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Biomedical subjects

R Holland

Publications and source records attributed to R Holland.

At least 127 records · Page 7Linked to original sources

The current detectability of breast cancer in a mammographic screening program. A review of the previous mammograms of interval and screen-detected cancers.

BACKGROUND: The occurrence of an interval cancer in a mammographic screening program is indicative of a suboptimum effect on mortality, because the very aim of the screening is to detect as many cancers as possible and at their earliest possible stage. In several studies, the previous screening mammograms of patients with an interval cancer were reviewed and the reasons for the "missed diagnosis" were classified into four categories: "screening error" (20-29%), "minimal sign present" (30-40%), "radiographically occult" (33-58%), or "radiographically occult at diagnosis" (occult both at previous screening and diagnosis; 7-16%). A similar procedure was followed in the Nijmegen screening project with patients recently diagnosed as having interval cancer or screen-detected cancer. METHODS: The previous screening mammograms of 40 interval and 44 screen-detected cases from the breast cancer screening program in Nijmegen were reviewed and categorized as specified above. These breast cancers were diagnosed clinically before the patient was invited to the eighth screening round (interval cancer) or were detected at the eighth screening round (screen-detected cancer). All these patients had been screened in the seventh round (1987-88). RESULTS: Thirteen percent of all cases were classified as "screening error," 38% as "minimal sign present," 43% as "radiographically occult," and 6% as "radiographically occult at diagnosis." In nearly half of the screen-detected cancers, minimal signs appeared to be present on the previous screening mammogram 2 years before the diagnosis. CONCLUSIONS: Annual instead of biennial screening may advance detection in most of the "screening error" cases as well as in some in the categories "minimal sign present" and "radiographically occult" at the previous screening. Meticulous analysis of the radiologic characteristics of the "minimal sign present" cases may very well lead to results showing that earlier detection is possible without a significant decrease in the specificity of the screening test.

Breast Neoplasms↗

Age-dependent growth rate of primary breast cancer.

BACKGROUND: Currently, there have been no reports of clear-cut beneficial effects of regular screening with mammography at a mean screening interval of 2 years in women younger than 50 years of age. It may be that, because of a higher growth rate of breast cancer, more frequent screening is necessary if any effect is to be observed in this age group. However, good quantitative estimates for the growth rate in different age groups are lacking. METHODS: The study group consisted of cancers diagnosed in women who participated in a screening program with serial mammography available. The growth rate, expressed as the tumor volume doubling time, was calculated on the assumption of exponential growth. The analysis was based, not only on the increase in tumor volume for cancers with at least two mammograms showing a measurable tumor nucleus shadow (n = 85), but also on censored values, calculated for cancers showing no growth (n = 6) and for cancers showing only a measurable tumor nucleus shadow on the mammogram at diagnosis (n = 109). In calculating these latter growth rates, the density of the breast parenchyma was taken into account. RESULTS: The median volume doubling time of the primary breast cancers diagnosed in women aged 50-70 years was 157 days (95% confidence limits, 121-204 days). This was significantly longer than in women younger than 50 years of age at diagnosis (80 days; 95% confidence limits, 44-147 days). Primary breast cancer in women older than 70 years of age at diagnosis grew even more slowly (median, 188 days; 95% confidence limits, 120-295). CONCLUSIONS: To observe a beneficial effect of screening, if any, for women younger than age 50 years, more frequent screening than in the older age group is necessary.

Age Factors↗

Transcription factor IIA stimulates the expression of classical polIII-genes.

Protein fractions containing TFIIA, a transcription factor known to be involved in transcription initiation by RNA polymerase II and 5'-regulated polymerase III genes (e.g. U6), were tested for their role in in vitro transcription of classical pol III genes. These fractions were shown to stimulate a basal transcription system, reconstituted from highly purified fractions hTFIIIB and hTFIIIC. We demonstrate that this stimulating activity isolated from HeLa cells coelutes over at least six chromatographic steps with hTFIIA. Moreover the native molecular mass and the stability of this activity against heat treatment are comparable to those of hTFIIA. Finally we show that recombinant TFIIA from Saccharomyces cerevisiae can substitute for the human factor in pol III transcription in vitro which proves that TFIIA is also involved in the efficient expression of classical pol III genes.

Humans↗

Healing process of dogs' pulpless teeth after apicoectomy and root canal filling at different levels.

Dogs' teeth with infected root canals, were submitted to apicoectomy and the root canals were filled flush or 2 mm short. In a third group the canals were left unfilled and only the access openings were closed. One hundred and eighty days after the treatment, the animals were killed and the specimens prepared for histological analysis. Repair was not observed in the teeth with unfilled root canals. The healing observed in the teeth with root canals filled flush was less complete than the healing observed when the root canals were filled 2 mm short.

Animals↗

The Australian Incident Monitoring Study. Oesophageal intubation: an analysis of 2000 incident reports.

There were 35 oesophageal intubations in the first 2000 incidents reported to the Australian Incident Monitoring Study (AIMS). These reports confirm existing impressions that misplacement of the endotracheal tube can occur in trained as well as untrained hands, and that auscultation is an unreliable test. On the other hand, the value of capnography is emphasised, with no false positives in the 16 cases in which the instrument was used. There was one false negative. Over the 4 years of the AIMS study, reports have declined in frequency. It is possible that the early detection of oesophageal intubation by capnography has altered its status to the extent that anaesthetists no longer regard it as a "critical" incident. It is highly recommended that the presence of the expected concentration of carbon dioxide in expired air be confirmed by capnography immediately after any endotracheal intubation.

Accidents↗

The Australian Incident Monitoring Study. System failure: an analysis of 2000 incident reports.

Although 70-80% of problems have some component of human error, its overall contribution to many problems may be small; studies of complex systems have revealed that up to 85% are primarily due to deficiencies in the lay-out and processes of the system. The anaesthetist has to operate in a complex system; many problems originate from deficiencies in this system. Information of relevance to system failure was extracted from the first 2000 incidents reported to the Australian Incident Monitoring Study (AIMS). A system-based deficiency directly contributed to one-quarter of problems (four-fifths if human factors are included), some aspect of the system minimized the adverse outcome in over half of all cases (four-fifths if human factors are included), and in two-thirds (three-quarters if human factors are included) a system-based strategy would have been helpful; the system was implicated in 90% of all incidents (97% if human factors are included). Regardless of whether or not all human error should be regarded as part of the "system", attempts to modify its incidence and nature have to emanate from the system. AIMS reporting pathways and the organizations involved in developing and implementing strategies to improve the system operate at four levels. Level I involves the use of AIMS reports by hospitals and group practices for audit at a local level. Level II involves AIMS participants sending forms to the AIMS central office; collated information is then sent back to contributors by newsletter. Level III involves interaction between AIMS and the major professional bodies and level IV interaction between AIMS, these bodies and a variety of national and international agencies. Over 100 topics were identified from the AIMS data for consideration at one or more of these levels. AIMS has the potential not only to play a vital practical role in the continued enhancement of the quality of anaesthetic practice, but also to provide a valuable resource for research at the increasingly important interface between human behaviour and complex systems.

Accidents↗

Attachment and conduct disorder: the Response Program.

An increasing number of youths are being identified as suffering from behavioural problems that cause difficulties in their family and peer relations which in turn reduces their chances of academic and vocational success. There is growing concern regarding their level of aggressiveness. The common diagnosis given to these disaffiliated youths is conduct disorder. To date, most treatment programs for conduct disorder have been unsuccessful. A review of recent studies indicates that the disruption of attachment may be an important feature that underlies the wide range of symptoms that are typically found in youths with conduct disorder. A community-oriented program designed to ensure long term care for these youths is described in this paper, and the findings of a six month follow-up evaluation are presented. Results indicated that communities, caregivers, and youths responded positively to the program; caregivers reported significant reductions in a broad range of psychiatric symptoms in youths, and youths reported a significant reduction in symptoms of conduct disorder.

Adolescent↗

An original stereomicroscopic analysis of the mammary glandular tree.

In the 1970s, Wellings developed and reported extensively on a technique for a three-dimensional (3D) analysis of breast lesions. Drawbacks of this subgross sampling technique were that it was laborious, rather time-consuming and only allowed prospective studies. Furthermore, the stereomicroscopic aspect of the lesions studied was not diagnostic and each sample had to be studied histologically after paraffin embedding to determine the diagnosis. The present study introduces an original method enabling the exploration of the 3D structure of the mammary glandular tree from a paraffin-embedded sample. This procedure is quicker than the Wellings' technique, permits retrospective study and enables a 3D analysis of previously identified histological structures. Stereomicroscopic aspects of non-malignant lesions such as single multiple or metaplastic cysts, adenosis, ductal-lobular hyperplasia and malignant in situ neoplasms are illustrated. Our results confirm Wellings' concept that most minimal lesions arise in the terminal ductulo-lobular units. We also show that ductal carcinoma in situ may grow continuously by extending through the glandular tree but may also have a multifocal or stepwise progression in some cases.

Breast Neoplasms↗

Influence of irrigation and intracanal dressing on the healing process of dogs' teeth with apical periodontitis.

Dogs' teeth with apical periodontitis were treated endodontically, Dakin's solution being used in an experimental group as the irrigation solution, and camphorated paramonochlorophenol as an intracanal dressing. For a second group of teeth, the irrigation solution used was physiologic saline, dry cotton only being placed into the pulpal chamber to take the place of an intracanal dressing. In a second visit, overinstrumentation and a new application of the same kind of dressing were performed, the root canals being then filled with gutta-percha cones and zinc oxide-eugenol cement. Other specimens were treated, in one visit, where physiologic saline or Dakin's solution were the irrigation solutions. The animals were sacrificed 6 months after the obturation of the root canals. Histologic exams showed better results for the experimental group where Dakin's solution and camphorated paramonochlorophenol had been used, with signs of repair characterized by newly formed cementum and bone tissue, as well as a marked reduction in size of the periapical lesions. No differences were seen in the results with physiologic saline or Dakin's solution as irrigants.

Animals↗

One-view versus two-view mammography in baseline screening for breast cancer: a review.

Two-view mammography is generally preferred as an initial screening examination because the number of missed carcinomas and false positive results in one-view mammography is considered too large. The present review was performed to assess the difference in screening quality between one- and two-view mammography. Nineteen previous studies were reviewed and differences in sensitivity as well as specificity between two-view and one-view mammography were calculated. The results ranged from -5.7% to 19.4% (median 3.9%), and 2.7% to 36.1% (median 14.8%), respectively, and indicate a higher screening quality of two-view mammography. However, in the studies considered there is a large variation in study population, screening tests used and assessment of disease outcome, which makes the numerical results less conclusive. None of the studies provided adequate information for deciding whether two-view mammography in baseline screening for breast cancer is preferable to one-view mammography. If a screening programme using one-view mammography has already achieved high sensitivity and specificity, the value of an additional craniocaudal view is only marginal.

Breast Neoplasms↗

The contribution of routine follow-up mammography to an early detection of asynchronous contralateral breast cancer.

The role of routine mammography was assessed in the early detection of asynchronous contralateral breast cancer (ACBC). The breast cancer patient populations of two cities, Nijmegen and Eindhoven, The Netherlands, which were subjected to a well-defined follow-up program, were compared. The program consisted of regular physical examination and annual mammography in Nijmegen and physical examination only in Eindhoven. From 1975 until 1987, 24 ACBC patients were detected within a group of 880 breast cancer patients in Nijmegen (3%) and, from 1971 until 1984, 14 ACBC patients within a group of 411 patients in Eindhoven (3%). In Nijmegen, eight of the 23 evaluable patients (35%) had a contralateral tumor with a histologic size smaller than 10 mm or an in situ carcinoma, compared with one of the 14 of the Eindhoven patients (7%), whereas 18 of the 24 (75%) versus eight of the 14 patients (57%) were node-negative. Thus annual mammography is very likely a contribution in the early detection of contralateral breast cancer as compared with follow-up by regular physical examination only.

Breast Neoplasms↗

Basal cell-specific and hyperproliferation-related keratins in human breast cancer.

In normal breast tissue and in noninvasive breast carcinomas, various keratin-14 antibodies were reactive predominantly with the basal/myoepithelial cell layer, although mainly in terminal and larger ducts luminal cells sometimes also were stained. A similar reaction pattern was found with an antibody directed against keratin 17, although this antibody was more often found negative than keratin 14 in the pre-existing myoepithelial cells in intraductal carcinomas. Furthermore antibodies reactive with hyperproliferation-related keratins 6 and 16 were used. One of these (LL025) was completely negative in normal breast tissue and noninvasive breast carcinomas. However 10% of the invasive carcinomas were diffusely or focally positive with this latter antibody, while in 18 of 115 cases of invasive breast carcinomas studied, a basal cell phenotype was detected. A relatively high concordance was found between the carcinomas immunostaining with the basal cell and the hyperproliferation-related keratins, but not between these markers and the proliferation marker Ki-67. This supports the conclusion that basal cells in breast cancer may show extensive proliferation, and that absence of Ki-67 staining does not mean that (tumor) cells are not proliferating.

Antibodies, Monoclonal↗