Outcome of a structured surveillance programme in women with a familial predisposition for breast cancer.

We aimed to prospectively evaluate the efficacy of a multi-modal surveillance programme for the early detection of familial breast cancer. Ultrasound, mammography and breast magnetic resonance imaging were evaluated in 413 women who participated in a prospective study with a median follow-up of 2.2 years (range 1-6.75 years). Of these, 49 women carried a BRCA mutation, 203 were at high and 161 at moderate risk. Breast carcinomas diagnosed within the programme were compared with 297 carcinomas previously observed in the risk group and 7894 carcinomas documented in the regional cancer registry within the same time period. Overall, 41 breast carcinomas and no interval carcinoma were detected. The detection rates averaged 107.2/1000 for mutation carriers with highest rates between 20 and 39 years of age, 45.8/1000 for high-risk women with highest rates between 40 and 49 years of age and 23.9/1000 for moderate-risk women with highest rates between 50 and 74 years of age. Overall, 82.8% of the breast carcinomas were node negative and 85.4% pre-invasive or smaller than 2 cm. In comparison, of breast carcinomas detected outside the programme only 47.8% were node negative (P=0.0005) and 43.8% pre-invasive or smaller than 2 cm (P<0.000 01). Of those gathered in the local cancer registry 55.7% were node negative (P=0.004) and 47.6% pre-invasive or smaller than 2 cm (P<0.000 01). Our data indicate that (1) there is a strong correlation between breast cancer detection rates, risk status and age at disease onset and (2) a multi-modal surveillance programme can detect early-stage hereditary breast carcinomas.

Outcome of muscle and bone development in congenital heart disease.

Muscles and bones of patients with congenital heart disease (CHD) are subject to various potentially deleterious influences during growth. The aim of the present study was to analyse the outcome of bone and muscle parameters in adolescents and young adults with a spectrum of CHD. Bone and muscle parameters of the forearm were examined at two standard sites, 4% and 65%, in 29 adolescents and young adults with CHD, aged 14-24 years, by quantitative computed tomography. For the entire study population, bone and muscle parameters did not deviate significantly from the reference values except for age- and gender-corrected body height (ASDS-height: -0.6+/-1.2, p=0.01). Both age- and gender- and height- and gender-corrected (HSDS) abnormal bone mass (BMC) was found at the distal radius in patients with Fontan repair (ASDS-BMC4%: -1.5+/-0.9, p=0.008; HSDS-BMC4%: -1.2+/-1.0, p=0.05) and in those in NYHA class III (ASDS-BMC4%: -1.3+/-0.4, p=0.001; HSDS-BMC4%: -1.4+/-0.5, p=0.004). There was minimal overlap between Fontan patients (n=6) and NYHA class III (5 Fontan patients were in NYHA class I or II). In conclusion, most patients with CHD show a normal muscle and bone development in proportion to their reduced body height. Further follow-up is required to determine whether patients in a worse clinical status (NYHA III) and those with single ventricle physiology are at increased risk of osteoporosis and fractures.

Nonlinear progression of Parkinson disease as determined by serial positron emission tomographic imaging of striatal fluorodopa F 18 activity.

BACKGROUND: The investigation of disease progression provides important information on the dynamics of cell death in Parkinson disease (PD). OBJECTIVE: To determine the progression of dopaminergic impairment in PD with the use of positron emission tomography (PET). DESIGN: Longitudinal prospective cohort study with a follow-up period of 64.5 +/- 22.6 months (mean +/- SD). SETTING: University hospital. PATIENTS: A consecutive sample of patients with PD (N = 31; age at symptom onset, 53.6 +/- 11.3 years) with a wide range of symptom duration and severity at the time of study entry. INTERVENTIONS: Investigation by serial fluorodopa F 18 ([(18)F]fluorodopa) PET as a marker for striatal dopaminergic function. MAIN OUTCOME MEASURES: Changes in caudate and putaminal [(18)F]fluorodopa influx constant (K(i)) values. RESULTS: In patients with PD, the decline rate of putaminal [(18)F]fluorodopa K(i) correlated inversely with disease duration before study inclusion (r = -0.46, P = .01) and positively with baseline K(i) values (r = 0.44, P = .01), indicating a negative exponential loss of dopamine neurons. Annual disease progression rates ranged from 4.4% in the caudate nucleus to 6.3% in the putamen. A mean preclinical period of 5.6 +/- 3.2 years was calculated with symptom onset at a putaminal K(i) threshold of 69% from controls. Assuming nonlinear progression kinetics, the required sample size to prove neuroprotection with the use of [(18)F]fluorodopa PET was found to increase strongly with the preceding symptom duration of study subjects. CONCLUSION: These data suggest that the neurodegenerative process in PD follows a negative exponential course and slows down with increasing symptom duration, contradicting the long-latency hypothesis of PD.

How thrombus model impacts the in vitro study of interventional thrombectomy procedures.

RATIONALE AND OBJECTIVES: Numerous experimental models are used to investigate the effectiveness of thrombectomy devices. We aimed to study the systematic effects of different in vitro thrombus models on the results of experimental thrombectomy and examined how thrombi formed in vitro and ex vivo differ. METHODS: Three variables involved in human in vitro thrombogenesis were investigated: spontaneous or thrombin-induced clotting, age (1 or 5 days old), and storage temperature (4 degrees C or 21 degrees C). The fibrin content of in vitro and fresh or old ex vivo thrombi was measured by histologic studies. Ten experiments were performed with each of 8 different in vitro thrombus types using (1) ultrasound thrombolysis, (2) Oasis thrombectomy, (3) Amplatz thrombectomy, and (4) Straub-Rotarex catheters. Thrombus weight was measured after standardized treatment. RESULTS: The fibrin content was markedly lower in all in vitro than in fresh and old ex vivo thrombi. In vitro thrombus type had no impact on the effectiveness of ultrasound thrombolysis and Amplatz thrombectomy. Thrombogenesis type affected Oasis and Straub-Rotarex catheter use. Storage temperature had a systematic impact on the outcome of Oasis thrombectomies. CONCLUSION: The fibrin content of in vitro thrombi differs substantially from that of fresh and old ex vivo human thrombi. Experimental conditions may systematically impact experimental evaluation of thrombectomy procedures. In vitro thrombi with thrombin-induced thrombogenesis should be favored for use in thrombectomy experiments.

Translocation of iris pigment epithelium in patients with exudative age-related macular degeneration: long-term results.

PURPOSE: To report the practicability and efficacy of autologous iris pigment epithelium (IPE) translocation in exudative age-related macular degeneration (ARMD) over 1 year. METHODS: The consecutive interventional case series included 56 patients with exudative ARMD. During vitrectomy the submacular neovascular membrane (CNV) was removed and IPE cells, harvested from a peripheral iridectomy, were injected into the submacular space. Included were patients with subfoveal occult CNV (11 eyes), classic CNV (10 eyes), mixed CNV (17 eyes), CNV with a pigment epithelial detachment (13 eyes) or CNV with a hemorrhage (5 eyes). Outcome measures were visual acuity, foveal fixation, size of CNV and rate of recurrence based on fluorescence angiographic imaging. RESULTS: All patients underwent successful surgical removal of the CNV with consecutive subretinal IPE injection. Visual acuity was better than 20/100 in 19 patients preoperatively and in 18 patients postoperatively. A visual acuity of 20/100 or less was found in 37 patients preoperatively and in 38 patients postoperatively. Mean preoperative visual acuity (1.0+/-0.3 logMAR units) did not change significantly after 1 year (1.0+/-0.3 logMAR units). Ten eyes (18%) developed a recurrence. Fixation within the surgically denuded area could be demonstrated in 25 eyes (45%). CONCLUSIONS: Autologous IPE translocation for ARMD over one year can preserve foveal function on a low level, but cannot improve visual acuity. IPE translocation is technically feasible with a low rate of complications. Continued research seems justified to improve functional outcome.

The influence of tutor qualification on the process and outcome of learning in a problem-based course of basic medical pharmacology.

Limited access to expert tutors is a problem that can be addressed by using tutors from different stages of medical or non-medical (under-, post-) graduate education. To address whether such differences in qualification affect the results of process evaluation by participants or their learning outcome (exam results), we analysed the data of a 4-year prospective study performed with 787 3rd-year medical students (111 groups of 5-10 participants) taking an obligatory problem-based learning (PbL)-course of basic pharmacology. We compared peer tutors (undergraduate medical students, >/=4th year), non-expert (junior) staff tutors (physicians, pharmacists, veterinarians, biologists, or chemists during postgraduate education), and expert (senior) staff tutors (completed postgraduate education). Evaluation scores related to PbL gave the highest values for senior staff-led groups. The tutor's performance score of peer-led groups did not differ from those of staff-led groups, but the score obtained from groups tutored by junior staff was lower than that obtained with senior staff tutors. Students' weekly preparation time tended to be lower in peer-led groups, while learning time spent specifically on exam preparation seemed to be increased compared to PbL-groups of staff tutors. As a putative confounding variable, tutors' experience in coaching PbL-groups was also investigated. Groups led by experienced tutors, defined as tutors with at least one term of previous PbL tutoring, were found to have significantly higher evaluation scores. Interestingly, neither tutors' subject-matter expertise (peer students, junior staff, or senior staff) nor their teaching-method expertise showed any influence on PbL-groups' mean test scores in a written exam. This indicates that the effect of tutor expertise on the learning process is not associated with a difference in learning outcome when just factual knowledge is assessed by traditional methods.