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Biomedical subjects

J M Thompson

Publications and source records attributed to J M Thompson.

At least 91 records · Page 5Linked to original sources
PubMed1996

Inhaled misoprostol blocks guinea pig antigen-induced bronchoconstriction and airway inflammation.

Inhaled E-type prostaglandins (PGE) have been shown to modulate responses to both allergic and nonallergic provocation. Misoprostol, a PGE1 analog, was developed as an antiulcer agent because it prevents gastrointestinal ulceration. Little is known about the effect inhaled misoprostol has on the airway and whether its potential antiasthmatic activity would be similar to other PGEs. Nebulizied solutions of misoprostol and PGE2 effectively blocked the acute bronchospasm caused by a subsequent inhaled antigen challenge in actively sensitized guinea pigs. The minimal concentration to result in a significant reduction in specific airway resistance was 3 and 30 micrograms/ml for misoprostol and PGE2, respectively. Exposure to a 300 micrograms/ml nebulized misoprostol solution provided significant protection for 2 h. Eosinophil recovery in bronchoalveolar lavage performed 24 h after antigen challenge was significantly reduced by 72%. In a chronic model of antigen-induced airway inflammation in which guinea pigs are given multiple antigen exposures over a 3-wk period, both misoprostol and its free acid-active metabolite 5C-30695 significantly reduced bronchoalveolar lavage eosinophils by 50 to 55%. Treatment with TRFK5, a monoclonal antibody to interleukin-5, resulted in a 76% decrease in eosinophil recovery. The combination of antibronchoconstrictive and anti-inflammatory effects suggests that inhaled misoprostol may be an effective treatment for the acute and chronic symptoms of asthma.

Administration, Inhalation↗
PubMed1996

Employer purchasing of health care benefits: marketing implications of an organizational buying perspective.

While health care providers recognize employers as key purchasers of health benefits, there is little understanding of how employers make these important buys. We propose a model of health benefits acquisition using an organizational buying perspective, and discuss findings from a study of employee benefits managers. Critical marketing implications are presented.

Administrative Personnel↗
PubMed1996

Causes of horse-related injuries in a rural western community.

OBJECTIVE: To determine the causes of horse-related injuries in a rural western community. DESIGN: Prospective identification of persons with horse-related injuries and retrospective interviews with patients or witnesses to determine causes. SETTING: A small rural community in Alberta where the western style of riding predominates. PATIENTS: All patients presenting to two family medicine clinics or to the Sundre General Hospital emergency department. MAIN OUTCOME MEASURES: Factors contributing to the injury as recalled by patients or witnesses, and characteristics of the persons, horses, and injuries. RESULTS: Two thirds of the 150 injuries were caused primarily by horses and one third primarily by patients risk taking or inattention. The most common horse behaviour that caused injuries was "spooking," but several other behaviours also were identified as primary causes. The injuries were varied and relatively severe. Only one person was wearing a helmet. CONCLUSIONS: Horse-related injuries often are caused by characteristic horse behaviours.

Accidents, Occupational↗
PubMed1996

Immunomagnetic CD4+ and CD8+ cell depletion for patients at high risk for severe acute GVHD.

Acute GVHD remains a major problem in allogeneic BMT, in particular when donors other than HLA-identical siblings are used. To determine the efficacy of an immunomagnetic method for depletion of CD4+ and CD8+ lymphocytes from the marrow graft, a series of 15 patients was studied. Thirteen patients had matched unrelated donors, and two patients had related donors. Cyclosporine was used as GVHD prophylaxis in combination with CD4+ and CD8+ depletion, which removed 94.1 +/- 3.2%, 97.0 +/- 5.1%, and 96.7 +/- 3.1% of CD3+, CD4+ and CD8+ cells, respectively. All patients engrafted promptly with AGC > 500/mm3 after a median of 16 days post-BMT. Acute GVHD grade II-IV developed in 0/2 related transplants and 4/13 MUD transplants; only one patient had grade III-IV acute GVHD. No late graft failure was observed. Three patients relapsed; two had advanced disease at the time of BMT. Seven patients are alive and in CCR after a median of 497 days; actuarial survival is 39% at 24 months. The fever syndrome observed with selective CD8+ cell depletion was not seen with the combined CD4+ and CD8+ cell depletion. Immunomagnetic CD4+ and CD8+ cell depletion of marrow grafts, in combination with in vivo cyclosporine, is a simple, reproducible and effective method to decrease the incidence and severity of acute GVHD in patients at high risk for this complication after allogeneic BMT.

Acute Disease↗
PubMed1995

Total norepinephrine spillover, muscle sympathetic nerve activity and heart-rate spectral analysis in a patient with dopamine beta-hydroxylase deficiency.

Dopamine-beta-hydroxylase (D beta H) is the enzyme responsible for intraneural conversion of dopamine to norepinephrine. Its deficiency results in failure of norepinephrine synthesis, excessive dopamine release and orthostatic hypotension. We studied a young patient with this deficiency using the currently available methods to assess sympathetic function namely measurement of norepinephrine kinetics, microneurography to assess muscle sympathetic nerve activity (MSNA), and heart-rate spectral analysis. We compared these findings with those in 24 young healthy controls, and 4 patients with peripheral autonomic failure (PAF). Recordings were made in our subject before and after 5 months of treatment with L-threo-3,4-dihydroxyphenylserine (DOPS) (which is converted directly into L-norepinephrine bypassing the D beta H enzymatic step); measurements were made at rest in the supine position and after 15 min of 30 degrees head-up tilt. Our subject with D beta H deficiency had a high resting nerve firing rate (40.3 bursts/min) compared with the mean value in normal controls (19.3 bursts/min), and an appropriate increase in nerve firing rate during tilt. Total body norepinephrine spillover at rest was very low, 38 ng/min, compared with age-matched normals (519 +/- 43.3 ng/min, mean +/- SEM), and epinephrine secretion was undetectable. Conversely, the plasma concentrations of dopamine, DOPAC, HVA and DOPA were raised. At rest, low-frequency heart-rate variability (0.1 Hz) was absent with preservation of the respiratory-related high-frequency peak. In contrast, the PAF subjects had no detectable muscle sympathetic nerve activity, very low levels of norepinephrine spillover and epinephrine secretion and a reduction in heart rate variability at all frequencies. After 5 months treatment with L-threo-3,4-dihydroxyphenylserine (DOPS) in the D beta H deficiency patient there was a dramatic clinical improvement with resolution of the orthostatic symptoms, dramatic reduction in MSNA activity at rest, and return of plasma norepinephrine, norepinephrine spillover, DHPG and MHPG to within the normal range, indicating intraneuronal production of norepinephrine.

Adolescent↗
PubMed1995

Public health policy on bed sharing and smoking in the sudden infant death syndrome.

AIMS: Further develop New Zealand public health policy on infant bed sharing by quantifying the number of sudden infant death syndrome (SIDS) cases attributable to bed sharing among infants of smoking and nonsmoking mothers. METHODS: A large nation-wide case control study covering a region with 78% of all births in New Zealand during 1987-90. Interviews were completed with parents of 393 (81.0% of total) cases who died from the sudden infant death syndrome in the postneonatal age group, and 1592 (88.4% of total) controls who were a representative sample of all hospital births in the study region. RESULTS: The proportion of control infants who usually bed shared in the last 2 weeks was 65.7% in Maori, 73.7% in Pacific Island people and 35.5% in Europeans (44.5% in all ethnic groups combined, and half of these for less than 2 hours per night). There was an interaction between maternal smoking and infant bed sharing on the risk of sudden infant death separately in Maori, Pacific Island and European infants with the risk being highest in infants exposed to both risk factors. 26% of SIDS deaths were explained by bed sharing among infants of smoking mothers (who comprised 16% of the total infant population) and 3% by bed sharing among infants of non-smoking mothers (28% of total infant population). CONCLUSION: Infant bed sharing is common. The majority of SIDS deaths that are attributed to be sharing occur among infants of smoking mothers. A policy which advises all infants not to bed share is estimated to potentially save an extra 3% of SIDS compared to a policy targeted only on infants of smoking mothers. If public attitudes are favorable to bed sharing, there could be a marginal cost (against its acceptance) by including infants of non-smoking mothers in the recommendation not to bed share. These findings should not be interpreted as indicating that bed sharing where the mother is a nonsmoker is safe or protective against SIDS.

Beds↗
PubMed1995

Effects of aging on the responsiveness of the human cardiac sympathetic nerves to stressors.

BACKGROUND: Aging increases human sympathetic nervous activity at rest. Beause of the probable importance of neural stress responses in the heart as triggers for clinical end points of coronary artery disease, it is pertinent to investigate whether sympathetic nervous responses to stresses are increased by aging. METHODS AND RESULTS: We applied kinetic methods for measuring the fluxes to plasma of neurochemicals relevant to sympathetic neurotransmission in younger (aged 20 to 30 years) and older (aged 60 to 75 years) healthy men during mental stress (difficult mental arithmetic), isometric exercise (sustained handgrip), and dynamic exercise (supine cycling). The increase in total norepinephrine spillover to plasma with mental stress was unaffected by age. In contrast, the increase in cardiac norepinephrine spillover was two to three times higher in the older subjects (P < .05). The probable mechanism of this higher cardiac norepinephrine spillover was reduced neuronal reuptake of the transmitter, because age had no influence on the overflow of the norepinephrine precursor, dihydroxyphenylalanine, or intraneuronal metabolite, dihydroxyphenylglycol (levels of these two substances reflect rates of cardiac norepinephrine synthesis and intraneuronal metabolism), and the transcardiac extraction of plasma radiolabeled norepinephrine was lower in the older subjects (P < .05). An almost identical pattern of neurochemical response was seen with isometric exercise. During cycling, total norepinephrine spillover was 16% lower in the older men, but cardiac norepinephrine spillover was 53% higher. CONCLUSIONS: Reduced norepinephrine reuptake increases the overflow of the neurotransmitter to plasma from the aging heart during stimulation of the cardiac sympathetic outflow. Failure of transmitter inactivation at postjunctional receptors with aging would amplify the neural signal, and in the presence of myocardial disease could trigger adverse stress-induced cardiovascular events, particularly when accompanied by an age-dependent reduction in vagal tone. Reduction of postsynaptic adrenergic responsiveness with aging, however, might protect against this, as indicated by our finding that in no case was the heart rate increase during stress greater in older men, despite their having larger increases in cardiac norepinephrine spillover.

Adult↗
PubMed1995

Melatonin and puberty in female lambs exposed to EMF: a replicate study.

In an earlier study, we found no effects of 60 Hz electric and magnetic fields (EMF) from a 500 kV transmission line on serum melatonin patterns or on puberty in ten female Suffolk lambs (Ovis aries). We conducted a larger replicate study of 15 lambs exposed to a mean electric field of 6.3 kV/m and a mean magnetic field of 3.77 muT and 15 controls exposed to EMF two orders of magnitude weaker than in the line area. The replicate produced essentially the same results as our previous study.

Animals↗
PubMed1995

Intermittent treatment with human parathyroid hormone (hPTH[1-34]) increased trabecular bone volume but not connectivity in osteopenic rats.

Previous studies have determined that intermittent parathyroid hormone (PTH) therapy increases bone mass and improves biomechanical strength in osteopenic animal models. The purpose of this investigation was to determine if intermittent human parathyroid hormone (hPTH[1-34]) therapy increased trabecular bone volume and connectivity in a rat model of established osteopenia using three-dimensional (3D) ex vivo in situ morphometry by X-ray tomographic methods (XTM). Six-month-old retired Sprague-Dawley breeder rats were used. Thirty animals were ovariectomized (OVX) and six were Sham operated. On day 56, post-OVX, a prePTH-treatment OVX groups was sacrificed. The remaining OVX animals were randomized into four groups of six animals each, given injections 5 out of every 7 days for 28 days of either vehicle or hPTH(1-34) at 4, 40, or 400 microg/kg of body weight (BW)/day and were sacrificed on day 84 post-OVX. At sacrifice, the left proximal tibias were harvested for XTM scans. hPTH(1-34) at medium and high doses significantly increased trabecular bone volume and trabecular thickness compared with ovariectomized animals treated with vehicle (p<0.05). The trabecular bone volume was equal to or greater than the Sham-operated animals in both hPTH(1-34) 40 and 400 microg/kg of BW treatment groups. Trabecular bone connectivity decreased by nearly 50% compared to the S ham-operated group at day 84 post-OVX and did not increase with any of the hPTH(1-34) treatments. Intermittent hPTH(1-34) treatment is osteopenic OVX rats increased trabecular bone volume to control levels or higher by thickening existing trabeculae. Human PTH(1-34) did not re-establish connectivity when therapy was started after 50% of the trabecular connectivity was lost. We hypothesize that to re-establish trabecular connectivity, a therapeutic intervention would have to be given before a significant distance between trabeculae has developed. Further studies will need to be done to refute or confirm our hypothesis.

Animals↗
PubMed1995

The ownership difference in relative performance of rehabilitation specialty hospitals.

Despite the rapid growth in the number of rehabilitation specialty hospitals in recent years, there is little knowledge of the performance of these facilities. The recent growth in the number of for-profit rehabilitation providers and increasing competition among for-profit and not-for-profit rehabilitation hospitals have raised questions about differences in performance. This study analyzed differences in financial and operational performance between for-profit rehabilitation specialty hospitals and not-for-profit rehabilitation specialty hospitals for fiscal years ending in 1989 through 1992. Because rehabilitation hospitals are exempted from Medicare's Prospective Payment System, but subject to cost limits established under the Tax Equity and Fiscal Responsibility Act of 1982 (TEFRA), this study controlled for the influence of TEFRA by grouping hospitals into "new" and "existing" categories. The findings show significantly higher net revenue and profits in existing for-profit rehabilitation hospitals. In addition, existing for-profit rehabilitation facilities served a larger percentage of Medicare patients and had fewer employees than existing not-for-profit facilities. It was concluded that existing for-profit rehabilitation hospitals maximized their charges to increase their revenues. These findings have important policy implications for reimbursement alternatives under consideration for inpatient rehabilitation programs.

Financial Management, Hospital↗
PubMed1995

Streptococcus pneumoniae colonization in the young child: association with otitis media and resistance to penicillin.

OBJECTIVE: To determine the nasopharyngeal colonization rate of penicillin-susceptible and penicillin-resistant strains of Streptococcus pneumoniae in young children, and to assess its relationship with the incidence of otitis media. DESIGN: Observational study in 215 children younger than 6 years of age who received care in the Vanderbilt Vaccine Clinic from September 1, 1992, to August 31, 1993. RESULTS: Of 842 nasopharyngeal cultures obtained, results for 44% of the cultures were positive for S. pneumoniae; 73% of the isolates were serotypes 6, 14, 19, or 23. Younger children had significantly higher rates of pneumococcal colonization than older children, with a peak at 1 year of age. By microdilution susceptibility testing, 37% of the cultures with positive results were intermediately or highly resistant to penicillin. Significantly more serotype 19 and 23 isolates were penicillin resistant than organisms of other serotypes. Children younger than 2 years of age had a twofold higher percentage of resistant isolates than those older than 2 years of age. A significant association was noted between nasopharyngeal carriage of S. pneumoniae and acute otitis media (p = 0.0002); however, the incidence of acute otitis media did not differ significantly between children colonized with penicillin-susceptible or penicillin-resistant strains. Unresolved otitis media was diagnosed more often in children who were colonized with resistant organisms than in children colonized with susceptible strains (p = 0.04). CONCLUSIONS: There was a high rate of nasopharyngeal carriage of penicillin-resistant S. pneumoniae in this population of young children. Nasopharyngeal colonization was associated with an increased incidence of acute otitis media, and penicillin resistance was associated with an increased incidence of unresolved otitis media.

Acute Disease↗
PubMed1995

The abnormal aorta: a statistical definition and strategy for monitoring change.

OBJECTIVES: This study defines a protocol for monitoring the growth of small abdominal aortic aneurysms based on age-related abnormality thresholds, observed aortic growth patterns and the limits of precision of the measurement technique. DESIGN: 13000 men aged 60 - 75 years were invited to their GP's surgery for measurement of the maximum diameter of the infrarenal aorta. Seventy-six percent responded and measurement was possible in 97.1% of the respondents. The AP diameter of the aorta was measured according to a strict protocol, with a portable ultrasound scanner. SETTING: Cases were recruited from the conurbation of Birmingham and Solihull, U.K. CHIEF OUTCOME MEASURE: A statistical description of the differences in distributions of aortic diameters of four age groups of males. MAIN RESULT: The aorta expands in diameter during the seventh and eighth decade for up to 25% of all those screened. The order of magnitude of this change is similar to that previously attributed to the growth of small aneurysms. Age-related thresholds for abnormality should range from 24 mm for a 60 year old to 37 mm for a 75 year old. CONCLUSIONS: Using data on the expected maximum rate of change of the dilated aorta and statistically derived thresholds from this analysis a monitoring strategy is suggested for those with an abnormal aorta.

Aged↗
PubMed1995

Paclitaxel (Taxol) in relapsed and refractory ovarian cancer: the UK and Eire experience.

The purpose of our study was to investigate the efficacy and toxicity of paclitaxel in patients with relapsed or refractory epithelial ovarian cancer in the context of a large multicentre study performed in the UK and Eire. Patients with previously treated epithelial carcinoma of the ovary or fallopian tube who fulfilled the eligibility criteria were entered in the study. Eligibility criteria included: measurable or evaluable disease; Eastern Cooperative Oncology Group (ECOG) performance status 0-2; up to three prior chemotherapy regimens, one of which had to contain a platinum agent; adequate haematological, renal and hepatic function; and no significant cardiac history. Patients received either 175 mg m-2 or 135 mg m-2 paclitaxel. The lower dose was administered to patients who had received more than two prior chemotherapy regimens. Paclitaxel was given by i.v. infusion over 3 h every 21 days. Response was assessed at three-cycle intervals or earlier if required. A total of 155 patients were registered for the study in the UK of whom 140 were eligible for response and toxicity evaluation, and 12 patients were assessed for toxicity only. Hair loss was the most frequently reported toxicity, with 74% (119/152) of patients reporting grade 3 alopecia. The most frequently reported serious toxicity was neutropenia, with 49% (74/152) of patients experiencing neutropenia grade 3 or 4. The response rate was 16% [two complete responders (CR), 20 partial responders (PR)], the median duration of response was 275 days and median survival was 244 days. Paclitaxel is active in relapsed and platinum-resistant epithelial ovarian cancer. It is well tolerated and can be given in an out-patient setting. The UK and Eire experience is very similar to that of US investigators in this group of patients. Further work is required to assess the optimal use of the drug in both first- and second-line therapy.

Adolescent↗
PubMed1995

Regional sympathetic nervous activation after a large meal in humans.

1. To investigate the link between post-prandial thermogenesis and sympathetic nervous activation we have studied the effects of a single large meal on regional sympathetic nervous activity in healthy, lean subjects. 2. In nine male subjects, noradrenaline spillover was measured from the heart, kidney and liver using isotope dilution, both while fasting and after consumption of a high-energy liquid meal of composition 53% carbohydrate, 32% fat and 15% protein (energy value 2.64-3.51 MJ). Regional oxygen consumption, whole-body oxygen consumption and, in a subset of subjects, muscle sympathetic nerve firing (microneurography) were also measured. 3. Both whole-body oxygen consumption (P < 0.03) and total body spillover of noradrenaline (P < 0.01) rose after the meal, with peak increases of 24% and 56% respectively. Spillover of noradrenaline from the heart was unchanged, that from the hepatosplanchnic circulation increased marginally (0.377 nmol/min to 0.480 nmol/min, P = 0.09), while renal noradrenaline spillover more than doubled (0.440 nmol/min to 0.937 nmol/min, P < 0.05). Skeletal muscle sympathetic nerve activity (peroneal nerve) increased from 7.7 bursts/min at rest to peak at 17.9 bursts/min 60 min after the meal in the three subjects in whom stable recordings were obtained. 4. The meal increased oxygen consumption in the kidneys and liver significantly, from 11.5 +/- 1.6 ml/min to 14.5 +/- 1.1 ml/min and from 46 +/- 7 ml/min to 57 +/- 6 ml/min respectively (P < 0.05), but not in the heart. 5. Consumption of a large meal produces a substantial and relatively selective increase in sympathetic outflow to the kidneys and skeletal muscle. While resting regional oxygen consumptions and noradrenaline spillovers were related, the changes that occurred in each were unrelated, so that no direct relationship could be demonstrated between postprandial thermogenesis and sympathetic activity.

Adolescent↗
PubMed1995

Aging effects on human sympathetic neuronal function.

To study the effect of aging on human sympathetic nervous function, we applied kinetic methods for measuring the fluxes to plasma of neurochemicals relevant to sympathetic neurotransmission in younger (aged 20-30 yr) and older (aged 60-75 yr) healthy men. Mean plasma norepinephrine concentration was 66% higher in older men, attributable to 22% lower norepinephrine plasma clearance (P < 0.05) and 29% higher norepinephrine spillover to plasma (difference not statistically significant). Regional venous sampling disclosed that sympathetic outflow to all organs was not activated by aging. Renal norepinephrine spillover was normal in older men. Although spillover of norepinephrine from the heart was increased in older men, 21.1 +/- 11.4 ng/min compared with 11.4 +/- 8.6 ng/min (P < 0.05), diminished norepinephrine reuptake rather than increased cardiac sympathetic nerve firing was the most likely cause, although somewhat reduced intracardiac methylation of norepinephrine with aging also possibly contributed. The extraction of tritiated norepinephrine from plasma during transit through the heart was reduced, suggesting neuronal norepinephrine reuptake was lowered and overflow of the norepinephrine precursor dihydroxyphenylalanine and metabolites dihydroxyphenylglycol and 3-methoxy-4-hydroxy phenylglycol was normal, indicating that norepinephrine synthesis and release were not increased.

Adult↗
PubMed1995

The effect of ewe body condition at lambing on colostral immunoglobulin G concentration and lamb performance.

Body condition was scored at lambing (BCSL) on 101 mature (4 to 7 yr old) Polypay ewes and related to colostral immunoglobulin G (IgG) concentration and lamb performance. Colostrum samples were collected from each ewe within 12 h of lambing and litters of more than two lambs were reduced to two within 2 h of lambing. Colostral IgG concentrations decreased rapidly with time (b = -3.28; R2 = .2132) and linear regression analysis projected that colostral IgG concentrations would diminish to zero milligrams/milliliter by 23 h postpartum. Body condition score at lambing varied from 2.5 to 3.5 and had no effect on colostral IgG concentration, which averaged 79 +/- 5.6 mg/mL, adjusted to the time of parturition. Total birth weights of lambs were higher for the oldest ewes (7 yr old), but this group had the lowest prolificacy. This age group weaned the lowest total lamb weight and number of lambs. Total weight of lambs born was not affected by BCSL. Lamb mortality from birth to weaning was 19.0% and was not affected by BCSL, sex, litter size, or breed of sire, but the older (7 yr old) ewes had greater lamb mortality. Total weight of lamb weaned was not affected by BCSL, although ewes with a BCSL of 3.0 tended ( P = .11) to wean more kilograms of lamb than ewes with a BCSL of 3.5. Ewes bred to Polypay rams weaned more total weight of lamb than those bred to Columbia rams, which was due to increased survival rate to weaning for the Polypay rams. We conclude that, within a range of 2.5 to 3.5, BCSL is not an important factor affecting the colostral IgG concentration, total weight of lamb born, lamb mortality, or total weight of lamb weaned.

Animals↗
PubMed1995

Cortisol secretion and growth in ewe lambs chronically exposed to electric and magnetic fields of a 60-Hertz 500-kilovolt AC transmission line.

A study was conducted to determine whether chronic exposure of ewe lambs to the electric and magnetic fields (EMF) of a high-voltage ac transmission line affected cortisol secretion and growth. Twenty Suffolk ewe lambs were assigned randomly in equal numbers to a control and treatment group. Treatment from 2 to 10 mo of age consisted of continuous exposure within the electrical environment of a 60-Hz, 500-kV transmission line (mean electric field 6 kV/m, mean magnetic field 40 mG). Treated lambs were confined directly beneath the transmission line; control lambs were maintained in a pen of similar construction 229 m from the line where the EMF were at ambient levels (mean electric field < 10 V/m, mean magnetic field < .3 mG). Cortisol was analyzed by RIA in serum of blood samples collected at .5- to 3-h intervals over eight 48-h periods. All ewe lambs were weighed weekly and side-patch wool growth was measured biweekly. Cortisol secretion occurred in a circadian rhythm; daytime serum concentrations were greater (P < .05) than nighttime concentrations for both groups. Concentrations of cortisol did not differ between the control and exposed ewe lambs. Weight gain and wool fiber length and diameter also were not affected by treatment. These data suggest that chronic exposure of developing ewe lambs to 60-Hz environmental EMF does not affect concentrations of cortisol secretion, body weight gain, and wool growth.

Animals↗