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Biomedical subjects

B Dijkstra

Publications and source records attributed to B Dijkstra.

13 recordsLinked to original sources

The prevention of breast cancer.

BACKGROUND: Despite advances in the early detection and treatment of breast carcinoma, the mortality and morbidity rates associated with this disease remain high. Primary prevention, therefore, offers the best chance of making a major impact on outcome. METHODS: The aim was to review the rationale, current stage of development and adverse effects of the strategies involved in the primary prevention of breast carcinoma. A review of the literature was undertaken by searching the MEDLINE database for the period 1966-2002 without language restrictions. RESULTS AND CONCLUSION: Currently, the only agent to have general approval for chemoprevention of breast carcinoma is tamoxifen. Women who derive the greatest benefit in terms of risk reduction from tamoxifen are premenopausal with a 5-year Gail risk factor of more than 1.66 per cent, postmenopausal with a 5-year Gail risk factor of more than 3 per cent, and postmenopausal without a uterus. In these specific subgroups, tamoxifen should be considered for the chemoprevention of breast carcinoma. Raloxifene, retinoids, aromatase inhibitors and cyclo-oxygenase 2 inhibitors require further clinical investigation before adoption in this context. Surgical intervention should largely be limited to those women who have a BRCA1 or BRCA2 mutation.

Antineoplastic Agents, Hormonal↗

The role of molecular staging in malignant melanoma.

AIMS: To review the role of tyrosinase RT-PCR in the detection of clinically occult metastatic disease, both within the regional lymph nodes and peripheral blood of patients with malignant melanoma. Secondly, to assess whether the detection of such minimal disease has clinical implications for patients with melanoma. METHODS: A review of the literature was undertaken by searching the MEDLINE database for the period 1966-2002 without any language restrictions. Keywords included 'Molecular staging of melanoma', 'Reverse transcription polymerase chain reaction', 'Malignant melanoma' and 'Tyrosinase'. CONCLUSIONS: Detection of tyrosinase RT-PCR positive cells within the peripheral blood correlates with the clinical stage of malignant melanoma, the primary tumour thickness and other known prognostic indicators. Positive tyrosinase RT-PCR is associated with a reduction of disease-free survival and overall survival. Current studies demonstrate a higher rate of recurrence in RT-PCR positive patients with clinical stage II and III disease. Implications of a positive result within the regional lymph nodes are less well defined. A significant correlation has been demonstrated between positive results and increasing primary melanoma thickness. However, a large number of false-positive results have been demonstrated, due to benign naevi and schwann cells, which may hamper any statistically significant conclusions being reached.

Clinical Trials as Topic↗

Anti-human epidermal growth factor receptor 2 monoclonal antibody therapy for breast cancer.

BACKGROUND: Advances in molecular biology and improved understanding of tumour biology have led to the development of novel treatments for cancer. Trastuzumab (Herceptin; Genentech, San Francisco, California, USA) is a monoclonal antibody directed against human epidermal growth factor receptor (HER) 2 protein, which is overexpressed in a wide variety of human cancers, including 20-30 per cent of human breast cancers. HER-2 plays an important role in oncogenic transformation, tumorigenesis and metastatic spread. Overexpression is associated with a poor prognosis and predicts a poor response to several treatment modalities. METHOD: Literature relating to the monoclonal antibody was identified by a Medline literature search and by cross-referencing from the references of seminal articles on the subject. Four major clinical trials were identified and reviewed. RESULTS AND CONCLUSION: In clinical trials approximately 15-20 per cent of patients with HER-2-overexpressing tumours benefited from treatment with trastuzumab. In sensitive patients the antibody appeared to have intrinsic anticancer activity when given as a single agent. In combination chemotherapy it appeared to act synergistically with other agents. Ongoing research is evaluating trastuzumab in combination with numerous standard chemotherapy regimens and with other novel chemotherapeutic agents. Clinical trials have also revealed several serious side-effects of monoclonal antibody therapy. Most notable is an unpredictable cardiotoxicity, especially when used in combination with anthracycline-based chemotherapy regimens.

Anthracyclines↗

Pregnancy-associated breast cancer.

Twelve premenopausal women diagnosed with pregnancy-associated breast cancer between May 1985 and October 1999 were reviewed. Three patients were diagnosed in the first trimester of pregnancy, five in the second trimester, and three during the third trimester. There was one patient who was five weeks postpartum. At the time of diagnosis nine patients had lymph node involvement and two of these had metastatic disease. Four patients received primary chemotherapy. The remainder had surgery. Five patients died, two had metastatic disease at time of diagnosis, median survival was 31 months. There were three fetal deaths, one termination and two during primary chemotherapy. The diagnosis of breast cancer during pregnancy is difficult. Presentation is usually at an advanced stage. Surgery can be safely performed during pregnancy and adjuvant chemotherapy should not be postponed until after delivery.

Adult↗

Parathyroid localisation--current practice.

In patients with primary hyperparathyroidism, neck exploration by an experienced parathyroid surgeon is curative in excess of 95% of cases. Considerable efforts have been devoted to improving parathyroid imaging. New radionucleotide agents and scanning procedures have markedly improved the success rate of localization studies with subsequent development of minimally invasive surgical techniques. In this article we review the different localization techniques and their current role in parathyroid surgery for primary hyperparathyroidism

Humans↗

Protective effect of appendectomy on the development of ulcerative colitis: matched, case-control study.

PURPOSE: Appendectomy and cigarette smoking have been suggested to reduce the chance of developing ulcerative colitis. A case-control study was undertaken to determine the relative incidence of appendectomy in patients with ulcerative colitis. METHODS: This case-control study examined the incidence of appendectomy in patients with ulcerative colitis and patients attending an orthopedic outpatient clinic. RESULTS: Of 100 patients with ulcerative colitis, 75 pairs were matched for age, gender, and cigarette smoking. The ulcerative colitis group had an appendectomy rate of 8 percent (6/75), compared with 21 percent in the control group (P = 0.018). The odds ratio was 3.5 (95 percent confidence interval, 1.15-10.6). CONCLUSIONS: No previous study has examined the effect of appendectomy, controlling for cigarette smoking. This study confirms that appendectomy protects against or reduces the chance of development of ulcerative colitis. A possible immunological explanation for this effect is advanced.

Adolescent↗

Management and outcome of popliteal artery aneurysms in a New Zealand provincial centre.

BACKGROUND: The experience of management of popliteal artery aneurysms (PAA) in a provincial centre is described. METHODS: Patients were identified from vascular audit, and case notes were reviewed retrospectively. RESULTS: There were 17 patients with 23 PAA over 12 years. All patients were male, with a mean age of 73 years. Other aneurysms were present in 77% of patients, 59% had bilateral PAA and 41% had an associated abdominal aortic aneurysm (AAA). Mean follow-up was 3 years, 3 months (range, 1 month - 7 years). There were 11 acute procedures, and 12 elective. Reconstruction with bypass and ligation of the aneurysm was performed in all elective and 9/11 acute procedures. Of the 21 bypass procedures, 17 used autologous vein, three used GoreTex, and 1 composite graft. There were two PAA that were not reconstructable. All the vein grafts remained patent during the time of follow-up, but two of the three GoreTex grafts failed. Successful reconstruction was achieved in 11/12 elective and 9/11 acute cases. All grafts in the acute group remained patent during the time of follow-up (mean, 3.5 years), in the elective group 11/12 grafts (91%) remained patent (mean follow-up, 2.5 years). CONCLUSIONS: An excellent outcome was achieved in both elective and acute procedures. Autologous vein grafts appear to give better results than synthetic grafts. Due to the high incidence of multiple aneurysms, screening for other aneurysms is suggested.

Aged↗

The alpha/beta hydrolase fold.

We have identified a new protein fold--the alpha/beta hydrolase fold--that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta sheet, not barrel, of eight beta-sheets connected by alpha-helices. These enzymes have diverged from a common ancestor so as to preserve the arrangement of the catalytic residues, not the binding site. They all have a catalytic triad, the elements of which are borne on loops which are the best-conserved structural features in the fold. Only the histidine in the nucleophile-histidine-acid catalytic triad is completely conserved, with the nucleophile and acid loops accommodating more than one type of amino acid. The unique topological and sequence arrangement of the triad residues produces a catalytic triad which is, in a sense, a mirror-image of the serine protease catalytic triad. There are now four groups of enzymes which contain catalytic triads and which are related by convergent evolution towards a stable, useful active site: the eukaryotic serine proteases, the cysteine proteases, subtilisins and the alpha/beta hydrolase fold enzymes.

Acetylcholinesterase↗

Value of sentinel node biopsy in the management of breast cancer.

AIMS: To determine the rate of detection of the sentinel node using both blue dye and radioisotope, and the accuracy with which the sentinel node histology reflects the nodal status of the axilla in a series of patients with clinically node-negative breast cancer. PATIENTS AND METHODS: During a 32-month period from May 1998 to December 2000, 73 patients with clinically node-negative breast cancer underwent sentinel node biopsy immediately followed by formal axillary lymphadenectomy. The sentinel node(s) was identified using a combination of lymphoscintigraphy, blue dye and an intraoperative hand-held gamma probe. RESULTS: The mean age of the 73 patients was 58 years (range 32-83 years). Twenty-six per cent (19/73) had previous surgical/excisional biopsy. Pre-operative lymphoscintigraphy was positive in 74% (54/73) of patients. Combination of blue dye and radioisotope was better than either method in isolation for identifying the sentinel node, yielding a success rate of 96% (70/73). A total of 32 cases proved to have positive nodal disease on histological examination. In 44% (14/32) of patients, the sentinel node was the only positive node. Forty-seven per cent (15/32) of patients in whom the sentinel node was positive also had positive nodes in the axillary nodal basin. There were 3/32 false negative cases, giving a false negative rate of 9.4%. CONCLUSION: Sentinel node biopsy will have a role in the management of breast cancer. However, widespread adaptation of this technique awaits the results of prospective, randomised trials.

Adult↗

Safety guidelines for radiolocalised sentinel node resection.

BACKGROUND: Sentinel node radiolocalisation procedures are associated with low levels of radiation exposure. Radioactive material is present in the operating theatre and pathology laboratory. In most hospitals there are no official regulations in place for sentinel node radiation exposure. AIM: To establish guidelines on the safety of sentinel node mapping with emphasis on the management of radioisotopes. METHODS: The current literature regarding sentinel node procedures and radiation safety was reviewed. EU and US radiation safety regulations were scrutinised. RESULTS: Personnel involved in sentinel node procedures are exposed to low levels of radiation. These levels are not high enough to require designated radiation workers in the theatre and pathology laboratory. Awareness of radiation safety and certain precautions during the procedure and processing of the specimen can further reduce levels of exposure. CONCLUSION: Although low levels of radiation exposure are associated with sentinel node procedures, awareness of radiation safety and adherence to regulations, along with close interdepartmental co-operation, are recommended for further reduction in radiation exposure and safe application of this technique.

Breast Neoplasms↗

Tamoxifen as the primary treatment in elderly patients with breast cancer.

BACKGROUND: With the increasing incidence of breast cancer in patients over 70 years, there is interest in the best therapeutic approach. AIMS: To review the management of breast cancer in elderly women and to identify the factors involved in the decision to treat patients with tamoxifen as first line therapy. PATIENTS AND METHODS: Between 1986 and 1999, 302 female patients aged > or = 70 years presented with primary breast cancer, of whom 219 underwent surgery, 79 received tamoxifen as first line treatment and four received primary radiotherapy. A retrospective review was performed on these 79 patients and the outcome recorded. RESULTS: Of these 79 patients, data was available on 68. Follow-up ranged from one to 63 months (median 17 months). Co-morbidity was the principal reason for choosing first line tamoxifen therapy in 61% and patient preference in 11%. Tumour size was less than 5cm in 51%. In 25% tumour size decreased, in 24% it remained stable and in 27% it increased in size following tamoxifen therapy. Additional treatment was prescribed for 33% of patients. CONCLUSION: In the authors' experience, for those elderly patients suffering considerable co-morbidity or who refuse surgical intervention, tamoxifen is an acceptable alternative.

Aged↗

The value of sentinel node mapping for staging melanoma.

One of the most important prognostic features of malignant melanoma is the involvement of regional lymph nodes. Sentinel lymph node biopsy (SLNB) is increasingly used to stage melanoma in order to avoid lymph node dissection in patients who clinically have no lymph node involvement. We present a prospective study of 27 patients who underwent SLNB from November 1999. Lymphoscintigraphy was done on the day of surgery, and SLNB guided by blue dye and/or gamma probe performed. A sentinel node was identified in all 27 patients, mean age 46 years. The mean Breslow thickness was 1.63mm. Excision of 1-3 sentinel nodes (mean 1.5) was performed. In 3/27 patients metastatic disease was detected in the sentinel node, 2 patients had therapeutic lymph node dissections, and one had chemotherapy. There were no major complications. SLNB is a valuable technique for staging melanoma, however impact on overall survival requires longer follow up.

Adolescent↗