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Biomedical subjects

M J Gardner

Publications and source records attributed to M J Gardner.

At least 91 records · Page 5Linked to original sources
PubMed1994

Phylogenetic analysis of the rpoB gene from the plastid-like DNA of Plasmodium falciparum.

Malaria and other Apicomplexan parasites harbour two extrachromosomal DNAs. One is mitochondrial and the other is a 35-kb circle with some plastid-like features but whose provenance and function is unknown. In addition to genes for rRNAs, tRNAs and ribosomal proteins, the 35-kb circular DNA of Plasmodium falciparum carries an rpoBC operon which encodes subunits of a eubacteria-like RNA polymerase. The phylogenetic analysis of the complete rpoB sequence presented here supports our inference that the 35-kb circle is the remnant of a plastid genome.

Amino Acid Sequence↗
PubMed1994

The relationship between renin isoelectric forms and renin glycoforms.

Active renin can be separated into multiple isoelectric forms using shallow gradient isoelectric focusing and into multiple glycoforms using concanavalin A (Con A) affinity chromatography. The relationship between renin isoelectric forms and glycoforms has not been previously determined. In this study, each of three renin Con A glycoforms from rat kidney was composed of significantly different proportions of six renin isoelectric forms; glycoforms with the greatest affinity for Con A contained proportionally less of the acidic isoelectric forms than those with the least affinity for Con A. A set of compartmental models accurately predicted previously measured differential plasma clearance rates of the three renin glycoforms based on their corresponding isoelectric form proportions. We conclude that 1) each Con A renin glycoform is composed of significantly different proportions of isoelectric forms, and 2) the different proportions of isoelectric forms found in Con A glycoforms are sufficient to account for the differential renin plasma clearance rates demonstrated previously for renin glycoforms in the rat. These data suggest that the isoelectric and glycoform heterogeneity of active renin are, in fact, closely related and may result from variable and interrelated mannose (Con A affinity) and sialic acid (charge) attachments to renin.

Animals↗
PubMed1994

Fiber levels and disease in workers from a factory predominantly using amosite.

The Cape Boards Plant at Uxbridge produced insulation board containing amosite asbestos between 1947 and 1973 with only small amounts of chrysotile. After 1973 only amosite was used. In this study we examined lung samples from 48 workers who had been employed at the plant and who had come to autopsy. The study investigated the fiber levels against the lung pathology including amount of interstitial fibrosis and numbers of ferruginous bodies. The degree of interstitial fibrosis and number of asbestos bodies were graded and the tissues were analyzed by transmission electron microscopy and energy dispersive X-ray analysis and the fibers counted and typed. The 48 cases included 5 mesotheliomas and 14 lung cancers. The mineral analysis results were dominated by the amosite fiber levels. The amounts of chrysotile were relatively small. There were higher levels in lung cancer cases than mesotheliomas and higher levels in mesothelioma cases than those who had died from nonasbestos related diseases. Analysis of the lung tissues showed a consistent pattern of high amosite levels, which confirms the impression that amosite was the predominant form of asbestos used and also indicates that the factory had been a very dusty one.

Asbestos, Amosite↗
PubMed1993

Sequence and organization of large subunit rRNA genes from the extrachromosomal 35 kb circular DNA of the malaria parasite Plasmodium falciparum.

The malaria parasite Plasmodium falciparum carries an extrachromosomal 35 kb circular DNA molecule of unknown provenance. A striking feature of the circle is a palindromic sequence of genes for subunit rRNAs and several tRNAs, spanning ca. 10.5 kb. The palindrome has an intriguing resemblance to the inverted repeat of plastid genomes, and the sequence and putative secondary structure of the malarial large subunit (LSU) rRNA described in this report were used as the basis of a phylogenetic study. The malarial rRNA was found to be highly divergent in comparison with a selected group of chloroplast LSU rRNAs but was more closely related to them than to mitochondrial LSU rRNA genes.

Animals↗
PubMed1993

Is early discharge following isolated splenic injury in the hemodynamically stable child possible?

Nonoperative treatment of splenic injury is well accepted. Two questions have not been answered. (1) What is the intensity of monitoring required in the hemodynamically stable patient? (2) How long do patients need to be hospitalized? Ninety-one patients having computed tomography (CT) or surgically proven splenic injury were treated between September 1986 and September 1991. Excluded from the study were 16 patients requiring operation and 22 patients having multiple system injuries. All operations occurred within 24 hours of admission. No transfusions were required later than 48 hours following admission. The remaining 53 patients (58%) constitute the study group. CT classification of Buntain indicated 6 class I, 21 class II, 24 class III, and 2 class IV injuries. The mean Injury Severity Score (ISS) for the group was 6.98 +/- 3.43. Serial hematocrits for the patients treated without transfusions were followed until three consecutive determinations showed no change. The lowest average hematocrit for the nontransfused group was 30.96% +/- 4.47% and occurred on day 2.06 +/- 0.76. Eleven patients (23%) had left-sided pleural effusions that resolved without intervention. One patient had an ileus for 3 days. CT or ultrasound examination was obtained on day 5 to 7 to document healing before the patient was allowed out of bed and discharged. The average hospital stay was 7.06 +/- 2.24 days. Twenty-two patients were initially observed in the intensive care unit (ICU). Clearly the interval between hematocrit stability (average, 2.06 days) and discharge (average, 7.06 days) constitutes a time of minimal nursing care while utilizing bed space and health care dollars.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Audit filters in quality assurance in pediatric trauma care.

Quality assurance (QA) systems use audit filters to help identify not only deaths and medical complications, but also cases that reflect deficiencies in the timeliness or appropriateness of care. Through our trauma center QA process, we studied three groups of audit screens for trauma care: two set forth by the Committee on Trauma of the American College of Surgeons, a minimum set of 12 audit filters proposed in 1987 and an expanded version recently proposed in 1990 (studied retrospectively), and one set of filters already in use in our system. A peer review committee determined whether deaths and complication were preventable, and judged the timeliness and appropriateness of care. From July 1, 1989, through June 30, 1990, 844 admitted trauma patients came under QA review. During this period 13 (1.5%) died; 35 (4.1%) suffered at least one medical complication. 140 children (16.6%) violated one of the 12 minimum audit filters suggested by the Committee on Trauma (which includes deaths and medical complications), one of the additional filters used by the Trauma Program QA system, or both. Ninety patients (10.6%) failed one of the 12 minimum audit filters; 104 (12.3%) failed one of the additional filters used by the Trauma Program QA system. Filters that involved medical management issues (late operations, return to operating room, airway, failed reduction, infections, missed injuries, readmissions to intensive care unit, return to the emergency department) frequently involved aspects of inappropriate care (72.5%, 37/51 violations) and were associated with actual deaths or medical complications (52.9%, 27/51).(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1993

Renal artery occlusion in pediatric blunt abdominal trauma--decreasing the delay from injury to treatment.

The cases of seven children treated from 1980 through 1991 with blunt renal artery injuries were reviewed to determine (1) if computed tomography alone could eliminate the need for intravenous pyelography (IVP) or arteriography (ART); and (2) the causes of management delays. The diagnosis of arterial occlusion was suggested by the lack of renal contrast enhancement in six patients with CT scans and in two patients with IVP. In three patients ART was merely confirmatory. The diagnosis was suggested by IVP or CT scan within a mean of 4.7 hours of injury, but ART added an additional mean 2.3 hours to the diagnostic workup. There was an additional 3.9-hour average delay in the operating room before revascularization. Six patients underwent revascularization. Four had minimal function by postoperative renal scans. Renal artery occlusion is rapidly detected by contrast-enhanced CT scanning without IVP or ART. The time period from diagnosis to revascularization must be expedited to improve renal outcome.

Angiography↗
PubMed1993

The effects of unilateral stellate ganglion blockade on human cardiac function during rest and exercise.

INTRODUCTION: Left-sided stellate ganglion predominance has been proposed as a mechanism responsible for lethal ventricular arrhythmias, due to heterogenous ventricular repolarization. To determine the cardiovascular effects of such asymmetric sympathetic ganglion innervation in man, studies were performed in 15 patients undergoing unilateral stellate ganglion blockade for the management of chronic arm pain. METHODS AND RESULTS: Standard 12-lead ECGs, systemic blood pressure, body surface potential mapping, and radionuclide angiography were performed during rest and graded exercise before and after blockade. Successful unilateral blockade was accomplished in 13 of the patients, 11 of whom had right-sided blockade and two left-sided blockade. No significant changes due to blockade of stellate ganglia, including QT intervals, were detected during rest or graded exercise in standard ECGs. No cardiac rhythm disturbances occurred in these states. Body surface potential maps and arterial blood pressure were similar during resting supine and upright positions, as well as immediately after exercise before and after blockade. Unilateral ganglionic blockade did not modify resting or exercise cardiac ejection fractions. CONCLUSION: Unilateral stellate blockade in man does not induce untoward cardiovascular effects during rest or exercise.

Adult↗
PubMed1993

Pharmacokinetics of azithromycin in pediatric patients after oral administration of multiple doses of suspension.

Azithromycin is an azalide antibiotic. On the basis of data in adults, azithromycin appears to have a greater distribution into tissues, a longer elimination half-life, and a lower incidence of adverse effects than the macrolide antibiotic erythromycin. However, little about the pharmacokinetics of azithromycin in children is known. The objective of our study was to characterize the pharmacokinetics of azithromycin after oral administration of multiple doses of suspension to children with streptococcal pharyngitis. Fourteen children (6 to 15 years of age) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after this last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The mean +/- standard deviation for maximum concentration of drug in serum, time to maximum concentration of drug in serum, and area under the curve (0 to 24 h) were 383 +/- 142 ng/ml, 2.4 +/- 1.1 h, and 3,109 +/- 1,033 ng.h/ml, respectively. Concentrations in serum at 0 h (predose) and at 24, 48, and 72 h after the final dose were 67 +/- 31, 64 +/- 24, 41 +/- 17, and 29 +/- 14 ng/ml, respectively. Thus, once-daily administration of azithromycin resulted in sustained systemic exposure to the drug.

Administration, Oral↗
PubMed1993

Ethylene oxide: an assessment of the epidemiological evidence on carcinogenicity.

Mortality from cancer among workers exposed to ethylene oxide (EtO) has been studied in 10 distinct cohorts that include about 29,800 workers and 2540 deaths. This paper presents a review and meta-analysis of these studies, primarily for leukaemia, non-Hodgkin's lymphoma, stomach cancer, pancreatic cancer, and cancer of the brain and nervous system. The magnitude and consistency of the standardised mortality ratios (SMRs) were evaluated for the individual and combined studies, as well as trends by intensity or frequency of exposure, by duration of exposure, and by latency (time since first exposure). Exposures to other workplace chemicals were examined as possible confounder variables. Three small studies by Hogstedt initially suggested an association between EtO and leukaemia, but in seven subsequent studies the SMRs for leukaemia have been much lower. For the combined studies the SMR = 1.06 (95% confidence interval (95% CI) 0.73-1.48). There was a slight suggestion of a trend by duration of exposure (p = 0.19) and a suggested increase with longer latency (p = 0.07), but there was no overall trend in risk of leukaemia by intensity or frequency of exposure; nor did a cumulative exposure analysis in the largest study indicate a quantitative association. There was also an indication that in two studies with increased risks the workers had been exposed to other potential carcinogens. For non-Hodgkin's lymphoma there was a suggestive risk overall (SMR = 1.35, 95% CI 0.93-1.90). Breakdowns by exposure intensity or frequency, exposure duration, or latency did not indicate an association, but a positive trend by cumulative exposure (p = 0.05) was seen in the largest study. There was a suggested increase in the overall SMR for stomach cancer (SMR = 1.28, 95% CI 0.98-1.65 (CI 0.73-2.26 when heterogeneity among the risk estimates was taken into account)), but analyses by intensity or duration of exposure or cumulative exposure did not support a causal association for stomach cancer. The overall SMRs and exposure-response analyses did not indicate a risk from EtO for pancreatic cancer (SMR = 0.98), brain and nervous system cancer (SMR = 0.89), or total cancer (SMR = 0.94). Although the current data do not provide consistent and convincing evidence that EtO causes leukaemia or non-Hodgkin's lymphoma, the issues are not resolved and await further studies of exposed populations.

Ethylene Oxide↗
PubMed1993

A cohort study of workers exposed to formaldehyde in the British chemical industry: an update.

A cohort study of workers exposed to formaldehyde in the British chemical industry in any one of six factories has been extended after the earlier published report in 1984. A further eight years of follow up to the end of 1989 have been included for the originally reported 7660 workers first employed before 1965, and a first follow up to the same date has been carried out for 6357 workers first employed since 1964. Extensive checking of the database has taken place including records at the factories, the MRC Environmental Epidemiology Unit, and the National Health Service Central Register. The updated findings include one death from nasal cancer compared with 1.7 expected in this number of men during the follow up period--which gives no support to the original hypothesis based on animal experimental data that formaldehyde may be a nasal carcinogen in humans. There have been no cases of nasopharyngeal cancer in the cohort compared with an estimated 1.3 expected--which gives no support to the findings in a similarly designed study in the United States of an excess of cancers of the nasopharynx associated with exposure to formaldehyde. There has been a slight excess of about 12% for lung cancer with 402 deaths compared with about 359 expected. This is similar to that found in the United States study, but higher than we reported earlier before the checking procedures and extended follow up. Further analysis gives no definitive indication of this excess of lung cancer being clearly related to formaldehyde exposure, and the increase is within that generally thought consistent with possible confounding effects of cigarette smoking (although no data are available on this point).

Chemical Industry↗
PubMed1993

Influence of growth hormone deficiency on growth and body composition in rats: site-specific effects upon adipose tissue development.

Neonatal female rats were treated for 3 weeks (short term) or 8 weeks (long term) with antiserum to rat GH (anti-rGH) with or without replacement therapy with recombinant bovine GH (bGH). Body weight gain and tail length were significantly suppressed within the first 3 weeks and were even more markedly suppressed when treatment was continued for 8 weeks. When treatment was stopped in short-term-treated animals the rate of body weight gain recovered, although without evidence of catch-up growth. These effects were all normalized by concurrent treatment with bGH. Long-term anti-rGH treatment caused a profound reduction (80%) in the number of differentiated adipocytes in two internal fat depots, whilst the subcutaneous depot was only moderately affected (20%). In contrast, after recovery from short-term treatment with anti-rGH, the internal depots were only marginally decreased in both weight and adipocyte numbers, whereas the subcutaneous depot was actually doubled in size compared with controls, due entirely to an increase in the number of differentiated adipocytes. These data clearly demonstrate for the first time that GH is required for the differentiation of adipocytes in vivo. In addition, the results demonstrate distinct effects at different anatomical sites and suggest that GH may be one factor responsible for the differences described in numerous metabolic parameters and hormonal sensitivities of adipose tissue derived from different locations within the body.

Adipose Tissue↗
PubMed1992

Homologies between the contiguous and fragmented rRNAs of the two Plasmodium falciparum extrachromosomal DNAs are limited to core sequences.

Plasmodium falciparum contains two extrachromosomal DNAs, a 6 kb linear element and a 35 kb circular DNA; both encode rDNA sequences. The 6 kb element rDNAs comprise fragments of both large and small subunit rRNAs. Comparison of these with corresponding rDNA sequences from the 35 kb DNA and E. coli show that sequences conserved between the three are largely confined to highly conserved core regions; in fact, most of the 6 kb rDNA sequences correspond to core regions. Both the 6 kb element and 35 kb rDNAs show less conservation to each other than to E. coli sequences, suggesting that the two extrachromosomal DNAs of P. falciparum are not closely related. The characteristics of the fragmented rRNAs from the 6 kb element suggest they are functional, possibly in mitochondrial ribosomes.

Animals↗
PubMed1992

Subcellular fractionation of the two organelle DNAs of malaria parasites.

Malaria parasites contain two extrachromosomal DNAs, a 6 kb repetitive linear molecule which is assigned on the basis of its genetic content to the mitochondria, and a 35 kb transcriptionally active circular molecule whose intracellular location is not known. We used the polymerase chain reaction to detect and estimate the numbers of both molecules in sub-cellular fractions derived from the rodent parasite Plasmodium yoelii. The two DNA molecules were not coordinately partitioned by the fractionation process, the 6 kb molecule being more abundant, relative to the 35 kb circle, in a fraction enriched for mitochondria, the converse being true for a less dense fraction of unknown identity. This implies that the two molecules are located in different cellular compartments, and is consistent with other evidence suggesting they have different evolutionary origins.

Animals↗
PubMed1992

Discrimination between myocardial infarct and ventricular tachycardia patients using magnetocardiographic trajectory plots and iso-integral maps.

Magnetocardiograms were recorded from 30 normal (N) subjects, 15 myocardial infarct (MI) patients, and 15 ventricular tachycardia (VT) patients. Discrimination between the groups was affected by iso-integral magnetic field mapping (MFM) and trajectory plotting of MFM extrema. Iso-integral MFM for the QRST, QRS, and ST-T intervals was created for each test group member. A polarity score, based on the number of extrema features present, was assigned to each iso-integral MFM. Differences in group mean integral of QRST map polarity scores were significant (p less than 0.05) between MI and N, between VT and N (p less than 0.005), and between MI and VT (p less than 0.05) subjects. integral of ST-T map polarity scores were significantly (p less than 0.0001) different between VT and N and between MI and VT (p less than 0.001) subjects. Discrimination between MI and VT patients, based on polarity score difference, was 56% accurate using integral of QRS maps and 73% accurate using integral of ST-T maps. For each subject, time-normalized MFM was used to construct trajectory plots of the maxima and minima in the QRS and ST-T intervals. Discrimination between MI and VT patients was based upon intergroup differences in fragmented trajectory plots. When the number of discrete trajectories and/or the total number (F) of trajectory points at which discrete trajectories coexist were considered, QRSmin trajectory plots were significantly (p less than 0.05) different for VT and N, but not for MI and N subjects. The significant (p less than 0.05) difference between MI and VT trajectory plots enabled 76% accuracy for MI and VT identification. ST-Tmax trajectory plots show significantly (p less than 0.0001) higher F values for VT patients facilitating accurate (87%) discrimination between MI and VT patients. These results suggest that the abnormalities of repolarization processes, displayed by MFM as multipolar integral of ST-T maps and/or as fragmented trajectory plots of ST-T extrema, may be useful indicators of the arrhythmia substrate/processes that characterize VT and vulnerable MI patients.

Diagnosis, Differential↗