Primary amebic meningoencephalitis in a patient with AIDS: unusual protozoological findings.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
S Brown
Publications and source records attributed to S Brown.
The 1993 Survey of Recent Mothers: issues in survey design, analysis and influencing policy.
The 1993 Survey of Recent Mothers was a statewide postal survey of 2224 women who gave birth in Victoria in 2 weeks in 1993, excepting those who had a stillbirth or whose baby was known to have died. The survey questionnaire was mailed to women 6-7 months after the birth. The response rate, excluding duplicate responses, one woman who had a stillbirth and those whose questionnaires were returned unknown at the mailing address, was 62.5% (1336/2138). The questionnaire covered care in pregnancy, birth and the first 6 months. In each section, women were asked to give an overall rating of care, and to answer questions on specific aspects of care. Closed and open-ended questions were included. The paper discusses the advantages and disadvantages of the study design, the processes used for developing the questionnaire, methodological issues in analysis using both quantitative and qualitative methods, and relevance of the study to policy.
Adolescent↗
Analysis of Neisseria gonorrhoeae in Ontario, Canada, with decreased susceptibility to quinolones by pulsed-field gel electrophoresis, auxotyping, serotyping and plasmid content.
The incidence of Neisseria gonorrhoeae with reduced susceptibility to quinolones increased from 0.18% (63 of 3285) in 1992 to 0.56% (15 of 2663) in 1993 and 0.62% (46 of 2846) in 1994. In all, 65 of the 67 isolates of Neisseria gonorrhoeae with decreased susceptibility to quinolones were characterised by pulsed-field gel electrophoresis (PFGE), auxotyping, serotyping and plasmid content. The strains were distributed among 14 auxotype/serovar (A/S) classes. Thirty isolates (46.2%) which were penicillin-susceptible with ciprofloxacin MIC90 of 0.12 mg/L and norfloxacin MIC90 of 1.0 mg/L belonged to a single A/S class, OUHL/IA-2. All but two of the 30 isolates had identical PFGE restriction profiles with NheI restriction endonuclease. Fifteen isolates (23.1%) with MICs in the intermediate (or resistant) categories for penicillin and with ciprofloxacin and norfloxacin MIC90 of 0.25 and 4.0 mg/L and (0.5 and 4.0 mg/L) respectively, belonged to A/S class P/IB-1. The 15 isolates showed nine different patterns with NheI and eight patterns with SpeI restriction endonucleases. Two of three beta-lactamase-producing (PPNG) isolates belonged to A/S class P/IB-5 and had a dissimilar PFGE restriction profile with NheI endonuclease; the other isolate belonged to A/S class P/IB-8. The remaining 17 isolates were distributed among 11 A/S classes. Three isolates within the common A/S class NR/IB-1 were subdivided into two types by PFGE as were three isolates belonging to A/S class NR/IB-2. Overall the 65 isolates of N. gonorrhoeae were distributed into 30 NheI and 26 SpeI macrorestriction profiles. All but one isolate harboured the 2.6-MDa cryptic plasmid and 18 isolates carried the 24.5-MDa transferable plasmid. The three PPNG isolates carried the 4.5-MDa Asian beta-lactamase-producing plasmid and a 25.2-MDa conjugative plasmid was found in the two TRNG isolates.
4-Quinolones↗
Cell cycle phase specificity of putative cyclin-dependent kinase variants in synchronized alfalfa cells.
The eukaryotic cell division cycle is coordinated by cyclin-dependent kinases (CDKs), represented by a single major serine/threonine kinase in yeasts (Cdc2/CDC28) and a family of kinases (CDK1 to CDK8) in human cells. Previously, two cdc2 homologs, cdc2MsA and cdc2MsB, have been identified in alfalfa (Medicago sativa). By isolating cDNAs using a cdc2MsA probe, we demonstrate here that at least four additional cdc2 homologous genes are expressed in the tetraploid alfalfa. Proteins encoded by the new cdc2MsC to cdc2MsF cDNAs share the characteristic functional domains of CDKs with the conserved and plant-specific sequence elements. Transcripts from cdc2MsA, cdc2MsB, cdc2MsC, and cdc2MsE genes are synthesized throughout the cell cycle, whereas the amounts of cdc2MsD and cdc2MsF mRNAs peak during G2-to-M phases. The translation of Cdc2MsA/B, Cdc2MsD, and Cdc2MsF proteins follows the pattern of transcript accumulation. The multiplicity of kinase complexes with cell cycle phase-dependent activities was revealed by in vitro phosphorylation experiments. Proteins bound to p13suc1-Sepharose or immunoprecipitated with Cdc2MsA/B antibodies from cells at G1-to-S and G2-to-M phase boundaries showed elevated kinase activities. the Cdc2MsF antibodies separated a G2-to-M phase-related kinase complex. Detection of histone H1 phosphorylation activities in fractions immunoprecipitated with antimitotic cyclin (CyclinMs2) antibodies from G2-to-M phase cells indicates the complex formation between this cyclin and a kinase partner in alfalfa. The observed fluctuation of transcript levels, amounts, and activities of kinases in different cell cycle phases reflects a multilevel regulatory system during cell cycle progression in plants.
Amino Acid Sequence↗
Adult acute leukaemia--a retrospective study of 66 consecutive patients.
BACKGROUND: Advances in therapy and supportive care have improved the outlook for many patients with acute leukaemia, however elderly patients have increased treatment-related toxicity and shorter survival. Most clinical trials have selected patient populations with young median ages and it is therefore difficult to apply results to the general population where the majority of patients presenting with acute leukaemia are over 60 years. There is little information in the literature guiding appropriate treatment of these patients. AIMS: To determine the relationship between age, treatment received, and outcome in patients presenting with acute leukaemia. METHODS: A retrospective analysis was performed on all patients presenting to Prince Henry's Hospital and Monash Medical Centre with acute myeloid leukaemia (AML) or acute lymphocytic leukaemia (ALL) during a five year period. RESULTS: Sixty-six patients (51-AML, 15-ALL) presented with acute leukaemia between March 1989 and April 1994. Median patient age was 63 years; 32% of patients received supportive therapy only; 86% of patients with ALL and 58% of patients with AML commencing remission-induction chemotherapy entered a complete remission. Median survival for patients receiving only supportive therapy was three months. Median survival in patients under 55 years was almost twice as long as patients over 55 years receiving similar treatment (AML-eight vs four months p = 0.023; ALL-3.5 vs seven months p = 0.029). CONCLUSIONS: Median survival for acute leukaemia is inversely proportional to age. Applying results from selected series to elderly patients with acute leukaemia is inappropriate.
Adult↗
Reasons to stay, reasons to go: results of an Australian population-based survey.
BACKGROUND: Debate about early obstetric discharge is occurring simultaneously in several different countries. An Australian population-based survey of recent mothers investigated women's views about shorter postnatal stays and assessed the impact of early discharge on important maternal health outcomes. METHOD: Women's views and experiences of length of hospital stay were gathered by means of a statewide postal survey of all women who gave birth in Victoria, Australia, during two weeks in 1993. Questionnaires were mailed to women 6 to 7 months after the birth; 62.5 percent (n = 1336) responded. RESULTS: Most of the sample (64%) stayed in hospital for 5 or more days after the birth, 26.6 percent left on day 3 or 4, and 9.4 percent on day 1 or 2. Compared with women who stayed for 5 or more days, women who left in the first 48 hours were more likely to be multiparous; to have attended public models of care (public hospital clinic, shared care, public general practitioner, birth center); not to have private health insurance; to have experienced a lower level of obstetric intervention; and to have a very low income. Twenty-one percent of women who left within 48 hours, and 26 percent of those who left on day 3 or 4 described their stay as too short. Women who left on day 3 or 4, or within 48 hours, were not more likely to experience any of the adverse outcomes investigated in the study: breastfeeding problems, low confidence about caring for the baby, or depression 6 to 7 months after birth. Women who left on day 3 or 4 had slightly lower rates of breastfeeding at 3 and 6 months than women staying for longer or shorter periods. CONCLUSION: Concerns about possible adverse outcomes resulting from shorter postnatal stays were not borne out by the study findings. Large and carefully designed randomized trials are needed to resolve continuing uncertainties about the safety and possible benefits of shorter hospital stays.
Adult↗
Sudden unexplained death in epilepsy: observations from a large clinical development program.
PURPOSE: The present study was conducted to determine the rate of sudden unexplained death in epilepsy (SUDEP) in a well-defined cohort of patients included in the lamotrigine (LTG) clinical development database. METHODS: A panel of scientists experienced in the area of SUDEP was assembled and provided with case summaries on all deaths (n = 45) reported during the initial clinical development of LTG. The panel developed a set of criteria for classifying cases as SUDEP (definite or highly probable), possible SUDEP, or non-SUDEP. This classification algorithm was then applied to the LTG cases, and SUDEP rates were calculated using patient-years of exposure as the denominator. RESULTS: At the time of the study, 4,700 patients (5,747 patient-years of exposure) were included in the worldwide LTG clinical trials database. In this cohort, 45 deaths were reported. Eighteen were judged by the panel to be SUDEP, 6 were defined as possible SUDEP, 20 were judged to be due to other causes (non-SUDEP), and 1 lacked sufficient data from which to make a classification. The overall SUDEP rate (definite/ highly probable SUDEP and possible SUDEP combined) was calculated to be 3.5 in 1,000 patient-years of exposure to LTG. CONCLUSIONS: The rate of SUDEP in this cohort of patients was comparable to the rate that would be expected in young adults with severe epilepsy (the subgroup of patients believed to be at highest risk of SUDEP). The data suggest that the rate of SUDEP in the LTG clinical development program is a function of the clinical trial population and is unrelated to drug treatment.
Adolescent↗
Ibuprofen and paracetamol: relative safety in non-prescription dosages.
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Acetaminophen↗
Specific PCR assay for direct detection of intestinal microsporidia Enterocytozoon bieneusi and Encephalitozoon intestinalis in fecal specimens from human immunodeficiency virus-infected patients.
A routine assay based on the PCR was developed for the detection of Enterocytozoon bieneusi and Encephalitozoon intestinalis in fecal samples. Two oligonucleotide primer pairs from a conserved region in the small-subunit rRNA genes of E. bieneusi (primer pair V1 and EB450) and E. intestinalis (primer pair V1 and SI500) were used to amplify microsporidian DNA. We achieved specific amplification of a 382-bp DNA fragment in E. intestinalis and a 353-bp DNA fragment in E. bieneusi. Boiling of the samples appeared to be most effective for DNA extraction. Fecal samples containing fewer than 10 microsporidia gave a positive result in the PCR assay. Fecal specimens from 30 human immunodeficiency virus-infected patients with microsporidiosis and fecal specimens from 42 patients suspected of having microsporidiosis were investigated by the PCR assay. The PCR assay was validated against standard staining methods (the Uvitex 2B and Chromotrope 2R staining methods) and immunofluorescence assay specific for E. intestinalis. This comparative study has shown that PCR improved species determination and can thus be considered a fast and reliable method for the detection and identification of each intestinal species.
AIDS-Related Opportunistic Infections↗
Latex allergy: epidemiological study of 1351 hospital workers.
OBJECTIVE: To determine the prevalence of latex sensitisation among a large group of healthcare workers, study the occupational and non-occupational factors associated with latex allergy, and characterise latex exposure in air and by gloves. METHODS: All 2062 employees of a general hospital in Hamilton, Ontario, Canada who regularly used latex gloves were invited to participate in a cross sectional survey, representing the baseline phase of a prospective cohort morbidity study. Attempts were made to recruit employees who were diagnosed with latex allergy before the survey. Glove extracts were assayed for antigenic protein, and area and personal air samples were obtained on two occasions (summer and winter) to estimate exposure to airborne latex protein. A questionnaire on medical and occupational information was administered by an interviewer. Skin prick tests were performed with latex reagents, three common inhalants, and six foods. RESULTS: The mean (SD) latex protein concentrations were 324 (227) micrograms/g in powdered surgical gloves and 198 (104) micrograms/g in powdered examination gloves. Personal latex aeroallergen concentrations ranged from 5 to 616 ng/m3. There was a total of 1351 (66%) participants. The prevalence of positive latex skin tests was 12.1% (95% confidence interval (95% CI) 10.3% to 13.9%). This prevalence did not vary by sex, age, hospital, or smoking status but subjects who were latex positive were significantly more likely to be atopic (P < 0.01). Participants who were latex positive were also significantly more likely to have positive skin tests to one or more foods (Mantel-Haenszel odds ratio (OR) adjusted for atopy 12.1, 95% CI 7.6 to 19.6, P < 10(-9)). Work related symptoms were more often reported among latex positive people, and included hives (OR 6.3, 95% CI 3.2 to 12.5), eye symptoms (OR 1.9, 95% CI 1.2 to 2.8), and wheezy or whistling chest (OR 4.7, 95% CI 2.8 to 7.9). The prevalence of latex sensitivity was highest among laboratory workers (16.9%), and nurses and physicians (13.3%). When the glove consumption per healthcare worker for each department was grouped into tertiles, the prevalence of latex skin test positivity was greater in the higher tertiles of glove use for sterile (surgical) gloves (P < 0.005) but not for examination gloves. CONCLUSIONS: In this large, cross sectional study of healthcare workers, the prevalence of latex sensitisation was 12.1% (9.5% among all those eligible), and there were significant associations with atopy, positive skin tests to certain foods, work related symptoms, and departmental use of gloves per healthcare worker. This cohort is being followed up prospectively and will be retested to determine the incidence of development of latex sensitivity.
Adult↗
Endoscopic laser therapy in malignant tracheobronchial obstruction using sequential Nd YAG laser and photodynamic therapy.
BACKGROUND: Because the survival after treatment of advanced inoperable endo-tracheobronchial carcinoma is so poor, a pilot study was undertaken to evaluate the combined cumulative effect on survival of neodymium yttrium aluminium garnet (Nd YAG) laser followed by photodynamic treatment used endoscopically. METHODS: Seventeen patients who presented between January 1992 and March 1996 with inoperable tracheobronchial lesions causing more than 50% endoluminal obstruction were selected to enter the pilot study. Initially they had bronchoscopic Nd YAG laser treatment to debulk the tumour, and this was followed six weeks later by photodynamic therapy to treat the residual tumour. RESULTS: All patients had symptomatic relief and at least a partial response, and seven had a complete response for 3-6 months. Eight of the 17 (47%) survived for at least two years and 11 (65%) survived for a year or more. The median survival of the 10 patients who had died by the time of writing was 18.5 months (range 5-39), 95% confidence interval (CI) 9.9 to 29.5. CONCLUSIONS: Combined Nd YAG laser and endoscopic photodynamic therapy may be an effective palliative treatment for patients with inoperable endotracheobronchial cancer.
Aged↗
Whole cell Cl- conductances in mouse choroid plexus epithelial cells do not require CFTR expression.
Whole cell patch-clamp studies were performed with tissue isolated from the cystic fibrosis (CF) transgenic Cftrm1cam mouse, to determine whether anion currents in choroid plexus epithelial cells require the expression of cystic fibrosis transmembrane conductance regulator (CFTR). Inclusion of 0.25 mM adenosine 3',5'-cyclic monophosphate (cAMP) and 375 nM protein kinase A (PKA) in the pipette solution caused a significant activation of a Cl(-)-selective, inward-rectifying conductance in cells from wild-type and CF mice. The small, outward currents observed in wild-type and CF animals, however, were not activated by cAMP-PKA. There were no significant differences in the size of currents between wild-type, heterozygote, and CF cells in the presence or absence of cAMP-PKA. A second whole cell conductance was activated when cells from wild-type mice were swollen. These volume-activated currents were Cl- selective and exhibited outward rectification. They were Ca2+ independent and ATP dependent and blocked by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and 5-nitro-2-(3-phenylpropylamino)benzoic acid. The volume-activated channels were also activated in CF mutant cells, and there was no significant difference in the size of the volume-activated currents between wild-type, heterozygote, and CF cells. It is concluded that CFTR neither contributes to the whole cell conductance nor regulates the other anion conductances in choroid plexus epithelial cells.
Animals↗
Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons.
Cannabinoids and their analogues have been found to inhibit N- and P/Q-type Ca2+ currents in cell lines and sympathetic neurons transfected with cannabinoid CB1 receptor. However, the effects of cannabinoids on Ca2+ currents in the CNS are largely unexplored. In this study we investigated whether these compounds inhibit Ca2+ channels in cultured rat hippocampal neurons. With the use of antibodies directed against the amino-terminus of the CB1 receptor, we found that in 5-day cultures pyramidally shaped neurons expressed somatic CB1 receptors, whereas in 4-wk cultures the receptor was predominately located on neurites. In early cultures, the cannabimimetic WIN 55,212-2 reversibly inhibited whole cell Ba2+ current in a concentration-dependent (K(1/2) = 21 nM) and pertussis-toxin-sensitive fashion. Inhibition was reduced by the CB1 antagonist SR141716. The current was unaffected by the nonpsychoactive enantiomer WIN 55,212-3. Maximal inhibition by the nonclassical cannabinoid agonist CP 55,940 and by an endogenous cannabinoid, anandamide, were similar to that seen with maximal concentrations of WIN 55,212-2. The Ba2+ current modulated by cannabinoids was carried by N-type (omega-conotoxin-GVIA-sensitive) and P/Q-type (omega-conotoxin-MVIIC-sensitive) channels. These results demonstrate cannabinoid-receptor-mediated inhibition of distinct Ca2+ channels in central neurons. Because the channels that underlie these currents are chiefly located presynaptically, and are required for evoked neurotransmitter release, our results suggest a major role for cannabinoids (endogenous and exogenous) in the modulation of synaptic transmission at CNS synapses.
Animals↗
Racial differences in risk factors for atherosclerosis. The ARIC Study. Atherosclerosis Risk in Communities.
This paper describes black/white differences in risk factors for atherosclerosis in the large multicenter Atherosclerosis Risk in Communities (ARIC) Project sponsored by the National Heart, Lung, and Blood Institute. It is based on data collected at baseline in ARIC's four geographically distinct clinical centers. Participants were randomly selected (4264 black and 11,479 white men and women, ages forty-five to sixty-four years at entry). There were striking differences in obesity between black and white women, higher fasting glucose and greater prevalence of diabetes in blacks, and lower high-density lipoprotein values in white men. Not unexpectedly, blood pressure in black participants exceeded that in whites. Clustering of multiple risk factors was more common in the black population. Conversely, prevalence of no risk factors was greatest among whites. In conclusion, while African-Americans and Caucasians share much the same group of risk factors for atherosclerosis, there are clinically important racial differences in emphasis.
Arteriosclerosis↗
Excess mortality of schizophrenia. A meta-analysis.
BACKGROUND: This paper presents a structured review of the published information on the mortality of schizophrenia. METHOD: A meta-analysis of the literature. RESULTS: Schizophrenia has a significantly increased mortality from natural and unnatural causes. Twenty-eight percent of the excess mortality is attributable to suicide and 12% to accidents. The rest of the excess mortality is from the same broad range of conditions which cause deaths in the general population. Further interpretation is hampered by confounding variables, wide confidence intervals and reservations about generalising from individual cohorts. CONCLUSIONS: The available evidence suggests that schizophrenia is associated with a large increased mortality from suicide and a moderate increased mortality from natural causes. A number of possible interventions have been identified, but we do not yet have reliable means of detecting any changes in mortality which might result.
Accidents↗
Phase II trial of oral altretamine for relapsed ovarian carcinoma: evaluation of defining response by serum CA125.
PURPOSE: A phase II study was performed of oral altretamine in 71 patients with ovarian carcinoma who entered clinical complete remission with CA125 levels less than 35 U/mL after initial or second-line chemotherapy, and relapsed more than 6 months later. Response was compared between standard and CA125-based criteria. PATIENTS AND METHODS: Altretamine 260 mg/m2 was given in divided doses daily for 14 days per month. Response was evaluated according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 45 of 66 eligible patients. Response was assessed according to precise CA125 criteria in 51 patients based on either a confirmed > or = 50% or > or = 75% decrease in CA125 levels. RESULTS: A combination of domperidone, dexamethasona, and chlorpromazine at night controlled toxicity in most patients, which was mainly nausea (National Cancer Institute criteria grade 2 or 3 in 27), vomiting (grade 2 or 3 in 19, grade 4 in one), and tiredness (grade 2 or 3 in 15). Responses (complete plus partial) were seen in 18 (40%; 95% confidence interval [CI], 25.4% to 54.6%) of those evaluated according to EORTC criteria and in 20 (39%; 95% CI, 25.5% to 52.9%) of those evaluated according to CA125 level. The overall response rate was 26 of 57 (45.6%) and was related to treatment-free interval: 6 to 12 months, 35%; 12 to 24 months, 52%; and greater than 24 months, 67%. The medium duration of response was 8 months. CONCLUSION: Oral altretamine is a useful agent in patients-who relapse after previously responsive ovarian cancer. Response evaluation by a strict CA125 definition gave a similar estimate of the efficacy of altretamine as EORTC criteria.
Administration, Oral↗
Conservation of the Notch signalling pathway in mammalian neurogenesis.
The Notch pathway functions in multiple cell fate determination processes in invertebrate embryos, including the decision between the neuroblast and epidermoblast lineages in Drosophila. In the mouse, targeted mutation of the Notch pathway genes Notch1 and RBP-Jk has demonstrated a role for these genes in somite segmentation, but a function in neurogenesis and in cell fate decisions has not been shown. Here we show that these mutations lead to altered expression of the Notch signalling pathway homologues Hes-5, Mash-1 and Dll1, resulting in enhanced neurogenesis. Precocious neuronal differentiation is indicated by the expanded expression domains of Math4A, neuroD and NSCL-1. The RBP-Jk mutation has stronger effects on expression of these genes than does the Notch1 mutation, consistent with functional redundancy of Notch genes in neurogenesis. Our results demonstrate conservation of the Notch pathway and its regulatory mechanisms from fly to mouse, and support a role for the murine Notch signalling pathway in the regulation of neural stem cell differentiation.
Animals↗
Hemispheric asymmetries for the temporal resolution of brief auditory stimuli.
This study investigates a left-hemisphere (LH) advantage for the discrimination of fine temporal events within the auditory modality in 24 normal adults. Brief noise bursts were delivered monaurally to the left or right ears, half of which contained a gap lasting between 2 and 8 msec. Subjects were required to indicate whether or not the noise burst contained a gap. Research within this area has yielded conflicting results. It is possible that variations in gap position or the properties of the noise burst may have contributed to this conflict. The effect of gap position was investigated by systematically varying the position of the gap during half of the trials. White noise bursts were used to avoid the use of spectral cues. Reaction time, response bias, and response error measures revealed a right-ear (and hence LH) advantage for gap detection. Stable gap positions were recognized more accurately than variable gap positions. Gap position had no effect on the observed LH advantage. These results suggest that the auditory properties of noise burst, rather than gap position, play an important role in the discrepancies observed in this area.
Adolescent↗