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Biomedical subjects

R Holland

Publications and source records attributed to R Holland.

At least 19 recordsLinked to original sources
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Breast tumors: comparative accuracy of MR imaging relative to mammography and US for demonstrating extent.

PURPOSE: To evaluate the comparative accuracy of magnetic resonance (MR) imaging relative to mammography and ultrasonography (US) for assessing the extent of breast tumors. MATERIALS AND METHODS: Histologic results and preoperative imaging findings (mammography, US, MR imaging) were analyzed regarding tumor size and multifocality of 61 tumors in 60 women undergoing mastectomy for carcinoma. RESULTS: In 10% of cases, the index tumor was not seen at mammography. With US, 15% of the index tumors were not recognized, while MR imaging missed 2% of the index tumors. On mammographic and US images, tumor size was underestimated significantly (P < .005), by 14% and 18%, respectively, while MR imaging showed no significant difference in size compared with that found in a pathologic evaluation. Mammography showed 31% of the additional invasive lesions, while US showed 38% and MR imaging showed 100%. CONCLUSION: MR imaging was the most accurate of the three preoperative imaging modalities in assessing the size and number of malignant lesions in the breast.

Adult↗
PubMed1994

Efficacy of mammographic screening of the elderly: a case-referent study in the Nijmegen program in The Netherlands.

BACKGROUND: Only a few small studies have been conducted to examine the usefulness of mammographic screening in elderly women. These studies suggest that the screening-related reduction in breast cancer mortality rates is less than the estimated 20%-40% reduction observed for women aged 50-70 years at the time of their first screening. PURPOSE: We have studied the efficacy of continued mammographic screening for breast cancer of elderly women within our screening program. METHODS: In 1975, a breast cancer screening program was started in the city of Nijmegen. The Netherlands. During each biennial screening round, approximately 30,000 women aged 40 years and older were personally invited to participate. Single-view mammography was administered. The present study was conducted using a case-referent design. In order to be eligible for inclusion in this study, women had to have been invited to participate in the mammography screening program at least twice, with the most recent invitation having occurred when each woman was 65 years or older. The cases studied comprised 33 women in this group who had died of breast cancer at some point during 1977 through 1988. Referents were matched for age at last invitation to screening prior to the diagnosis of breast cancer and for the number of previous invitations to screenings. Five referents were randomly selected for each case. Breast cancer mortality rate ratios (RR) were calculated for several categories of attendance to the screening. RESULTS: The RR of those who attended the last screening versus those who failed to do so was 0.58 (95% confidence interval [CI] = 0.24-1.41); for women aged 65-74, the RR was 0.34 (95% CI = 0.12-0.97) and for women aged 75 or over, 2.87 (95% CI = 0.62-13.2). The RR of those who attended the screening before and after the age of 65, relative to those who attended before 65 only, was 0.26 (95% CI = 0.05-1.32). CONCLUSION: Although self-selection bias was present in our data, it was not likely to be responsible for the beneficial effect in women aged 65-74 at the time of invitation to screenings. It probably was responsible for the reversed RR (RR > 1) in the group of women 75 years and older. IMPLICATION: Continuation of mammographic screening until at least the age of 75 years may lead to a reduction of breast cancer mortality among elderly women.

Age Factors↗
PubMed1994

Age-specific effectiveness of the Nijmegen population-based breast cancer-screening program: assessment of early indicators of screening effectiveness.

BACKGROUND: The benefits of mammographic screening for breast cancer are not clear for women less than 50 years old. PURPOSE: Our aim was to evaluate the effectiveness of breast cancer screening in different age groups. METHODS: A mammographic breast cancer-screening program with a 2-year screening interval has been under way in Nijmegen, The Netherlands, since 1975. After eight rounds, more than 40,000 women have been invited to participate. All breast cancer cases diagnosed in the invited population, whether detected by screening or clinically, have been considered in this study. The age groups are younger than 50 years, 50-69 years, and 70 years or older at last invitation before diagnosis. Our assessment of the effectiveness of screening is based on the proportion of screen-detected cancers among all cancers and on the disease stage at diagnosis. RESULTS: For women younger than 50, compliance was 75%, and 37% (85/230) of the cancers were detected by screening. The age group 50-69 years had a compliance of 65% with 48% (288/595) of cancers detected by screening, and the group 70 years or older had a 25% compliance with 35% (108/305) of cancers detected by screening. The sizes of the cancers detected by screening were smaller than those detected clinically for all age groups. The age group under 50 showed no substantial difference in the proportion of positive axillary lymph node status between screening-detected and clinically diagnosed cancers, while among older women, the proportion of lymph node involvement was substantially higher for clinically detected cases. A significantly lower frequency of advanced stages was observed in screen-detected compared with clinically diagnosed cancers for women 50 years of age or older (P < .001) but not in women under 50 (P = .35). CONCLUSIONS: No positive effect of the biennial screening program is apparent for women under age 50. For women aged 50 and above, the screen-detected cancers have a more favorable stage distribution than clinically diagnosed cancers, a prerequisite for a reduction in breast cancer mortality.

Adult↗
PubMed1994

Introduction of continuous regional techniques for postoperative paediatrics patients: one years' experience from two hospitals.

AIM: To review the use, safety and efficacy of continuous regional techniques in children and neonates. METHODS: The records of all children who received postoperative continuous regional analgesic techniques during the year 1992 at the Starship Children's Hospital and Waikato Base Hospital were reviewed. In both post operative care units orders, procedures and protocols were standardised. RESULTS: A total of 80 children received these techniques. Patients were cared for in high dependency nursing areas. The two techniques used were epidural and interpleural analgesia. Epidural: The majority (68) had epidural catheters and of these 13 infants were in their first month of life. Major problems occurred in six (9%) of children receiving epidurals--two blocks failed completely, two suffered subarachnoid puncture, one had respiratory depression and one developed a foot-drop. The blockade failure and subarachnoid punctures occurred early in the establishment of paediatric epidural analgesic services. Minor problems included the necessity for morphine supplementation in three (4%) children, leaks about the catheter in seven (10%), nausea and vomiting in six (9%), two (3%) developed pruritus and one block was ceased because of concerns expressed about masking symptoms of compartmental compression. Interpleural: twelve patients were treated with this technique. One neonate suffered a convulsion. CONCLUSION: Major continuous regional techniques in paediatric patients are effective, but because of potential complications, there is a requirement that these blocks be performed, monitored and cared for by staff experienced and trained with these procedures.

Anesthesia, Conduction↗
PubMed1994

Effect of root canal status on periodontal healing after surgical injury in dogs.

This study was carried out to observe if the status of the root canal might influence the healing process of surgically prepared experimental periodontal lesions. Forty tooth roots from four dogs were divided into four different groups: a) root canals with vital pulps, b) root canals open to the oral environment, c) root canals infected and filled with zinc oxide eugenol cement, and d) root canals infected and filled with calcium hydroxide. By means of a surgical intervention, a cavity was prepared in the medium portion of the roots. Six months later, the specimens were removed and prepared for histological analysis. The results, which were submitted to statistical analysis, showed that the status of the root canals influenced the healing process of the experimental periodontal lesions. In the groups where the root canals were filled, calcium hydroxide gave the best results. In the group with root canals left open to the oral environment, resorption of the dentin of the experimental cavities, was the most obvious observation. However, it did not prevent the repair process, only slowed it down.

Analysis of Variance↗
PubMed1994

MR characterization of suspicious breast lesions with a gadolinium-enhanced TurboFLASH subtraction technique.

PURPOSE: To assess the utility of gadolinium-enhanced dynamic magnetic resonance (MR) imaging with turbo fast low-angle shot (TurboFLASH) technique in the differentiation of benign from malignant lesions of the breast. MATERIALS AND METHODS: Contrast material-enhanced MR images were obtained at intervals of 2.3 seconds for 2 minutes. After the first four images were obtained, contrast medium was intravenously injected within 10 seconds. Lesions that enhanced within 11.5 seconds after the aorta opacified were regarded as malignant. Lesions that enhanced more than 11.5 seconds after the aorta were regarded as benign. A centrifugal pattern of enhancement was regarded as a sign that a lesion was benign. RESULTS: Eighty-seven lesions were evaluated. Histologic examination showed 65 lesions were malignant and 22 were benign. Gadolinium-enhanced TurboFLASH imaging had a sensitivity of 95%, a specificity of 86%, and an overall accuracy of 93% in differentiating benign from malignant lesions. CONCLUSION: Gadolinium-enhanced TurboFLASH imaging is a valuable method in the examination of breast lesions suspected of being malignant.

Breast↗
PubMed1994

Long term outcome of an attachment-based program for conduct disorder.

There is increasing concern among professionals and the public about the level of violence and antisocial behaviour among our youth. This has been coupled with confusion and a sense of helplessness about which types of interventions are most effective in responding to these difficulties. Some professionals and advocacy groups are calling for tougher disciplinary responses to violence and antisocial behaviour, including changes in the Young Offenders Act. Yet, such interventions are rarely effective in producing the desired reductions in these behaviours. Other professionals have called for better forms of treatment. However, few treatments have been shown to be effective in bringing about long term reductions either in aggressive behaviour or in the concomitant psychological difficulties experienced by these youths. In this paper, a description is presented of an approach to understanding conduct disorder that focuses on attachment as an organizing principle of behaviour and affect. Also, a description is presented of a community-oriented program that is based on attachment theory, as well as the results of the program evaluation at six, 12 and 18 months following discharge. The findings replicate and extend earlier findings reported by Holland et al (1) on the effectiveness of this approach.

Adolescent↗
PubMed1994

Ductal carcinoma in situ: a proposal for a new classification.

Details of a proposed new classification for ductal carcinoma in situ (DCIS) are presented. This is based, primarily, on cytonuclear differentiation and, secondarily, on architectural differentiation (cellular polarisation). Three categories are defined. First is poorly differentiated DCIS composed of cells with very pleomorphic, irregularly spaced nuclei, with coarse, clumped chromatin, prominent nucleoli, and frequent mitoses. Architectural differentiation is absent or minimal. The growth pattern is solid or pseudo-cribriform and -micropapillary (without cellular polarisation). Necrosis is usually present. Calcification, when present, is amorphous. Second, at the other end of the spectrum is well-differentiated DCIS, composed of cells with monomorphic, regularly spaced nuclei containing fine chromatin, inconspicuous nucleoli, and few mitoses. The cells show pronounced polarisation with orientation of their apical border towards intercellular spaces usually resulting in cribriform, micropapillary and clinging patterns, although a solid pattern of well-differentiated DCIS also occurs. Necrosis is uncommon. Calcifications, when present, are usually psammomatous. The third category, intermediately differentiated DCIS, is composed of cells showing some pleomorphism but not so marked as in the poorly differentiated group. There is, however, always evidence of polarization around intercellular spaces, although this is not so pronounced as in the well-differentiated group. These two criteria, cytonuclear differentiation and architectural differentiation, have been found to be more consistent throughout a DCIS lesion than previously employed criteria of architectural pattern or the presence or absence of necrosis.

Breast Neoplasms↗
PubMed1994

Microcalcifications associated with ductal carcinoma in situ: mammographic-pathologic correlation.

Because of the large scale use of mammography, the incidence of ductal carcinoma in situ (DCIS) has been increased fivefold to sixfold. The majority of these tumors are detected by mammographically significant microcalcifications. Their mammographic and histologic appearance is rather characteristic for the different types of DCIS. Microcalcifications associated with poorly differentiated DCIS appear on the mammogram as either linear, often branching, or as granular microcalcifications which are usually coarse. They correspond to the amorphous type calcifications on histology. Microcalcifications associated with well-differentiated DCIS appear on the mammogram usually as multiple clusters of fine granular microcalcifications, which correspond to the clusters of laminated, crystalline calcifications on histology. The distribution of DCIS is typically unicentric and segmental. In a series of 119 mastectomies, only a single case had a multicentric distribution. Based on the extent of microcalcifications, mammography usually underestimates the size of DCIS; although this discrepancy is less than 2 cm in 80% to 85% of the cases if state-of-the-art mammography, including magnification views, is used. Close co-operation between radiologist, pathologist, and surgeon is essential for the optimum management of patients with DCIS.

Breast Neoplasms↗