CSF spectrophotometry in the diagnosis of subarachnoid haemorrhage.
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Bilirubin↗
Biomedical subjects
A M Ward
Publications and source records attributed to A M Ward.
S. cerevisiae has three pathways for DNA interstrand crosslink repair.
Yeast mutants, snm1 (pso2-1), rev3 (pso1-1), and rad51, which display significant sensitivity to interstrand crosslinks (ICLs) have low relative sensitivity to other DNA damaging agents. SNM1, REV3, and RAD51 were disrupted in the same haploid strain, singly and in combination. The double mutants, snm1 Delta rev3 Delta, snm1 Delta rad51 Delta and rev3 Delta rad51 Delta were all more sensitive to ICLs than any of the single mutants, indicating that they are in separate epistasis groups for survival. A triple mutant displayed greater sensitivity to ICLs than any of the double mutants, with one ICL per genome being lethal. Therefore, Saccharomyces cerevisiae appears to have three separate ICL repair pathways, but no more. S-phase delay was not observed after ICL damage introduced by cisplatin (CDDP) or 8-methoxypsoralen (8-MOP) during the G1-phase, in any of the above mutants, or in an isogenic rad14 Delta mutant deficient in nucleotide excision repair. However, the psoralen analog angelicin (monoadduct damage) induced a significant S-phase delay in the rad14 Delta mutant. Thus, normal S-phase in the presence of ICLs does not seem to be due to rapid excision repair. The results also indicate that monoadduct formation by CDDP or 8-MOP at the doses used is not sufficient to delay S-phase in the rad14 Delta mutant. While the sensitivity of a rev3 Delta mutant indicates Pol zeta is needed for optimal ICL repair, isogenic cells deficient in Pol eta (rad30 Delta cells) were not significantly more sensitive to ICL agents than wild-type cells, and have no S-phase delay.
Cisplatin↗
Association of adult coeliac disease with irritable bowel syndrome: a case-control study in patients fulfilling ROME II criteria referred to secondary care.
BACKGROUND: Irritable bowel syndrome has a high prevalence. Consensus diagnostic criteria (ROME II) based on symptoms have been established to aid diagnosis. Although coeliac disease can be misdiagnosed as irritable bowel syndrome, no prospective study has been published in which patients with this disorder are investigated for coeliac disease. We aimed to assess the association of coeliac disease with irritable bowel syndrome in patients fulfilling ROME II criteria. METHODS: We undertook a case-control study at a university hospital. 300 consecutive new patients who fulfilled Rome II criteria for irritable bowel syndrome, and 300 healthy controls (age and sex matched) were investigated for coeliac disease by analysis of serum IgA antigliadin, IgG antigliadin, and endomysial antibodies (EMA). Patients and controls with positive antibody results were offered duodenal biopsy to confirm the possibility of coeliac disease. FINDINGS: 66 patients with irritable bowel syndrome had positive antibody results, of whom 14 had coeliac disease (11 EMA positive, three EMA negative). Nine patients with positive antibody results were lost to follow-up or refused biopsy (only one EMA-positive patient refused biopsy), and 43 had normal duodenal mucosa. Two controls, both of whom were EMA positive, had coeliac disease. Compared with matched controls, irritable bowel syndrome was significantly associated with coeliac disease (p=0.004, odds ratio=7.0 [95% CI 1.7-28.0]). INTERPRETATION: Patients with irritable bowel syndrome referred to secondary care should be investigated routinely for coeliac disease. With only EMA, three of 14 cases would have been missed.
Adult↗
Pre- and post-analytical factors that may influence use of serum prostate specific antigen and its isoforms in a screening programme for prostate cancer.
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Adult↗
Prostate specific antigen: biology, biochemistry and available commercial assays.
Prostate specific antigen (PSA) is the marker of choice in the management of prostate cancer. However, PSA is not a simple molecule, existing in the serum in five isoforms and a number of molecular configurations and complexes. The elucidation of the biochemistry of PSA has increased the potential use of the marker in the diagnosis of prostate malignancy. This review summarizes the clinical use of PSA in the management of prostate disease and the assays available in the UK. Assay calibration in relation to the World Health Organization 1st International Standard for Prostate Specific Antigen (90:10) has increased conformity between the various commercial assay kits, and the non-equimolar kits have largely been superseded or withdrawn. Special reference is made to evaluations performed on behalf of the Medical Devices Agency of the Department of Health.
Adenocarcinoma↗
Saccharomyces cerevisiae lacking Snm1, Rev3 or Rad51 have a normal S-phase but arrest permanently in G2 after cisplatin treatment.
The role of Snm1, Rev3 and Rad51 in S-phase after cisplatin (CDDP) DNA treatment has been examined. When isogenic deletion mutants snm1 delta, rev3 delta and rad51 delta were arrested in G1 and treated with doses of CDDP causing significant lethality (<20% survival in the mutant strains), they progressed through S-phase with normal kinetics. The mutants arrested in G2 like wild-type cells, however they did not exit the arrest and reenter the cell cycle. This finding demonstrates that these genes are not required to allow DNA replication in the presence of damage. Therefore, Snm1, Rev3 and Rad51 may act after S to allow repair. At high levels of damage (<40% survival in wild-type cells) S-phase was slowed in a MEC1-dependent fashion. The cross-link incision kinetics of snm1 delta and rev3 delta mutants were also examined; both showed no deficiencies in incision of cross-linked DNA.
Antineoplastic Agents↗
Association of chronic urinary symptoms in women and Ureaplasma urealyticum.
UNLABELLED: OBJECTIVES. To determine the incidence of Ureaplasma urealyticum in women experiencing chronic urinary symptoms and to determine whether antibiotic therapy targeting these organisms is effective. METHODS: Forty-eight consecutive women referred to our academic medical center for chronic voiding symptoms and possible interstitial cystitis underwent urologic evaluation, including culture screening for U. urealyticum and Mycoplasma hominis. Patients with positive cultures were treated with a 1-g dose of azithromycin; persistent infection was treated with 7 days of doxycycline, ofloxacin, or erythromycin. Patients reported symptom severity (0, mild; 3, severe) and voiding frequency before and 6 months after treatment. RESULTS: Positive cultures were obtained in 23 (48%) of 48 patients; 22 had U. urealyticum and 1 had M. hominis. All had negative cultures after treatment. The mean symptom severity score improved with treatment (2.2 to 0.7, P <0.001), and the mean urinary frequency decreased (9.2 daily to 6.8 daily, P <0.001). Two of the 23 patients experienced no improvement; one had detrusor instability and the other had medically related urinary frequency. Of the 25 patients with negative cultures, interstitial cystitis was established in only 9 (19% of the total sample). CONCLUSIONS: Although often overlooked or improperly treated, U. urealyticum and M. hominis infections may account for a large proportion of unexplained chronic voiding symptoms. Culture and treatment should be considered before pursuing more costly and invasive tests.
Adolescent↗
A case for co-ordinated investigation and reporting of hypersensitivity-type drug reactions in the UK.
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Adverse Drug Reaction Reporting Systems↗
Assessment of latex allergy in a healthcare population: are the available tests valid?
BACKGROUND: Latex allergy can cause serious, preventable work-related health problems in healthcare workers who are a high risk group for this form of allergy. Type I hypersensitivity can produce life-threatening systemic effects, and involves an allergen-specific immunoglobulin (IgE) response to proteins found in latex. The estimated prevalence of latex 'allergy' in healthcare workers varies widely (2.8% - 18%), and studies do not always distinguish between those who are positive in an assay for latex-specific IgE and those with clinical allergy. OBJECTIVE: To assess the performance of four in-vitro methods and three skin testing methods for detecting latex-specific IgE in a group of UK healthcare workers. Test results were compared with reported clinical symptoms defined by questionnaire. METHODS: Skin prick testing was carried out on volunteers using three reagents: (a) stallergenes commercial latex extract (Cedex, France); (b) an in-house latex glove extract; and (c) a fresh glove piece. Specific IgE levels were determined using Pharmacia AutocapTM (Uppsala, Sweden), Pharmacia UnicapTM (Uppsala, Sweden), DPC Immulite(R) (Los Angeles, USA) and Hycor HytecTM (Irvine, California, USA) methods. Each volunteer completed a questionnaire detailing latex exposure and allergic history. RESULTS: In vitro methods for detecting specific IgE to natural rubber latex were positive in 3.6%, to 43.6% of the same population. Skin prick tests positivity varied between 2. 9% and 14.3% with different extracts. From the subjects tested 9.1% reported symptoms which could be consistent with type I allergy, although none had been given a pre-existing diagnosis of latex allergy, and 43.6% of volunteers reported symptoms consistent with type IV hypersensitivity or irritant dermatitis. Contingency tables and chi-squared analysis revealed no correlation between most methods. No correlation was shown between symptoms consistent with type I allergy and any in vitro or skin testing method for latex-specific IgE. CONCLUSIONS: A wide variation between testing procedures was found, and no method could be correlated with reported symptoms of type I allergy. At least one in vitro specific IgE assay produced a high percentage of positive results at variance with the clinical symptoms in volunteers. A clinical history is essential in establishing type I hypersensitivity to latex and test results should not be used in isolation. The incidence of clinical sensitization may be seriously over-estimated if only laboratory parameters are used.
Adult↗
Differences in teaching about the acute sore throat within one medical faculty.
OBJECTIVES: To examine the consistency of teaching about the acute sore throat in four departments in one medical faculty, and to determine whether there is agreement between what is taught and the evidence-based literature. DESIGN: Cross-sectional study. SUBJECTS: 71 undergraduates and 15 postgraduate general practice registrars and four lecturers. RESULTS: Differences were identified in teaching about the diagnostic value of a throat swab, a full blood count and clinical scoring, as well as on the use of penicillin in suspected streptococcal pharyngitis. Only one department based their teaching on the evidence-based literature. No department discussed issues of cost-effectiveness. Half of the students identified discrepancies in the teaching about the sore throat and were initially confused by them. CONCLUSION: One method of resolving disagreement between teachers from different disciplines is to rely on the evidence-based literature. This type of study can be useful in curricular development and in correcting teaching inconsistencies within a faculty.
Acute Disease↗
Evaluation of a pilot project to use computers in a rural general practice term.
In 1998, the Department of General Practice (Faculty of Medicine and Dentistry, University of Western Australia) ran a pilot project to use computers in a sixth year rural general practice term. Students were provided with a laptop computer to take into rural and remote areas throughout Western Australia during their 4-week clinical attachment. An email mailing list was set up for course participants to share experiences and complete set learning activities specifically related to rural general practice. An evaluation of this pilot project found that students felt less isolated on rural attachments, course outcomes were improved and rural preceptors were more involved in the programme. The development of a teaching and learning programme that involves the use of computers in rural general practice for undergraduate students has the potential to improve the quality of their medical education.
Education, Distance↗
Hepatic iron accumulation over time in European starlings (Sturnus vulgaris) fed two levels of iron.
European starlings (Sturnus vulgaris) were used as a passerine bird model to examine the effect of dietary iron on the level of hepatic iron in birds. Nestling and fledgling starlings (n = 56) were raised on a controlled-iron diet. When birds maintained constant body weight, they were assigned in pairs to cages, and baseline sampling was performed. Pairs were then assigned to one of two diets: the controlled-iron diet (168 ppm, dry basis) or a high-iron diet (3,035 ppm, dry basis). Dry-matter intake and iron consumption were recorded. Dry-matter intake did not differ between the dietary treatment groups and was stable during treatment periods. Iron intake was higher in the high-iron group (P < 0.05). Birds were euthanized at baseline, 8 wk, and 16 wk. Body, liver, and spleen weights were measured. Hepatic iron and copper concentrations were determined. Body weight did not differ between the two treatment groups or among individuals for the study duration. Liver iron concentration differed over time and between treatment groups. Birds receiving both treatments had similar liver iron content at week 8 (3,107 +/- 228.6 ppm and 3,122 +/- 306.2 ppm high and controlled iron, respectively; P > 0.05), but by week 16, birds consuming the high-iron diet had greater hepatic iron levels than those consuming the controlled-iron diet (5,929 +/- 937.2 ppm and 3,683 +/- 229.5 ppm high and controlled iron, respectively; P < 0.05). Birds on the controlled-iron diet also had higher hepatic iron at 16 wk than at 8 wk. Liver copper decreased over time in all birds regardless of treatment. Results show that both dietary iron level and duration of time influenced hepatic iron storage. The controlled-iron diets still allowed accumulation of hepatic iron in an 8-wk period.
Animals↗
Chronic obstructive pulmonary disease, with and without alpha-1-antitrypsin deficiency: management practices in the U.K.
Alpha-1-antitrypsin deficiency is a common genetic defect associated with the development of severe and rapidly progressive lung disease. This study was undertaken to determine whether respiratory physicians manage patients with alpha-1-antitrypsin (AAT) deficiency differently from patients with chronic obstructive pulmonary disease (COPD) without alpha-1-antitrypsin deficiency. In addition we obtained physicians' views on who should be tested for AAT deficiency. A questionnaire was administered to 88 respiratory physicians based throughout the U.K. (44 in teaching hospitals). The main outcome measures were pulmonary function tests, radiological assessment, frequency of repeat testing, follow-up and screening protocol for alpha-1-antitrypsin deficiency. Subjects with homozygous (PiZ) AAT deficiency were more likely to: 1. have baseline and full pulmonary function testing including dynamic flow rates, static lung volumes, and gas transfer; 2. have more comprehensive assessment with high resolution computed tomography (HRCT) thorax and repeated radiological assessment (with annual chest radiography); 3. be followed-up routinely; and 4. have family members tested for alpha-1-antitrypsin deficiency. Testing remains limited for AAT deficiency and is mainly restricted to young patients with COPD. COPD assessment and management is influenced by the presence of AAT deficiency, which may reflect the poorer prognosis of such patients due to more rapid decline. Assessment and monitoring could be simplified to forced expired manoeuvres, although limited HRCT thorax and tests of gas transfer may prove more sensitive to progression of emphysema. Testing for AAT deficiency in the U.K. remains restricted, which will influence the detection rate for AAT deficiency. A wider policy of testing was advocated by the WHO will detect more patients and also influence our understanding of the natural history of the condition.
Adult↗
Chlamydia trachomatis infection mimicking testicular malignancy in a young man.
A young man with a low risk history for sexually transmitted diseases presented with an apparently longstanding, previously asymptomatic scrotal mass, highly suggestive of testicular malignancy on palpation. Ultrasound sited the lesion in the epididymis. Although there was no evidence of urethritis, chlamydia polymerase chain reaction testing was positive. Tumour markers were negative. Complete clinical and radiological response was achieved after a long course of doxycycline treatment, without surgical exploration of the scrotum, confirming the diagnosis of chlamydial epididymitis.
Adult↗
Mechanisms of apoptosis in T cells from patients with renal cell carcinoma.
Tumors may escape immune recognition and destruction through the induction of apoptosis in activated T lymphocytes. Results from several laboratories suggest that FasL (L/CD95L) expression in tumors may be responsible for this process. In this study of patients with renal cell carcinoma (RCC), we provide evidence for two mechanisms of T-cell apoptosis. One mechanism involves the induction of apoptosis via FasL expression in tumor cells. This is supported by several observations, including the fact that tumor cells in situ as well as cultured cell lines expressed FasL mRNA and protein by a variety of techniques. The FasL in RCC is functional because in coculture experiments, FasL+ tumors induced apoptosis in Fas-sensitive Jurkat T cells and in activated peripheral blood T cells but not in resting peripheral blood T cells. Most importantly, antibody to FasL partially blocked apoptosis of the activated T cells. Moreover, Fas was expressed by T cells derived from the peripheral blood (53% median) and tumor (44.3% median) of RCC patients. Finally, in situ staining for DNA breaks demonstrated apoptosis in a subset of T cells infiltrating renal tumors. These studies also identified a second mechanism of apoptosis in RCC patient peripheral T cells. Whereas these cells did not display DNA breaks when freshly isolated or after culture for 24 h in medium, peripheral blood T cells from RCC patients underwent activation-induced cell death after stimulation with either phorbol 12-myristate 13-acetate/ionomycin or anti-CD3/CD28 antibodies. Apoptosis mediated by exposure to FasL in tumor cells or through T-cell activation may contribute to the failure of RCC patients to develop an effective T-cell-mediated antitumor response.
Apoptosis↗
Epitope expression in nine commercial kits for the determination of anti-thyroid peroxidase (TPO) antibodies.
Anti-thyroid peroxidase (TPO) antibodies, from patients with autoimmune disease, bind predominantly to two neighbouring, non-identical, conformational domains referred to as domains A and B. In recent years a number of ELISA assays have been developed for the detection of anti-TPO antibodies, however, considerable variation between the different commercial assay kits has been documented in inter-laboratory surveys (UK NEQAS). This investigation assessed the differences between nine commercial ELISA assays currently available in the UK. The anti-TPO kits varied in terms of their imprecision and accuracy and in the density of coated antigen. Recombinant antigen containing kits demonstrated partial destruction of the B epitope, possibly due to the close proximity of both epitope regions in the recombinant molecule. None of the kits expressed only one epitope although there were differences in the degrees of expression of each epitope. Clinicians should be aware of the variability of the numbers generated, when interpreting test results.
Analysis of Variance↗
Prediction of local recurrence of ductal carcinoma in situ of the breast using five histological classifications: a comparative study with long follow-up.
The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening and the more widespread use of breast-conserving surgery have led to a search for histological features associated with the risk of recurrence. In a case control study of 141 patients with long follow-up, we compared the ability of five morphological classifications to predict recurrence after local excision. A significant correlation was not found between recurrence and growth pattern when a traditional classification based on architecture was used nor with necrosis when a scheme based principally on this feature was employed. A correlation was, however, found between recurrence and "differentiation" as defined by nuclear features and cell polarization in a classification recently formulated by the European Pathologists Working Group (EPWG), but this failed to reach statistical significance at the 5% level. A stronger and statistically significant correlation was found between nuclear grade as defined by the EPWG and recurrence when cell polarization was disregarded, using the classification currently employed by the UK National Health Service and European Commission-funded Breast Screening Programmes. This was attributable to a small number of recurring cases being downgraded as a consequence of exhibiting polarized cells. A significant correlation between histology and recurrence was also observed using the Van Nuys classification, which is based on nuclear grade and necrosis. Whether the tumor recurred as in situ or invasive carcinoma was unrelated to histological classification, as was the time course over which it occurred. These findings strongly support the use of nuclear grade to identify cases of DCIS at high risk of recurrence after local excision, but further work is necessary to determine whether nuclear grade or necrosis is more appropriate to subdivide the non-high-grade cases.
Adult↗
Should continent diversion be performed in patients with locally advanced bladder cancer?
OBJECTIVES: To assess the effect of local, regional, and distant recurrence on pouch function in patients with locally advanced bladder cancer treated by cystectomy and continent diversion. METHODS: A review of 64 consecutive patients undergoing orthotopic (n = 40) or continent cutaneous (n = 24) urinary diversion was performed; 25 patients (39.1%) had locally advanced cancers as defined by deep muscle invasion, extension into perivesical fat, stromal invasion of the prostate, or node-positive disease. Patients were followed at 6-month intervals with physical examination, assessment of voiding function, and computed tomography (CT) scans. RESULTS: The pelvic recurrence rate was 4.7% in the overall group and 12% in patients with locally advanced disease. In the 39 patients with organ-confined tumors, 34 (87%) are alive without evidence of recurrence and have normal pouch function with a median follow-up of 27 months. Four patients in this group receiving systemic chemotherapy for clinical recurrences have retained normal pouch function until last follow-up or death. In the 25 patients with locally advanced tumors, 15 (60%) are alive without evidence of recurrence and have normal pouch function with a median follow-up of 15 months. Seven patients in this group received a median three cycles of adjuvant chemotherapy, and 4 patients received chemotherapy for clinically evident recurrences. Surgical recovery did not delay the onset of adjuvant therapy in any patient, nor did problems specifically related to the presence of a continent pouch delay any cycle of chemotherapy in those patients treated for recurrent disease in either group. Only 1 patient (1.5%) experienced treatment-related toxicity related to the presence of a continent diversion. CONCLUSIONS: This experience suggests that the use of orthotopic or continent cutaneous diversions after cystectomy in patients with locally advanced bladder cancer is safe, does not interfere with the delivery of subsequent therapy, and allows most patients to anticipate normal pouch function even in the presence of recurrent disease.
Adult↗