Search PubMedSearch

Biomedical subjects

J R Jones

Publications and source records attributed to J R Jones.

At least 19 recordsLinked to original sources

Continuing increase in mesothelioma mortality in Britain.

Mesothelioma is closely related to exposure to asbestos, and mesothelioma mortality can be taken as an index of past exposure to asbestos in the population. We analysed mesothelioma mortality since 1968 to assess the current state of the mesothelioma epidemic, and to predict its future course. We found that rates of mesothelioma in men formed a clear pattern defined by age and date of birth. Rates rose steeply with age showing a very similar pattern in all five-year birth cohorts. By date of birth, rates increased from mid-1893 to mid-1948, and then fell. Relative to the 1943-48 cohort, the risk for the 1948-53 cohort is 0.79 and for the 1953-58 cohort 0.48. Despite these falls, if the age profile of rates for these cohorts follows the pattern of past cohorts, their predicted lifetime mesothelioma risks will be 1.3%, 1.0%, and 0.6%. Combining projections for all cohorts results in a peak of annual male mesothelioma deaths in about the year 2020 of between 2700 and 3300 deaths. If diagnostic trend is responsible for a 20% growth in recorded cases every 5 years--an extreme but arguable case--and if this trend has now ceased, the peak of annual male deaths will be reduced to 1300, reached around the year 2010. Analysis of occupations recorded on death certificates indicate that building workers, especially plumbers and gas fitters, carpenters and electricians are the largest high-risk group. These data indicate that mesothelioma deaths will continue to increase for at least 15 and more likely 25 years. For the worst affected cohorts--men born in the 1940s--mesothelioma may account for around 1% of all deaths. Asbestos exposure at work in construction and building maintenance will account for a large proportion of these deaths, and it is important that such workers should be aware of the risks and take appropriate precautions.

Adult

D2-specific discriminative stimuli: parameters, blocking, and rebound.

This study characterizes the cue properties of quinpirole (LY 171555), a selective D2 agonist, and the blocking capabilities of spiperone, a selective D2 antagonist. After rats were trained to discriminate 0.025 mg/kg quinpirole from distilled water, a dose-response curve and time course of the quinpirole discriminative stimulus were determined. The effectiveness of three doses of spiperone in blocking the discriminative stimulus produced by 0.02 mg/kg quinpirole was then assessed. Finally, the time course of spiperone's blocking action was determined. Given the putative selective action of these drugs on D2 receptors and the parametric data presented here, it was predicted that following chronic treatment with spiperone, a rebound increase in quinpirole-appropriate responding would occur. Neither chronic treatment with spiperone nor chronic treatment with haloperidol produced the predicted changes. This result, however, may be confined to the specific dose and time parameters used.

Animals

Current UK opinion on thromboprophylaxis in orthopaedic surgery: its use in routine total hip and knee arthroplasty.

We surveyed all surgically qualified members of the British Orthopaedic Association as to their views on thromboprophylaxis in routine total hip and knee replacement. The response rate was 92%. In total hip replacement, 13-15% of surgeons used no method of prophylaxis at all, 18-22% did not use a mechanical method of prophylaxis, while 26% did not use a pharamacological agent; 36% believed low-dose anticoagulant thromboprophylaxis to be a medicolegal necessity while 47% disagreed with this. In total knee replacement, 18-33% of surgeons used no method of prophylaxis at all, 20-26% did not use a mechanical method of prophylaxis, while 54-58% did not use a pharmacological agent; 12 believed low-dose anticoagulant thromboprophylaxis to be a medicolegal necessity, while 64% disagreed with this. We conclude that mechanical methods remain a popular method of thromboprophylaxis and pharmacological methods, while commonly used, are not seen as a medicolegal requirement in lower limb arthroplasty and are used less often in total knee replacement.

Anticoagulants

Laryngeal mask airway: an alternative for the difficult airway.

The laryngeal mask airway (LMA) was invented by Dr. Archie Brain at the London Hospital, Whitechapel, in 1981. Dr. Brain's main objective for the LMA was that it would provide a better method of maintaining a patient's airway than by face mask. Also, the LMA would be less hemodynamically stressful than with insertion of an endotracheal tube. The LMA consists of a silicone rubber tube connected to a miniature silicone mask. The perimeter of the mask consists of an inflatable elliptical cuff, which forms a tip at the distal aspect of the LMA. The aperture bars in the dome of the mask lift the epiglottis away, so the lumen remains unobstructive. The LMA forms a low pressure seal around the larynx. The LMA is contraindicated in any situation where the patient is at risk for pulmonary aspiration. The LMA is not a substitute for a properly placed endotracheal tube in this situation. The American Society of Anesthesiologists' difficult airway algorithm recommends the insertion of an LMA when ventilation and/or intubation are difficult. The distal aperture of the LMA is in close approximation to the vocal cords, so a 6.0-mm internal diameter endotracheal tube can be passed over an intubating stylet or a pediatric fiberoptic bronchoscope to secure a patient's airway.

Contraindications

Differential regulation of neuronal sodium channel expression by endogenous and exogenous tyrosine kinase receptors expressed in rat pheochromocytoma cells.

The biological activity of growth factors that act through receptor tyrosine kinases (RTKs) can differ dramatically, depending on both the properties of the RTKs and the cellular environment in which the RTKs are expressed. To determine the ability of different RTKs to elicit ras-independent responses central to neuronal differentiation, we analyzed voltage-dependent sodium (Na) channel expression in rat pheochromocytoma (PC12) cells after activation of a variety of endogenously and exogenously expressed RTKs. In PC12 cells expressing trkB (Ip et al., 1993), the increase in Na current density caused by brain-derived neurotrophic factor (BDNF) was similar to that observed upon activation of endogenous trkA by NGF. BDNF also increased type II Na channel mRNA expression, as did neurotrophin-3 in PC12 cells expressing trkC (Tsoulfas et al., 1993). In contrast, insulin did not increase type II Na channel mRNA expression or Na current density in PC12 cells, while epidermal growth factor (EGF) elicited small, yet reproducible increases in type II Na channel mRNA and Na current density when compared to NGF, even upon coexpression of an EGF receptor/p75 receptor chimera (Yan et al., 1991). Finally, in PC12 cells expressing beta-platelet-derived growth factor (PDGF) receptors (Heasley and Johnson, 1992), PDGF increased type II Na channel mRNA and Na current density to the same extent as NGF. The results show the capabilities of these RTKs in eliciting Na channel expression and the specificity arising due to differences in their intrinsic properties.

Animals

3H-n.m.r. studies of multiple conformations and dynamic processes in complexes of folate and methotrexate with Lactobacillus casei dihydrofolate reductase.

[7,3',5'-3H3]- and [7,9-3H3]-folic acid and [7,3',5'-3H3]methotrexate (MTX) have been prepared and 3H-n.m.r. spectra obtained for their complexes with Lactobacillus casei dihydrofolate reductase (DHFR). The 3H results confirm the presence of three pH-dependent different conformational forms in the complex DHFR.NADP+.folate. The folate benzoyl ring could be shown to be in essentially the same environment in the different forms, with the major differences being associated with the pterin ring. The appearance of a single resonance for the 3',5'-tritons showed that the benzoyl ring is flipping rapidly in all three forms. In contrast, the MTX complex was shown to exist as a single conformational state with the benzoyl ring flipping rate being too low to give a single averaged signal for the 3',5'-nuclei over the temperature range 283-313 K.

Escherichia coli

Koro: culture-bound disorder or universal symptom?

A case report is presented of koro associated with a depressive illness in a 31-year-old male Briton. The specificity or otherwise of koro as culture bound and a distinct nosological entity is discussed.

Adult

The consequences of the isotope effect on proline dehydrogenation rates estimated by the tritium loss method.

Loss of tritium from a substrate is often used to estimate the rate of dehydrogenation. However, loss of 3H may be much slower than loss of H because of the tritium isotope effect. In order to assess the impact of the tritium isotope effect, loss of 3H from the C-5 position of proline during dehydrogenation by rat liver mitochondria and bacteroids from soybean (Glycine max [L.] Merrill) nodules was compared with appearance of 14C in products of [14C]proline dehydrogenation. Incubations were carried out in the presence of o-aminobenzaldehyde (added to trap the initial product, delta 1-pyroline-5-carboxylate). The fraction of total 14C products trapped by o-aminobenzaldehyde varied from 0.07 to 0.75 depending upon experimental conditions. With rat liver mitochondria, dehydrogenation of [14C]proline was between 3.27 and 9.25 times faster than dehydrogenation of 3H proline, depending upon assay conditions. Soybean nodule bacteriods dehydrogenated [14C]proline about 5 times faster than [3H]proline. We conclude the following: (i) the rate of proline dehydrogenation may be greatly underestimated by the tritium assay because of the tritium isotope effect, and (ii) the 14C assay may underestimate the rate of proline dehydrogenation if it is assumed that o-aminobenzaldehyde quantitatively traps delta 1-pyrroline-5-carboxylate under all conditions. The simplicity of the tritium assay makes it attractive for routine use. However, its use requires determination of the tritium isotope effect, under the specific conditions of the assay, in order to correct the results. The considerations discussed here have broad applicability to any dehydrogenase assay employing tritium loss.

Animals

The effects of amphetamine on body weight and energy expenditure.

Although there is evidence suggesting that, in addition to suppressing food consumption, amphetamine reduces body weight by increasing energy expenditure, there is little consistency among the few studies examining that factor. In this experiment, the effect of amphetamine on daily energy consumption, within-day body weights, and hourly measures of metabolic rate (MR) and respiration quotient (RQ) were assessed. Daytime drug injections decreased total energy consumption, produced biphasic changes over time in MR, and persistently lowered RQ values. In contrast, nighttime injections of drug had little effect on energy consumption and MR but did reduce RQ for the first 4 postinjection hours. These effects show that amphetamine effects interact with the circadian organization of behavior and suggest that rodent studies of anorectic agents have more relevance for humans if drugs are given during the night, when rats are normally awake and eating. From this study, it seems clear that amphetamine reduces body weight by altering metabolic rate and fat metabolism in rats when the drug is given during the day.

Animals

Effects of amphetamine on food intake and weight: timing of injections and food access.

Although the effects of amphetamine on food consumption and body weight in nondeprived animals are of interest for theoretical and clinical reasons, there are only a few studies on this topic in the literature. In Experiment 1, independent groups of nondeprived rats were given daily injections of 0, 1, 2, 5, or 10 mg/kg d-amphetamine sulfate shortly after light onset for 30 days. While drug treatment did not affect food consumption, all amphetamine-treated groups lost weight over the initial 12 days and then, over the final 18 days of treatment, gained weight at the same rate as controls. Experiment 2 assessed whether the effects of amphetamine on these measures are influenced by the timing of the daily injections relative to the light-dark cycle. As in Experiment 1, injections of amphetamine at light onset again produced weight loss while not affecting food consumption, whereas injections of the drug at light offset did not reliably affect either measure. Experiment 3 showed that the relationships among variables observed in nondeprived animals remain the same in animals restricted to 12 h of access to food each day and replicated the amphetamine-induced hyperphasia observed earlier by Jones and Caul (9).

Animals

Occupational exposures in California wildland fire fighting.

Industrial hygiene measurement of exposures to wildland fire fighters was conducted in northern California during three consecutive fire seasons (1986-1989) in conjunction with three separate health effects studies. Chemicals that were monitored included carbon monoxide, total and respirable particulates, polyaromatic hydrocarbons (PAHs), crystalline silica, aldehydes, and benzene. Measurements were taken at both wildland fires and prescribed (planned) burns. A variety of collection methods were employed--colorimetric detector tubes and a CO monitor were used for direct-reading area measurements; colorimetric diffusion tubes, filter cassettes, sorbent tubes, and passive vapor monitors were used for determining personal time-weighted average exposures. A new screening method (National Institute for Occupational Safety and Health Method 2539) was used to identify the presence of specific aldehydes. Results show that wildland fire fighters may at times be exposed to concentrations of carbon monoxide, total or respirable particulates, or silica at levels near or higher than recommended occupational exposure limits, although group means were generally well below the limits. Time-weighted average formaldehyde levels, measured in a few instances above 0.37 mg/m3 (0.3 ppm), indicate a potential for formaldehyde-induced eye or respiratory irritation under these conditions. Certain characteristics of the work such as high altitude, temperature, and breathing rate; extended work shifts; and additional off-shift exposures suggest that adjustment of 8-hr exposure limits may be necessary to provide adequate protection. In part, because of the rigors of performing industrial hygiene measurements under fire fighting conditions, data are limited and could not be considered representative of the full range of exposures fire fighters may encounter.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational

An epidemiologic study of cancer and other causes of mortality in San Francisco firefighters.

To test the hypothesis that firefighter exposures may increase cancer risk, mortality rates were calculated for 3,066 San Francisco Fire Department firefighters employed between 1940 and 1970. Vital status was ascertained through 1982, and observed and expected rates, rate ratios (RR), and 95% confidence intervals (CI) were computed using United States death rates for comparison. The total number deceased (1,186) was less than expected and there were fewer cancer deaths than expected. However, there were significant excess numbers of deaths from esophageal cancer (12 observed, 6 expected), cirrhosis and other liver diseases (59 observed, 26 expected), and accidental falls (21 observed, 11 expected). There were 24 line-of-duty deaths, which were primarily due to vehicular injury, falls, and asphyxiation. Heart disease and respiratory disease deaths occurred significantly less often than expected. It was concluded that the increased risks of death from esophageal cancer and cirrhosis and other liver diseases may have been due to firefighter exposures, alcohol consumption, or interaction between alcohol and exposures. Because this was an older cohort and firefighter exposures have changed due to the increasing use of synthetic materials, it is recommended that the effects of modern-day exposures be further studied.

Accidental Falls

Regiospecific deuteriation and tritiation of various drugs using a homogeneous rhodium trichloride catalyst.

The deuteriation and tritiation of a number of drugs containing carboxyl, amide, aralkylamine, and anilide functional groups have been investigated using homogeneous rhodium trichloride as a catalyst. Good incorporation of deuterium was observed and the regiospecificity for ortho exchange was very high for most of the drugs studied. Similarly, with tritium, good incorporation (specific activities) and regiospecificities were achieved in many cases. Satisfactory results were also obtained from the small number of heterocyclic-containing drugs that were included in the present study.

Catalysis

Rebound cue state following a single dose of haloperidol.

It has been reported that chronic administration of haloperidol produces an amphetamine-like rebound cue state. The experiments reported here were designed to assess whether a similar rebound phenomenon would result from a single dose of haloperidol. Rats were trained to discriminate .5 mg/kg amphetamine from distilled water. Five groups were formed to allow testing of haloperidol's effect at 12, 18, 24, 30, and 36 hr postinjection. Each animal was given 0, .5, 1.0, and 1.5 mg/kg haloperidol at its appropriate injection time in a counterbalanced fashion with one week between each test. A shift in the dose-response function of amphetamine that occurred during these weeks, however, precluded appropriate analysis of haloperidol's effects. Given this result, a second experiment was conducted using a between-subjects design. Half of the animals were injected with 1 mg/kg haloperidol 23 hr prior to testing, whereas the others were injected with distilled water. When tested, the haloperidol group responded 33% of the time on the amphetamine-correct lever, whereas the control group responded at 20%. The observation of posthaloperidol rebound in the between-subjects study and the failure to find significant temporal patterns of rebound phenomena using a within-subjects design have both theoretical and methodological importance.

Amphetamine

Ultrasonography in slipped capital femoral epiphysis. Diagnosis and assessment of severity.

We used ultrasonography to study 26 hips with slipped capital femoral epiphyses. In recently slipped epiphyses the ultrasound image revealed a step at the anterior physeal outline (mean 6.4 mm), diminished distance between the anterior acetabular rim and the femoral metaphysis (mean 4.3 mm) and an effusion. As metaphyseal remodelling progressed the physeal step decreased. The femoral neck appeared straighter in hips which had been symptomatic for longer than three weeks. It was possible to measure posterior epiphyseal displacement without projectional errors and the method was accurate in diagnosing minimal slip and in staging displacement. The suggested criteria are, less than 7 mm for a mild slip, 7 to 11 mm for a moderate slip and more than 11 mm for a severe slip. We recommend ultrasonography for the diagnosis, staging and follow-up management of slipped upper femoral epiphysis.

Adolescent

Purification and properties of parathyroid hormone-related peptide isolated from milk.

The occurrence and properties of PTH-related peptide (PTH-RP) in milk was investigated. PTH-RP was purified to homogeneity from human and bovine milk using heat and acid to precipitate milk proteins followed by ion exchange chromatography and reverse-phase HPLC. The peak of PTH-RP from HPLC was detected using a sensitive bone cell bioassay. A single band of peptide was detected on silver-stained polyacrylamide gels, which migrated as a 20-21-kDa macromolecule. PTH-RP isolated from either human or bovine milk had similar electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The partially purified bovine PTH-RP stimulated cAMP production in UMR106-01 and OK cell lines and elicited a concentration-dependent inhibition of sodium-dependent phosphate transport in OK cells. Incubation of milk extracts with an anti-PTH antiserum did not affect their bioactivity, whereas an antihuman PTH-RP 1-34 antiserum markedly reduced the cAMP response of UMR106-01 cells to the immunoabsorbed milk extracts. A PTH antagonist, norleu PTH 3-34, blocked the stimulation of cAMP production in UMR106-01 cells treated with milk extracts. PTH-RP immunoreactivity and bioactivity occurred in milk extracts of diverse animals from both eutherian and metatherian (marsupial) species. Porcine colostrum also had immunoreactive PTH-RP, although the levels were lower than the immunoreactive PTH-RP concentrations observed in milk samples collected at 7 and 14 days of lactation. Thus, a 20-21-KDa PTH-RP is secreted into milk where it could play a role in the development of suckling, newborn animals.

Adenylyl Cyclases

Remodelling after pinning for slipped capital femoral epiphysis.

We assessed 70 hips at an average of 7.1 years after pinning for slipped upper femoral epiphysis to determine the frequency of remodelling, what factors influence it and its effect on the clinical outcome. Remodelling was defined by a new classification of the anterior femoral head-neck profile as seen on the lateral radiograph. Remodelling occurred in 50% of hips with a head-shaft angle of 30 degrees or more; the probability of remodelling was significantly less the greater the degree of slip, but was significantly increased if the triradiate cartilage was open at the time of presentation. We found no significant effect for age, sex, weight or length of symptoms. The range of internal rotation was significantly greater in those hips that remodelled. We support the treatment of moderate slips in skeletally immature patients by pinning in situ, since the probability of satisfactory remodelling was 75% for slips of 40 degrees or less.

Adolescent