Diet manipulation and prevention of aging, cancer and autoimmune disease

PURPOSE OF REVIEW: Dietary supplementation and other dietary regimens have become increasingly popular in the US population. Information regarding how different dietary constituents interact when consumed simultaneously is needed. This review examines the recent literature on how different dietary constituents may interact physiologically when consumed in combination. Furthermore, the potential human relevance of calorie restriction and nonclassical function of vitamin E is discussed. RECENT FINDINGS: Long-term calorie restriction in monkeys has shown similar beneficial effects as has been shown in rodents. Limited calorie restriction studies in humans have shown promise in reducing the incidence of heart disease and breast cancer. The combination of calorie restriction and omega-3 fatty acids may be a more potent antiinflammatory diet than either regimen alone. The type of fiber that is most protective against colon cancer may be dependent on the type of dietary fat consumed simultaneously. Vitamin E derivatives that possess no antioxidant activity may be potent inhibitors of cancer, but not normal, cell growth. SUMMARY: Dietary modification has shown its greatest beneficial effect when started prior to or immediately after the onset of disease. Also, understanding how the subtypes or isoforms of nutrients function is important since their physiological effects may be drastically different. It is important to understand the entire dietary profile of an individual when making dietary recommendations because one nutrient, or dietary ingredient, may enhance or cancel out the beneficial effects of another dietary ingredient.     

Small-fenestra cochleostomy for MED-EL electrode

Although the physical characteristics of cochlear implant electrode arrays vary substantially among manufacturers, many otolaryngologists have adopted a surgical cochleostomy technique that is similar for all of them. The objective of this study was to compare the insertion dynamics of the MED-EL Flex electrode using two different sized cochleostomies. Six temporal bones were prepared with either a small fenestra ( approximately 1.0 mm) or a large fenestra ( approximately 1.8 mm) cochleostomy and the electrodes inserted under video fluoroscopy. The resulting video images were analysed for depth of insertion as well as dynamic flexion of the electrode during insertion. The study demonstrated that small-fenestra cochleostomies have a 'pool cue' or 'billiard cue' effect, stabilizing the electrode cable and resulting in easier and deeper insertions. This is achieved by limiting the buckling of the electrode just inside the cochleostomy site.     

Can students' reasons for choosing set answers to ethical vignettes be reliably rated? Development and testing of a method

Although ethics is an important part of modern curricula, measures of students' ethical disposition have not been easy to develop. A potential method is to assess students' written justifications for selecting one option from a preset range of answers to vignettes and compare these justifications with predetermined 'expert' consensus. We describe the development of and reliability estimation for such a method -- the Ethics in Health Care Instrument (EHCI). Seven raters classified the responses of ten subjects to nine vignettes, on two occasions. The first stage of analysis involved raters' judging how consistent with consensus were subjects' justifications using generalizability theory, and then rating consensus responses on the action justification and values recognition hierarchies. The inter-rater reliability was 0.39 for the initial rating. Differential performance on questions was identified as the largest source of variance. Hence reliability was investigated also for students' total scores over the nine consensus vignettes. Rater effects were the largest source of variance identified. Examination of rater performance showed lack of rater consistency. D-studies were performed which showed acceptable reliability could nevertheless be obtained using four raters per EHCI. This study suggests that the EHCI has potential as an assessment instrument although further testing is required of all components of the methodology.     

Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer

Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients.     

Validation of the Quintero staging system for twin-twin transfusion syndrome

OBJECTIVE: To validate an established staging system for twin-twin transfusion syndrome. METHODS: Prospective observational study in a tertiary referral fetal medicine center of 52 consecutive cases of twin-twin transfusion syndrome. Each pregnancy was assessed longitudinally for a variety of prognostic factors including fetal biometry, amniotic fluid volume, arterial and venous Doppler sonogram abnormalities, and the presence of hydrops. Data were used to determine stage at diagnosis and first treatment, and worst stage throughout pregnancy. Perinatal outcome was assessed by stage. Management comprised serial amnioreduction, septostomy, selective reduction, or delivery, alone or in combination. RESULTS: Median gestation at presentation and first treatment were both 21 weeks (range 14-34 and 15-34), and at delivery it was 29 weeks (range 16-40). Sixty-three percent of pregnancies (33 of 52) were at least stage III at presentation. Forty-five percent of pregnancies (22 of 49) progressed to a more advanced stage. Overall survival was 47% (47 of 100), with no difference between donor and recipient fetuses (40% [20 of 50] versus 54% [27 of 50] [chi(2) P =.5]). Survival rates were 58% (15 of 26), 60% (six of ten), 42% (20 of 48), 43% (six of 14), and 0% (none of two) for stages I-V, respectively, with no significant influence of stage at presentation on survival. Survival was poorer where stage increased, versus decreased (27% [12 of 44] versus 94% [17 of 18] chi(2) P <.001). Kaplan-Meier survival curves indicated that staging at presentation identified pregnancies at greater risk of earlier rather than later gestational perinatal loss. CONCLUSION: The Quintero staging system did not distinguish good from bad outcome at presentation, and thus should be used with caution in guiding initial management of twin-twin transfusion syndrome. However, prognosis was influenced by a change in stage, and pregnancies progressing to higher stage disease were at increased risk of earlier perinatal loss. Staging may thus be more useful in monitoring disease progression.     

Serial aggressive platelet transfusion for fetal alloimmune thrombocytopenia: platelet dynamics and perinatal outcome

OBJECTIVES: Our purpose was to describe the fetal loss rate and platelet dynamics in fetal alloimmune thrombocytopenia managed by serial platelet transfusions. METHODS: Retrospective analysis over 10 years of consecutive pregnancies affected by fetal alloimmune thrombocytopenia requiring in utero platelet transfusions. RESULTS: There were 2 perinatal losses in 12 pregnancies managed by 84 platelet transfusions. One was obviously procedure related from exsanguination despite platelet transfusion. The attributable procedure related fetal loss rate was 1.2% per procedure but 8.3% per pregnancy. The median rate of fall in fetal platelet count per day after transfusion was lower at the placental cord insertion (n = 54) 40.5 x 10(9)/L (range, 5.4-96.1 x 10(9)/L) compared with that at the intrahepatic vein (n = 30) 50.9 x 10(9)/L,(range, 29.5-91 x 10(9)/L) (P = .0009). CONCLUSION: Pooling our results with those previously published yields a cumulative risk of serial weekly transfusions of approximately 6% per pregnancy, indicating the need for development of less invasive approaches.     

X-linked inheritance of Dandy-Walker variant

We report a family in which two sisters had three male fetuses with isolated Dandy-Walker variant (DWV) diagnosed on antenatal ultrasound. DWV is one part of a spectrum of abnormalities related to Dandy-Walker malformation (DWM) which commonly occur in association with other anomalies with or without chromosome abnormalities. The majority of cases are sporadic but rare reports of recurrence in siblings exist. This is the second report suggesting that isolated DWM/DWV can be inherited as an X-linked recessive trait.     

Essence of care involving nursing students

In 2001 the Department of Health published The Essence of Care, which aims to improve patient care by identifying and measuring good practice benchmarks. Educators and trainers need to integrate such initiatives into course curricula and develop innovative approaches to enable the contribution of nursing students. This paper describes the initial phase of collaborative work between the University of Southampton's School of Nursing and Midwifery and the local NHS trust which was designed to achieve these aims, including the development of a good practice evaluation tool which students complete at the end of their clinical placements.