Three-dimensional contrast-enhanced power Doppler ultrasonography and conventional examination methods: the value of diagnostic predictors of prostate cancer

OBJECTIVE: To investigate the value of three-dimensional contrast-enhanced power Doppler ultrasonography (3D-CE-PDU) in the diagnosis of prostate cancer and to compare 3D-CE-PDU with digital rectal examination (DRE), prostate-specific antigen (PSA) levels, grey-scale ultrasonography (GSU) and PDU. PATIENTS AND METHODS: The study comprised 30 patients with localized prostate cancer scheduled to undergo radical prostatectomy and 29 with clinical BPH scheduled to undergo transurethral microwave thermotherapy. The 3D-CE-PDU examinations were carried out using 2.5 g of microbubble ultrasound contrast medium; the images were stored digitally to allow off-line analysis. All the reconstructed 3D images of the prostate were evaluated blindly in random order by two investigators (one expert and one novice). The images were scored according to asymmetry (0-2) and vessel distribution (0-3). Marked asymmetry (2) and/or a focal increase in vascularity (> 2) were considered as suspicious for prostate malignancy. Diagnostic predictions using the DRE, PSA level, GSU, PDU, 3D-CE-PDU and their combinations were investigated using receiver operating characteristic (ROC) curves. RESULTS: True-positive and true-negative rates of the 3D-CE-PDU were 87% (26/30) and 79% (23/29), respectively, for the expert observer. The sensitivity of 3D-CE-PDU was higher than that of DRE, GSU and PDU, but not PSA level, and the specificity was lower, again except for PSA level. However, when compared with those of the other modalities in single-test evaluations, 3D-CE-PDU, and a combination of 3D-CE-PDU and PSA level, had the largest area under the ROC curve (0. 830 and 0.933, respectively). The diagnostic agreement between the examiners was 76% (Cohen kappa statistic, 0.5). CONCLUSION: In this selected group of patients, 3D-CE-PDU alone was a better diagnostic tool than the DRE, PSA level, GSU or PDU alone. The most suitable diagnostic predictor for prostate cancer was a combination of 3D-CE-PDU and PSA level.     

Mitochondrial dysfunction associated with a mutation in the Notch3 gene in a CADASIL family

BACKGROUND: Cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by recurrent subcortical ischemic strokes and dementia caused by mutations in the Notch3 gene. In Drosophila melanogaster, Notch signaling has a pleiotropic effect, affecting most tissues of the organism during development. OBJECTIVE: To characterize a potential mitochondrial dysfunction associated with mutations in the Notch3 gene. METHODS: Biochemical, histochemical, molecular, and genetic analyses were performed on muscle biopsy specimens and fibroblasts obtained from patients of a Spanish family with CADASIL. Additional biochemical and molecular analyses of the N(55e11) mutant of D. melanogaster were performed. RESULTS: In muscle biopsy specimens, a significant decrease was found in the activity of complex I (NADH [reduced form of nicotinamide adenine dinucleotide] dehydrogenase), and in one patient, histochemical analysis showed the presence of ragged-red fibers with abnormal cytochrome c oxidase staining. Reduced fibroblast activity of complex V (ATP synthase) was found. Supporting data on patients with CADASIL, it was found that the mutation N(55e11) in Drosophila decreases the activity of mitochondrial respiratory complexes I and V. CONCLUSIONS: Mitochondrial respiratory chain activity responds, directly or indirectly, to the Notch signaling pathway. Mitochondrial dysfunction in patients with CADASIL may be an epiphenomenon, but results of this study suggest that the pathophysiology of the disease could include a defect in oxidative phosphorylation.     

A daily rhythm in glucose tolerance: a role for the suprachiasmatic nucleus

The suprachiasmatic nucleus (SCN), the biological clock, is responsible for a 24-h rhythm in plasma glucose concentrations, with the highest concentrations toward the beginning of the activity period. To investigate whether the SCN is also responsible for daily fluctuations in glucose uptake and to examine how these fluctuations relate to the rhythm in plasma glucose concentrations, SCN-intact rats and SCN-lesioned rats were injected intravenously with a glucose bolus at different time points. We found an increase in glucose uptake toward the beginning of the activity period, followed by a gradual reduction in glucose uptake toward the end of the activity period. The daily variation in glucose tolerance seemed not to be caused by fluctuations in insulin responses of the pancreas but by a daily variation in insulin sensitivity. Lesioning the SCN resulted in the disappearance of the daily fluctuation in glucose uptake and insulin sensitivity. Interestingly, SCN-lesioned rats showed an enhancement in glucose tolerance that could not be explained by higher insulin responses or enhanced insulin sensitivity. Therefore, these findings suggest a role for the SCN in insulin-independent glucose uptake. The present results further show that the daily rhythm in glucose tolerance follows the same pattern as the daily rhythm in plasma glucose concentrations. We hypothesized that the biological clock prepares the individual for the upcoming activity period by two separate mechanisms: increasing plasma glucose concentrations and making tissue more tolerant to glucose.     

The relationship of the International Prostate Symptom Score and objective parameters for diagnosing bladder outlet obstruction. Part I: when statistics fail

PURPOSE: We evaluated the International Prostate Symptom Score and correlated it with objective means of determining bladder outlet obstruction. MATERIALS AND METHODS: Beginning in May 1996, 460 men 41 to 88 years old (mean age plus or minus standard deviation 60.4 +/- 9.4) were prospectively included in this study. Symptoms were evaluated using the International Prostate Symptom Score, and digital rectal examination, outpatient cystoscopy, prostate specific antigen determination and transrectal ultrasound were done. Urodynamic evaluation included uroflowmetry, filling cystometry and pressure flow study. RESULTS: Linear regression was done to correlate scores with measurable parameters. We noted no correlation of the total, obstructive symptoms or irritative symptoms score with objective parameters, including the average and maximum flow rate, post-void residual urine, prostate size and Sch?fer grade. CONCLUSIONS: Prostatic symptom scores are qualitative. Using them to quantify the degree of obstruction or evaluate therapy is questionable.     

Edmond Sergent (1876-1969) and the Pasteur Institute of Algeria]

Edmond Sergent, supported by a distinguished team of colleagues, directed the Pasteur Institute of Algeria for over 60 years, from 1900 to 1963. As a student of Emile Roux, Sergent had received a Pasteurian training. His institute devoted extensive study to malaria. Sergent defined the concept of prevention and extended it to other pathologies. For many years, the Institute persevered in carrying out successful antimalarial campaigns such that Algeria was freed of the disease. In 1916-1917, Sergent and his brother were called upon to organise anti-malarial efforts for the Armée d'Orient. By way of systematic and energetic curative and prophylactic measures, they were able to eradicate the disease. In 1908, the Sergent brothers were the first to discover the role of the louse in the transmission of another disease, relapsing fever. The Pasteur Institute team also discovered the sand fly vector which transmits the parasite causing leishmaniasis. The Sergents found a new form of oculonasal myiasis, called "Thimni". In addition, they led effective campaigns against tuberculosis based on BCG vaccination administered throughout Algeria. The Pasteur Institute of Algeria conducted important research in plant and animal diseases. For example, they detected a trypanosome agent causing dromedary "debab", as well as its vector, the horsefly. They also studied in depth bovine piroplasmosis, which causes widespread and destructive disease, and demonstrated the role of the tick in promoting transmission generally. Their work in botany included the discovery that a Fusarium-type fungus was the causal agent for "ba?oudh", the main disease of date palms. They also demonstrated the basic role of the fruit fly in alcoholic grape fermentation.     

Acute bulbar palsy due to myelomeningocele and Chiari II malformation

We describe a case of a 10-year-old girl with myelomeningocele and type II Chiari malformation. She presented with an acute bulbar palsy requiring mechanical ventilation. Surgical decompression of the brainstem was performed and, because of a phrenic nerve palsy, surgical plication of the right diaphragm was also required. The patient s evolution was favourable. We discuss the various forms of clinical presentation of this pathology as well as its management. The importance of early diagnosis and surgical correction are also stressed as a key factor for favourable evolution.