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Biomedical subjects

R Holland

Publications and source records attributed to R Holland.

At least 91 records · Page 5Linked to original sources

Electropotential evaluation as a new technique for diagnosing breast lesions.

A new approach, termed the Biofield test, may have the potential to augment the process of diagnosing breast cancer. This technique is based on the analysis of skin surface electrical potentials measured by an array of specially designed sensors which are placed on the breasts. Measurements are recorded noninvasively and then analyzed using pattern recognition algorithms to produce an immediate and objective assessment of breast tissue in vivo. Initial clinical trials suggests that the test can achieve a sensitivity of approximately 90% and a specificity of 40-50%, which indicates that the test might be useful for excluding cancer when it is, in fact, absent. Although research to date has focused on the differential diagnosis of suspicious breast lesions, future applications could include breast cancer screening, close surveillance and diagnosis of recurrent cancers in breasts previously treated with conservative therapy, and monitoring the effectiveness of breast cancer therapies. Improvements and new applications are expected to occur as additional research and validation in actual clinical settings is performed.

Algorithms↗

The treatment of conduct disorder: perspectives from across Canada.

OBJECTIVE: To provide a synopsis of treatment programs for conduct-disordered children in Canada. METHOD: Five groups of authors from British Columbia, Ontario, Quebec, and New Brunswick describe their approaches to the treatment of children with conduct disorder. RESULTS: All programs emphasize the needs to use multimodal treatment schemes, including day and short-term residential care, and to base programs on identified factors associated with the development of conduct disorder. CONCLUSION: Specific forms of treatment of conduct disorder are promising but are often hampered by social and political agendas.

Adolescent↗

Mammographic screening after the age of 65 years: evidence for a reduction in breast cancer mortality.

We evaluated whether regular mammographic screening of women aged 65 years or older affected breast cancer mortality. In Nijmegen, a population-based screening program for breast cancer was started in 1975, with biennial mammography for women aged 35-64 years. Since 1977, elderly women have also been participating. For the present case-control study, women were selected who were over 64 years of age at the most recent invitation. Eighty-two of them had died from breast cancer. For these cases, 410 age-matched population controls were selected. The ratio of breast cancer mortality rates of the women who had participated regularly (ie., in the 2 most recent screening rounds prior to diagnosis) vs. the women who had not participated in the screening was 0.56 (95% CI = 0.28-1.13). The rate ratio was 0.45 in the women aged 65-74 years at the most recent invitation (95% CI = 0.20-1.02), whereas it was 1.05 in the women aged 75 years and older (95% CI = 0.27- 4.14). While the breast cancer survival rate of the non-participant patients was fairly equal to that of patients from a control population, the underlying incidence rate of breast cancer was higher in the participants than in the non-participants. Therefore, we conclude that bias was present, but that it had decreased our effect estimate. The real reduction in breast cancer mortality due to regular screening will be even larger. Regular mammographic screening of women over age 65 (at least up to 75 years) can reduce breast cancer mortality by approximately 45%.

Aged↗

Age-specific sensitivities of mammographic screening for breast cancer.

The sensitivity of the mammographic screening test in the biennial screening program of Nijmegen is assessed by analyzing the occurrence of interval cancers, i.e. cancers surfacing clinically in the interval between a negative screening examination and the subsequent scheduled examination. The difference between the observed number of interval cancers and the expected number of clinically manifest cancers in the absence of screening for the interval period reflects the number of cancers detected by screening. The expected number should be limited by the number of those cancers that were not detectable at the time of the screening examination because their size was under the threshold of mammographic detectability (5 mm). In contrast to other sensitivity studies we took these 'fast growing' cancers into consideration, the numbers of which are estimated in each of the six-month periods of the two-year interval using age-specific tumor volume growth rates for three age groups: < 50, 50-69, and > or = 70 years. In patients under age 50, the sensitivity was 64% for cancers which would become clinically manifest within one year after screening. This sensitivity was lower than those obtained from the 50-69 and > or = 70 age groups, being 85% and 80%, respectively. For cancers that would become clinically manifest 12-18 months after screening, sensitivity decreases to 22% in the under age 50 group, and to 56% and 65% in the two above age 50 groups, respectively. We conclude that even when adjusted for growth rate, the mammographic screening test has a poor performance in the under age 50 group.

Adult↗

An evaluation of an ambulatory manometry system in assessment of antroduodenal motor activity.

While abnormalities in antroduodenal motor function have been documented in both organic and "functional" disorders, controversy surrounds the ideal manometric technique. We sought, therefore, to evaluate a digital solid-state ambulatory system. Sixteen normal volunteers underwent 24-hr recordings of antroduodenal motility. Following catheter placement, a standardized meal was ingested in the laboratory; thereafter, subjects were ambulatory and assumed normal diet and activities. The system was well tolerated; subjects reported that it did not affect their usual activities. Migrating motor complex (MMC) activity was identified in each subject (mean frequency: 4.1 MMCs/24 hr, range 1-8); on average 1.9 (range 0-4, frequency 0.1/hr) occurred while awake and 2.1 (range 0-5, 0.3/hr, P < 0.05 vs awake) during sleep. The fed response was evaluated by calculating a motility index (MI) at 30-min intervals from 30 min before to 120 min following meal ingestion. Postprandially, MI was maximal during the first 30 min following meal ingestion: MI (mean +/- SD) 30 min before vs 30 min after meal in the antrum: 4.16 +/- 1.42 vs 5.33 +/- 0.72 (P < 0.05), duodenum: 4.04 +/- 0.80 vs 4.57 +/- 0.47 (P < 0.05), respectively. None of the other postprandial intervals were significantly different from baseline. There was no significant difference in MI between the standard and ad libitum meals. Retrograde catheter migration (mean 5.6, range 1-10 cm) occurred in relation to all meals: as a consequence, antral recordings were lost following 60% of all meals, thereby limiting meaningful analysis of the antral fed response. We conclude, firstly, that while an ambulatory antroduodenal manometry system is well tolerated and reliably records duodenal motility, postprandial catheter migration limits antral recordings, and, secondly, that a motility index calculated during the first 30 min following an ad libitum meal accurately reflects the fed motor response.

Adult↗

Apical leakage after root canal filling with an experimental calcium hydroxide gutta-percha point.

This study was an in vitro analysis of the apical seal of root canals filled with an experimental calcium hydroxide gutta-percha point. One hundred and ten recently extracted human permanent teeth with a single root were used. The root canals were biomechanically prepared, and some received a dressing of calcium hydroxide for 7 days. Root canals not dressed were filled by the lateral condensation technique with either regular gutta-percha or calcium hydroxide gutta-percha points. The dressed root canals were filled with the same sealers and regular gutta-percha points. The specimens were placed into a 2% methylene blue dye solution under vacuum, and the apical leakage was linearly evaluated. The experimental groups with calcium hydroxide dressing and the one with calcium hydroxide gutta-percha points exhibited significantly (p < 0.05) less leakage than the groups filled with regular gutta-percha points. The results obtained indicated that calcium hydroxide gutta-percha points produced an improvement in the apical sealing quality of the root canal filling.

Analysis of Variance↗

Purification of tributyrin esterase from Lactococcus lactis subsp. cremoris E8.

A tributyrin esterase was purified from Lactococcus lactis subsp. cremoris E8 using FPLC chromatography. This was the major esterase activity observed in strain E8 and was associated with a single protein with a subunit molecular mass of 29 kDa and a holoenzyme of molecular mass 109 kDa. The enzyme was active against tributyrin and p-nitrophenyl butyrate. The N-terminal sequence of the enzyme was determined. The enzyme had a pH optimum in the neutral range, was stable on freezing at -20 degrees C, and had a half life of 1 h at 50 degrees C.

Amino Acid Sequence↗

Mammographic screening after the age of 65 years: early outcomes in the Nijmegen programme.

We studied outcomes of mammographic screening in women older than 65 years. In 1975, breast cancer screening was started in Nijmegen, The Netherlands, for women aged 35-65 years. Since 1977, approximately 7700 older women have also been invited for biennial one-view mammography. This report is based on ten screening rounds from 1975 to 1994. The results of the subsequent screening rounds in the age groups 65-69 years, 70-74 years and 75 years and older were: participation rates 55%, 39% and 15%; screen-detected cancer rates 5.6%, 6.9% and 7.8%; interval cancer rates 2.0%, 1.8%, and 3.5%; and predictive values of referral 62%, 64% and 62% respectively. In all age groups, screen-detected patients had smaller tumours and a lower prevalence of axillary lymph node involvement than unscreened patients. Our conclusion is that, in women aged 65 years, and older, breast cancer can be detected at an earlier stage by mammographic screening.

Age Factors↗

Prognosis of younger and older patients with early breast cancer.

The use of mammography in recent years has resulted in an increase in the detection of small breast cancers. The beneficial effects of early detection on breast cancer mortality seem to differ with age. To obtain more insight into this matter we studied the long-term prognosis of patients with early invasive breast cancers (T1) in three age groups: 144 patients of age 40-49, 402 patients of age 50-69 and 192 patients 70 years or older at diagnosis. In all age groups, patients with a tumour of 1 cm or less have a longer breast cancer specific survival than patients with a tumour larger than 2 cm. The survival advantage in the case of tumours of a size rounded to 1.5 cm compared with tumours larger than 2 cm in the under age 50 group was marginal (and not significant). However, older patients with tumours of this size do have a significantly improved survival. It is more difficult to improve survival in younger patients through early detection, partly because of an apparent early metastatic potential of their tumours. A reduction in breast cancer mortality might be expected in women younger than 50 years of age only if a substantial proportion of the invasive cancers are detected before their size exceeds 1 cm.

Adult↗

Fluvoxamine in prevention of relapse in bulimia nervosa: effects on eating-specific psychopathology.

In a double-blind, placebo-controlled study of 72 patients with bulimia nervosa treated successfully with inpatient psychotherapy, the efficacy of fluvoxamine in maintaining improvement was tested. Fluvoxamine and placebo, respectively, were given over a period of about 15 weeks (2-3 weeks inpatient titration phase, 12 weeks outpatient relapse-prevention [maintenance] phase). The variables assessed concerned bulimic behavior and other aspects of eating disorders, global status, depression, anxieties, obsessive-compulsive behavior, and other aspects of psychopathology. Because the dropout rate was relatively high (N = 27 [33%]) and because it was considerably higher in the fluvoxamine group (19 out of 37 subjects), analyses were performed on the intent-to-treat sample (ideally including all 72 subjects). Results of the completer sample analyses (including only those subjects who finished the study) are briefly presented for comparison. In both the intent-to-treat and the completer analyses, the following scales showed fluvoxamine to have a significant effect in reducing the return of bulimic behavior: (1) self-ratings: Eating Disorder Inventory (EDI)-bulimia, urges to binge in previous week and the number of actual binges in the previous week; (2) expert ratings: Psychiatric Status Rating Scales for Bulimia nervosa, Structured Interview for Anorexia and Bulimia nervosa (SIAB)-"total score," SIAB-subscale "fasting," and SIAB-subscale "vomiting." Two further variables (EDI-total score and SIAB-subscale "bulimia") showed the superior relapse prevention effects of fluvoxamine compared with placebo for the completer sample, while they did not reach significance for group-by-time interactions in the intent-to-treat sample. During a final, short (4-week) off-medication phase, no effect of the discontinuation of medication was observed.

Adolescent↗

Long term breast cancer screening in Nijmegen, The Netherlands: the nine rounds from 1975-92.

STUDY OBJECTIVE: To assess the performance of breast cancer screening in different age categories over two decades. DESIGN: Important determinants of reduced breast cancer mortality such as attendance, mammography performance, cancer detection, and disease stage were recorded. SETTING: Nijmegen, The Netherlands, 1975-92. SUBJECTS: Since 1975 more than 40,000 women aged 35 years and older have been invited biennially for breast screening in a population based project in Nijmegen. MAIN RESULTS: Rates of attendance, referral, detection, and disease stage were calculated, as well as the specificity of screening mammography and the predictive value of referral and biopsy. From round 3 onwards, the attendance rate of women younger than 50 years stabilised at 70%, in women of 50-69 years it was 62%, and in women aged 70 and over it was 22%. In these three age categories, the referral rates of a positive screening mammography per 1000 screened women were 4.9, 6.2, and 11.8, respectively. Specificity rates were between 99% and 100%. Current predictive values of referral were high: in the specific age categories 39%, 59%, and 68% of the referred women had cancer. Detection rates remained fairly stable over the rounds 4-9, at 1.9, 3.6, and 8.0 cancers per 1000 screened women. In the two year period between screening the numbers of interval cancers per 1000 screened women were 2.2, 2.2, and 2.9, for the three age categories respectively. With regard to invasive cancers detected during screening, the percentage of small tumours (< or = 20 mm on the mammogram) was 84% in each age category. For women younger than 50 years, the proportion of intraductal carcinoma in all the cancers detected at screening was 40%, while it was 15% in the other age categories. CONCLUSION: Throughout the nine rounds, the screening outcomes were found to be adequate, particularly considering the high specificity rate and the predictive value of referral without the interference of a low detection rate. Although the occurrence of interval cancers seemed high, it was similar to other screening programmes. Despite a relatively low referral rate, the ratios of screen detected versus interval cancer cases were favourable. Well organised screening programmes can achieve good mammography results without too many false positives. It is important that women continue to participate in a screening programme because cancer can still be detected even after several successive negative screening examinations.

Adult↗

Bovine hereditary zinc deficiency: lethal trait A 46.

Bovine hereditary zinc deficiency, also referred to as Adema disease, is an autosomal recessive disorder which results in inadequate amounts of zinc being absorbed from the gastrointestinal tract and leads to a number of clinical abnormalities. Using semen from a homozygous affected bull and obligate heterozygote cows in embryo transfer studies, 7 offspring were obtained. These included 5 affected calves and 1 heterozygous carrier; the seventh calf died within 48 hours of birth undiagnosed. One unaffected, unrelated bull calf was raised as a control. All the calves were raised and maintained under similar management conditions designed to minimize secondary complications that would obscure the clinical and biochemical observations of a zinc deficient state. The first clinical manifestation of zinc deficiency was diarrhea, followed by skin lesions, poliosis, and a decreased ability to sustain a suckle reflex. Trace mineral analysis of plasma blood samples revealed that plasma zinc concentrations of all the calves were normal at birth; however, they gradually declined in affected calves over the course of 3-8 weeks postpartum to below 0.5 ppm. Biochemical analysis of serum samples showed alkaline phosphatase activity consistently paralleled changes in the plasma zinc concentrations. The oral administration of zinc acetate caused a reversal of all clinical, biochemical, and histologic abnormalities in affected calves. The study of these affected calves allows further insight into the biological role of zinc as well as provides an animal model for the continued investigation of the human homologue acrodermatitis enteropathica.

Acrodermatitis↗

Infection control.

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Anesthesiology↗

Effect on breast cancer mortality of biennial mammographic screening of women under age 50.

The effects on breast cancer mortality seen after 16 years of biennial screening of younger women are assessed in this prospective cohort study. Since 1975 some 13,500 women, aged 35-49 in 1975, were invited to participate in the Nijmegen screening programme comprising a mammographic examination every 2 years. By the end of 1990, 75 women had died of breast cancer out of the 332 cases diagnosed after the start of the screening project. Women from the same birth cohort, living in Arnhem, a neighbouring city with a comparable population and without a screening project, were used as controls. In this city, 74 breast cancer deaths out of 284 cases occurred during the same period. In Nijmegen, after 16 years of follow-up, breast cancer mortality showed a non-significant reduction of 6% (95% confidence interval: 32% reduction, 29% excess). In the relevant period, after a time lag of 10 years from the start of the programme, this reduction rose to 20% (95% confidence interval: 48% reduction, 23% excess). No reduction in breast cancer mortality was observed in the first decade of screening. For a later period, a shift towards a reduction emerges, but the data are as yet inconclusive.

Adult↗

Tumor necrosis factor (TNF)-alpha activates c-raf-1 kinase via the p55 TNF receptor engaging neutral sphingomyelinase.

TNF-alpha mediates proliferation, functional activation and apoptotic death of cells depending upon its concentration and target cell type. The signaling pathways used by TNF-alpha to mount these responses are, at present, not completely understood. We report here that TNF-alpha promotes dose- and time-dependent phosphorylation and activation of the c-raf-1 kinase engaging the type I p55 TNF receptor (TNF-R). c-raf-kinase activation was duplicated by an agonistic monoclonal antibody directed against the p55 TNF-R. Moreover, ectopic expression of the human p55 TNF-R in murine pre-B 70Z/3 cells was sufficient to confer c-raf-1-kinase activation by human TNF-alpha. By inhibiting intracellular activation of acidic sphingomyelinase (SMase) and by using deleted forms of the type I TNF-R it was shown that the neutral, but not the acidic SMase, participated in TNF-alpha-mediated phosphorylation and activation of the c-raf kinase. TNF-alpha-induced transcriptional activation of a heterologous promoter construct harboring the AP-1 binding site was also mediated by the type I p55 TNF-R. In this case the initiation of transcription required the same cytoplasmic domain as that responsible for activation of c-raf-1 kinase and was liberated in the presence of a dominant negative mutant of c-raf-1.

Animals↗