatment failed for 8 (18.2%) versus 20 (46.5%), respectively (P = .009). Adverse effects occurred in 26% of patients overall. Doxycycline alone cannot be recommended for a first-line regimen of oral maintenance treatment of melioidosis.
Adolescent↗
Comparison of imipenem and ceftazidime as therapy for severe melioidosis.
An open, prospective, randomized, comparative treatment trial was conducted to compare the therapeutic efficacy of high-dose intravenous imipenem and ceftazidime for acute severe melioidosis. Adult Thai patients with suspected acute, severe melioidosis were randomized to receive either imipenem, at a dosage of 50 mg/(kg x d), or ceftazidime, at a dosage of 120 mg/(kg x d), for a minimum of 10 days. The main outcome measures were death or treatment failure. Of the 296 patients enrolled, 214 had culture-confirmed melioidosis, and 132 (61.7%) of them had positive blood cultures. Mortality among patients with melioidosis was 36.9% overall. There were no differences in survival overall (P = .96) or after 48 hours (P = .3). Treatment failure after 48 hours was more common among patients treated with ceftazidime (P = .011). Both treatments were well tolerated. Imipenem is a safe and effective treatment for acute severe melioidosis and may be considered an alternative to ceftazidime.
Adolescent↗
Stable marker on flagellin gene sequences related to arabinose non-assimilating pathogenic Burkholderia pseudomallei.
Using PCR-based isolation and sequence analysis of the flagellin gene from two distinct biotypes of Burkholderia pseudomallei, a 15-bp deletion was found within the variable domain of the gene in isolates capable of assimilating arabinose (Ara+). This finding led to the development of a PCR-based method in order to differentiate and identify pathogenic B. pseudomallei for epidemiological study. A pair of specific primers was designed covering the 15-bp deletion region at the variable domain. PCR-amplification products of 176 and 191 bp in size were detected from 41 Ara+ isolates and 39 Ara - isolates of B. pseudomallei, respectively. Moreover, flagellin gene fragments of other bacterial species tested in this study were not amplified using these primers. The results suggest that the flagellin gene sequences of both B. pseudomallei biotypes in this region are stable and distinct. This method can be applied and useful for the epidemiological study of B. pseudomallei.
Amino Acid Sequence↗
Aminoglycoside and macrolide resistance in Burkholderia pseudomallei.
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Aminoglycosides↗
Diagnosis of Penicillium marneffei infection by quantitation of urinary antigen by using an enzyme immunoassay.
Penicillium marneffei is a major cause of opportunistic infection in patients with AIDS in north and northeastern Thailand. A method for the quantitation of P. marneffei antigen in urine was developed by using fluorescein isothiocyanate-labelled purified rabbit hyperimmune immunoglobulin G in an enzyme-linked immunosorbent assay. This method was evaluated with 33 patients with culture-proven penicilliosis and 300 controls (52 healthy subjects, 248 hospitalized patients without penicilliosis) from the same area in which penicilliosis is endemic. Urinary antigen was found in all 33 (100%) patients with penicilliosis, with a median titer of 1:20,480. With undiluted samples, 67 (27%) of 248 hospital patients and 3 (6%) of 52 healthy controls were reactive. At a cutoff titer of 1:40, the urine antigen detection assay had a diagnostic sensitivity of 97% and specificity of 98% (positive predictive value, 84%; negative predictive value, 99.7%). This test offers a valuable and rapid method for the diagnosis of penicilliosis in patients with AIDS and could be a useful addition to conventional diagnostic methods in areas in which penicilliosis is endemic.
Adult↗
A comparison of lysis centrifugation, pour plate, and conventional blood culture methods in the diagnosis of septicaemic melioidosis.
AIMS: To determine whether quantitative blood culture methods could improve the diagnosis of septicaemic melioidosis. METHODS: A comparison of conventional broth based blood cultures, a pour plate method, and a commercial lysis centrifugation (Isolator 10) blood culture system was conducted in 71 Thai patients with severe melioidosis. The time to identification of B pseudomallei was recorded for each method. RESULTS: 42 patients (59%) were septicaemic. Compared with conventional blood culture, the Isolator and pour plate methods had sensitivities of 81% and 61%, respectively. The median times to a positive culture were: Isolator 39.3 hours, pour plates 45.5 hours, broth culture 61.8 hours (p < 0.001 Isolator v broth). There was a significant inverse correlation between Isolator tube or pour plate quantitative counts and time to detection (r = -0.44 and -0.57, respectively). Mortality was higher in patients who were septicaemic. CONCLUSIONS: Routine use of one of these quantitative methods, in addition to conventional broth culture, may lead to earlier diagnosis of septicaemic melioidosis.
Adolescent↗
Monitoring human cytomegalovirus viral load in peripheral blood leukocytes of renal transplant recipients by a simple limiting dilution-PCR assay.
To assess the clinical relevance of a semi-quantitative measurement of human cytomegalovirus (HCMV) DNA in renal transplant recipients within the typical clinical context of a developing country where virtually 100% of both receptors and donors are seropositive for this virus, we have undertaken HCMV DNA quantification using a simple, semi-quantitative, limiting dilution polymerase chain reaction (PCR). We evaluated this assay prospectively in 52 renal transplant patients from whom a total of 495 serial blood samples were collected. The samples scored HCMV positive by qualitative PCR had the levels of HCMV DNA determined by end-point dilution-PCR. All patients were HCMV DNA positive during the monitoring period and a diagnosis of symptomatic infection was made for 4 of 52 patients. In symptomatic patients the geometric mean of the highest level of HCMV DNAemia was 152,000 copies per 10(6) leukocytes, while for the asymptomatic group this value was 12,050. Symptomatic patients showed high, protracted HCMV DNA levels, whereas asymptomatic patients demonstrated intermittent low or moderate levels. Using a cut-off value of 100,000 copies per 10(6) leukocytes, the limiting dilution assay had sensitivity of 100%, specificity of 92%, a positive predictive value of 43% and a negative predictive value of 100% for HCMV disease. In this patient group, there was universal HCMV infection but relatively infrequent symptomatic HCMV disease. The two patient groups were readily distinguished by monitoring with the limiting dilution assay, an extremely simple technology immediately applicable in any clinical laboratory with PCR capability.
Antibodies, Viral↗
TP53 genetic alterations in head-and-neck carcinomas from Brazil.
In this study we investigated the incidence of mutations and loss of heterozygosity (LOH) of the TP53 gene in DNA samples from paired tumor and adjacent normal tissue from 90 patients with untreated squamous-cell carcinoma of the head and neck. Evidence for TP53 mutations were demonstrated in 53% (48/90) of the cases analyzed. All cases were also examined for loss of heterozygosity, using a PCR-based polymorphic marker at TP53. LOH was found in 36 out of 72 (50%) informative cases. Direct sequencing of PCR products was performed in 45 cases with evidence of mutations. The sequencing results revealed the presence of base-substitutions (67%), deletions (29%) and insertions (4%). Of the base-substitutions, 70% were transitions and 30% were transversions. Demographic variables, tumor site, stage (TNM), family history of cancer, lymph-node involvement and histological grade were not important predictors of TP53 mutations. Nor did TP53 genetic alterations correlate with survival status. In conclusion, we show that TP53 genetic alterations are frequent in head-and-neck tumors, but are not associated with clinicopathological variables or disease progression. Our study provides an evaluation of the spectrum of TP53 mutations in the pathogenesis of head-and-neck carcinoma in Brazil.
Alcohol Drinking↗
Does chronic smoking influence fibrinolytic potential in type 1 diabetes mellitus?
Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) were studied in 18 smokers and 18 closely matched non-smokers, all of whom had Type 1 diabetes mellitus (DM). None of the patients had advanced complications of diabetes. The t-PA and PAI-1 antigen levels were measured in plasma before and after venous occlusion, and were normal in Type 1 diabetes regardless of smoking status. Platelet PAI-1 levels were also measured and were found to be normal both in smokers and non-smokers. In smokers with Type 1 DM, plasma PAI-1 was significantly correlated with triglycerides. The normal fibrinolytic potential found in smokers with diabetes contrasts starkly with the significantly elevated plasma PAI-1 reported in smokers without diabetes. In smokers, triglycerides may effect low levels of PAI-1 release into plasma; this process may be significantly augmented in the presence of smoking-induced insulin resistance. The lack of endogenous insulin release in Type 1 diabetes may obviate the characteristic rise in plasma PAI-1 found in smokers who do not have diabetes.
Adult↗
Biomphalaria spp: identification of the intermediate snail hosts of Schistosoma mansoni by polymerase chain reaction amplification and restriction enzyme digestion of the ribosomal RNA gene intergenic spacer.
The intermediate hosts of S. mansoni in South America, B. glabrata, B. tenagophila, and B. straminea, were identified by restriction fragment length polymorphism (RFLP) analysis of the internal transcribed spacer region of the rRNA gene. The restriction patterns obtained with DdeI were the most informative of the eight enzymes that were tried. The RFLP profiles obtained using this enzyme are highly distinctive and exhibit low levels of intraspecific polymorphism even between specimens collected from diverse regions of Brazil, Argentine, Paraguay, and Uruguay. The method proved useful for the identification of DNA extracted from eggs, permitting species identification while preserving the living adult specimens for further studies.
Animals↗
Evolution and the inevitability of human cancer.
Natural selection, which is absolutely dependent on genetic differences between individuals, is the process by which life has evolved on this planet. Genetic variability is ultimately depended on the occurrence of new mutations in the germ-line of species. The rate at which this occurs appears not to be arbitrary or dependent on chance external events. Rather the available evidence suggests that it is highly controlled and determined by endogenous processes. However, the body does not have separate mechanisms for controlling mutation frequency in the germinal and somatic lineages and the selective process described inevitably has also led to somatic cells being subject to mutation accumulation. Indeed, since mutation frequency increases exponentially with time, the human somatic mutation frequency at approximately 80 years of age in epithelial tissues appears to be more than 10-fold higher than in the human germline. This normal but highly elevated somatic mutation frequency is sufficient to account for the complex multi-step process of human tumorigenesis even in the absence of the effects of major external mutagens or rare transitions to even more elevated mutation frequencies. Thus, scrutiny of the apparently disparate biological phenomena of evolution and tumorigenesis leads to the postulate that they are in fact two interdependent manifestations of the same underlying process and that given an evolutionary process dependent on mutation accumulation then cancer in long lived organisms is an inevitable consequence.
Biological Evolution↗
Polarity of mutations in tumor-associated microsatellite instability.
Many factors have been implicated in influencing the rate of microsatellite mutations, including the length and base composition of the repeat motif, number of repeats, base composition of flanking sequences and, perhaps most importantly, degree of perfection of the repeats. The latter is of clinical relevance, since in both spino-cerebellar ataxia and fragile X syndrome, alleles with imperfect repeats appear to be much more stable than perfect ones. As yet, the relative importance of increased replication slippage and decreased mismatch repair efficiency in the preference of mutations to occur within perfect repeats has not been fully determined. D13S308E is an asymmetric trinucleotide repeat microsatellite with the sequence (CAT)3CAC(CAT)CAC(CAT)2CAC(CAT)CAC(CAT)15, thus containing two parts: an 11-repeat imperfect portion (underlined above) and a 15-repeat perfect one (bold). We sequenced eight new mutant alleles of D13S308E from three human gastric tumors with instability in this and other microsatellites. In all mutations the size variation occurred exclusively in the perfect part of the microsatellite. These results constitute direct evidence that the molecular basis of microsatellite alterations seen in normal cells is similar to those that occur in human tumors with extensive microsatellite instability. The investigation of mechanisms involved in microsatellite mutations has been handicapped by the fact that they are rare events. The microsatellite instability observed in malignant tumors provides us with a useful general system to study these mechanisms.
Adenocarcinoma↗
Characterization of a Schistosoma mansoni homologue of the gene encoding the breast basic conserved protein 1/L13 ribosomal protein.
The Schistosoma mansoni gene sequence encoding the breast basic conserved protein 1/ribosomal protein L13 has been isolated from an adult worm cDNA library using the Expressed Sequence Tag strategy. The cDNA codes for a putative protein of 184 amino acids which is approximately 55% identical to other eukaryotic L13 ribosomal proteins. A PCR amplified genomic fragment containing the coding region of the gene was seen to possess only a single large intron interrupting the open reading frame. Studies of gene expression by RT-PCR showed the transcript is expressed in distinct stages of the parasite life cycle. The cDNA was also hybridized with an ordered cosmid library of S. mansoni and the identified cosmids were mapped to chromosomes 3 and W by chromosomal in situ suppression hybridization.
Amino Acid Sequence↗
The management of pulmonary tuberculosis in adults notified in Scotland in 1993.
The management of pulmonary tuberculosis (TB) in Scotland in 1993 was studied by asking the physicians responsible for all 321 adult cases of the disease notified that year to complete a standardized questionnaire relating to drug treatment and bacteriology. The response rate to the questionnaire was 100%. Isoniazid and rifampicin were used together in initial therapy in 98.4% of cases, while pyrazinamide was prescribed in 90.3% of cases, broadly in keeping with existing treatment guidelines. However, considerable variability was observed both in the drug regimens employed, and in the duration of initial and continuation phases of chemotherapy. Treatment regimens were therefore frequently at variance with published recommendations. Among patients prescribed drug regimens other than those recommended satisfactory completion of therapy was less common. Microbiological confirmation was provided for 84% of cases in which clinical samples were submitted. However, in approximately 11% of cases, no clinical samples were submitted. Closer adherence to existing treatment guidelines and more rigorous pursuit of microbiological confirmation should further improve the overall management of pulmonary TB in Scotland.
Adolescent↗
Starting home nebulizer therapy: patients' expectations and subsequent outcome at 2 months.
Twenty-six patients with severe COPD or asthma completed standard questionnaires before, and 2 months after, starting home nebulized bronchodilator therapy. Patients' perceived illness severity and their expectations of treatment with regard to symptoms were examined in the first questionnaire, and outcome was assessed in the second. Before treatment started patients expected a definite improvement in all symptoms studied. After treatment the group showed only a marginal subjective improvement in all symptoms. The improvement attained with regard to breathlessness, ability to get out and about, and general quality of life was significantly lower than had been expected. While home nebulized bronchodilator therapy is well tolerated and confers some subjective benefit in selected individuals, patients appear to have unrealistically high expectations of treatment.
Asthma↗
ONSA, the São Paulo Virtual Genomics Institute. Organization for Nucleotide Sequencing and Analysis.
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Agriculture↗