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Biomedical subjects

M Waller

Publications and source records attributed to M Waller.

At least 19 recordsLinked to original sources
PubMed2006

Radiological findings of screen-detected cancers in a multi-centre randomized, controlled trial of mammographic screening in women from age 40 to 48 years.

AIM: To elucidate the mammographic findings of screen-detected cancers in women screened between 40-48 years, and to establish the frequency and nature of abnormal findings on previous mammograms in women with screen-detected cancers. METHODS: A radiology review panel consisting of three experienced breast radiologists viewed the screening mammograms in chronological order, confirming that any abnormalities detected corresponded to the cancers detected at later screens. An analysis correlating mammographic features with median invasive size and the proportion measuring less than 10 and 15mm was performed. RESULTS: Two hundred and thirty-two women had screen-detected invasive cancers with mammograms available for review. The most frequent features seen at diagnosis were spiculate mass, ill-defined mass, granular calcification, deformity and comedo calcification. Thirty-four percent of mammograms showed calcification. The mammographic sign associated with smallest median size was calcification. Calcification was also the mammographic abnormality most frequently associated with cancers <10mm in size. In total there were 147 abnormal previous screens of 87 women. The most commonly missed features were granular microcalcification, deformity and ill-defined mass. Of the missed abnormalities 20% were classified as malignant, 43% as subtle change and 32% as non-specific. CONCLUSION: Compared with older women, screen-detected cancer in younger women more commonly manifests as calcification and less frequently a spiculate mass. Calcification is the sign most frequently associated with invasive cancers <10mm in size. Calcification and deformity are the signs most frequently seen on the previous mammograms of women with screen-detected cancer.

Adult↗
PubMed2006

A UK-based investigation of inter- and intra-observer reproducibility of Gleason grading of prostatic biopsies.

AIMS: The frequency of prostatic core biopsies to detect cancer has been increasing with more widespread prostate specific antigen (PSA) testing. Gleason score has important implications for patient management but morphological reproducibility data for British practice are limited. Using literature-based criteria nine uropathologists took part in a reproducibility study. METHODS: Each of the nine participants submitted slides from consecutive cases of biopsy-diagnosed cancer assigned to the Gleason score groups 2-4, 5-6, 7 and 8-10 in the original report. A random selection of slides was taken within each group and examined by all pathologists, who were blind to the original score. Over six circulations, new slides were mixed with previously read slides, resulting in a total of 47 of 81 slides being read more than once. RESULTS: For the first readings of the 81 slides, the agreement with the consensus score was 78% and overall interobserver agreement was kappa 0.54 for Gleason score groups 2-4, 5-6, 7, 8-10. Kappa values for each category were 0.33, 0.56, 0.44 and 0.68, respectively. For the 47 slides read more than once, intra-observer agreement was 77%, kappa 0.66. The study identified problems in core biopsy interpretation of Gleason score at levels 2-4 and 7. Patterns illustrated by Gleason as 2 tended to be categorized as 3 because of the variable acinar size and unassessable lesional margin. In slides with consensus Gleason score 7, 13% of readings were scored 6 and in slides with consensus 6, 18% of readings were scored 7. CONCLUSIONS: Recommendations include the need to increase objectivity of the Gleason criteria but limits of descriptive morphology may have to be accepted.

Biopsy↗
PubMed2006

A study of Gleason score interpretation in different groups of UK pathologists; techniques for improving reproducibility.

AIMS: To test the effectiveness of a teaching resource (a decision tree with diagnostic criteria based on published literature) in improving the proficiency of Gleason grading of prostatic cancer by general pathologists. METHODS: A decision tree with diagnostic criteria was developed by a panel of urological pathologists during a reproducibility study. Twenty-four general histopathologists tested this teaching resource. Twenty slides were selected to include a range of Gleason score groups 2-4, 5-6, 7 and 8-10. Interobserver agreement was studied before and after a presentation of the decision tree and criteria. The results were compared with those of the panel of urological pathologists. RESULTS: Before the teaching session, 83% of readings agreed within +/- 1 of the panel's consensus scores. Interobserver agreement was low (kappa = 0.33) compared with that for the panel (kappa = 0.62). After the presentation, 90% of readings agreed within +/- 1 of the panel's consensus scores and interobserver agreement amongst the pathologists increased to kappa = 0.41. Most improvement in agreement was seen for the Gleason score group 5-6. CONCLUSIONS: The lower level of agreement among general pathologists highlights the need to improve observer reproducibility. Improvement associated with a single training session is likely to be limited. Additional strategies include external quality assurance and second opinion within cancer networks.

Humans↗
PubMed2005

Randomised controlled trial of mammographic screening in women from age 40: predicted mortality based on surrogate outcome measures.

A trial in the UK to study the effect on mortality from breast cancer of invitation for annual mammography from the age of 40-41, has randomised a total of 160 921 women in the ratio 1 : 2 to the intervention and control arms. All breast cancers diagnosed in the two arms have been identified, and the histology reviewed. This paper presents the results of an interim analysis using surrogate outcome measures to compare predicted breast cancer mortality in the two arms based on 1287 cases diagnosed to 31.12.1999. Due to earlier diagnosis, there is currently an 8% excess of invasive breast cancers in the intervention arm. The ratio of predicted deaths at 10 years in the intervention arm relative to the control arm, adjusted for this excess diagnosis, ranges from 0.89 (95% confidence interval (CI) 0.78-1.01) to 0.90 (95% CI 0.80-1.01). Screening from age 40 may result in a lower reduction in breast cancer mortality than that observed in other trials including women below age 50. This analysis based on surrogate outcome measures suggests that a reduction in breast cancer mortality may be observed in this trial. However, a number of assumptions have been necessary and firm conclusions must await the analysis of observed mortality from breast cancer.

Adult↗
PubMed2004

Monitoring and evaluating the performance of the UK NHS Cervical Screening Programme: monitoring performance by using cytology outcomes adjusted for population characteristics.

Current quality assurance measures used in the NHS cervical screening programme (NHSCSP) include a review of laboratories with percentages of moderate/severe and borderline/mild smear results outside the 10th-90th percentiles. The method is limited by the fact that many of these outlier smear percentages may reflect laboratories covering populations with low or high risk and/or short or long average screening intervals. This paper outlines a new approach to aid the detection of outlier laboratories, by using data collected at the primary care trust (PCT) or health authority (HA) level and making allowances for population characteristics and screening interval. The setting is the NHSCSP in England using annual data provided by HAs. Data from the screening year 2000-01 is used to illustrate the methodology, although the methods can also be applied to data at the PCT level (now being collected for 2002-03 onwards). Percentages of smear results have been analysed against a series of explanatory variables using logistic regression models. These explanatory variables include Townsend deprivation index, uptake-corrected ethnic minority composition, a measure of screening interval, area type and region. An expected percentage of borderline/mild and moderate/severe smears is estimated from the models and an observed : predicted ratio (OPRmod/sev and OPRbord/mild) calculated. Low values are suggestive of relative undercalling and high values overcalling, after allowance for population characteristics. Analysis of data for 2000-01 showed that the OPRmod/sev for the 99 HAs varied from 0.68 to 1.44. Laboratories with low percentages of moderate/severe smears, but associated with PCTs or HAs with OPRmod/sev values closer to unity may not need to be investigated as their observed rates are consistent with predicted rates based on population characteristics. The method could also be directly applied to laboratories if further information on the population covered by each laboratory were routinely collected.

Female↗
PubMed1998

Comparison of the MB/BacT system with a revised antibiotic supplement kit to the BACTEC 460 system for detection of mycobacteria in clinical specimens.

The MB/BacT system (MB/BacT) with a revised antibiotic supplement kit was compared with the BACTEC 460 system (BACTEC 460) in a test of 488 specimens submitted for mycobacterial culture from 302 patients. Twenty-four Mycobacterium tuberculosis isolates were detected by the BACTEC 460 versus 23 isolates by the MB/BacT. Mean time until detection of M. tuberculosis isolates identified by both systems was 11.9 days for the BACTEC 460 versus 13.7 days for the MB/BacT (P = 0.046). M. avium complex was detected in 12 specimens by the MB/BacT versus 10 specimens by the BACTEC 460. Only 8 of 14 (57%) M. avium isolates were detected by both systems, with a mean time until detection of 10.1 days for the BACTEC 460 and 14.2 days for the MB/BacT (P = 0.009). The BACTEC 460 and the MB/BacT detected M. gordonae in four specimens, but only a single specimen was positive by both systems. One M. fortuitum isolate and one of five M. kansasii isolates were recovered only by the BACTEC 460. The bacterial overgrowth rate was 7.0% for the MB/BacT versus 4.1% for the BACTEC 460. We found the MB/BacT to be comparable to the BACTEC 460 for mycobacterial detection. Even though time until detection with the MB/BacT was slightly longer (1.8 days longer for M. tuberculosis and 4.1 days for M. avium [mean values]) and the bacterial overgrowth rate was somewhat higher, the decreased labor, the availability of a computerized data management system, and the noninvasive, nonradiometric aspects of the MB/BacT offset these relative disadvantages and make it an acceptable alternative for use in the diagnostic laboratory.

Anti-Bacterial Agents↗
PubMed1995

Advocacy groups for breast cancer patients.

Breast cancer patient advocacy groups emerged in the 1990s to support and empower women with breast cancer. Women with cancer and oncologists tend to have divergent perspectives on how breast cancer prevention should be defined and what the priorities for research should be. As their American counterparts have done, breast cancer patient advocates in Canada are seeking greater participation in decision making with respect to research. To date they have had more input into research policy decisions than into the planning of specific projects. In 1993 the National Forum on Breast Cancer recommended that women with breast cancer should have more input into the research process; breast cancer patient advocates will continue to actively pursue this objective.

Breast Neoplasms↗
PubMed1994

Radioiodine therapy during an unknown remained pregnancy and radiation exposure of the fetus. A case report.

PURPOSE: A papillary thyroid cancer staged as p T2N3M0 was treated in a 28-year-old woman by surgery, percutaneous radiation and radioiodine therapy (10 single applications ranging from 3300 to 3840 MBq with an average radioactivity of 3350 MBq). In the course of radioiodine therapy an attended gynaecologist found the woman pregnant in the 24th week of gravidity. Because the pregnancy remained unknown until this time radioiodine was administered during the 2nd and the 22nd week of pregnancy, each time 3700 MBq. Because of the risk of malformations this pregnancy was interrupted after consultation and taking the recommendations of the so-called Danish rule as a basis for the decision. METHODS: Ovarian and fetal doses as well as the fetal thyroid exposure has been estimated as exactly as possible using data at hand. The fetus was studied with regard to possible consequences of radiation exposure by pathologico-anatomical, cytogenetic and radiobiological methods. RESULTS: The accumulated ovarian doses resulting from the radioiodine administrations before pregnancy was estimated to 2200 mGy, the fetal doses resulting from the two administrations during pregnancy to 250 mGy in each case, and the fetal thyroid dose to between 90 Gy and 900 Gy for the 2nd therapy during pregnancy. In the fetus the most important changes were found within the thyroid gland (atrophy, sclerosis, subcapsular interstitial fibrosis, necrobiosis of follicular epithelial cells). On the other hand, analysing the karyotype using dermal fibroblastic cell cultures, no radiation induced chromosomal aberrations were seen. CONCLUSION: Despite of all precautionary measures it seems to be conceivable that in extremely rare cases--in our 35-year experience with more than 20,000 radioiodine therapies only the present case--an early pregnancy may remain undetected. The results of these studies give useful information on effects to be expected as a result of radioiodine application during certain periods of pregnancy. They may help to extend the radiobiological knowledge with regard to the fetal period.

Abortion, Therapeutic↗
PubMed1993

Zinc loss in sweat of athletes exercising in hot and neutral temperatures.

Zinc (Zn) loss from sweat of 9 male and 9 female athletes exercising under hot (35 degrees C, HE) and neutral (25 degrees C, NE) conditions was examined. Subjects exercised at 50% VO2max on a cycle ergometer for 1 hr during each trial. Cell-free sweat samples were analyzed for Zn by atomic absorption spectrophotometry. There was a significant interaction of time, gender, and temperature for whole-body sweat rates (WBSR). WBSR for males were higher during both trials and at each time. WBSR from the second half of exercise were higher than those from the first half for both sexes and temperature conditions. Sweat Zn concentration was higher in the NE than in the HE, but when the sweat rates were included, the rate of Zn loss was no different between HE and NE. Zn concentration of the sweat for the first half of exercise was over twice that of the second half. Sweat Zn concentration of the men was no different than that of the women; however, due to greater sweat rate, men had significantly higher Zn losses. Although total Zn losses are estimated to be relatively low compared to the RDA, exercise at moderate intensities may increase surface Zn losses.

Adult↗
PubMed1993

Dehydration testing and the diagnosis of Menière's disease: case report.

A 34-year-old female presented to our clinic with complaints of hearing loss, tinnitus, and severe rotational vertigo. A test battery including complete audiometric testing, auditory brainstem response (ABR) audiometry, electronystagmography (ENG), electrocochleography (ECoG), and dehydration testing was performed. Monitoring of hearing sensitivity, speech understanding, and ECoG responses following administration of a dehydrating agent were sensitive measures of cochlear function and confirmed the diagnosis of Meniere's disease. The induced changes also contributed to the therapeutic measures recommended.

Adult↗
PubMed1993

Daily subcutaneous administration of recombinant human erythropoietin (rhEPO) in peritoneal dialysis patients: a European dose-response study.

In a prospective randomized open multicenter study, 107 anemic (Hct < = 28%) peritoneal dialysis (PD) patients were treated with s.c. rhEPO daily. The mean observation period was 299 days (range 14-479 days). Patients were randomly assigned to 3 groups with different initial doses: 5 U/kg (G5), 10 U/kg (G10), 20 U/kg (G20). Initial doses were maintained for at least 8 weeks unless the target Hct (30-35%) was achieved earlier. The weekly increase of Hct was significantly (p < 0.05) dose-dependent: 0.19% in G5, 0.5% in G10 and 0.94% in G20. In case of insufficient response (< 0.5% per week), the dose was doubled every 4 weeks. Final doses on achieving the target Hct ranged from 5 to 40 U/kg (median 20 U/kg). The dose was then reduced to 50% and adjusted individually. The median maintenance dose was 9.9 U/kg/day. No tendency towards higher blood pressure or intensification of antihypertensive treatment was observed. When rhEPO is administered daily, 10 U/kg/day (70 U/kg weekly) is the recommended starting dose. The need for higher doses used in unsatisfactory response, should lead to further examination to rule out iron deficiency and other reasons for non-response. The median maintenance dose reported here is the lowest published in the literature for PD patients and seems to be linked to the daily injections.

Anemia↗
PubMed1990

[Secondary malignomas following radiotherapy of breast carcinoma: a case report].

Numerous cases of radiation-induced malignoma have been described, where the radiation osteosarcomas are placed in the foreground. In this article a case of a female patient is described who developed not only a radiation-induced osteosarcoma but also a thyroid gland carcinoma after a previous postsurgical mamma carcinoma whereby the irradiation dose of the radiation sarcoma is about 64 Gy and for the thyroid gland carcinoma about 12 Gy.

Adenoma↗
PubMed1987

Reproducibility of auditory brain-stem evoked responses as a function of the stimulus, scorer and subject.

The reproducibility of auditory brain-stem evoked response (ABR) measurements was determined in a series of studies. ABRs were recorded from pre-term (32 and 36 weeks) newborns, term newborns, and adults to 3 different stimuli. Records were scored blindly with no knowledge of the subject, stimulus eliciting the response, or other records by that subject. Two scorers (inter-scorer reliability) and a single scorer over time (intra-scorer reliability) could score records using explicit criteria with a high degree of agreement. In contrast variability between replicate records to the same stimulus from the same subject was considerable. Intra-subject variability was not strongly affected by the age of the subject but was a function of the eliciting stimulus (the low intensity and fast repetition rate stimuli elicited more variable responses than loud, slow stimuli) and the wave measured (wave I latency was significantly more variable than the other measurements). Healthy, term newborns were studied to investigate the reproducibility of ABRs in the first few days after birth. There was a rapid reduction in ABR latency in the first 6-12 h after birth and a more gradual reduction thereafter. The prolonged latencies observed immediately after birth were associated with an elevation in ABR threshold. The reduction in latency was observed in vaginal and cesarean deliveries. These same effects were observed for amplitude of the ABR, but the trends were generally not significant. Despite the large changes in ABR latency within the first few days after birth, ABR latencies in response to some stimuli were significantly correlated between sessions separated by all intervals tested, ranging from 2 h to 2 days.

Adult↗
PubMed1984

Effective sterilization of a plastic film rack isolator with 'Alcide'.

A 'use challenge' test of the sterilizing ability of 'Alcide' was devised against a 'cocktail' of 8 selected bacteria and 2 fungi. The organisms were used to coat the inside of an isolator prior to sterilization with 'Alcide' solution. After exposure to the solution for 24 h, no organisms could be recovered from the surfaces of the isolator. No operator discomfort was observed during preparation of the 'Alcide' solution.

Animals↗
PubMed1983

Factors influencing bonding of bromelain agglutinators and their Fab fragments.

The complex of bromelain agglutinators and their homologous Fab fragments is dissociated by gel chromatography under certain conditions. When albumin is present as a source of thiol groups, Fab fragments previously treated with N-ethylmaleimide (NEM) will dissociate from the agglutinators (fluid phase). If anti-Rh Fab fragments are bound to Rh-positive erythrocytes, the agglutinates are not dissociated by thiols (cellular phase). Prior to erythrocyte sensitization, the agglutinator site on Fab fragments can be blocked by thiol-disulfide exchange. Once the Fab fragments are coated on erythrocytes, the agglutinator site is more readily available than it was prior to sensitization, as evidenced by inhibition with 0.01 M NEM. The differences between the bonding characteristics of the fluid phase and the cellular phase and the influence of mercaptoalbumin on the agglutinator-Fab complex suggest that the agglutinators are not antibodies.

Antibodies, Anti-Idiotypic↗