Assessment of vascular reactivity in rat brain glioma by measuring regional blood volume during graded hypoxic hypoxia

While morphological and molecular events during angiogenesis in brain glioma have been extensively studied, the functional properties of tumour vessels have yet received little attention. We have determined changes in regional blood volume (BV) during graded hypoxic hypoxia using susceptibility contrast magnetic resonance imaging in a model of rat brain glioma. Nine anaesthetised and ventilated rats with C6 glioma were subjected to incremental reduction in the fraction of inspired oxygen (FiO(2)): 0.35, 0.25, 0.15, 0.12, 0.10 and reoxygenation to 0.35. At each episode, BV was determined in peritumoral, intratumoral and contralateral regions. Baseline BV values (FiO(2) of 0.35) were higher in peritumoral than in the contralateral and intratumoral regions. Progressive hypoxia resulted in a graded increase in BV in contralateral and peritumoral regions. At FiO(2) of 0.10, BV increases were comparable between these two regions: 49+/-22% (s.d.) and 28+/-17% with respect of control values, respectively. These BV changes reversed during the reoxygenation episode. By contrast, the intratumoral region had a significant increase in BV at FiO(2) of 0.10 only, with no evidence of return to the basal value during reoxygenation. Immunohistochemical staining of alpha-smooth muscle actin confirmed reactivity of vessels in the peritumoral region. Our findings indicate that peritumoral vessels present a vascular reactivity to hypoxia, which is comparable to that of nontumoral vessels. A method is thus available for noninvasively demonstrating whether any particular vascular modifying strategy results in the desired outcome in terms of tumour blood volume changes.     

Towards a prevention of dementia?

Many studies have shown that high blood pressure and, to a lesser extent, other vascular risk factors could be the target of interventions aiming to reduce the incidence of dementia. Two large controlled trials have demonstrated that blood pressure lowering drugs have a significant effect on the risk of dementia including Alzheimer's disease. On another hand, large epidemiological studies have shown associations between different vascular factors and dementia. Overall, these data suggest that interventions aiming to reduce the level of vascular risk factors might prevent dementia. The expected benefit of these interventions could be estimated from data provided by epidemiological studies, but large population-based controlled studies are needed to demonstrate the efficacy of preventive interventions.     

The Mydriasert insert: an alternative to eye drops for preangiographic mydriasis

PURPOSE: Mydriasert is an insoluble ophthalmic insert, gradually releasing two well-known active ingredients: phenylephrine and tropicamide. It is indicated in presurgical mydriasis. The purpose was to evaluate its efficacy in obtaining mydriasis required for fluorescein angiography. MATERIAL AND METHODS: The ability of Mydriasert to provide mydriasis (defined by a pupillary diameter of at least 7 mm) compatible with a bilateral angiographic examination in optimal conditions was evaluated by a comparative, randomised versus active treatment (eye drops) open trial in 72 patients. RESULTS: All the patients obtained a stable mydriasis allowing angiography. In the Mydriasert group, mydriasis preparation required a mean of 10 min more (Student t test: p<0.001); however, near eyesight recovery was 15 min shorter on average (log-rank test<0.01%) and amounts of active ingredients administered to provide mydriasis were 5-10 times higher in the eye drops reference group. Cardiovascular parameters remained in the normal range in both groups. Three patients of the Mydriasert group presented one ocular symptom of local intolerance, which disappeared in 15 min (exact Fisher test not significant between the treatment groups, p=0.2394). No superficial punctate keratitis was detected during the trial. CONCLUSION: The treatment by Mydriasert can prepare preangiographic mydriasis as well as the reference treatment. The time required for mydriasis is slightly longer. Near eyesight recovery, faster with Mydriasert, could provide an improvement in patient safety and comfort at the end of the ophthalmologic visit.     

Up-dated ophthalmological screening and follow-up management for long-term antimalarial treatment

The early detection of macular toxicity linked to long-term antimalarial treatment requires regular ophthalmological screening based on patients'classification based on their results compared to successive controls. Patients are classified as "low risk" with screening every 18 months if all of the following criteria are met: age under 65 years, no associated renal, hepatic or retinal disease, treatment for less than 5 years, dose less than or equal to 6,5mg/kg/d for hydroxychloroquine and 3mg/kg/d for chloroquine (for a lean patient's weight); "at risk, without fundus findings" with screening every 12 months if one of the following criteria is met: age over 65 years (at the start of or during treatment), antimalarial treatment for more than 5 years, daily dose higher than recommended, presence of renal and/or hepatic disease; "at risk, with fundus findings" with screening every 6 months if a retinal dysfunction has been detected and even if treatment is established or followed. Screening consists of an in-depth clinical examination and at least two complementary tests of macular function: color vision (desaturated-Panel-D15 test) and/or static macular perimetry (central 10 degrees) and/or macular electroretinography (pattern ERG/multifocal ERG). If any changes or anomalies are found between two successive check-ups, the state of the retina can be assessed by angiography and global retinal function by full-field-ERG and electro-oculogram (EOG). The progression from one check-up to the next decides whether a course of treatment will be followed.     

An atypical case of malignant hypertensive retinopathy in a young child

Stage IV hypertensive retinopathies in children have been described, but their incidence appears to be rare. Most etiologies are nephropathies. The authors present a clinical case of malignant high blood pressure in a young girl whose ophthalmological tests detected an unusual nephropathy, the Ask-Upmark kidney, illustrating the importance of determining high blood pressure chronicity and using Kirkendall's classification. Systematic fluorescein angiography and NMR on atypical subjects prevents the diagnosis of Leber neuroretinis, the main differential diagnosis. Early treatment of high blood pressure can avoid complications such as macular exudes.     

Cluster analysis in geographical epidemiology: the use of several statistical methods and comparison of their results

BACKGROUND: The increasing interest in environmental epidemiology has been followed by the development of many statistical tests for detecting disease clustering near a point source. The objectives of this study were to compare several tests to detect disease clustering, among which modelisation using Markov Chain Monte Carlo methods. METHODS: We compared six statistical methods for detecting disease clustering of bladder cancer around an industrial centre of Isère (France) for the period 1983-1997: Stone's test, score test, and two log-linear modelisations (with and without corrections for extra-Poisson variations) using two ways of parameters estimation (maximum likelihood and Markov Chain Monte Carlo methods). RESULTS: The results of the Stone test and the score test are not in favour of a higher risk of bladder cancer around the considered point source. The conclusions brought by the log linear modelisations are the same, but the results obtained using the Markov Chain Monte Carlo Method are very dependant of prior distributions determined for the different parameters. CONCLUSION: Markov Chain Monte Carlo methods, which allow taking into account complex geographical effects, seem well adapted to cluster analysis in geographical epidemiology. However, they remain difficult to implement.     

Modular training in practical medicine: electronic evaluation of student education in general practice

Effective from spring 2004, new regulations for undergraduate medical education in Germany require a two-week practical training in general practice. Similar to other forms of medical education, this practical training should be regularly evaluated by students. With regard to special conditions of the training, we preferred a web based evaluation. Since adequate models were not available, we designed, implemented and tested an electronic way of evaluation. The following aspects turned out to be of special importance: teamwork, time, data protection and cost. Meanwhile, the evaluation is established and still accessible as demo-version for visitors of the home page. This electronic evaluation of medical training in general practice is highly appropriate for a timely evaluation allowing us to obtain a comparison between students' expectations and actual experience as well as a continuous supervision and to provide feedback to the participating practices. This is an important step for quality assurance of medical education in practices inside and outside the university.     

Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy

The aim of this study was to evaluate the predictive value of five different biological factors in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy: (1) tumour grade scored according to the Elston-Ellis classification, (2) hormonal receptor (HR) status; (3) tumour cell proliferation evaluated by Ki-67 staining, (4) HER-2 and topoisomerase II alpha (TopoIIalpha) expression evaluated by immunohistochemistry (IHC), (5) HER-2 and TopoIIalpha amplification evaluated by real-time polymerase chain reaction (PCR). 119 patients with operable breast cancer were treated with six cycles of FEC (100 5-fluorouracil (5-FU) 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2). Tumour response was assessed clinically and by computed tomography (CT) scan, then by pathological assessment. The clinical overall response (OR) was 80%, with 19% of complete responders (CR). The radiological OR was 71%, with 16% of CR. A pathological CR was demonstrated in 13% of the patients according to the Sataloff classification. In the multivariate analysis, the absence of HR expression and Ki-67 > or = 20% were predictive for a clinical CR. A high tumour grade was predictive for a pathological CR. Overexpression or amplification of HER2 or Topollcalpha were not predictive of response.