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Purpose: Increasing numbers of older women are affected by early breast cancer, because of prolonged life expectancy and the increasing incidence of breast cancer with age. The role of adjuvant therapy for this population is still a matter of debate. We reviewed the long-term outcome of a mature trial comparing endocrine treatment versus no adjuvant therapy in older women with node-positive breast cancer., Patients and Methods: From 1978 to 1981, 349 women 66 to 80 years of age with pathologically involved lymph nodes after total mastectomy and axillary clearance were randomly assigned to receive 12 months of adjuvant tamoxifen plus low-dose prednisone (p+T) or no adjuvant therapy. Three hundred twenty patients were eligible., Results: At 21 years' median follow-up, 1 year of p+T significantly prolonged disease-free survival (DFS; P =.003) and overall survival (P =.05; 15-year DFS, 10% +/- 3% v 19% +/- 3%; hazard ratio, 0.71; 95% CI, 0.58 to 0.86). When comparing competing causes of failure (breast cancer recurrence and deaths before breast cancer recurrence), p+T was far superior in controlling breast cancer recurrence (P =.0003), but the improvement was seen mainly in soft tissue sites. Conversely, patients in the p+T group were more likely to die before a breast cancer recurrence (P =.03)., Conclusion: This trial demonstrates that significant treatment benefits continue to be observed in older patients treated for 1 year with p+T. Despite issues relating to competing causes of failure, older breast cancer patients can benefit from treatment and should be considered for trials of adjuvant systemic therapy.

A constant challenge in nursing education is effectively teaching competencies and allowing students to safely practice essential nursing skills. Faculty members must develop sound methods of instruction to achieve program outcomes, which determine program effectiveness, assure professional readiness, and meet accreditation standards. To this end, the use of videotaping is suggested. Videotaping offers a safe way for students to practice skills and develop confidence prior to actual performance. This article reviews the literature on videotaping and discusses videotaping as used at Central Missouri State University baccalaureate school of nursing. Videotaping is a teaching-learning strategy used to help students develop effective communication, physical assessment, and selected psychomotor skills. Videotaping also provides students with a mechanism for detailed instructor feedback to improve performance.

Background: In postmenopausal women, a history of any fracture is an important risk factor for a future hip fracture. Whether similar findings apply to aging men remains to be established. We conducted a systematic review and meta-analysis of the literature to compare men and women with respect to the relative risk of hip fracture after a wrist or spine fracture., Methods: Studies published in full from January 1982 through September 2002 in English, French, or German were identified from the PubMed database and from reference lists of retrieved articles. We included cohort studies that reported fractures associated with minimal trauma of the wrist or spine as a risk factor for a subsequent hip fracture among (white) women and men who were fifty years old or older. Data were extracted by two independent reviewers and were checked for accuracy in a second review. Differences in assessments were resolved by consensus of the two reviewers., Results: Nine cohort studies were included in this meta-analysis: five studies were conducted in the United States and four, in Europe. After homogeneity of association was demonstrated across all studies, a fixed-effects meta-analysis was used to calculate pooled relative risks with 95% confidence intervals. Among postmenopausal women, the relative risks for a future fracture of the hip after a fracture of the wrist or spine were 1.53 (95% confidence interval, 1.34 to 1.74; p < 0.001) and 2.20 (95% confidence interval, 1.92 to 2.51; p < 0.001), respectively. In older men, these relative risks were 3.26 (95% confidence interval, 2.08 to 5.11; p < 0.001) and 3.54 (95% confidence interval, 2.01 to 6.23; p < 0.001), respectively. Fractures of the distal part of the radius increased the relative risk of hip fracture significantly more in men than in women (p = 0.002). The impact of a spine fracture, conversely, did not differ between genders (p = 0.11). Sensitivity analyses with use of random-effects methodology confirmed these findings to be robust., Conclusions: This meta-analysis suggests that a previous spine fracture has an equally important impact on the risk of a subsequent hip fracture in both genders. The prospective association between a Colles fracture and a subsequent hip fracture, however, is significantly stronger among men than among postmenopausal women. Men with a Colles fracture are at high risk for a future hip fracture and should be evaluated as candidates for preventive measures.

Aim: To assess the equity of access to dialysis treatment in New Zealand renal services., Methods: All patients with chronic renal failure assessed by NZ renal services for whom a decision regarding dialysis was made in the years 1997 and 1998 were entered into the study. Information collected included patient demographics, cause of renal failure, scores for comorbidity and activities of daily living (ADL), renal centre and dialysis decision., Results: Records were available for 823 patients, of whom 710 were offered dialysis and 676 accepted treatment. Compared with those who accepted an offer of dialysis, those not offered treatment were older (67.4 vs 53.3 years, p <0.001), and had higher scores for comorbidity (340 vs 128, p <0.001) and ADL (150 vs 32, p <0.001), but there was no difference in primary disease incidence. Patients at one centre were referred with significantly higher average comorbidity, and at two centres with significantly different ADL scores, than those referred to the reference centre. The acceptance rate was significantly lower at one centre when adjusted for age, ethnicity, gender, and comorbidity and ADL scores., Conclusions: Of all referred patients, 13.7% were not offered dialysis treatment. They had significantly higher comorbidity, and were older and more disabled than those patients offered treatment. There was one centre with a significantly lower adjusted acceptance rate.

When conventional treatment of unexplained infertility has not been successful, the next choice lies between either gonadotrophin treatment with intrauterine insemination (FSH/IUI) and IVF. Cohort studies indicate that FSH/IUI is less effective while the cost per birth is higher with IVF. The relevant evidence should come from randomized controlled trials, but the results need to be recalculated for the outcome of greatest interest, a singleton live birth. Judged by this standard, FSH/IUI is statistically superior to no treatment, but the effect is small in couples with unexplained infertility. By the same standard, IVF is superior to FSH/IUI treatment, but this benefit is achieved only at considerable cost. The evidence is not robust, comprising only a few trials which involve a minute fraction of the existing patients with unexplained infertility. Current best evidence is consistent with a progression from low-tech to high-tech treatment, but it is not convincing enough to support a rigid management protocol. A large multicentre factorial trial is needed to evaluate the relative value of existing empiric treatments for unexplained infertility.

Background: The objective of this study was to clarify the prognostic and predictive value of immunoreactivity for the cyclin-dependent kinase inhibitor p27(Kip1) in patients with early-stage breast carcinoma and to investigate its relation with clinicopathologic features and other markers., Methods: Immunoreactivity for p27 protein was analyzed on tumor slides from 461 patients who were enrolled in the International Breast Cancer Study Group (IBCSG) Trial V (median follow-up, 13 years), including 198 patients with lymph node negative disease and 263 patients with lymph node positive disease. Tumors with < 50% immunoreactive neoplastic cells were considered low expressors. Immunoreactivity for p27 was correlated with several clinicopathologic characteristics. Disease free survival (DFS) and overall survival were analyzed according to p27 immunoreactivity and treatment group., Results: In the lymph node negative population, decreased p27 immunoreactivity was associated with higher tumor grade (P = 0.001) and HER-2/neu overexpression (P = 0.04). In the lymph node positive population, low p27 expression was associated with higher tumor grade (P = 0.01), low expression of thymidylate synthase (P = 0.001), and higher Ki-67 expression (P = 0.007). DFS was not significantly different according to p27 status in either lymph node negative patients (10-year DFS: low p27 expression, 53% +/- 5%; high p27 expression, 55% +/- 5%) or in lymph node positive patients (10 year DFS: low p27 expression, 33% +/- 4%; high p27 expression, 32% +/- 4%). However, in the lymph node negative population, the benefit of one course of perioperative chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil was confined exclusively to patients with tumors that showed reduced p27 immunoreactivity (P = 0.03; test for interaction)., Conclusions: This analysis indicates that p27 immunoreactivity has little if any prognostic value in patients with early-stage breast carcinoma. However, these findings suggest that, in patients with breast carcinoma who have negative lymph node status, reduced p27 immunoreactivity is associated with HER-2/neu overexpression and may be predictive of a benefit from the early administration of adjuvant chemotherapy., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11224)

Background: The psychological processes involved in the delay between noticing breast symptoms and seeking medical care are not well understood., Methods: We evaluated 85 women referred to a specialist breast clinic prior to their clinic appointment. We assessed the relationship between delay and the type of breast symptom, immediate emotional response to the symptom, perceived risk of breast cancer, fear of breast cancer treatment, and disclosure of the breast symptom to others., Results: Delay was unrelated to demographic factors but was related to the type of breast symptom; women who had a breast lump waited a significantly shorter time period before visiting the doctor than those without a breast lump. Initial symptom distress on the discovery of the breast symptom was also significantly related to delay. Knowledge of a friend or family member with breast cancer, perceived risk of breast cancer and fear of breast cancer treatment, and disclosure of the symptom to a partner or other person were all unrelated to delay., Conclusions: The results show the importance of the type of symptom and initial emotional distress in delay and highlight the importance of widening public perceptions of breast symptoms other than breast lumps in order to reduce delay times.

Background: The number of mitoses and, thus, the proliferative capacity of a tumor is one of the most crucial variables for tumor grading. The Ki-67 nuclear antigen may be considered as an alternative to mitotic counts in grading schemes and as a single parameter that can be used in fine-needle aspirates and small biopsies., Methods: Immunohistochemistry using the anti-Ki-67 antibody MIB-1 was performed on 434 breast carcinoma specimens from the International Breast Cancer Study Group (formerly Ludwig) Trial V. Three groups based on Ki-67 percent were used to replace the mitotic counts component in the Nottingham grade (NHG) to produce the Nottingham/Ki-67 grade (NKG) and to assess Ki-67 as a single parameter., Results: In both the lymph node positive subgroup and the lymph node negative subgroup, the NKG and Ki-67 group was correlated significantly with Bloom-Richardson grade (BRG), NHG, and Nottingham type. Tumor size in the lymph node negative cohort and estrogen receptor status, progesterone receptor status, and c-erbB-2 expression in the lymph node positive cohort also were correlated significantly with NKG. Ki-67 percentage was correlated significantly with c-erbB-2 expression in the lymph node positive cohort only. NKG was similar to BRG and NHG when it was evaluated for prognostic significance. Patients with higher categoric Ki-67 percentages had worse overall and disease free survival in all groups except for the untreated, lymph node negative group., Conclusions: Ki-67 detection represents a valuable tool and is a good objective substitute for mitotic counts when used in a grading system. When it is used alone, Ki-67 detection provides valuable information, although it is necessary to combine this with other parameters in the study of core biopsies and fine-needle aspirates., (Copyright 2003 American Cancer Society.)

Icodextrin is a starch-derived, high molecular weight glucose polymer, which has been shown to promote sustained ultrafiltration equivalent to that achieved with hypertonic (3.86%/4.25%) glucose exchanges during prolonged intraperitoneal dwells (up to 16 h). Patients with impaired ultrafiltration, particularly in the settings of acute peritonitis, high transporter status and diabetes mellitus, appear to derive the greatest benefit from icodextrin with respect to augmentation of dialytic fluid removal, amelioration of symptomatic fluid retention and possible prolongation of technique survival. Glycaemic control is also improved by substituting icodextrin for hypertonic glucose exchanges in diabetic patients. Preliminary in vitro and ex vivo studies suggest that icodextrin demonstrates greater peritoneal membrane biocompatibility than glucose-based dialysates, but these findings need to be confirmed by long-term clinical studies. This paper reviews the available clinical evidence pertaining to the safety and efficacy of icodextrin and makes recommendations for its use in peritonal dialysis.

Persistent elevation of aspartate aminotransferase (AST) activity in serum due to the presence of a macroenzyme form of AST (macro-AST) may lead to diagnostic confusion in many clinical conditions, particularly those associated with chronic liver disease. We describe a case of macro-AST arising in an adult female with a false-positive hepatitis C virus (HCV) RNA test result that was not accompanied by other biochemical or histologic evidence of liver disease. The presence of macro-AST in serum was confirmed utilizing size-exclusion, high performance liquid chromatography (HPLC) and Protein G-agarose beads to precipitate immune complexes of AST and immunoglobulin G followed by centrifugation and AST activity measurements in the supernatant. A brief review of the clinical enzymology of AST and methods used to quantify serum macro-AST activity is provided.

Aims: To investigate the extent of patient delay in new patients with self-detected breast symptoms referred to a specialist breast clinic. To examine the association between delay and sociodemographic factors, the practice of breast self-examination (BSE), how the breast symptom was discovered, and personal experience of breast cancer in family and friends., Methods: Eighty five women referred to the South Auckland Health Breast Clinic completed a questionnaire and interview after arrival at the clinic and prior to their consultation with the medical specialist. Delay was measured as the time interval between initial self-detection of a breast symptom and first contact with a general practitioner (GP) for evaluation of the symptom. Analysis of patient characteristics and delay time was conducted using Pearson product moment correlations, t-test for independent samples and one way analysis of variance (ANOVA) where appropriate., Results: The median delay time between initial breast symptom detection and seeing a GP was 14 days. Of the total sample of 85 women, 40% had seen their doctor within 7 days, 52% within 14 days, 69% within 30 days, and 14% had waited over 90 days. Delay time was not significantly associated with any sociodemographic factors. No difference in delay time was found between the ethnic groups of European, Maori or Pacific women. No difference in delay was shown between those women who performed regular BSE and those who did not. However, women who discovered their breast symptom by chance or through BSE had a shorter delay time than women experiencing breast pain. Although experience of a friend or family member with breast cancer was not significantly associated with delay, there was a trend for women who had a family member with breast cancer to have a longer delay time before seeing their GP., Conclusions: This study is the first in New Zealand to investigate the extent of patient delay for women with self-detected breast symptoms and the factors influencing this delay. The majority of women saw their doctor within one month of self-detection of a breast symptom, however 14% delayed over three months before seeing their GP. Women who had a family member with breast cancer tended to respond to their breast symptom by delaying seeking medical attention, suggesting that risk perceptions of developing breast cancer may influence delay times in seeking medical help. Results from this study are taken from women referred by their GP to a specialist breast clinic. Certainly, further clarification of the factors that influence delay involving broader patient groups is vital to the development of public education initiatives aiming to encourage women to seek prompt medical evaluation of breast symptoms.

Objective: To analyze the occurrence of deliveries after spontaneous conception in patients who have discontinued unsuccessful intracytoplasmic sperm injection (ICSI) treatment., Design: Cohort follow-up study., Setting: Tertiary referral center., Patient(s): Between July 1992 and December 1993, 200 Belgian women younger than 37 years underwent 433 consecutive unsuccessful ICSI cycles with freshly ejaculated sperm and eventually discontinued their treatment., Intervention(s): Ultrasound-guided oocyte retrieval and ICSI., Main Outcome Measure(s): Delivery after 25 weeks following a spontaneous pregnancy., Result(s): The mean age at the time of the last oocyte pick-up was 31.0 +/- 3.9 years. The mean time interval between the last ICSI and the end of the follow-up period was 47.7 +/- 12.1 months. Twenty-three spontaneous pregnancies ending in delivery after 25 weeks were observed (11.5%). The cumulative delivery rate reached a plateau of 10% after 36 months of follow-up. The mean time interval (from last oocyte retrieval) for spontaneous pregnancy to occur after discontinuing ICSI treatment was 20.2 +/- 13.7 months. Proportional hazards analysis showed that delivery rate was reduced by 2.0% per year of infertility., Conclusion(s): This study suggests that duration of infertility appears to be predictive of the likelihood of live delivery after spontaneous conception following an unsuccessful ICSI treatment.

In early C. elegans embryos, signaling between a posterior blastomere, P2, and a ventral blastomere, EMS, specifies endoderm and orients the division axis of the EMS cell. Although Wnt signaling contributes to this polarizing interaction, no mutants identified to date abolish P2/EMS signaling. Here, we show that two tyrosine kinase-related genes, src-1 and mes-1, are required for the accumulation of phosphotyrosine between P2 and EMS. Moreover, src-1 and mes-1 mutants strongly enhance endoderm and EMS spindle rotation defects associated with Wnt pathway mutants. SRC-1 and MES-1 signal bidirectionally to control cell fate and division orientation in both EMS and P2. Our findings suggest that Wnt and Src signaling function in parallel to control developmental outcomes within a single responding cell.

The relationship between a physician and a biomedical firm is often important, and can be useful to both parties. However, there is a danger that the substantial resources available to a biomedical firm might sometimes be used to interfere with a physician's independent professional judgment. For the reputation and good conduct of the profession and the industry, and for the welfare of patients, it is essential that this does not happen. Total absence of communication would prejudice the undoubted good which collaboration can achieve. This paper sets out what the Royal College of Physicians currently believes are appropriate boundaries: to the acceptance of gifts; to sponsorships and subsidies for meetings; to the conduct of meetings with industry representatives; and other matters. We believe that clearly stated guidance will benefit the biomedical industry and physicians alike.

This study estimates the projected costs of multiple births resulting from assisted conception cycles (in vitro fertilization with or without intracytoplasmic sperm injection and ovarian stimulation with gonadotrophin). The estimates are modelled from the volume of services, treatment success and multiple gestation rates in recent registry data. The coverage is restricted to hospital costs associated with delivery and the trends are projected to 2000 in the United States. Sensitivity analyses tested different assumptions about per annum trends in effectiveness, multiple pregnancy rates and health costs. The national cost of in vitro fertilization cycles is US$470.2 million (£313.5 million) and the cost of the multiple pregnancies from in vitro fertilization is US$639.9 million (£426.7 million). The national cost of ovarian stimulation cycles is US$166.6 million (£111.1 million) and the cost of the multiple pregnancies from ovarian stimulation is US$257.3 million (£171.6 million). Although costs are a limited indicator of the burden of illness, the projected national cost of multiple pregnancy associated with assisted conception in 2000 is greater than the base cost of the treatment. Prevention of multiple pregnancy in assisted conception cycles should be a priority.

Periodontal diseases are Gram-negative anaerobic infections that can occur in women of childbearing age (18 to 34 years). In the present investigation we sought to determine whether the prevalence of maternal periodontal infection could be associated with preterm low birth weight (PLBW), controlling for known risk factors and potential covariates. A case-control study of 124 pregnant or postpartum mothers was performed. PLBW cases were defined as a mother with a birth of less than 2,500 g and one or more of the following: gestational age <37 weeks, preterm labor (PTL), or premature rupture of membranes (PROM). Controls were normal birth weight infants (NBW). Assessments included a broad range of known obstetric risk factors, such as tobacco use, drug use, alcohol consumption, level of prenatal care, parity, genitourinary infections, and nutrition. Each subject received a periodontal examination to determine clinical attachment level. PLBW cases and primiparous PLBW cases (n = 93) had significantly worse periodontal disease than the respective NBW controls. Multivariate logistic regression models, controlling for other risk factors and covariates, demonstrated that periodontal disease is a statistically significant risk factor for PLBW with adjusted odds ratios of 7.9 and 7.5 for all PLBW cases and primiparous PLBW cases, respectively. These data indicate that periodontal diseases represent a previously unrecognized and clinically significant risk factor for preterm low birth weight as a consequence of either PTL or preterm PROM. J Periodontol 1996;67:1103-1113., (© 1996 American Academy of Periodontology.)