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Biomedical subjects

J Griffiths

Publications and source records attributed to J Griffiths.

At least 55 records · Page 3Linked to original sources

Pathology attributed to Mycobacterium chelonae infection among farmed and laboratory-infected Atlantic salmon Salmo salar.

This study was promoted following concern over increasing mortality on 2 farms rearing Atlantic salmon Salmo salar in the Shetland Isles, Scotland. A Mycobacterium sp. was isolated from moribund, market-sized Atlantic salmon. Biochemical tests, lipid analysis and PCR (polymerase chain reaction) techniques confirmed the bacterium to be Mycobacterium chelonae. Multiple greyish-white miliary granuloma-like nodules were observed in several tissues. Dense hard-packed nodules contained abundant acid-fast bacteria. Atlantic salmon injected with M. chelonae remained sub-clinically infected, demonstrating the chronic nature of this disease. The source of the pathogen was not identified.

Animals↗

The induction of apoptosis by a positively charged methylene blue derivative.

Identifying the cellular responses to photodynamic therapy (PDT) is important if the mechanisms of cell death are to be fully understood. PDT with a methylene blue analog DO15 yielded mitochondrial photodamage whilst membrane and lysosomal integrity were maintained. Apoptosis was detected using the DNA stain HO342, by the appearance of 50 kb fragments and by DNA ladder formation. The release of mono- and oligonucleosomes was further quantified using an ELISA protocol. Large DNA fragments were observed immediately following illumination, and nucleosomes were detected at 1-2 h post-treatment. Increasing the dose 4-fold accelerated the apoptotic response to PDT. This is the first report of a thiazine photosensitiser inducing apoptosis and is consistent with recent proposals suggesting that release of mitochondrial components may play an important role in the mechanism of cell death.

Animals↗

The photodynamic response of two rodent tumour models to four zinc (II)-substituted phthalocyanines.

Four novel zinc (II)-substituted phthalocyanines, varying in charge and hydrophobicity, were evaluated in vivo as new photosensitizers for photodynamic therapy. Two rat tumours with differing vascularity were used: a mammary carcinoma (LMC1) and a fibrosarcoma (LSBD1), with vascular components six times higher in the latter (10.8%+/-1.5) than in the former (1.8%+/-1.4). Each sensitizer was assessed for tumour response relative to normal tissue damage, and optimum doses were selected for further study, ranging from 0.5 to 20 mg kg(-1). Interstitial illumination of the tumours was carried out using a 200-microm-core optical fibre with a 0.5 cm length of diffusing tip, at either 680 or 692 nm, depending on the sensitizer. Light doses of between 200 and 600 J were delivered at a rate of 100 mW from the 0.5-cm diffusing section of the fibre. Maximum mean growth delays ranged from 9 to 13.5 days depending on sensitizer and type of tumour, with the most potent photosensitizer appearing to be the cationic compound. Histopathological changes were investigated after treatment to determine the mechanism by which tumour necrosis was effected. The tumours had the appearance of an infarct and, under the conditions used, the observed damage was shown to be mainly due to ischaemic processes, although some direct tumour cell damage could not be ruled out.

Animals↗

Surgery for stress incontinence: factors associated with a successful outcome.

OBJECTIVE: To investigate which patient and health-service factors are predictive of outcome after surgery for stress incontinence. PATIENTS AND METHODS: In all, 232 women were assessed before and 3, 6 and 12 months after surgery for stress incontinence. Twelve patient characteristics and seven health-service factors were considered. Successful outcome was assessed in four ways: avoidance of complications after discharge, reduction in symptom severity. reduction in the social impact of stress incontinence, and improvement in activities of daily living (ADL). Relationships between possible predictors and outcome were explored using logistic regression models. RESULTS: Complications were less likely (r2=0.11) in women over 50 years of age, with no comorbidity and no urgency/urge incontinence, operated on by a gynaecologist. Reduction in symptom severity was more likely (r2=0.21) in younger women (< or = 50 years) with little limitation in their ADL, who suffered from severe or very severe stress incontinence symptoms but no urgency or urge incontinence, and who underwent preoperative urodynamic tests. A reduction in symptom impact was more likely (r2 = 0.15) in women in whom symptoms were having a moderate or severe impact, who were not grossly overweight, and who underwent a colposuspension or needle suspension performed by a gynaecologist. The only factor associated with improvement in ADL was the preoperative ADL score, i.e. the more limited a woman, the greater the likelihood of improvement (r2=0.15). The study provided evidence to support several of the widely held views about surgical success. Good outcomes were more likely if there is no urge incontinence, there is no or only mild comorbidity, no or only slight obesity, urodynamic investigations are conducted, and the surgeon is a gynaecologist. In contrast, there was no evidence that outcomes are worse if patients have undergone previous surgery for incontinence. Outcomes were also not related to grade of surgeon, surgeon's workload, or teaching status of the hospital. CONCLUSION: The relative importance of different factors depends on the outcome of interest, i.e. impairment (complications), disability (symptom severity) or handicap (symptom impact and ADL). These findings might help to improve clinical practice by indicating those characteristics that are associated with a greater likelihood of a good outcome. The results could also aid evaluation and audit of surgery, having identified the main prognostic factors that need to be considered when comparing the outcome of different procedures, surgeons or hospitals. Before doing so, the predictive models described in this paper need to be tested using an independent dataset.

Activities of Daily Living↗

Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications.

OBJECTIVE: To determine whether prophylactic, low dose controlled-release aspirin improves outcome for pregnant women and their babies in Barbados. DESIGN: Randomised placebo-controlled trial. SETTING: The Queen Elizabeth Hospital, Barbados. POPULATION: All women attending antenatal clinics between 12 and 32 weeks of gestation were eligible, if without specific contraindications to aspirin and unlikely to deliver immediately. METHODS: Randomisation was computer-generated in the antenatal clinic; 1822 women were allocated to receive 75 mg controlled-release aspirin and 1825 matching placebo. MAIN OUTCOME MEASURES: Proteinuric pre-eclampsia, other pregnancy-induced hypertension, pregnancy duration, birthweight, stillbirths and neonatal deaths, major neonatal events. RESULTS: All but three women from each group were followed up successfully. Forty-four percent were primigravid, and 8% had previous obstetric complications. There were no significant differences between the allocated treatment groups in the incidence of proteinuric pre-eclampsia (40 [2.2%] of those allocated aspirin, compared with 46 [2.5%] allocated placebo), of preterm delivery (255 [14.0%] vs 270 [14.8%]), of birthweight < 1500 g (32 [1.7%] vs 33 [1.8%]) or of stillbirth and neonatal death (44 [2.4%] vs 38 [2.1%]). Aspirin was not associated with excess risk of maternal or fetal bleeding. CONCLUSIONS: The results of this study in Barbados do not support the routine use of low dose aspirin for prevention of pre-eclampsia or its complications, confirming results of previous large trials in other settings.

Adult↗

Detection of antinuclear antibodies: comparative evaluation of enzyme immunoassay and indirect immunofluorescence methods.

OBJECTIVE: To evaluate a commercial microtiter enzyme immunoassay for antinuclear antibodies (ANA) by comparing the results of tests performed with this assay to an established indirect immunofluorescence method performed on human epitheliod cell substrate slides. DESIGN: Both analytical methods were used to test for the presence and levels of ANA in stored sera from 313 patients previously shown to have detectable ANA and from 102 healthy control subjects. Follow-up tests for specific autoantibodies (anti-dsDNA antibodies and antibodies to extractable nuclear antigens [ENA]) were performed on all sera from patients. The medical histories of all patients were reviewed to determine the presence of systemic rheumatic diseases (SRDs). Different cut-off levels of positivity were examined to determine the sensitivity and predictive values of positive results on the enzyme immunoassay for detecting patients with SRDs or sera with positive tests for specific autoantibodies. RESULTS: Among patients with clinically diagnosed SRDs (n = 197), the enzyme immunoassay was positive for ANA (> or =1 U) in 100% and the indirect immunofluorescence method was positive (titer > or =40) in 95.4% of cases. Among ANA-positive patients with no SRDs (n = 116), testing by enzyme immunoassay and indirect immunofluorescence yielded positive results in 97.6% and 75.6% of cases, respectively. Among healthy control subjects, each of the two methods was positive in 15% of cases. As expected, most patients with SRDs had higher levels of ANA than did ANA-positive patients with other clinical diagnoses. A cut-off level of > or =3 U on the enzyme immunoassay correctly classified 77% of patients with a SRD as "positive" and 88% of patients with other clinical diagnoses as "negative." The probability of detecting a positive result for specific autoantibodies on second-order testing increased directly with the level of ANA. A cut-off level of > or =3 U had a sensitivity of 92% for identifying sera with positive specific autoantibodies, and results > or =3 U had a predictive value of 52% for a positive second-order test result. CONCLUSION: Enzyme immunoassay is substantially equivalent to indirect immunofluorescence for detecting clinically important ANA. Cut-off levels for positive results on the enzyme immunoassay can be established that optimize the usefulness of this method in diagnostic algorithms for specific autoantibodies.

Antibodies, Antinuclear↗

Impact of surgery for stress incontinence on morbidity: cohort study.

OBJECTIVES: To describe the impact of surgery for stress incontinence on the severity of symptoms, other mental and physical symptoms, and overall health. To describe the incidence of postoperative complications. DESIGN: Prospective cohort study; questionnaires completed by patients before and 3, 6, and 12 months after surgery. Questionnaires completed by surgeons both before and after surgery. SETTING: 18 hospitals in the North Thames region. SUBJECTS: 442 women treated surgically for stress incontinence between January 1993 and June 1994. 367 women returned the 3 month questionnaire; 364 returned the 6 month questionnaire; and 359 returned the 12 month questionnaire. 49 surgeons provided perioperative information on 285 of the 442 women and postoperative information on 278. MAIN OUTCOME MEASURES: Stress incontinence symptom severity index, other urinary symptoms, bowel function, mental health, complications, global measures. RESULTS: Most women (288; 87%) reported an improvement in the severity of their stress incontinence, though only 92 (28%) were cured (continent). These improvements persisted for at least 12 months. The likelihood of improvement was similar regardless of whether urodynamic pressure studies had been conducted before surgery. Following surgery, women were less likely to suffer from urinary frequency, nocturia, postvoid fullness, dysuria, and urgency. While mental health improved for 194 (71%), a quarter of women reported deterioration. Only 37 (10%) were satisfied with postoperative pain control. A third experienced one or more complications while in hospital, most commonly difficulty urinating. This problem affected 1 in 11 women after discharge. A year after surgery two thirds of women reported feeling better (251; 72%), that the outcome met or exceeded their expectations (230; 66%), and that they would recommend the operation to a friend in a similar situation (239; 68%), and that they would recommend the operation to a friend in a similar situation (239; 68%). Surgeons tended to be more optimistic about the effects of surgery; they were satisfied with the outcome in 176 (85%) cases and would again treat 245 (94%) of the women as they had done previously. CONCLUSIONS: Although surgery reduces the severity of stress incontinence it is not as effective as current textbooks suggest. Women considering surgery should be provided with more accurate information on the likelihood of an improvement in symptoms and the occurrence of complications, including postoperative pain. Urgency and urge incontinence should not be considered contraindications to surgery. The need for urodynamic assessment before surgery should be reappraised.

Cohort Studies↗

Neuroendocrine measures and lymphocyte subsets in depressive illness: influence of a clinical interview concerning life experiences.

The effects of a clinical interview concerning either positive or negative day-to-day events on lymphocyte subpopulations, and on plasma cortisol, ACTH and norepinephrine, were determined in depressive patients (major depressive and dysthymic) and in normal controls. Irrespective of its content, the interview provoked an elevation of circulating natural killer (NK) cells, suggesting that this effect was related to either a change in mood state (regardless of its valence) or to the stress associated with the interview procedure. Since the interview did not influence plasma cortisol, ACTH or norepinephrine, it is likely that the NK cell variations were independent of these endocrines. Although basal NK cells were elevated in the depressive group relative to controls, the extent of the NK cell increase provoked by the interview was comparable in depressive and control subjects. The failure to detect differences between these populations could not be attributed to ceiling effects precluding more pronounced alterations in the depressed subjects. Indeed, variations of circulating cell subtypes were found to be exquisitely sensitive to differences in stressor intensity. In a subset of control subjects, a more potent stressor (anticipation of an academic examination) increased the plasma endocrine levels, increased circulating NK cell number beyond that associated with the interview stress, and provoked an increase of several T cell subsets (CD3, CD4 and CD8). Evidently, while a clinical interview may be sufficiently stressful to influence circulating NK cells, the stress of such a procedure seems no greater in depressed than in control subjects. It is suggested that although depressed patients may exhibit higher basal NK levels, this effect is likely not related to increased reactivity to stressors.

Adrenocorticotropic Hormone↗

Regional variation in intervention rates: what are the implications for patient selection?

BACKGROUND: Whereas geographical variations in intervention rates are well recognized, little is known about their implications for patient selection. This study looks at how the relative probability of being treated in different regions within England vary with a person's need for treatment, and whether higher intervention rates are associated with a greater probability of treatment at all levels of need or confined to only certain levels. METHODS: The method was modelling of retrospective data from population surveys, patient cohort studies and population intervention rates. Two southern regions (SW Thames and Wessex) and two northern regions (Northern and Mersey) were compared. Subjects were men aged 55 years and above in the population with urinary symptoms suggestive of benign prostatic hyperplasia and men undergoing surgical treatment. The ratio of probability of surgery in the southern regions to that in the northern regions by level of symptom severity was determined. RESULTS: The rate of surgery in the southern regions was 26.5 per cent higher than in the north. A higher proportion of patients in the north had severe symptoms before surgery (58 per cent vs 52 per cent; p = 0.002). The probabilities of being operated on in a given year varied by symptom severity in both the north and the south. The probability was higher in the south at all levels of symptom severity: none/mild (ratio = 1.44; p > 0.01), low-moderate (ratio = 1.35; p = 0.003), high-moderate (ratio = 1.53; p < 0.0001), and severe (ratio = 1.15; p > 0.01). On testing the sensitivity of the key assumptions by assuming a more severe distribution of symptoms in the south, the differences at none/mild and low-moderate symptom levels were enhanced but differences at high-moderate and severe symptom levels were reversed. CONCLUSIONS: As few men with mild symptoms qualify for surgery and most men with severe symptoms are operated on, any difference in patient selection between high and low rate regions is inevitably confined to the intermediate group of men with moderate symptoms. Surgeons appear to be rationing their resources in a sensible way, though perhaps not as stringently as could be achieved.

Bayes Theorem↗

Extended wear disposable soft contact lenses as an alternative to photorefractive keratectomy: report of 4 years experience.

PURPOSE: To establish whether, in a well-informed population, the use of extended wear disposable soft contact lenses (EWDSCL) poses an unacceptable risk to vision and corneal health due to complications associated with their use. METHODS: A 4 year retrospective review of EWDSCL, involving 371 patients in Melbourne from a single general ophthalmology practice. The important aspects of this group were that all patients were given written instructions about the methods of ensuring initial and ongoing cleanliness of lenses, no lenses were cleaned and reinserted, and no solutions other than the saline in the original packaging, and comfort crops, were used. Two types of EWDSCL were used in powers from -9.0 to +6.0 D, and with an initial aim of 4 weeks uninterrupted extended wear. Follow-up was from 2 to 52 months, with an average of 24 months. RESULTS: Of the 354 patients followed up, 236 (66%) regularly wore them on an extended overnight basis, and of these 180 (76%) wore them for the suggested 4 week period before renewal of lenses. In the 471 eyes of 236 patients, adverse reactions occurred at the following rates, marginal infiltrates (12 cases, 2.5%); corneal oedema (10 cases, 2%) peripheral corneal vascularization (2 cases, 0.4%); and presumed infective keratitis (1 case, 0.2%). No eyes lost one or more lines of Snellen acuity. CONCLUSIONS: When disposable soft contact lenses do not come into contact with cleaning solutions, saline from bottles or aerosol cans, or storage cases, their use on an extended wear basis (up to 4 weeks continuous) appears to be associated with a low risk of minor or major complications. The results of this review indicate that controlled usage of EWDSCL is safer than previous reports have indicated.

Adolescent↗

Adult acute leukaemia--a retrospective study of 66 consecutive patients.

BACKGROUND: Advances in therapy and supportive care have improved the outlook for many patients with acute leukaemia, however elderly patients have increased treatment-related toxicity and shorter survival. Most clinical trials have selected patient populations with young median ages and it is therefore difficult to apply results to the general population where the majority of patients presenting with acute leukaemia are over 60 years. There is little information in the literature guiding appropriate treatment of these patients. AIMS: To determine the relationship between age, treatment received, and outcome in patients presenting with acute leukaemia. METHODS: A retrospective analysis was performed on all patients presenting to Prince Henry's Hospital and Monash Medical Centre with acute myeloid leukaemia (AML) or acute lymphocytic leukaemia (ALL) during a five year period. RESULTS: Sixty-six patients (51-AML, 15-ALL) presented with acute leukaemia between March 1989 and April 1994. Median patient age was 63 years; 32% of patients received supportive therapy only; 86% of patients with ALL and 58% of patients with AML commencing remission-induction chemotherapy entered a complete remission. Median survival for patients receiving only supportive therapy was three months. Median survival in patients under 55 years was almost twice as long as patients over 55 years receiving similar treatment (AML-eight vs four months p = 0.023; ALL-3.5 vs seven months p = 0.029). CONCLUSIONS: Median survival for acute leukaemia is inversely proportional to age. Applying results from selected series to elderly patients with acute leukaemia is inappropriate.

Adult↗

Getting the message across: the development and evaluation of a health education video in general practice.

While many practices use, purchase or hire videos for health education purposes, a general practice in the North East of Scotland developed its own video. The practice staff were able to incorporate practice information and health education messages while using a local theme where all scenes in the video were either from within the town itself (where the practice is based) or within the surgery and all those appearing in the video are patients, local residents, and surgery staff. After showing in the waiting room of the surgery for two months, the video was evaluated for its potential to convey health information and its effectiveness in triggering patients to pick up specially designed healthy living leaflets on smoking, exercise, diet or alcohol that accompanied the video or to discuss health topics from the video. The evaluation showed that 84% of the patients interviewed watched the video and many provided positive comments. Whilst the video provided information in a comprehensible format and it was appreciated by many of the patients, few had picked up the leaflets or discussed any of the health issues with their GPs.

Adolescent↗

Primary dysthymia: a study of several psychosocial, endocrine and immune correlates.

The relationship between primary dysthymia (chronic, low grade depression) and indices of major and minor life stresses, uplifts and coping styles was examined. Additionally, circulating lymphocyte subsets were assessed in dysthymic patients to determine their relationship to stress/coping factors or plasma levels of cortisol, ACTH or norepinephrine. Primary dysthymia was found to be associated with increased minor stressors (daily hassles), reduced uplifts, as well as particular reliance on emotion-focused rather than problem-oriented coping strategies. Interestingly, among dysthymics, the early onset group exhibited a greater degree of hassles and greater emotion-focused coping compared to the late onset subgroup. Although hassles and coping styles were correlated with depressed mood, only coping styles predicted severity of depressed affect. It seems that although dysthymia is characterized by increased hassles and reduced uplifts, these variables do not distinguish between the severity of the depressive affect, whereas the coping styles employed in the face of the increased hassles and reduced uplifts are more closely aligned with depression severity. Dysthymia was associated with elevated levels of circulating natural killer (NK) cells. Since levels of plasma cortisol, ACTH or norepinephrine were not increased in the dysthymic subjects, it is likely that the elevated NK cell number was unrelated to these neuroendorcrine measures. In control subjects circulating NK cells were inversely related to the severity of hassles recently encountered, while in dysthymic patients stress and coping factors were unrelated to NK cell numbers. Thus, it appears that the altered NK cells in dysthymic patients were not related to the increased stress perception and altered coping which characterize these patients.

Adaptation, Psychological↗

Adding retinal photography to screening for diabetic retinopathy: a prospective study in primary care.

OBJECTIVE: To evaluate whether adding retinal photography improved community screening for diabetic retinopathy. SETTING: Mobile screening unit at rural and urban general practices in south west England. SUBJECTS: 1010 diabetic patients from primary care. DESIGN: Prospective study; patients were examined by ophthalmoscopy by general practitioners or opticians without fundal photographs and again with photographs, and assessments were compared to those of an ophthalmologist. MAIN OUTCOME MEASURES: Whether fundal photography improved the sensitivity of detection of retinopathy and referrable diabetic retinopathy, and whether this sensitivity could be improved by including a review of the films by the specialist. RESULTS: Diabetic retinopathy was detected by the ophthalmologist in 205 patients (20.5%) and referrable retinopathy in 49 (4.9%). The sensitivity of the general practitioners and opticians for referrable retinopathy with ophthalmoscopy was 65%, and improved to 84% with retinal photographs. General practitioners' sensitivity in detecting background retinopathy improved with photographs from 22% to 65%; opticians' sensitivity in detecting background retinopathy improved from 43% to 71%. The sensitivity of detecting referrable retinopathy by general practitioners improved from 56% to 80% with photographs; for opticians it improved from 75% to 88%. CONCLUSIONS: Combining modalities of screening by providing photography with specialist review of all films in addition to direct ophthalmoscopy through dilated pupils improves assessment and referral for diabetic retinopathy by general practitioners and opticians. With further training and experience, primary care screeners should be able to achieve a sensitivity that will achieve an effective, acceptable, and economical community based screening programme for this condition.

Ambulatory Care↗

Development of a symptom severity index and a symptom impact index for stress incontinence in women.

Stress incontinence is a common problem among women, yet there is no adequately validated instrument for measuring women's views of its severity (disease-specific health status). The only instrument for measuring the impact or bothersomeness of symptoms (disease-specific quality of life) has poor internal consistency. This paper describes the development and psychometric assessment of two new indexes, a Symptom Severity Index and a Symptom Impact Index. Following several qualitative enquiries, a questionnaire was developed and administered to 442 women undergoing stress incontinence surgery. The face and content validity of the items comprising the indexes was good. The Severity Index (0-20) showed good variability (median 14, interquartile range 6) and adequate internal consistency (alpha 0.76). The Impact Index (0-12) also had good variability (median 5, interquartile range 3.5) and internal consistency (alpha 0.80). Convergent and discriminant validity were demonstrated for both indexes. Test-retest reliability was high. While responsiveness is still to be tested, the two indexes are psychometrically strong and can be used to measure the severity and impact of stress incontinence in women.

Adult↗

Differential sexual activity of isolated and group-housed male mice: influence of acute d-amphetamine sulfate administration.

It is established that group housing can impair sexual activity of male mice, and that central catecholamines are involved in male sexual response, but it is not known whether catecholamine mechanisms are involved in sexual impairment in grouped males. Injections of 0, 0.22, 0.67, 2.0, or 6.0 mg/kg of d-amphetamine sulfate were administered 1 h before testing to individually and group-housed male C57BL/6J mice. Isolated mice showed more mounts, intromissions, and ejaculations and shorter response latencies than did group-housed mice. The latencies to first mount, intromission, and ejaculation were nonmonotonically related to dosage, being shortest at the lowest dosage in isolated mice, but significantly elevated by the higher dosages in both isolated and grouped males. The number of ejaculations was significantly elevated by moderate dosages in both isolated and grouped mice, peaking at the 2.0 mg/kg dosage in isolated mice and at 0.67 mg/kg in grouped mice. Nevertheless, amphetamine treatment generally failed to eliminate differences between males from isolated and grouped backgrounds.

Animals↗

Differential sexual activity of isolated and group-housed male mice: lack of substantial influence of acute or chronic naloxone administration.

Influences of naloxone upon male sexual behavior were examined using two different baseline activity levels: individually and group-housed mice. In Experiment 1, single injections of 0,12.5, or 50 micrograms per animal were administered before testing. Isolated mice showed more sexual activity than did grouped mice; naloxone failed to alter those differences. In Experiment 2, a similar result was obtained despite administration of 50 or 150 micrograms per animal of naloxone. In Experiment 3,0 or 50 micrograms of naloxone was administered to isolated or grouped males daily on the 5 days before testing. Isolated mice showed performance superior to that of grouped mice, but there was no effect of the drug. In Experiment 4, doses of 0. 12.5, or 50 micrograms of naloxone were given to isolated or grouped males twice daily for 7 days prior to testing, producing little effect. These results suggest that the influences of prior social condition on male sexual activity are robust in the face of naloxone administration.

Aggression↗