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Biomedical subjects

S Hollis

Publications and source records attributed to S Hollis.

At least 73 records · Page 4Linked to original sources
PubMed1995

Efficacy of D0870 compared with those of itraconazole and amphotericin B in two murine models of invasive aspergillosis.

D0870 is a novel azole antifungal compound. It was compared with conventional amphotericin B and itraconazole therapy in two murine models of invasive aspergillosis, one a systemic nonimmunocompromised mouse model and the other a temporarily neutropenic mouse respiratory model. D0870 was given orally and achieved measurable concentrations in serum approximately proportional to the daily dose with accumulation over time if it was given twice daily. Amphotericin B at 3.3 mg/kg of body weight was given intraperitoneally for four to six doses, and itraconazole was given orally in a cyclodextrin suspension at 5 to 50 mg/kg daily or twice daily (BID). The duration of therapy varied from 7 to 14 days. In the nonimmunocompromised mouse model, D0870 at 25 mg/kg BID was slightly inferior to amphotericin B and itraconazole with regard to mortality, with a median survival of 20 days for the three groups (P = 0.03 compared with amphotericin B). However, D0870 at 25 mg/kg BID was inferior to amphotericin B (but not itraconazole) with respect to renal culture (P = 0.01) and brain culture (P = 0.0001) results. Only amphotericin B was statistically superior to controls with regard to mortality. In the neutropenic mouse respiratory model, D0870 at 50 mg/kg/day was superior to amphotericin B, itraconazole, and controls with regard to mortality. D0870 at both 25 and 50 mg/kg/day was statistically superior to controls with regard to lung culture results (P = 0.004 to 0.04). A second experiment with a higher inoculum showed that no drug regimen was effective in that model. In all models low doses and concentrations of D0870 in serum were ineffective. D0870 has some efficacy for the treatment of invasive aspergillosis when it is given at modest doses.

Amphotericin B↗
PubMed1995

Persistent grossly elevated erythrocyte sedimentation rate in elderly people: one year follow-up of morbidity and mortality.

The significance of a very elevated erythrocyte sedimentation rate (ESR) in elderly patients is debated. In a retrospective study, we searched the records of a laboratory providing the sole service to a health district for ESR measurement and identified all non-surgical and non-psychiatric patients over the age of 65 who had had an ESR above 50 mm/h. Diagnoses and mortality in a 1-year follow-up were determined from case notes. Four hundred and nine subjects (median age 75; range 65-99) were identified and data on 401 of these (155 male, 246 female; median ESR 80 mm/h, range 50-148) were adequate for 1 year follow-up. Forty-eight percent had a persistently raised ESR (two values > 50 mm/h separated by at least 14 days; group 1); 39% had a single ESR measurement only (group 2), and 13% had a transiently raised ESR (group 3). The commonest diagnosis in group 1 patients was rheumatological disease (51.8%), followed by infection (31.9%) and non-haematological malignancy (11%). Infection was the commonest diagnosis in groups 2 (47.4%) and 3 (43.7%), followed by non-haematological malignancy (19.9%) in group 2 and rheumatological disease (20.4%) in group 3. In only 1 in 20 cases was no diagnosis apparent at 1 year. The standardised mortality ratio (SMR) of the combined groups 1 and 2 (482; CI: 421-544) was strikingly raised, and even more so if patients with rheumatoid arthritis were excluded (542; CI 458-625). Where there were sufficient numbers of deaths to make SMR estimations valid, a gradient of mortality against the level of the ESR could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Immunometric assays of luteinizing hormone (LH): differences in recognition of plasma LH by anti-intact and beta-subunit-specific antibodies in various physiological and pathophysiological situations.

Restricted immunoreactivity of plasma luteinizing hormone (LH) has been described in some subjects when assayed with certain methods involving antibodies against intact LH. We have compared the performance of the Amerlite LH-30 (A) and Delfia LHSpec (D) assays (which include anti-intact and beta-specific antibodies, respectively) in normal and pathological conditions. As shown previously, results of the two systems were highly correlated with each other and, as we show here, with those of a bioassay. We found eight outliers (results outside the 95% confidence interval of the regression) among 427 samples studied from 121 subjects. Of the outliers, five had Delfia results in a range (< 1 IU/L) that was associated with poor assay precision for that assay, and the ratios of their values by both methods (A:D ratios) were very low. This ratio was affected by endocrine status, e.g., was lower in postmenopausal women than in premenopausal controls, and varied intraindividually within the same menstrual cycle. The restricted immunoreactivity described previously for assays involving anti-intact LH antibodies may, in part, reflect these differences, which, in turn, may reflect the presence of isoforms (e.g., glycoforms) that are differentially recognized by assays that have different antibody configurations.

Antibodies↗
PubMed1994

Trauma audit--closing the loop.

The philosophy of medical audit and methods of data collection and statistical analysis have been extensively reviewed but less has been written about the effect of audit on medical practice. The measurement of performance is only valuable if it identifies areas of concern and stimulates appropriate change. This paper describes the work of the Salford Trauma Audit Group which has been developed at Hope Hospital, the problems that have been recognized, the strategies that have been introduced to effect change and their influence on management and outcome. Analysis of performance reveals an initial fall in adjusted mortality rate from severe injury after the introduction of resuscitation teams, the adherence to Advanced Trauma Life Support protocols and an integrated multidisciplinary approach to trauma care. Problems remain and there is continuing concern about trauma management in the hospital. This has been reinforced by performance feedback through the Trauma Audit Group which has attracted the interest of senior clinicians in several specialties.

Emergencies↗
PubMed1994

Anticardiolipin, anticentromere and anti-Scl-70 antibodies in patients with systemic sclerosis and severe digital ischaemia.

OBJECTIVE: Following observation of weakly positive anticardiolipin (aCL) antibodies in four of eight patients with systemic sclerosis (SSc) and severe digital ischaemia requiring amputation, the association between the presence of these and other antibodies and severe peripheral ischaemia in patients with SSc was examined. METHODS: ACL antibodies (IgG and IgM), anticentromere and anti-Scl-70 antibodies were measured in a further 60 patients with SSc over a one year period. Thirty one of the 68 patients in whom aCL antibodies were assayed had 'severe ischaemia', having suffered digital ischaemia severe enough to warrant amputation (13 patients), surgical debridement or admission for intravenous vasodilator therapy. RESULTS: There was no difference in aCL positivity between those with severe ischaemia and those without, nor between those who had amputations and those who had not. Three of the 31 patients (10%) with severe ischaemia had IgG and eight (26%) IgM aCL antibodies in weak to moderate titre compared to 10 (27%) and 6 (16%) respectively of the remaining patients (p = 0.06 for IgG and p = 0.25 for IgM, Fisher's exact test). Seventeen of the 31 patients (55%) with severe ischaemia were anticentromere antibody positive compared with nine of 37 (24%) without ischaemia (p = 0.01). Six patients with severe ischaemia had anti-Scl-70 antibodies compared with two of the 37 without ischaemia (p = 0.08). CONCLUSIONS: The findings do not support an association between aCL antibodies and severe ischaemia in SSc, but confirm the previously reported association between anticentromere antibodies and severe peripheral ischaemia. Although anti-Scl-70 antibodies were present only in a small number of patients, there was also a tendency for these to be associated with severe ischaemia, suggesting that patients with either anticentromere or anti-Scl-70 antibodies should be considered at risk of digital loss.

Adult↗
PubMed1994

Evaluation of human postprandial antral motor function using ultrasound.

We used high-resolution ultrasound to characterize postprandial antral excursion characteristics in 15 healthy volunteers. Antral circumference was repeatedly measured in the sagittal plane anterior to the abdominal aorta, at 15-min intervals following ingestion of a standard meal. At each recording period, the maximal and minimal antral circumference was noted. In seven volunteers, antral circumference was studied continuously for 5 min at each 15-min recording period to assess the frequency and regularity of antral excursions. Antral circumference increased immediately after meal ingestion from preprandial values of 64 +/- 2.6 (means +/- SE) to 138 +/- 3.1 mm and then gradually decreased with meal emptying to 72 +/- 2.6 mm at 90 min. The continuous recordings of antral images revealed that antral circumference transiently decreased at regular intervals; the interval between successive excursions was 20.1 +/- 0.2 s. There was no change in the excursion interval with emptying. The excursion amplitude decreased from 33 +/- 3.9 mm immediately post-meal ingestion to 13 +/- 1.5 mm at 90 min (r2 = 0.62 +/- 0.07). The ratio between the excursion amplitude and circumference of the relaxed antrum changed only slightly with time (slope = 0.0009 +/- 0.00003). Comparison of repeat studies in 10 volunteers showed a low intra-individual variation for postprandial antral circumference and excursion amplitude.

Adult↗
PubMed1994

Relaxation responses of the human proximal stomach to distension during fasting and after food.

The responses of the human proximal stomach to distension were studied in 22 healthy volunteers using an intragastric polyethylene bag, inflated progressively in 30-ml steps until the limit of tolerated volume was reached. Three successive inflations were carried out during the fasting state followed by a fourth inflation after ingestion of 250 ml of either a nutrient meal or isosmolar saline. The first inflation showed an initial nonlinear pressure rise (slope of logged pressure vs. volume = 114.6 +/- 10.0 log mmHg/ml x 10(-5)), which was then followed by the development of a plateau phase, in which further distension did not increase intragastric pressure. The slopes of the subsequent fasting inflations were significantly lower than that of the first inflation (P < 0.01) but were similar to each other (slope 83.0 +/- 5.4 and 79.8 +/- 5.7 log mmHg/ml x 10(-5)), indicating that distension-induced gastric relaxation had occurred. After saline ingestion, responses to distension were similar to those during the fasted state. After the nutrient meal ingestion, however, the slope decreased to 60.3 +/- 7.7 log mmHg/ml x 10(-5) (P < 0.01 vs. saline), indicating nutrient-induced gastric relaxation. Our study demonstrates that the pressure-volume characteristics of the proximal stomach are modulated both by distension and by the presence of nutrients in the upper gut, which appear to operate independently.

Adult↗
PubMed1994

Micronutrient antioxidant status in patients with primary Raynaud's phenomenon and systemic sclerosis.

OBJECTIVE: To investigate the possibility that micronutrient antioxidant status is an important factor in determining the severity of Raynaud's phenomenon (RP) and in differentiating between patients with primary Raynaud's phenomenon (PRP) and those in whom Raynaud's is secondary to systemic sclerosis (SSc). METHODS: Four micronutrient antioxidants (selenium, vitamin E, beta-carotene and ascorbic acid) and 2 "markers" of free radical associated activity were assayed in peripheral blood from 10 patients with PRP, 9 with limited cutaneous SSc (ISSc), 9 with diffuse SSc (dSSc) and 15 healthy control subjects. RESULTS: Plasma ascorbic acid was reduced in all 3 groups of patients: median level 10.6 mg/l in controls, 4.8 mg/l in PRP (p < 0.01), 2.5 mg/l in ISSc (p < 0.01) and 6.8 mg/l in dSSc (p < 0.05). A reduction in serum selenium was especially found in dSSc (median 75 micrograms/l compared to 100 micrograms/l in controls, p < 0.05). In keeping with these deficiencies, the serum concentration of 9, 11, linoleic acid was elevated in RP patients: median values for the molar ratio of the isomer to the parent fatty acid were 1.91% in controls, 3.70% in ISSc (p < 0.05) and 3.85% in dSSc (p < 0.01). Smoking patients showed lower levels of ascorbic acid and higher levels of the linoleic isomer than nonsmokers. CONCLUSION: Deficiencies of ascorbic acid and selenium may predispose towards irreversible tissue injury in RP patients and cigarette smoke may be an independent risk factor. Micronutrient antioxidant supplements may be of therapeutic value.

Aging↗
PubMed1993

Indications for cholecystectomy: the results of a consensus panel approach.

A consensus panel approach was used in Israel to develop a list of clinical indications for which there was agreement that cholecystectomy should be performed. Nine physicians from different disciplines were asked to score a list of 266 clinical indications for cholecystectomy. Each indication was scored on a scale of 1 (inappropriate, i.e. health risks exceed health benefits) to 9 (appropriate, i.e. benefits exceed risks). Each indication also included one of four comorbidity levels (none to high). Agreement and disagreement were defined and panelists met to discuss, modify and rescore the list. The composition of the panel and definitions of agreement had a considerable impact on the preparation of a list of agreed, appropriate indications for cholecystectomy. Gastroenterologists in the panel were less likely to recommend surgery than either surgeons or general internists both before and after the panel discussion. Following the discussion the level of agreement (defined as after discarding the highest and lowest score all of the remaining seven panelists were in a 3-point range) increased from 39% to 46% (p < 0.08) and disagreement decreased from 27% to 18% (p < 0.01). Fifty-nine of the 266 indications were considered appropriate with agreement.

Attitude of Health Personnel↗
PubMed1993

The agreed indications and contra-indications for cholecystectomy.

Indications as to which patients should undergo cholecystectomy remain, at least in part, a matter of controversy. In 1987, a panel of nine Israeli physicians from different specialties established a list of indications for the performance of cholecystectomy based on the literature available at the time. The panel agreed that cholecystectomy was appropriate for 59 indications and that it was inappropriate for 58. The major indications for surgery were biliary colic and acute cholecystitis. Patients who were asymptomatic or had vague symptoms were not recommended to undergo surgery unless they had stones in the common bile duct and were less than 71 years of age. Patients with pancreatitis were recommended for surgery if they had stones in the common bile duct and did not have a history of alcohol abuse. Performing a cholecystectomy at the same time as abdominal surgery was being performed for other reasons was indicated only if the patient was symptomatic from his gall-stones.

Acute Disease↗
PubMed1993

Major histocompatibility complex variants and articular disease severity in rheumatoid arthritis.

In the light of associations previously described between DR4, DQw7, the C4B null allele and Felty's syndrome, and between Dw14, the C4A null allele and rheumatoid vasculitis, we have looked for associations between these and other DRB1, DQB, DQA and C4 encoded variants, and articular disease severity assessed radiologically in 119 subjects with RA but without major extra-articular features. The association of DR4 with more severe disease and DR1 and DR2 with mild disease was confirmed but no associations were found between the presence of DQw7, Dw14, C4A or C4B null alleles and articular disease severity. This suggests that the associations noted previously between these markers and extra-articular disease features of Felty's syndrome or rheumatoid vasculitis are unlikely to reflect an overall effect on disease severity but more likely to represent associations with these particular extra-articular disease subsets.

Arthritis, Rheumatoid↗
PubMed1993

Physiological oestradiol administration does not change the biological to immunological ratio of LH in serum from post-menopausal women.

OBJECTIVE: We investigated the effect of chronic physiological concentrations of oestradiol on the bioactivity (B) and immunoactivity (I) of LH in serum using radioimmunoassay (RIA) and a sensitive immunoradiometric (IRMA) assay. DESIGN: Twelve post-menopausal, hysterectomized women received a 50-mg subcutaneous E2 implant, in the absence of progestogen treatment. Pretreatment serum samples were obtained on two occasions for measurement of E2 and FSH by radioimmunoassay and for measurement of LH by bioassay (BIO), immunoradiometric assay and radioimmunoassay. Further serum samples were obtained monthly for 6 months for assay as above. RESULTS: The serum E2 level (basal levels < 70 pmol/l) rose following implant (P < 0.01) peaking at 1 month (mean 454, range 356-580 pmol/l) and remaining within premenopausal physiological levels for 6 months. There were falls in FSH, LH-RIA, LH-IRMA and LH-BIO (P < 0.001). There was no change in the B:I ratio for B:I-RIA or B:I-IRMA for LH which were 1.8 and 3.3, respectively pretreatment and 1.7 and 2.9 after 1 month's treatment. CONCLUSION: The treatment of post-menopausal women with 50-mg E2 subcutaneous implants produces physiological premenopausal E2 levels for at least 6 months. There is no change in the B:I ratio of LH using either the RIA or IRMA during chronic E2 treatment.

Biological Assay↗
PubMed1993

Growth in atopic eczema.

Growth was studied in 68 children aged 2-12 years with atopic eczema. Height SD scores were significantly correlated with the surface area of skin affected by eczema. The mean height of 41 patients with less than 50% of their skin surface affected (group I) was normal (mean SD score -0.11). The 27 children with more than 50% of their skin affected (group II) were significantly shorter (SD score -0.83) and were also short allowing for their parental target height. The predicted heights were also normal in group I but were lower than expected in group II. Regression analysis suggested that height was most dependent on parental height. The extent of the disease had a significant additional effect, whereas dietary treatment and treatment with topical steroids had only marginal additional effects. The growth of children with eczema affecting less than 50% of the skin surface area appears to be normal, and impaired growth is confined to those with more extensive disease.

Age Determination by Skeleton↗
PubMed1993

Trauma audit: clinical judgement or statistical analysis?

Comparisons have been made between two methods currently used to assess the effectiveness of management of major trauma. These are the review of fatal cases by senior clinicians and the use of statistical analysis of severity scores. The former was assessed by a re-examination of the Coroners' reports of 508 patients reviewed by senior clinicians at the request of The Royal College of Surgeons of England Working Party on the Management of Patients with Major Injuries. The latter was based on the 665 fatalities on the files of the UK Major Trauma Outcome Study. The two groups of patients had comparable age and sex profiles and broadly similar ranges of injury severity. There were major differences between and inconsistencies within the two assessments. Clinicians more frequently judged death avoidable in those with very severe injuries. In contrast, the statistical analysis suggested, paradoxically, that the proportion of avoidable deaths in those patients who had minor injuries was less than the proportion of avoidable deaths in those who had more serious injuries. These variations underline the limited values of retrospective peer review and will not encourage clinicians to adopt currently available statistical methods. Further refinements of anatomical and physiological scoring systems and their integration to provide a statistically valid and clinically acceptable measure of outcome are essential prerequisites to the wider introduction and success of trauma audit.

Adolescent↗
PubMed1992

Preliminary analysis of the care of injured patients in 33 British hospitals: first report of the United Kingdom major trauma outcome study.

OBJECTIVE: To measure the effectiveness of management of major trauma in the United Kingdom. DESIGN: Review of the care of all seriously injured patients seen over two years. SETTING: 33 hospitals which receive patients who have sustained major trauma. SUBJECTS: 14,648 injured patients admitted for more than three days, transferred or admitted into an intensive care bed, or dying from their injuries. MAIN OUTCOME MEASURE: Death or survival in hospital within three months of the injury. RESULTS: 21% of seriously injured patients (1299) took longer than one hour to reach hospital. Time before arrival at hospital was not related to severity of injury. A senior house officer was in charge of initial hospital resuscitation in 57% (826/1445) of patients with an injury severity score > or = 16. More senior staff were commonly responsible for definitive operations, but only 46% (165/355) of patients judged to require early operation arrived in theatre within two hours. Mortality for 6111 patients sustaining blunt trauma and treated in the 14 busiest hospitals was significantly higher (actual 408, predicted 295.6, p < 0.001) than in a comparable North American dataset. Large differences in the 14 hospitals assessed could not be explained by variations in case load or facilities. In contrast, the outcome of the 4.1% (597) of patients with penetrating injuries was better than that of a comparable group in the United States. Analysis of the 415 penetrating injuries with complete data showed that 15 patients died (19.3 predicted; p = 0.04). CONCLUSIONS: The initial management of major trauma in the United Kingdom remains unsatisfactory. There are delays in providing experienced staff and timely operations. Mortality varies inexplicably between hospitals and, for blunt trauma, is generally higher than in the United States.

Emergency Medical Services↗