Biomedical subjects
Publications and source records attributed to M E Ward.
An intriguing case of transient language disturbance following anaesthesia is described which may throw some light on the way languages are stored in the brain. A review of the existing literature and its relevance to this unique case is discussed.
OBJECTIVE: Bacteria have been implicated in the pathogenesis of many types of inflammatory arthritides. The aim of this study was to identify any bacterial DNA in synovial fluid (SF) from patients with a range of inflammatory arthritides. METHODS: A highly sensitive, broad-range, nested polymerase chain reaction (PCR) protocol targeting the bacterial 16S rRNA gene was designed and applied to SF from 65 patients with a range of rheumatic diseases. RESULTS: Bacterial DNA was detected in 26 SF samples, including eight from patients with rheumatoid arthritis and five with juvenile arthritides. PCR products were identified by sequencing and searching of bacterial genomic databases; 'best fits' included Haemophilus influenzae, Bordetella and Yersinia. CONCLUSIONS: These finding suggest an association between bacterial infection and inflammatory arthritides in some patients. Further research is required to determine the role of these organisms in the pathogenesis and whether such patients might respond to prolonged antibiotic therapy.
Firearm wounds to the head are often fatal and are routinely encountered in the practice of forensic pathology in the United States. Often, the anatomic site of the entrance wound is used to support or refute the manner of death indicated by the scene investigation and/or circumstances of the case. The present retrospective study of 120 fatalities resulting from 140 firearm wounds to the head correlates the anatomic region of the entrance wound and range of fire with the manner of death. Other demographic data analyzed include age, race, and gender of the decedents, as well as evidence of drug and/or ethanol use. It is hoped that this study will provide concrete data to support the largely anecdotal associations between the specific site of entry of firearm injuries to the head and the manner of death.
Deaths due to hypothermia are usually accidental and are the result of exposure to extreme environmental temperatures. Often these individuals are intoxicated, elderly, or exposed to severe cold temperatures. We report the case of a blind, nonambulatory, elderly man who was found alive in his home in an unresponsive state. Core body temperature at hospital was 24 degrees C (75 degrees F). At autopsy, punctate hemorrhages were present in the stomach mucosa. A 4- x 7-cm pituitary adenoma extended from a dilated sella turcica, obliterated the optic chiasm, and compressed the base of the brain in the region of the hypothalamus. Compression in this region of the brain would disrupt the temperature regulatory function of the hypothalamus and create an individual who would be susceptible to minor fluctuations in ambient temperature. The manner of death was designated as natural. This is an unusual presentation of a pituitary adenoma in the current era of advanced imaging techniques in which microadenomas are often detected and treated.
OBJECTIVE: To review the literature for evidence that chronic infection with Chlamydia pneumoniae is associated with atherosclerosis and acute coronary syndromes. DATA SOURCES: MEDLINE and Institute of Science and Information bibliographic databases were searched at the end of September 1998. Indexing terms used were chlamydi*, heart, coronary, and atherosclerosis. Serological and pathological studies published as papers in any language since 1988 or abstracts since 1997 were selected. DATA EXTRACTION: It was assumed that chronic C pneumoniae infection is characterised by the presence of both specific IgG and IgA, and serological studies were examined for associations that fulfilled these criteria. Pathological studies were also reviewed for evidence that the presence of C pneumoniae in diseased vessels is associated with the severity and extent of atherosclerosis. DATA SYNTHESIS: The majority of serological studies have shown an association between C pneumoniae and atherosclerosis. However, the number of cases in studies that have reported a positive association when using strict criteria for chronic infection is similar to the number of cases in studies which found no association. Nevertheless, the organism is widely found in atherosclerotic vessels, although it may not be at all diseased sites and is not confined to the most severe lesions. Rabbit models and preliminary antibiotic trials suggest that the organism might exacerbate atherosclerosis. CONCLUSION: More evidence is required before C pneumoniae can be accepted as playing a role in atherosclerosis. Although use of antibiotics in routine practice is not justified, large scale trials in progress will help to elucidate the role of C pneumoniae.
AIMS: To examine the species specificity of the microimmunofluorescence test (MIF) and assess a time resolved fluoroscopic immunoassay (TRIA) for measuring IgG antibodies to C pneumoniae. METHODS: Sera from 1020 subjects were tested by MIF for IgG, IgM, and IgA antibodies to C pneumoniae, C trachomatis, and C psittaci; 501 serum samples were also tested by TRIA for IgG antibodies to C pneumoniae. RESULTS: C pneumoniae antibody titres as measured by MIF were correlated with those for C psittaci and trachomatis. It was estimated that on average, one third of the twofold dilution steps that make up the final C pneumoniae antibody titre may be due to cross reacting genus specific antibody. The results of TRIA correlated well with those of MIF. In 75% of cases, the TRIA result predicted a three titre range within which the actual MIF result would fall. CONCLUSIONS: MIF does not appear to be as species specific as claimed. TRIA is unlikely to be as specific but as it is completely objective, easier to perform, amenable to automation, and gives reproducible results, it is a rapid and useful method for comparing populations.
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The in vitro responses to ACh, flow, and hypoxia were studied in arterioles isolated from the diaphragms of rats. The endothelium was removed in some vessels by low-pressure air perfusion. In endothelium-intact arterioles, pressurized to 70 mmHg in the absence of luminal flow, ACh (10(-5) M) elicited dilation (from 103 +/- 10 to 156 +/- 13 microm). The response to ACh was eliminated by endothelial ablation and by the nitric oxide synthase antagonists NG-nitro-L-arginine (L-NNA; 10(-5) M) and NG-nitro-L-arginine methyl ester (L-NAME, 10(-5) M) but not by indomethacin (10(-5) M). Increases in luminal flow (5-35 microl/min in 5 microl/min steps) at constant distending pressure (70 mmHg) elicited dilation (from 98 +/- 8 to 159 +/- 12 microm) in endothelium-intact arterioles. The response to flow was partially inhibited by L-NNA, L-NAME, and indomethacin and eliminated by endothelial ablation and by concurrent treatment with L-NAME and indomethacin. The response to hypoxia was determined by reducing the periarteriolar PO2 from 100 to 25-30 Torr by changing the composition of the gas used to bubble the superfusing solution. Hypoxia elicited dilation (from 110 +/- 9 to 165 +/- 12 microm) in endothelium-intact arterioles but not in arterioles from which the endothelium had been removed. Hypoxic vasodilation was eliminated by treatment with indomethacin and was not affected by L-NAME or L-NNA. In rat diaphragmatic arterioles, the response to ACh is dependent on endothelial nitric oxide release, whereas the response to hypoxia is mediated by endothelium-derived prostaglandins. Flow-dilation requires that both nitric oxide and cyclooxygenase pathways be intact.
Adolescent males are considered to be an important genital chlamydial reservoir. However, there has been little information on urethral chlamydial infection in Thai adolescent males. About one fourth of males who are genital chlamydial reservoirs are asymptomatic. An appropriate means of defining the extent of chlamydial infection in adolescent males would be a non-invasive screening survey, instead of the conventional method of a deep swab cell culture, which is painful. The objectives of this study were to estimate the prevalence and to determine what factors should indicate the use of a screening test for urethral chlamydial infection in adolescent males residing in Chiang Mai. Chlamydial urethritis was detected by examining urine deposits for chlamydial antigen by enzyme immunoassay (EIA).
OBJECTIVE: To resolve how frequently Chlamydia trachomatis and Chlamydia pneumoniae DNA are present in the joints of unselected patients with reactive arthritis (ReA) and undifferentiated oligoarthritis, and to determine if there is an accompanying serologic or cellular antichlamydial immune response. METHODS: Two polymerase chain reaction (PCR) protocols to detect the plasmid of C. trachomatis and the outer membrane protein 1 gene of C. pneumoniae were developed for specific use with synovial fluid (SF). Subsequently, the assays were used to detect DNA from the 2 organisms in SF from 54 adult patients with rheumatic diseases, including 4 with sexually acquired ReA and 31 with undifferentiated oligoarthritis. The presence of chlamydial antibodies and SF lymphocyte proliferation responses were determined in parallel. RESULTS: The PCR protocols were species-specific and highly sensitive. SF samples from 15 patients (8 with undifferentiated oligoarthritis, 3 with ReA, 1 with rheumatoid arthritis, and 1 with psoriatic arthritis) were positive for C. trachomatis. There was no significant correlation between the presence of C. trachomatis DNA in the joint and a Chlamydia-specific synovial T cell response or a serologic response. C. pneumoniae was not detected in any of the 54 patients, although it was identified in the SF from a rheumatoid arthritis patient outside this study, demonstrating that the assay was capable of detecting the organism in the joint. CONCLUSION: C. trachomatis DNA was present in ReA patients and in nearly one-third of unselected patients with undifferentiated oligoarthritis, which further supports the hypothesis that it plays an important role in disease pathogenesis. However, its presence did not correlate with evidence of an antichlamydial immune response. Despite previous anecdotal reports, C. pneumoniae does not appear to be a major cause of undifferentiated oligoarthritis or ReA.
AIMS: Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMist, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain. METHODS: Aersolised pulmonary fentanyl base 100-300 microg was administered to healthy volunteers using SmartMist and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects. RESULTS: Plasma concentrations from SmartMist were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged approximately 100%, and was > 50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes. CONCLUSIONS: Fentanyl delivery using SmartMist can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae.
The hemodynamic response to reductions in systemic oxygen availability serves to redistribute blood flow and maintain vital organ function. The efficacy of this response depends on the degree to which hypoxia alters the function of the vascular tissues themselves. In this study we have evaluated these effects in rats exposed to 10% oxygen for 0 (control), 12, and 48 h and for 48 h followed by 12 h of normoxic recovery. In aortic segments from each group, the cumulative concentration response relationships were constructed for phenylephrine and KCl. Maximum tension generated during activation by these agents was reduced after both 12 and 48 h of hypoxic exposure. After 48 h of hypoxia, the maximum tension during activation by phenylephrine was 0.46 +/- 0.04 vs. 1.31 +/- 0. 09 g/mg dry wt for the control group (P < 0.05 for difference). The maximum tension during activation by KCl was similarly affected (0. 32 +/- 0.02 vs. 0.98 +/- 0.06 g/mg dry wt, 48 h of hypoxia vs. control, respectively; P < 0.05 for difference). Exposure to hypoxia did not alter the EC50 for either agent. Twelve hours of normoxic recovery did not fully restore contractility after 48 h of hypoxia. In aortic rings from control rats, endothelial removal enhanced contraction, whereas, in rings from rats exposed to hypoxia, removal of the endothelium was associated with a decrease in maximum tension. Prolonged exposure to hypoxia results in impairment of systemic arterial smooth muscle contractility. This is partly compensated by the release of vasoconstricting substances from the endothelium.
This study was undertaken to investigate the reported association between Chlamydia pneumoniae and Mycoplasma pneumoniae infection and the expression of asthma-related symptoms. One hundred and eight children with asthma symptoms, aged 9-11 yrs, completed a 13 month longitudinal study. The children maintained a daily diary of respiratory symptoms and peak flow rates. When respiratory symptoms were reported an investigator was called and a nasal aspirate obtained. In total 292 episodes were reported. After the study 65 children provided samples when asymptomatic. The presence of infection was investigated by the polymerase chain reaction for C. pneumoniae and M. pneumoniae and C. pneumoniae secretory immunoglobulin A (IgA) was detected by amplified enzyme immunoassay. C. pneumoniae detections were similar between the symptomatic and asymptomatic episodes (23 versus 28%, respectively). Children who reported multiple episodes also tended to remain PCR positive for C. pneumoniae suggesting chronic infection (p< 0.02). C. pneumoniae-specific secretory-IgA antibodies were more than seven times greater in subjects who reported four or more exacerbations in the study compared to those who reported just one (p<0.02). M. pneumoniae was found in two of 292 reports and in two of 65 asymptomatic samples. In conclusion, chronic Chlamydia pneumoniae infection is common in schoolage children and immune responses to C. pneumoniae are positively associated with frequency of asthma exacerbations. We suggest that the immune response to chronic C. pneumoniae infection may interact with allergic inflammation to increase asthma symptoms. In contrast Mycoplasma pneumoniae was not found to be important in this study.
The aim of this study was to assess the influence of prolonged in vivo hypoxia on cerebellar nitric oxide (NO) production. Conscious rats were exposed to 10% O2 (balanced N2) for 12 or 48 hr (arterial PO2 between 35 and 39 mmHg). The animals were then killed, and the cerebella were quickly frozen. NO production was measured in vitro by monitoring the conversion of L-[3H]arginine to L-[3H]citrulline. Protein and mRNA expressions of the neuronal (nNOS) and endothelial (ecNOS) isoforms of nitric oxide synthases were assessed by using immunoblotting and semiquantitative reverse transcription-polymerase chain reaction, respectively. We also measured mRNA expression of GTP cyclohydrolase I, the rate-limiting enzyme in the synthesis of NOS cofactor, tetrahydrobiopterin, and mRNA and protein expressions of argininosuccinate synthase and argininosuccinate lyase, essential enzymes for the recycling of L-citrulline to L-arginine. Prolonged in vivo hypoxia resulted in a time-dependent increase in cerebellar nitric oxide synthase activity and a significant rise in mRNA and protein expressions of nNOS isoform; however, ecNOS protein expression declined significantly. There was also a rise in mRNA expression of GT cyclohydrolase I; however, neither mRNA nor protein expression of argininosuccinate synthase and argininosuccinate lyase changed significantly in hypoxic animals. These results suggest that prolonged hypoxia increases cerebellar NO formation as a result of upregulation of cerebellar nNOS expression, whereas ecNOS expression declines. We propose that cofactor availability for NO production may also increase during hypoxia because of upregulation of GTP cyclohydrolase I expression. Recycling of L-citrulline to L-arginine, however, remains unchanged.
BACKGROUND: Successful pharmacotherapy of pain often depends on the mode of drug delivery. A novel, unit dose, aqueous aerosol delivery system (AERx Pulmonary Drug Delivery System) was used to examine the feasibility of the pulmonary route for the noninvasive systemic administration of morphine. METHODS: The study had two parts: (1) a dose-ranging study in four subjects with three consecutive aerosolized doses of 2.2, 4.4, and 8.8 mg (nominal) morphine sulfate pentahydrate at 40-minute intervals, and (2) a crossover study, on separate days, in six subjects with 4.4 mg (nominal) aerosolized morphine sulfate administered over 2.1 minutes on three occasions and intravenous infusions of 2 and 4 mg over 3 minutes. Subjects were healthy volunteers from 19 to 34 years old. Arterial blood was sampled for a total of 6 hours and plasma morphine concentrations were measured by gas chromatography-mass spectrometry. RESULTS: In part 1, plasma morphine concentrations were proportional to dose. In part 2, the mean +/- SD peak plasma concentration (Cmax) occurred at 2.7 +/- 0.8 minutes after the aerosol dose, with mean values for Cmax of 109 +/- 85, 165 +/- 22, and 273 +/- 114 ng/ml for the aerosol and 2 and 4 mg intravenous doses, respectively. The bioavailability [AUC(0-360 min)] of aerosol-delivered morphine was approximately 100% relative to intravenous infusion, with similar intersubject variability in AUC for both routes (coefficient of variation < 30%). CONCLUSION: The time courses of plasma morphine concentrations after pulmonary delivery by the AERx system and by intravenous infusions were similar. This shows the utility of the pulmonary route in providing a noninvasive method for the rapid and reproducible systemic administration of morphine if an appropriate aerosol drug delivery system is used.
Parturients have the greatest risk of postdural puncture headache. use of a pencil-point needle, such as the 25 gauge Whitacre, has been associated with a lower incidence of PDPH. This observational study of 1009 obstetrical patients assessed possible factors related to the incidence of PDPH and other complications associated with spinal anesthesia using the 25 gauge Whitacre needle. The independent variables included procedure, maternal position at insertion, ease of insertion, intraoperative i.v. analgesia supplementation, use of intrathecal narcotics, parity and type of local anesthetic. Patients were followed daily during their hospitalization and questioned specifically about the presence of headache, its nature, onset and treatment. Two hundred and twenty-nine patients developed a headache postperatively but only 25 had postdural puncture headaches (overall incidence 2.5%). The PDPH typically presented on day 2 (median), range 1-4). Six patients (0.59%) required epidural blood patch. There were eight (0.8%) failed finals which were converted to general anesthesia. None of the factors evaluated were significant in predicting the occurrence of PDPH.
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The circulating B-cell responses to Chlamydia trachomatis of 60 children and 34 adults in The Gambia were characterized in a cross-sectional study of different grades of trachoma, using the enzyme-linked immunospot (ELISPOT) assay. Antibody-secreting cells (ASCs) specific to chlamydial major outer membrane protein (MOMP), heat shock protein 60, and whole elementary bodies were detected in children with no evidence of ocular disease, and the immunoglobulin (IgA) response was significantly increased in those with follicular trachoma. In marked contrast, children with the most intense ocular inflammation paradoxically had an almost completely absent B-cell response of all isotypes and to all chlamydial antigens, but with normal serum IgG and IgA responses, which was even lower than in the group with no ocular inflammation. Adults with or without evidence of trachomatous scarring had equivalent numbers of circulating B cells, principally IgA, to all chlamydial antigens. Plasmablasts secreting antibodies to MOMP were present in the urine of children in the absence of urogenital infection detectable by PCR, and relative numbers were 8 to 25 times higher than in blood, suggesting site-specific homing within a common mucosal immune system. These results suggest that ELISPOT assay of ongoing B-cell responses detects suppression of chlamydia-specific IgA ASCs during the proinflammatory response to ocular chlamydial infection seen in intense trachoma, which may play a role in tissue damage leading to trachomatous scarring.