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Biomedical subjects

M Jackson

Publications and source records attributed to M Jackson.

At least 91 records · Page 5Linked to original sources

Effects of temperature strategy during cardiopulmonary bypass on cerebral oxygen balance.

BACKGROUND: Cerebral injury is the most serious complication of cardiopulmonary perfusion (CPB). With the advent of warm heart surgery, the effect of temperature strategy during perfusion and its effect on cerebral oxygen balance needs further study. METHODS: Three groups of patients (n=8, each) undergoing coronary artery bypass graft (CABG) surgery were studied. Group H, M and N underwent CPB at 28 degrees C, 32 degrees C and normothermia (>36 degrees C), respectively. The extracorporeal circuit was primed with Hartmann's solution 2.5 l and flow of 1.8 l min(-1) m(-2) at 28 degrees C, and 2.4 1 min-1 m(-2) at 32 degrees C and normothermia. All patients had a 4F oximetry catheter (Opticath, Oximetrix, Abbott Laboratories) inserted in the right jugular bulb for continuous measurement of jugular venous oxygen saturation (sjvO2). Data was collected at six specific times: T1- within 5 min before initiation of CPB, T2 - within the first minute after CPB, T3 - during stable temperature on CPB (28 degrees C, 32 degrees C, >36 degrees C), T4 - during rewarming at 34 degrees C in groups H and M, 15 min before coming off CPB in group N, T5 - 15 min after CPB, T6 - skin closure. At each time mean arterial pressure (MAP) and sjvO2 were recorded. Arterial blood and jugular venous blood were sampled for measurement of arterial oxygen saturation (saO2) and jugular venous lactate (sjv(lactate)), respectively. RESULTS: SjvO2 values decreased at times T2, T3 and T4 when compared to baseline (p<0.05) but there were no significant group differences at any time. Cerebral arteriovenous oxygen saturation (a-jvO2) differences mirrored sjvO2 changes. Sjv(lactate) values increased from baseline following CPB but fell consistently with time - there were no significant group differences at each time point. SjvO2 and a-jvO2 values were not significantly correlated with sjv(lactate). CONCLUSION: During pump flows employed in this study, cerebral oxygen balance and perfusion appear unaffected by temperature.

Aged↗

Acute myocardial infarction at a university hospital: effect of race on short-term mortality.

Several studies have shown that African Americans who have an acute myocardial infarction (AMI) have a higher mortality rate and receive less aggressive cardiac intervention compared with whites. This observational study reports on the in-hospital mortality rate for AMI by race at a university tertiary referral hospital. Racial variation in clinical outcomes and treatment in the area of thrombolysis and acute revascularization was assessed. Data were retrieved from the National Registry on Myocardial Infarction (NRMI) for all 521 patients with AMI admitted to the critical care unit at the University of North Carolina between January 1991 and December 1994. Information collected included age, gender, race, cardiac catheterization results, thrombolytic therapy, coronary bypass surgery, mortality, and arrhythmia. African Americans had a lower in-hospital mortality rate compared with whites (2% versus 8% P < or = 0.03) and were also younger (61 +/- 13 SD versus 64 +/- 12 P = 0.02). Hypertension, diabetes mellitus, or prior myocardial infarction were similar in both groups. Of the 323 patients who received a cardiac catheterization, the extent of coronary disease and left ventricular ejection fraction was similar in both races. Finally, the use of thrombolysis, PTCA, or CABG was not influenced by race. In conclusion, the in-hospital mortality for African Americans at this university tertiary referral center was lower than for whites. This occurred despite a similar incidence in cardiac risk factors and similarly aggressive acute cardiac interventions in both white and African American patients. While African Americans experienced lower in-hospital mortality, this study does not address the pre-hospital and post-hospital risk. It does suggest that African Americans with AMI, who are comparably matched to whites for risk and receive similar cardiac interventions, may have a favorable in-hospital mortality.

Black or African American↗

Epizootiology of Chlamydia infections in two free-range koala populations.

The prevalence of Chlamydia pecorum and Chlamydia pneumoniae infections in two free-range koala populations was assessed using genus-specific PCR combined with species-specific DNA probe hybridisation. Population A had a very high overall level of chlamydial infection (85%) with significantly more of these infections being due to C. pecorum (73%) compared to C. pneumoniae (24%). The second population had a much lower prevalence of infection (10%) with equal levels of both species. An important finding of this study was that. while five of 24 C. pecorum-infected koalas had clinical signs of the disease (both ocular and urogenital sites), none out of seven C. pneumoniae-infected koalas had signs of clinical disease. This suggests that C. pecorum may be the more pathogenic of the two chlamydial species infecting this host. The level of infection (assessed by intensity of the specific hybridisation signal) also differed between chlamydial species, with C. pecorum infections ranging from low to high grade whereas C. pneumoniae infections were always low grade. When the age of infected koalas was examined, 58% of young, sexually immature koalas were found to have C. pecorum infections, increasing to 100% of koalas in the older age groups. This suggests that, in this population at least, young koalas are readily infected with C. pecorum from their mothers. While the infection levels with C. pneumoniae were too low to be statistically significant, again, sexually immature koalas were found to be infected. The recent separation of chlamydial infections in koalas into two species is beginning to indicate different epizootiologies for koala C. pecorum compared to koala C. pneumoniae.

Age Factors↗

Comparison of cytotoxic T-lymphocyte responses to hepatitis C virus core protein in uninfected and infected individuals.

Cytotoxic T lymphocytes have been implicated in the control of hepatitis C virus (HCV) infection. Recognition by cytotoxic T lymphocytes of epitopes within HCV core protein has been defined previously by in vitro stimulation with synthetic peptides. The aim of this study has been to examine cytotoxic T-lymphocyte responses generated against peptides produced naturally following intracellular processing of viral protein. Antigen-specific cytotoxic T-lymphocyte lines were generated from both HCV uninfected and infected individuals by culturing CD8+ T cells with autologous dendritic cells loaded intracytoplasmically with recombinant HCV core protein. Analysis of the epitopes recognized by core protein-specific cytotoxic T lymphocytes used synthetic peptides that were selected based on their predicted binding to HLA-A*0201 molecules. Core protein-specific cytotoxic T lymphocytes derived from HCV uninfected and infected individuals were able to lyse autologous target cells pulsed with each of 5 predicted epitopes. Generation of HCV-specific cytotoxic T lymphocytes using dendritic cells as antigen presenting cells provides a method of comparing the potential repertoire of cytotoxic T-lymphocyte responses to the responses that occur in chronically infected individuals. No evidence of a qualitatively different response by patient cytotoxic T lymphocytes was apparent which might explain persistence of the virus.

Cytotoxicity Tests, Immunologic↗

Actions of the D1 agonists A-77636 and A-86929 on locomotion and dyskinesia in MPTP-treated L-dopa-primed common marmosets.

Common marmosets show parkinsonian motor deficits following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration and develop dyskinesias during chronic L-dopa exposure. The D1 agonists A-77636 [(1R, 3S) 3-(1'-adamantyl)-1-aminomethyl-3, 4-dihydro-5, 6-dihydroxy-1H-2-benzopyran HCl] and A-86929 [(-)-trans 9, 10-hydroxy-2-propyl-4, 5, 5a, 6, 7, 11b-hexahydro-3-thia-5-azacyclopent-1-ena[c]phenanthrene hydrochloride] possess potent antiparkinsonian activity in the MPTP-treated marmoset and we now assess their influence on L-dopa-induced dyskinesias. MPTP-treated marmosets with stable motor deficits were treated with L-dopa plus carbidopa for 28 days to induce dyskinesias. Subsequently, they received A-86929 for 10 days, initially at 0.5 micromol/kg and then at 1.0 micromol/kg for a further 5 days. Several months later, L-dopa 12.5 mg/kg plus carbidopa 12.5 mg/kg was given orally twice daily for 7 days, followed by A-77636 1 micromol/kg for 10 days, and then both A-77636 and L-dopa plus carbidopa were given concurrently for 3 further days. In these L-dopa-primed animals, A-86929 effectively reversed akinesia and produced dose-dependent dyskinesias which were significantly less intense than those produced by L-dopa administration. A degree of behavioral tolerance was encountered, but antiparkinsonian activity was preserved and elicited behaviour was free of hyperkinesis and stereotypy and more naturalistic than that seen with L-dopa. After a week of twice-daily L-dopa dosing, administration of the long-acting D1 agonist A-77636 initially dramatically enhanced locomotion and reproduced dyskinesia with prominent dystonia, but after repeated administration of A-77636, dyskinesia and in particular chorea, gradually disappeared. Tolerance to locomotor stimulation greater than with A-86929 occurred, although activity remained significantly above baseline levels. There was a marked reduction in L-dopa-induced climbing, stereotypy and hyperkinesis and behaviour more closely resembled that of normal unlesioned marmosets. Upon reintroduction of L-dopa concurrently with continued A-77636 administration, dystonic, but virtually no choreic dyskinesias appeared and behaviour was once again free of stereotypy and hyperkinesis, contrasting dramatically with the presence of these behaviours along with abundant chorea when L-dopa is given alone. These results show a lesser liability of A-86929 and A-77636 to reproduce dyskinesia in L-dopa-primed MPTP-lesioned subjects while maintaining effective antiparkinsonian activity and producing a more naturalistic motor response. The differential effects of A-77636 on chorea and dystonia, with suppression of chorea and stereotypy on co-administration with L-dopa, may reflect an altered balance of activity in the direct and indirect striatofugal pathways. These results suggest a possible role for D1 agonists in the treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Polymorphisms in the glutamate transporter gene EAAT2 in European ALS patients.

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder characterised by degeneration of upper and lower motor neurons. Whilst the primary pathogenic trigger is unknown in most cases, evidence is mounting to implicate a role for glutamate-mediated neurotoxicity in the disorder. Recent studies have shown reduced levels of the mainly astroglial glutamate transporter EAAT2 in ALS motor cortex and spinal cord and multiple abnormal EAAT2 mRNA species in ALS brain tissue. One cause of the low EAAT2 levels may be that point mutations in the EAAT2 gene, EAAT2, result in an abnormal unstable protein. To test this hypothesis we analysed EAAT2 in 128 sporadic and 23 familial European ALS cases. No variants within the coding sequence of EAAT2 to affect the protein sequence nor in the consensus splice sites of the flanking intronic sequences were found in any cases, similar to findings in other reports. Frequent polymorphisms within the flanking intronic sequences of both exons 2 and 4 were seen but at similar frequencies in controls. Mechanisms other than mutations within the coding region of EAAT2 must therefore be responsible for the low levels of EAAT2 seen in most cases of ALS.

Amyotrophic Lateral Sclerosis↗

Sonographic considerations with multiple gestation.

Determination of chorionicity is of paramount importance in risk assessment and management. Best performed in the first trimester, dichorionic placentation can be reliably assumed when the membrane is easily seen, there is a "twin peak" sign, there are clearly separate placentas, and there is discordant fetal gender. In a monochorionic twin pregnancy, there is a single placental mass, the dividing membrane is difficult to visualize until the end of the first trimester, and the membrane inserts onto the placental surface without a peaked appearance. Amniotic fluid volume assessment is important in the management of twin pregnancy. Polyhydramnios-oligohydramnios may be a manifestation of twin-twin transfusion syndrome, although oligohydramnios with normal amniotic fluid volume in the other twin's sac may more likely be a sign of velamentous cord insertion, infection, or chromosomal or structural abnormality. Fetal growth discordance is common in twin pregnancy and is associated with increased perinatal mortality and morbidity. The most sensitive indicator of discordant twin growth is thought to be estimated fetal weight, and an intertwin difference of > or = 20% is considered significant. In the clinical care of a patient with twins, it is reasonably standard to confirm chorionicity with ultrasonography in the first or early second trimester. At about 20 weeks, a level II ultrasound for anatomic survey is indicated. In dichorionic pregnancies, ultrasound examinations are then performed at 26 to 28 weeks and every 3 to 4 weeks thereafter to follow growth and amniotic fluid volume. In monochorionic twins, we generally do an additional ultrasound at about 23 to 24 weeks, because of the risk of twin-twin transfusion syndrome. In the late third trimester, careful attention should also be given to fetal position, to help with delivery planning.

Amnion↗

Life threatening laryngeal toxicity following treatment with combined chemoradiotherapy for nasopharyngeal cancer: a case report with review of the literature.

Nasopharyngeal carcinoma is a rare cancer in Western society, however there is a higher incidence in Asian. Chinese and African populations. A significant number of Asians reside in Australia, and consequently patients with nasopharyngeal carcinoma are an increasing clinical problem. Radiotherapy has been the predominant treatment in the past, but more recently multi-modality treatments have been utilised. The results of an Intergroup trial, coordinated by the Southwest Oncology Group (SWOG) demonstrated markedly superior progression free and overall survival for combined chemoradiotherapy compared to radiotherapy alone. At three years progression free survival was 24% for the radiotherapy arm and 69% for the chemoradiotherapy group (P < 0.001), and three-year survival was 47% for the radiotherapy arm compared with 78% for the combined arm (P = 0.005). There was minimum toxicity reported for either of the arms and no treatment related deaths. Based on these survival data the administration of concomitant cisplatin and radiotherapy has become standard of care for nasopharyngeal carcinoma in the USA. Our institution has also adopted a similar combined therapy protocol for patients with stage III and IV nasopharyngeal cancer and good performance status. The patients treated at our institution have experienced significant side effects. We describe the case of a woman so treated with this protocol who subsequently developed severe life threatening laryngeal necrosis.

Antineoplastic Agents↗

Influence of culture conditions on production and freeze-drying tolerance of Paecilomyces fumosoroseus blastospores.

With the goal of developing a defined medium for the production of desiccation-tolerant blastospores of the bioinsecticidal fungus Paecilomyces fumosoroseus, we evaluated the impact of various media components such as amino acids, carbohydrates, trace metals and vitamins on hyphal growth and sporulation of P. fumosoroseus cultures and on the freeze-drying tolerance of blastospores produced under these conditions. A comparison of 13 amino acids as sole nitrogen sources showed that glutamate, aspartate, glycine and arginine supported biomass accumulations (12-16 mg ml-1) and blastospore yields (6-11 x 108 blastospores ml-1) comparable to our standard production medium which contains casamino acids as the nitrogen source. Using glutamate as the sole nitrogen source, tests with various carbohydrates showed that P. fumosoroseus grew best on glucose (18.8 mg biomass ml-1) but produced similar blastospore concentrations (7.3-11.0 x 108) when grown with glucose, glycerol, fructose or sucrose. P. fumosoroseus cultures grown in media with sodium citrate or galactose as the sole carbohydrate produced lower blastospore concentrations but more-desiccation-tolerant spores. Zinc was the only trace metal tested that was required for optimal growth and sporulation. In a defined medium with glutamate as the nitrogen source, vitamins were unnecessary for P. fumosoroseus growth or sporulation. When blastospores were freeze-dried in the absence of a suspension medium, residual glucose (>2.5% w/v) was required for enhanced spore survival. Thus, a defined medium containing basal salts, glucose, glutamate and zinc can be used to produce optimal concentrations of desiccation-tolerant blastospores of P. fumosoroseus.

Journal Article↗

Thoracic epidural infusions for post-thoracotomy pain: a comparison of fentanyl-bupivacaine mixtures vs. fentanyl alone.

A randomised double-blind clinical trial was conducted on 106 patients scheduled for pulmonary resection. Patients received an epidural infusion containing 0.1%, 0.2% bupivacaine or saline in combination with fentanyl 10 microgram.ml -1. Adequacy of analgesia was assessed at rest and during movement over 24 h. Analgesic efficacy was assessed using visual analogue scores and an observer/verbal ranking scale. Pain scores were higher in the fentanyl-only group at the 2 h assessment (p < 0.05). Otherwise, there were no between-group differences in pain scores or in the total amounts of epidural solution used. All patients received continuous haemodynamic monitoring. There were no between-group differences in the number of episodes of hypotension or in the number of interventions for hypotension. However, the use of intra-operative vasopressor and the incidence of temporary neurological complications was higher in the 0.2% bupivacaine group (p < 0.05). We conclude that, in the early postoperative period, the addition of bupivacaine 0.1% improves fentanyl epidural analgesia in patients undergoing lung resection and is not associated with the disadvantages seen with the addition of bupivacaine 0.2%.

Adult↗

Inactivation of the antigen 85C gene profoundly affects the mycolate content and alters the permeability of the Mycobacterium tuberculosis cell envelope.

The antigen 85 complex of Mycobacterium tuberculosis consists of three abundantly secreted proteins. The recent characterization of a mycoloyltransferase activity associated in vitro with each of these antigens suggested that they are potentially important for the building of the unusual cell envelope of mycobacteria. To define the physiological role of these proteins, the gene coding for antigen 85C was inactivated by transposon mutagenesis. The resulting mutant was shown to transfer 40% fewer mycolates to the cell wall with no change in the types of mycolates esterifying arabinogalactan or in the composition of non-covalently linked mycolates. As a consequence, the diffusion of the hydrophobic chenodeoxycholate and the hydrophilic glycerol, but not that of isoniazid, was found to be much faster through the cell envelope of the mutant than that of the parent strain. Taken together, these data demonstrate that: (i) antigen 85C is involved directly or indirectly in the transfer of mycolates onto the cell wall of the whole bacterium; (ii) the enzyme is not specific for a given type of mycolate; and (iii) the cell wall-linked mycolate layer may represent a barrier for the diffusion of small hydrophobic and hydrophilic molecules.

Acyltransferases↗

Infrared spectra of basal cell carcinomas are distinct from non-tumor-bearing skin components.

Infrared spectroscopy, by probing the molecular vibration of chemical bonds, directly indicates tissue biochemistry. An expanding body of literature suggests that infrared spectra distinguish diseased from normal tissue. The authors used infrared spectroscopy to examine basal cell carcinoma to explore distinctive characteristics of basal cell carcinoma versus normal skin samples and other skin neoplasms. Spectra of epidermis, tumor, follicle sheath, and dermis were acquired from unstained frozen sections, and analyzed qualitatively, by t-tests and by linear discriminant analyses. Dermal spectra were significantly different from the other skin components mainly due to absorptions from collagen in dermis. Spectra of normal epidermis and basal cell carcinoma were significantly different by virtue of subtle differences in protein structure and nucleic acid content. Linear discriminant analysis characterized spectra as arising from basal cell carcinoma, epidermis, or follicle sheath with 98.7% accuracy. Use of linear discriminant analysis accurately classified spectra as arising from epidermis overlying basal cell carcinoma versus epidermis overlying nontumor-bearing skin in 98.0% of cases. Spectra of basal cell carcinoma, squamous cell carcinoma, nevi, and malignant melanoma were qualitatively similar. Distinction of basal cell carcinoma, squamous cell carcinoma, and melanocytic lesions by linear discriminant analyses, however, was 93.5% accurate. Therefore, spectral separation of abnormal versus normal tissue was achieved with high sensitivity and specificity, which points to infrared spectroscopy as a potentially useful screening tool for cutaneous neoplasia.

Basal Cell Carcinoma↗

Classification of breast tumors by grade and steroid receptor status using pattern recognition analysis of infrared spectra.

Infrared (IR) spectroscopy applied to tissue sections yields complex spectra that provide a molecular fingerprint of the tissue. We have studied a cohort of 77 breast tumors by IR spectroscopy to develop an objective method for the assignment of grade of breast tumors. Although the major variations between spectra from different tumors were in absorptions arising from triglycerides (adipose tissue) and collagen, subtle changes in spectra could be detected that were independent of cellularity and tissue composition. Using a specific multivariate pattern recognition strategy to associate these changes in spectra with different tumor grades, we then were able to accurately reclassify tumors by grade (87% accuracy; kappa = 0.835). A similar approach allowed classification of steroid receptor status (93% accuracy; kappa = 0.852). We conclude that IR spectroscopy may have clinical utility in the objective assignment of breast tumor grade.

Breast Neoplasms↗