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Biomedical subjects

M E Jones

Publications and source records attributed to M E Jones.

At least 109 records · Page 6Linked to original sources

Modern malaria

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History, 20th Century↗

Prognosis in patients with left ventricular apical aneurysm diagnosed by thallium-201 or Tc-99m sestamibi SPECT images.

The prognosis of patients with left ventricular (LV) aneurysm diagnosed by thallium single-photon emission computed tomography (Tl-SPECT) or technetium-99m sestamibi SPECT (MIBI) has not previously been defined. Of 9,505 Tl or MIBI patients, 139 with apical infarct and probable LV aneurysm on tomographic images were identified. Patients were grouped by the presence of divergent versus parallel LV walls. Divergent walls show increasing separation of the walls as they approach the apex on vertical or horizontal long-axis slices. The degree of the deformation at the apex (divergent vs parallel walls), extent of impaired myocardium (total number of pixels in the defect/total number of pixels in the myocardium x 100%), percentage of reversibility, and segmental and total severity of standard deviations of perfusion defects were calculated. Seventy-six patients underwent contrast ventriculography. Patients with divergent walls (n = 57) were older (p = 0.05), had lower ejection fractions (p = 0.012), higher lung uptake (only Tl patients (p = 0.06), and more frequent ST elevation on the resting electrocardiogram (p = 0.009) than patients with nondivergent (parallel) walls. For both groups, the percent impaired myocardium was comparably high (44 +/- 9% vs 46 +/- 10%). Analysis of asynergic segments in 76 patients who underwent contrast ventriculography showed more akinetic, paradoxical, or aneurysmal segments in the apical region of the left ventricle in the group with SPECT divergent walls. Cox model analysis showed divergence as the significant correlate of death. At 5 years, survival for the group with divergent walls was 52% compared with 75% for those with nondivergent walls (p = 0.008). Despite significant apical LV impairment in both groups, mortality was almost twice as high in the group with divergent walls compared with patients with parallel walls. Thus, patients with LV aneurysm diagnosed by radionuclide SPECT perfusion imaging have a higher mortality when displaying a divergent wall pattern than patients with lesser deformity.

Aged↗

Toxin involvement in staphylococcal scalded skin syndrome.

The production of staphylococcal exfoliative toxin A (ETA) and toxin B (ETB), toxic shock syndrome toxin (TSST-1), and enterotoxins A-E was analyzed in 60 Staphylococcus aureus strains isolated from children with scalded skin syndrome (15 with generalized exfoliative syndrome, 28 with bullous impetigo, and 17 with staphylococcal scarlet fever). All strains isolated from patients with generalized exfoliative syndrome or bullous impetigo produced ETA and/or ETB and caused a Nikolsky's sign when injected subcutaneously into newborn mice. In contrast, exfoliative toxin was detected in an S. aureus strain from only one of 17 case of staphylococcal scarlet fever; the 16 other S. aureus strains produced TSST-1 and/or an enterotoxin. In conclusion, enterotoxins or TSST-1 are more frequently associated with staphylococcal scarlet fever than are exfoliative toxins. Hence staphylococcal scarlet fever may well represent an abortive form of toxic shock syndrome rather than a milder form of staphylococcal scalded skin syndrome.

Animals↗

Increasing access to health care: a study of pediatric nurse practitioner outcomes in a school-based clinic.

Pediatric nurse practitioners in school-based clinics have the potential to overcome access to care barriers for school-age children and their families by providing primary health care and linking these services with existing health and social services in the community. The article reports a study that examined health care delivered by a pediatric nurse practitioner in an elementary school setting and selected indices of access to health care (Medicaid certification; early periodic screening, diagnosis, and treatment; and linkage with existing resources). Findings suggest that greater availability of care may encourage parents to seek early preventive care for their children.

Ambulatory Care↗

Multicenter trial validation of a camera-based method to measure Tc-99m mercaptoacetyltriglycine, or Tc-99m MAG3, clearance.

PURPOSE: To evaluate an improved camera-based method for calculating the clearance of technetium-99m mercaptoacetyltriglycine (MAG3) in a multicenter trial. MATERIALS AND METHODS: Tc-99m MAG3 scintigraphy was performed in 49 patients at three sites in the United States and Canada. The percentage of the injected dose of Tc-99m MAG3 in the kidney at 1-2, 1.0-2.5, and 2-3 minutes after injection was correlated with the plasma-based Tc-99m MAG3 clearances. The data were combined with the results obtained in 20 additional patients in a previously published pilot study. RESULTS: Regression models correlating the plasma-based Tc-99m MAG3 clearance with the percentage uptake in the kidney for each time interval were developed; there was no statistically significant difference among sites in the regression equations. Correction for body surface area statistically significantly (P < .005) improved the correlation coefficient for each time interval. For the 1.0-2.5-minute interval, the body surface area-corrected correlation coefficient for the four combined sites was .87, and it improved to .93 when one outlier was omitted from the analysis. Similar results were obtained with the other time intervals. Independent processing by two observers showed no clinically important differences in the percentage dose in the kidney or in relative function. CONCLUSION: An improved camera-based method to calculate the clearance of Tc-99m MAG3 was validated in a multicenter trial.

Adolescent↗

Static versus dynamic prosthetic weight bearing in elderly trans-tibial amputees.

The purpose of this study was to compare prosthetic weight-bearing tolerance in the standing position to the dynamic vertical ground reaction forces (VGRF) experienced during walking in elderly dysvascular trans-tibial amputees. Ten unilateral trans-tibial amputees attending an amputee clinic (mean age = 67 +/- 6.5 years) were selected as subjects. Selection criteria were the level of amputation, age, medical fitness to participate and informed consent. Each participant completed five trials of standing (static) weight bearing measurement followed by 10 walking (dynamic) trials on a 10m level walkway, five trials for each limb, Static weight bearing (SWB) was measured using standard bathroom scales. Dynamic weight bearing (DWB) was measured during gait using a Kistler multichannel force platform. T-tests for dependent means indicated that the forces borne in prosthetic single limb stance (mean = 0.97 +/- 0.03 times body weight (BW)) were significantly lower than the forces borne by the prosthetic limb during the first peak (weight acceptance) VGRF (mean = 1.08 +/- 0.08 BW; t = -4.999; p = 0.001) and significantly higher than the midstance VGRF (mean = 0.82 +/- 0.07 BW; t = 5.401; p < 0.001). However, there was no significant difference between SWB and the second peak (push-off) VGRF generated by the prosthetic limb during walking (mean = 0.96 +/- 0.03 BW). It was concluded that clinical gait training may utilise SWB as a guide to an amputees' prosthetic weight bearing tolerance and requirements during walking.

Aged↗

Weight bearing and velocity in trans-tibial and trans-femoral amputees.

The purpose of this study was to review the clinical utility of static weight bearing (SWB) and maximal self-selected ambulatory velocity as objective quantifiable measures in an outpatient lower limb prosthetic clinic. Seventy-three (n = 73) consecutive trans-tibial (TTA) and trans-femoral amputees (TFA) attending an outpatient prosthetic clinic were studied. Prosthetic weight bearing was measured on a bathroom scale (mass in kg), normalised to body mass then expressed as a percentage and labelled static weight bearing (SWB). Maximum safe self-selected ambulatory velocity over a 10 metre level walkway (m/s) was measured with a stopwatch. The SWB mean for the TTA group was 94.93% range 77-100%) and 88.36% for the TFA group (range 43-100%). The mean ambulatory velocity was 1.70 m/s (range 0.07-5.75) for the TTA group and 0.78 m/s (range 0.10-1.54) for the TFA group. A statistically significant relationship (p < 0.05) was found between SWB and ambulatory velocity in trans-tibial and trans-femoral amputees in this study. A ceiling effect was noted in the trans-tibial group with 42% achieving 100% SWB through their prosthetic limb so it was concluded that ambulatory velocity was the more sensitive measure in established trans-tibial prosthetic limb users. SWB may be the more appropriate quantifiable measure for use in established trans-femoral prosthesis users. Prosthetic training programmes would benefit from the objective measurement of SWB. Once optimal SWB was achieved, ambulatory velocity would be the more sensitive measure of prosthetic use.

Adolescent↗

A modified Luria-Delbrück fluctuation assay for estimating and comparing mutation rates.

We have investigated the accuracy with which mutation rates may be estimated using a modification of the Luria and Delbrück fluctuation experiment protocol. The modification involves growing a larger-than-usual culture, and plating out a small aliquot of it. Monte Carlo simulations of the experiments confirm that the modification leads to a decrease in the coefficient of variation of the estimated mutation rate where this is based on the median number of mutants detected in a number of cultures grown in parallel. If sets of experimental and control cultures are compared using the Mann-Whitney U-test, then fractional increases in mutation rate can be reliably detected using relatively small numbers of cultures. The modified protocols promise better estimates of mutation rates, offer a powerful test of differences in mutation rates, and are easier to implement in practice.

Computer Simulation↗

Intrinsic activity and stability of bifunctional human UMP synthase and its two separate catalytic domains, orotate phosphoribosyltransferase and orotidine-5'-phosphate decarboxylase.

Human UMP synthase is a bifunctional protein containing two separate catalytic domains, orotate phosphoribosyltransferase (EC 2.4.2.10) and orotidine-5'-phosphate decarboxylase (EC 4.1.1.23). These studies address the question of why the last two reactions in pyrimidine nucleotide synthesis are catalyzed by a bifunctional enzyme in mammalian cells, but by two separate enzymes in microorganisms. From existing data on subunit associations of the respective enzymes and calculations showing the molar concentration of enzyme to be far lower in mammalian cells than in microorganisms, we hypothesize that the covalent union in UMP synthase stabilizes the domains containing the respective catalytic centers. Evidence supporting this hypothesis comes from studies of stability of enzyme activity in vitro, at physiological concentrations, of UMP synthase, the two isolated catalytic domains prepared by site-directed mutagenesis of UMP synthase, and the yeast ODCase. The two engineered domains have activities very similar to the native UMP synthase, but unlike the bifunctional protein, the domains are quite unstable under conditions promoting the dissociated monomer.

Catalysis↗

Bias caused by migration in case-control studies of prenatal risk factors for childhood and adult diseases.

Case-control studies of prenatal risk factors for disease in later life often ascertain cases from within a defined area, trace the birth records of those cases born within the area, and select controls from birth records within the same area. Bias can occur in these studies if the disease risk factors are related to migration from the area. The effects of this bias were examined in a study in Oxfordshire, England. Cases (n = 218) of diabetes in children and young adults born during 1965-1986 were identified from hospital discharges during 1965-1986; controls (n = 753) were selected from livebirths during 1965-1986. By 1987, 219 controls (29.1%) had migrated from Oxfordshire or died. Low maternal parity and high social class were strongly related to migration, more than the other perinatal factors studied. Migration, therefore, could lead to apparent associations of diabetes risk with parity or social class. For a general instance, the authors show how much bias is caused by different degrees of migration and of association between migration and a perinatal risk factor. Examples are given of how migration can produce apparent trends in risk as well as increased or decreased individual relative risks. If more than 25% of controls migrate, bias may be appreciable.

Adult↗

Cutaneous overexpression of NT-3 increases sensory and sympathetic neuron number and enhances touch dome and hair follicle innervation.

Target-derived influences of nerve growth factor on neuronal survival and differentiation are well documented, though effects of other neurotrophins are less clear. To examine the influence of NT-3 neurotrophin overexpression in a target tissue of sensory and sympathetic neurons, transgenic mice were isolated that overexpress NT-3 in the epidermis. Overexpression of NT-3 led to a 42% increase in the number of dorsal root ganglia sensory neurons, a 70% increase in the number of trigeminal sensory neurons, and a 32% increase in sympathetic neurons. Elevated NT-3 also caused enlargement of touch dome mechanoreceptor units, sensory end organs innervated by slowly adapting type 1 (SA1) neurons. The enlarged touch dome units of the transgenics had an increased number of associated Merkel cells, cells at which SA1s terminate. An additional alteration of skin innervation in NT-3 transgenics was an increased density of myelinated circular endings associated with the piloneural complex. The enhancement of innervation to the skin was accompanied by a doubling in the number of sensory neurons expressing trkC. In addition, measures of nerve fibers in cross-sectional profiles of cutaneous saphenous nerves of transgenics showed a 60% increase in myelinated fibers. These results indicate that in vivo overexpression of NT-3 by the epidermis enhances the number of sensory and sympathetic neurons and the development of selected sensory endings of the skin.

Animals↗

Mortality during 25 years of follow-up of a cohort with diabetes.

BACKGROUND: Diabetes is one of the most common chronic diseases in Western populations. There have been few large published cohort studies of people with diabetes that have had more than 10 years of follow-up, and none other than the present one are in the UK. Such studies are important to understand the long-term fatal consequences of diabetes and their variation over time and between countries. METHODS: Cause-specific mortality was analysed in follow-up from 1966-1970 to December 1992 of 5783 members of the British Diabetic Association living in England and Wales during 1966-1970. Comparison was made with age-, sex- and calendar year-specific mortality by cause in the general population of England and Wales. RESULTS: During the follow-up 3399 (58.8%) subjects died. The relative risk of all-cause mortality in the cohort compared to the general population was 2.31 in women and 1.58 in men (both P < 0.001).Relative risks were greater for women than men at almost all ages and for each major diabetes-related cause of death. Absolute excess ('attributable') mortality rates were also greater in women than in men, except at ages < 50. Half the deaths in each sex were from circulatory diseases and only 3.4% were from renal disease. The relative risks of mortality for all-causes and circulatory diseases were particularly great at younger ages, but changed little with duration of follow-up. At ages < 40 the relative risks for all-causes were 3.75 in men and 5.51 in women and for ischaemic heart disease were 10.44 and 25.25 respectively (all P < 0.001). At these ages one-third of deaths were due to acute complications of diabetes, suicides and accidents, whereas at older ages these accounted for only 4% of deaths. CONCLUSIONS: The mortality rates at young ages in the cohort were around twice those in Sweden, Norway and Israel, suggesting that many of the deaths in England and Wales are preventable. The results also indicate a particular need for investigation and amelioration of cardiovascular risk factors in English and Welsh patients, especially women.

Adolescent↗