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Biomedical subjects

A Reid

Publications and source records attributed to A Reid.

At least 55 records · Page 3Linked to original sources

Incidence of testicular germ-cell malignancies in England and Wales: trends in children compared with adults.

The incidence of testicular cancer has been increasing markedly in most industrialised countries. This rise is known to have affected young adults, but it is less clear whether it has affected other age groups, particularly children. We used data from the National Cancer Registry file at the Office of National Statistics (ONS) and the National Registry of Childhood Tumours to examine trends in testicular germ-cell malignancies overall in England and Wales from 1962 to 1990 and in children from 1962 to 1995. The incidence of testicular cancer at all ages rose by 3.4% (95% CI 3.3-3.6%) per annum from 1962 to 1990. A similar rise in the incidence of germ-cell malignancies occurred during the years for which histological information was available in the ONS files, 1971-1989 (3.4%; 3.1-3.6%), to which both seminomas and non-seminomas contributed equally. The incidence of non-seminomas in adults rose in men under age 55 years and declined in older men, whereas there were increases in the incidence of seminomas in both young and older men. Cohort analysis at young ages showed a marked rise in the risk of germ-cell malignancies up to the cohort born in 1955-1959 but no further rise for those born subsequently. The rise in the incidence of these tumours in young adults was paralleled by a similar trend, although less marked, in children aged under 15 years (1.3% per annum; 0.2-2.5%). The increase in risk for children in this very large data set alongside the rise in young adults is compatible with the hypothesis that childhood and adult testicular germ-cell malignancies may have some common risk factors, presumably pre-natal.

Adolescent↗

Relapse and mortality among HIV-infected and uninfected patients with tuberculosis successfully treated with twice weekly directly observed therapy in rural South Africa.

OBJECTIVE: To determine post-treatment relapse and mortality rates among HIV-infected and uninfected patients with tuberculosis treated with a twice-weekly drug regimen under direct observation (DOT). SETTING: Hlabisa, South Africa. PATIENTS: A group of 403 patients with tuberculosis (53% HIV infected) cured following treatment with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice weekly to 2 months and HR twice weekly to 6 months in the community under DOT. METHODS: Relapses were identified through hospital readmission and 6-monthly home visits. Relapse (culture for Mycobacterium tuberculosis) and mortality given as rates per 100 person-years observation (PYO) stratified by HIV status and history of previous tuberculosis treatment. RESULTS: Mean (SD) post-treatment follow-up was 1.2 (0.4) years (total PYO = 499); 78 patients (19%) left the area, 58 (14%) died, 248 (62%) remained well and 19 (5%) relapsed. Relapse rates in HIV-infected and uninfected patients were 3.9 [95% confidence interval (CI) 1.5-6.3] and 3.6 (95% CI 1.1-6.1) per 100 PYO (P = 0.7). Probability of relapse at 18 months was estimated as 5% in each group. Mortality was four-fold higher among HIV-infected patients (17.8 and 4.4 deaths per 100 PYO for HIV-infected and uninfected patients, respectively; P<0.0001). Probability of survival at 24 months was estimated as 59% and 81%, respectively. We observed no increase in relapse or mortality among previously treated patients compared with new patients. A positive smear at 2 months did not predict relapse or mortality. CONCLUSION: Relapse rates are acceptably low following successful DOT with a twice weekly rifampicin-containing regimen, irrespective of HIV status and previous treatment history. Mortality is substantially increased among HIV-infected patients even following successful DOT and this requires further attention.

AIDS-Related Opportunistic Infections↗

Infrainguinal revascularisation in the era of vein-graft surveillance--do clinical factors influence long-term outcome?

OBJECTIVES: To investigate the variables affecting the long-term outcome of infrainguinal vein bypass grafts that have undergone postoperative surveillance. DESIGN: A retrospective analysis. PATIENTS AND METHODS: Details of 299 consecutive infrainguinal vein grafts performed in 275 patients from a single university hospital were collected and analysed. All grafts underwent postoperative duplex surveillance. Factors affecting patency, limb salvage and survival rates were examined. These factors were gender, diabetes, hypertension, aspirin, warfarin, ischaemic heart disease, run-off, graft type, early thrombectomy, level of anastomoses and indication for surgery. RESULTS: The 6-year primary, primary assisted and secondary patency rates were 23, 47, and 57%, respectively. Six-year limb salvage and patient survival were 68 and 45%, respectively. Primary patency was adversely influenced by the use of composite vein grafts. Early thrombectomy was the only factor that significantly influenced secondary patency. Limb salvage was worse in diabetic limbs, limbs with poor run-off and in grafts that required early thrombectomy. Postoperative survival was better in males, claudicants and in patients who took aspirin. CONCLUSIONS: Although co-morbid factors did not influence graft patency rates, diabetes did adversely effect limb salvage. This study, like others before it, confirms that aspirin significantly reduces long-term mortality in patients undergoing infrainguinal revascularisation.

Angioplasty↗

Vitamin E, lipids, and lipid peroxidation products in tardive dyskinesia.

BACKGROUND: Lipid peroxidation has been postulated as a possible mechanism for neuronal damage in tardive dyskinesia, and this is supported by evidence of increased lipid peroxidation products in the cerebrospinal fluid of dyskinetic subjects. METHODS: In this study plasma levels of vitamin E and vitamin A, measured by high-performance liquid chromatography, and of thiobarbituric acid-reactive substances (TBARS), were determined in 16 schizophrenic patients with tardive dyskinesia, 16 nondyskinetic patients all assessed by Abnormal Involuntary Movement Scale (AIMS), and 10 normal control subjects. Plasma cholesterol and triglyceride were also measured throughout. Vitamin E levels in plasma were corrected for total lipids. RESULTS: Multivariate analysis of covariance showed significant differences when vitamin E and TBARS were compared in the three groups. Univariate t tests showed a significantly lower lipid-corrected vitamin E (p = .018) between the normal and dyskinetic group but not between the normal and the nondyskinetic schizophrenic patients. There was no difference in vitamin A levels between patients and normal controls. TBAR results showed a significant positive correlation between AIMS score and lipid-corrected TBARS. CONCLUSIONS: This study confirms an abnormality associating lipid peroxidation and tardive dyskinesia and extends this abnormality to measurements of lipid-corrected vitamin E in plasma.

Aged↗

The increasing workload required to maintain infrainguinal bypass graft patency.

BACKGROUND: To assess the impact upon the provision of a vascular service of the workload associated with maintaining infrainguinal bypass graft patency. DESIGN: A computerised prospective audit. MATERIALS AND METHODS: Between January 1990 and December 1995, all patients with infrainguinal bypass grafts were entered into a prospective computerised audit to monitor interventions for the maintenance of graft patency. Excluded from the study were interventions during the first 30 postoperative days and procedures not directly related to the graft. A graft surveillance programme was in operation throughout. RESULTS: During the study period a total of 131 patients with 144 grafts were admitted on 330 occasions and required 401 separate interventional procedures. There were 227 procedures in 72 femorodistal grafts, 116 in 38 below-knee femoropopliteal grafts and 58 interventions in the group of 34 above-knee femoropopliteal grafts. Radiological interventions accounted for almost 70% of this workload. CONCLUSION: The workload associated with the maintenance of infrainguinal bypass grafts increased considerably during the study period, and seems likely to increase further. Such interventions should therefore be considered when planning for vascular service provision.

Anastomosis, Surgical↗

General practitioners' attitudes to psychiatric and medical illness.

BACKGROUND: General practitioners are increasingly involved in the care of patients with long-term psychiatric disorders. We have previously reported that general practitioners are less willing to treat patients with schizophrenia than those without such a diagnosis, but this may have been attributable to a reluctance to treat patients with any psychiatric or chronic illness. We, therefore, examined general practitioners' attitudes to patients with chronic psychiatric or medical illnesses. METHODS: A random sample of 260 local general practitioners were each sent one of our case vignettes which were identical apart from mention of a previous diagnosis of schizophrenia, depression, diabetes or no illness. The general practitioners were asked to indicate their level of agreement with 13 attitudinal statements based on the vignette. RESULTS: One hundred and sixty-six (66%) of the general practitioners responded to the case vignettes. Those responding to the vignette about the patient with schizophrenia were less happy to have that patient on their practice list and were more concerned about the risk of violence and the child's welfare. Those responding to the depression vignette were more likely to offer the patient antidepressants or counselling; and those who replied to the diabetes case were most likely to refer the patient to a hospital specialist. These differences were not attributable to the personal or practice characteristics of the general practitioners. CONCLUSIONS: Patients with schizophrenia arouse concerns in general practitioners that are not simply due to those patients suffering from a psychiatric or chronic illness. Our results suggest that some patients with schizophrenia may find it difficult to register with a general practitioner and receive the integrated community-based health care service they require. Psychiatrists should provide education and support to general practitioners who look after patients with schizophrenia.

Adult↗

Trends in cancer incidence and mortality in Scotland: description and possible explanations.

Secular and cohort trends in mortality from cancer in Scotland during 1953-93, and incidence during 1960-90, were analysed using individual records from the national mortality and registration files. For certain cancer sites, the secular analyses of mortality were extended back to 1911 by use of published data. Mortality from cancer at older ages in Scotland has increased over the last 40 years. In each sex, this trend has been dominated by the effects of smoking: all-cancer rates and rates of lung cancer, now the most common fatal cancer in men and in women in Scotland, reached a peak in the cohort of men born at the turn of the century and the cohort of women born in the 1920s. For much of the period, the Scottish all-age rates of lung cancer were the highest reported in the world; they are now decreasing on a secular basis in men, but are still increasing in women. There have also been large increases at older ages in the incidence and mortality rates for cancer of the prostate in recent years. bladder cancer, nervous system cancer, non-Hodgkin's lymphoma, myeloma and leukaemia; for each there is likely to be a considerable artefactual element to the increase, with differing degrees of possibility that there may in addition be an element of real increase. Substantial decreases in mortality at all ages have occurred for stomach and colorectal cancers and substantial increases at all ages for pleural cancer and melanoma. Rates of mortality from breast cancer, the most common cancer in women in Scotland, have generally increased over the past 80 years; a temporary cessation in this upward trend occurred in the years during and after the Second World War, and recently rates have turned downward, probably at least in part because of better treatment. Mortality from ovarian cancer, the second most common reproductive-related female tumour in Scotland, has also increased at older ages. At younger ages, mortality from cancer in Scotland has decreased, especially in men, whereas incidence has not. This divergence, which has been a consequence of better treatment, has occurred especially for cancers of the testis and ovary, Hodgkin's disease and leukaemia. There have been increases at young adult ages, however, in both mortality from and incidence of oral and pharyngeal, oesophageal and laryngeal cancers in men, and melanoma and non-Hodgkin's lymphoma in each sex. Cervical cancer rates at young ages also increased, but this trend has reversed for incidence in the most recent birth cohorts. Incidence rates have also increased for testicular cancer in young adults and leukaemia in children. With the possible exceptions of non-Hodgkin's lymphoma and childhood leukaemia, the increasing rates are likely largely to reflect real rises in incidence, and they highlight the need for investigation of the causes of these cancers, and, when causes are known, for preventive action.

Adolescent↗

Otoacoustic emissions as a screening test for hearing impairment in children recovering from acute bacterial meningitis.

OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation.

Acute Disease↗

Leukemia-associated retinoic acid receptor alpha fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies.

In acute promyelocytic leukemia (APL), the typical t(15;17) and the rare t(11;17) translocations express, respectively, the PML/RARalpha and PLZF/RARalpha fusion proteins (where RARalpha is retinoic acid receptor alpha). Herein, we demonstrate that the PLZF and PML proteins interact with each other and colocalize onto nuclear bodies (NBs). Furthermore, induction of PML expression by interferons leads to a recruitment of PLZF onto NBs without increase in the levels of the PLZF protein. PML/RARalpha and PLZF/RARalpha localize to the same microspeckled nuclear domains that appear to be common targets for the two fusion proteins in APL. Although PLZF/RARalpha does not affect the localization of PML, PML/RARalpha delocalizes the endogenous PLZF protein in t(15;17)-positive NB4 cells, pointing to a hierarchy in the nuclear targeting of these proteins. Thus, our results unify the molecular pathogenesis of APL with at least two different RARalpha gene translocations and stress the importance of alterations of PLZF and RARalpha nuclear localizations in this disease.

Animals↗

Peripheral adenosine 5'-triphosphate enhances nociception in the formalin test via activation of a purinergic p2X receptor.

The pronociceptive effects of adenosine 5'-triphosphate (ATP) were examined in the low concentration formalin model (0.5%) by coadministration of ATP, ATP analogs (alpha,beta-methylene-ATP and 2-methylthio-ATP) and antagonists (suramin, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) with formalin and determining effects on the expression of flinching behaviours. Coadministration of ATP (5-500 nmol) with formalin enhanced phase 2 (12-60 min after injection) but not phase 1 (0-10 min after injection) responses. alpha,beta-methylene-ATP (0.5-50 nmol) but not 2-methylthio-ATP (50-500 nmol) produced a similar enhancement of activity, generating an order of potency of alpha,beta-methylene-ATP, ATP >> 2-methylthio-ATP. This enhancement was primarily expressed in the latter part of phase 2, 30-60 min after injection. Coadministration of suramin 50-500 nmol, a non-selective P2X and P2Y purinoceptor antagonist and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid 5-500 nmol, a selective P2X purinoceptor antagonist, dose-dependently inhibited the augmentation of the formalin response by ATP 50 nmol, but did not reduce the response to formalin itself. Pretreatment for 30 min with higher doses of suramin inhibited the response to formalin (0.5%, 1.5%) and this appeared to be by a systemically mediated action as it was seen following administration into the contralateral paw. The results of this study provide evidence in support of a P2X purinoceptor mediated augmentation of the pain signal by ATP. The delayed time-course of the effect suggests that it may occur in concert with other mediators that are recruited by the inflammatory process, rather than reflecting a direct depolarization of sensory nerves. Other behavioural paradigms may be required to examine the fast onset, direct effect. Suramin appears to exert both local and systemic effects on the expression of pain behaviours in response to formalin.

Adenosine Triphosphate↗

Acute otitis media and otitis media with effusion in children with bacterial meningitis.

Acute otitis media and otitis media with effusion (OME) have often been observed in children with bacterial meningitis. OME has also been proposed as the mechanism of reversible hearing loss after meningitis. In this controlled study, children with acute bacterial meningitis were studied using auditory brainstem responses (ABR), otoacoustic emissions, tympanometry and otoscopy. An age- and sex-matched control was recruited for each patient and the incidence of acute otitis media and OME was compared between the two groups. One hundred and twenty-four children with meningitis were studied. Ninety-two children (74 per cent) had meningococcal meningitis. Five patients (4 per cent) had conductive hearing loss (ABR threshold > or = 30 dB HL) at the time of discharge from hospital. None of the patients or controls had acute otitis media. Patients and controls were well matched for risk factors for OME and the prevalence of middle ear effusion in patients and controls was 7.2 per cent and 11.3 per cent respectively. The relative risk of OME in the children with meningitis was 0.64 (95 per cent confidence interval 0.29 to 1.42). After nine months, three of the five children with meningitis and conductive hearing loss had regained normal hearing. In contrast to previous reports, there was no relationship between bacterial meningitis and acute otitis media or OME in this study. Nevertheless, coincidental conductive hearing defects were identified as the cause of reversible hearing loss in three patients.

Acute Disease↗

Hearing loss during bacterial meningitis.

OBJECTIVE: To determine the natural history and pathogenesis of hearing loss in children with acute bacterial meningitis. DESIGN: Multicentre prospective study. SETTING: 21 hospitals in the south and west of England and South Wales. SUBJECTS: 124 children between the ages of 4 weeks and 16 years with newly diagnosed bacterial meningitis. METHODS: Children underwent repeated audiological assessment with the first tests being performed within six hours of diagnosis. By using a combination of otoacoustic emissions, auditory brainstem responses, and tympanometry the differences between cochlear, neural, and conductive defects were distinguished. RESULTS: Ninety two children (74%) had meningococcal and 18 (15%) had pneumococcal meningitis. All cases of hearing loss were apparent at the time of the first assessment. Three children (2.4%, 95% confidence interval (CI) 0.5 to 6.9%) had permanent sensorineural hearing loss. Thirteen children (10.5%) had reversible hearing loss of whom nine had an impairment that resolved within 48 hours of diagnosis. It is believed that this "fleeting' hearing loss has not been reported previously. The cochlea was identified as the site of the lesion in both the permanent sensorineural and reversible impairments. Hearing loss was more common in children who had been ill for more than 24 hours (relative risk 2.72; 95% CI 0.93 to 7.98). CONCLUSIONS: Sensorineural hearing loss developed during the earliest stages of meningitis. Permanent deafness was rare but 10% of the patients had a rapidly reversible cochlear dysfunction. This may have progressed to permanent deafness if the patients had not been treated promptly.

Acute Disease↗

Generic inhaled salbutamol versus branded salbutamol. A randomised double-blind study.

Generic substitution of salbutamol lags behind that of other drugs in Scotland and a negative perception by both patients and doctors may explain this. The aim of this study was to assess whether, in clinical practice, there was any difference in efficacy between branded salbutamol (Ventolin) and a generic preparation. Asthmatic patients using a Ventolin metered-dose inhaler at least twice a day for symptom relief were entered into a double-blind cross-over study, comparing Ventolin, blinded Ventolin and a generic salbutamol in random order for two weeks each. Daily peak flows, inhaler use and bronchodilator response were recorded. At the end of each treatment period patients rated their inhaler against their usual Ventolin on a 5-point scale. Forty patients were entered into the study; 90% received 1000 micrograms or more of inhaled steroids per day. Eleven patients dropped out during the run-in phase. In the remaining 29 patients, no significant difference between treatments could be found in any of the objective parameters measured. Fifty-five per cent of patients said they could detect a difference between the inhalers, and 45% noted a difference between their usual Ventolin and the open or blinded Ventolin. This study showed clinical equivalence between a generic and branded salbutamol. Patients' own assessment of their relief inhaler seems to be influenced by factors other than efficacy. The study highlights that careful encouragement is required when changing to a generic product and has particular implications for the forthcoming conversion to CFC-free products.

Administration, Inhalation↗

Inducible nitric oxide synthase demonstrated in allergic and irritant contact dermatitis.

Eight allergic patch test reactions, eight irritant skin reactions induced by 3% sodium lauryl sulphate and six normal controls were biopsied. Biopsies were immunohistochemically stained with a mouse monoclonal antibody to inducible nitric oxide synthase (iNOS), and staining was quantified by computerised image analysis. Human chondrocytes induced to express iNOS were used as a positive control. A significant increase in iNOS was found in both irritant and allergic contact dermatitis. There were no differences in the distribution of expression of iNOS. The antibody used was confirmed by Western blotting not to cross-react with the endothelial isoform of nitric oxide synthase (NOS) but did cross-react with a 150 kDa protein, which may be neuronal NOS or an isoform of neuronal NOS.

Adult↗