[Combination radiotherapy-immunotherapy in genitourinary cancer]. / Combinaison radiothérapie-immunothérapie en cancérologie génito-urinaire.

Immunotherapy occupies a growing place in urologic oncology, mainly for kidney and bladder cancers. On the basis of encouraging preclinical work, the combination of immunotherapy with radiotherapy aims to increase the tumor response, including in metastatic tumors, which raises many hopes, which this article reviews.

[Spinal anesthesia may diminish left ventricular function: a study by means of intraoperative transthoracic echocardiography]. / La anestesia subaracnoidea (espinal) podría disminuir la función ventricular izquierda: estudio con ecocardiografía transtorácica intraoperatoria.

BACKGROUND: Spinal anesthesia reduces arterial blood pressure mainly because of vasodilation secondary to blocking preganglionic fibers in the sympathetic nervous system. It is hypothesized, however, that spinal anesthesia may also be a direct cause of some degree of myocardial depression. These factors may be studied by means of transthoracic echocardiography to detect changes in left ventricular function following start of spinal anesthesia. MATERIAL AND METHODS: Left ventricular function was assessed in ASA 1 patients before spinal anesthesia, by means of measurements of left ventricular systolic and diastolic volumes, ejection fraction, the Doppler transmitral (E and A) and tissue (E', A', and Sm) inflow velocities, and the left ventricular outflow tract velocity. The measurements were repeated after the start of spinal anesthesia. RESULTS: Fifty-five patients (58% men; mean [SD] age, 46.9 [15.7] years) were studied. The spinal block caused a significant reduction in systolic and diastolic arterial blood pressures (P < .0009). Diastolic function also decreased (the E wave from 69.52 [11.24] to 61.59 [10.82] cm x s(-1) and the A wave from 50.18 [10.69] to 43.67 [13.75] cm x s(-1); P < .0001). Also reduced was the left ventricular outflow tract velocity, from 18.77 (4.89) to 15.64 (4.75) cm x s(-1) (P < .00001). There were no significant changes in systolic and diastolic volumes or ejection fraction. There was no correlation between the level of spinal block and the magnitude of changes. CONCLUSIONS: Left ventricular function was compromised after spinal anesthesia without significant changes in left ventricular volumes. We can infer that the reduction in arterial blood pressure after a spinal block might be due to some degree of direct ventricular depression.

[Echocardiography-derived Tei index during surgery, a predictor of postoperative cardiovascular complications]. / Indice ecocardiográfico de Tei durante cirugía no cardiaca como predictor de complicaciones cardiovasculares postoperatorias.

BACKGROUND AND OBJECTIVE: The Tei index is a Doppler echocardiographic parameter that reflects both systolic and diastolic myocardial function. Our aim was to monitor the Tei index by transesophageal echocardiography during noncardiac surgery to explore the correlation between this parameter and the incidence of postoperative cardiovascular complications. MATERIAL AND METHODS: Patients at risk of cardiovascular complications were enrolled. The Tei index was derived from the pattern of pulsed Doppler transmitral filling and aortic outflow, by dividing the sum of isovolumetric contraction and relaxation intervals by ejection time in milliseconds. RESULTS: Seventy-three patients (58% men) were enrolled. The mean (SD) age was 68 (12) years. Two groups were identified based on myocardial function. A Tei index over 0.35 defined group 2 (n = 25) and correlated with a larger number of postoperative cardiovascular events. In patients with a normal Tei index less than 0.35 (group 1, n = 48), the incidence of cardiovascular complications was lower. Hypotension occurred in 60% of patients in group 2 and 21% of those in group 1, hypertension in 24% of group 2 and 4.1% of group 1, and pulmonary edema in 8% of group 2 and 2.1% of group 1 (P < .05 for all comparisons). CONCLUSIONS: This pilot study found that patients with a high Tei index were more likely to develop postoperative cardiovascular complications. This index may provide a useful indicator to take into consideration in planning hemodynamic management when patients have a history of cardiovascular disease.

[Intraoperative transesophageal echocardiography and systolic anterior motion of the mitral valve: findings during noncardiac surgery]. / Ecocardiografía transesofágica intraoperatoria y movimiento sistólico anterior de válvula mitral: hallazgo intraoperatorio durante cirugía no cardíaca.

Systolic anterior motion is an under-recognized cause of acute systemic hypotension during noncardiac surgery. This dynamic event has come to light with the introduction of intraoperative transesophageal echocardiography, which provides anatomic and functional images in real time. The cause of this abnormal motion is still uncertain, although it is thought that changes in the shape and function of the left ventricle allow displacement of the mitral valve annulus so that 1 or more leaflets can be pulled toward the outflow tract and obstruct it during the systole. It is important to recognize and diagnose this phenomenon as a cause of hypotension during noncardiac surgery because it can be treated with volume replacement and beta-blockers. The results of such measures can be monitored on intraoperative echocardiographic images. Volume replacement should increase the size of the ventricle and the beta-blockers should decrease the hyperdynamic state. We report a case of abnormal systolic motion during noncardiac surgery that was managed with the help of echocardiography.

[How to organize the emergency department of primary care hospitals in the future? Nyon's regional hospital experience]. / Quelle organisation pour les services d'urgence des hôpitaux périphériques de demain? L'exemple de l'hôpital de Nyon.

Optimization of patients flow can decrease the overcrowding of the emergency department (ED) and improve the level of patient's satisfaction. The prospective analysis of 502 consecutive admissions at the Nyon regional hospital's ED shows a mean length of stay (LOS) of 145 minutes, for a majority of low-severity cases admitted during working hours. A significant LOS variability reveals transient episodes of overcrowding, which lead to an increase in the LOS of mainly ambulatory patients. Our analysis shows that both the ED's structure and the medical organization create a gap between ED performance as care provider and the patients' expectations, and suggests that a separation of low-versus high-complexity cases is necessary. Patients' flow analysis can detect ED overcrowding and may help find the appropriate solutions to reduce it.

Recombination of endogenous D2 dopamine receptor gene with a metallothionein promoter in GH4C1 cells confers functional and inducible D2 response.

We have previously shown that expression of a functional endogenous D2 short dopamine receptor is obtained in GH4C1 cells following transfection with a plasmid that confers resistance to neomycin (pRSVNeo) (Allard et al. (1993) Biochem. Biophys. Res. Commun. 193, 801-807). In order to better understand the mechanisms responsible for such a phenomenon, we cloned and sequenced the 5' region of the D2 gene present in native GH4C1 cells as well as the cDNA of transfected cells. No homology with the published sequence of the rat D2 dopamine receptor promoter was found; however, this region has perfect homology with the mouse metallothionein promoter. In cells expressing D2 receptor, the promoter is fully functional and can regulate dopaminergic D2 receptor mRNA levels and receptor expression in a dose-dependent manner in the presence of Zn2+ or Cd2+. The receptor level is raised from 500 to 3000 fmol/mg of protein in the presence of 100 microM of Zn2+. These results suggest that in GH4C1 cells, a recombination between the mouse metallothionein promoter and the D2 dopamine receptor took place. This system provides us with a cell line expressing an endogenous dopamine D2 receptor in which the level of expression can be easily modulated.

Risk of melanoma following adulthood cancer: a case-control study.

Melanoma is a severe skin cancer related to sun exposure. Whether this malignancy is linked to exposure to ionising radiation during adulthood is still controversial. This case-control study examined the risk of melanoma following treatment for an adulthood first malignant neoplasm (FMN). Cases were patients who presented with cutaneous melanoma after a first cancer in adulthood. Controls (3 per case) were patients free of melanoma, matched for age, duration of follow-up since the FMN, type of FMN, and followed in the same institution. A total of 57 cases and 171 controls were included. In the final multivariate analysis, no risk of melanoma was associated with radiotherapy (odds ratio (OR) for 1 Gy = 1.01, 95% confidence interval (95%CI) 0.96-1.07) nor hormonotherapy, whereas chemotherapy use (OR = 2.3, 95%CI 0.93-5.6) and having a history of familial cancer (OR = 2.8, 95%CI 1.3-5.9) exhibited a nearly significant risk. In conclusion, unlike the evidence for risk of exposure to ionising radiation during childhood, we did not substantiate a risk for association of melanoma with exposure to ionising radiation during adulthood. The risk associated with chemotherapy should justify the implementation of skin surveillance for early detection of melanoma in these patients.

Eimeria tenella microneme protein EtMIC3: identification, localisation and role in host cell infection.

The gene coding for Eimeria tenella protein EtMIC3 was cloned by screening a sporozoite cDNA library with two independent monoclonal antibodies raised against the oocyst stage. The deduced sequence of EtMIC3 is 988 amino acids long. The protein presents seven repeats in tandem, with four highly conserved internal repeats and three more divergent external repeats. Each repeat is characterised by a tyrosine kinase phosphorylation site, WRCY, and a reminiscent motif of the thrombospondin1 (TSP1)-type I domain, CXXXCG. The protein EtMIC3 is localised at the apex of free parasite stages. It is not detected in the early intracellular parasite stage but is synthesised in mature schizonts. Secretion of the protein is induced when sporozoites are incubated in complete medium at 41 degrees C. Strangely enough, the two independent mAb that allow cloning of EtMIC3 interfere with parasitic growth in different ways. One is able to inhibit parasite invasion whereas the other inhibits development. Expression and localisation of the protein EtMIC3 are consistent with a protein involved in the invasion process as is expected for a microneme protein.

Eimeria tenella: cloning and characterization of cDNA encoding a S3a ribosomal protein.

A lambda Zap II cDNA library was constructed from Eimeria tenella first- generation schizonts mRNA and screened with a mouse serum raised against this parasitic stage. This serum identified a clone encoding a S3a ribosomal protein (EtS3a). The 858-bp cDNA fragment, containing the entire parasitic gene encoded a highly basic protein of 264 amino acids (aa) with a molecular weight of 29.780kDa. Based upon amino acid sequence comparison, EtS3a is highly homologous to v-fos transformation effector (encoded by the fte-1 gene) and cyc-07 (a plant homologue of fte-1) and similar to the yeast MFT1 (encoded by the mitochondrial fusion targeting gene). The expressions of mammalian fte-1, plant cyc-07 and yeast MFT1 have all been shown to be cell-cycle-regulated and involved in protein synthesis at the level of the ribosome. Since EtS3a expression is also developmentally regulated, we suggest that this gene product is a functional homologue of fte-1, cyc-07 and MFT1 and an important molecule regulating the development of Eimeria tenella.

Differential localisation of an Eimeria tenella aspartyl proteinase during the infection process.

Aspartyl proteinases are essential for the survival of many pathogens. A single copy gene in species of Eimeria encodes an aspartyl proteinase, which we propose should be called eimepsin to conform to the commonly used names of this family of proteinases. An epitope map, constructed using BIAcore technology, confirmed the specificity of 14 mAbs for eimepsin and defined four antigenic domains, which were conserved between native and recombinant forms of eimepsin. In resting sporozoites, mAb defining antigenic domains I and II stained the refractile body organelles, whereas those defining antigenic domains III and IV stained cytoplasmic granules. During host cell invasion, the staining patterns of mAb defining antigenic domains I, III and IV changed dramatically with the apical tips of invading sporozoites becoming strongly stained. In contrast, mAb defining antigenic domain II continued to stain only the refractile bodies. During early schizogony, mAb to all four domains stained the single fused refractile body, but when schizonts matured, mAb to antigenic domains I, III and IV stained the apical tip of merozoites whereas those to antigenic domain II continued to follow the developmental redistribution of the refractile body. Irrespective of localisation, mAb to three antigenic domains recognised a polypeptide of 49 kDa, which from N-terminal sequencing corresponds to a mature form of eimepsin. Staining with fluorescent pepstatin localised a mature, active form of eimepsin to the refractile bodies of the sporozoite, schizont and first generation merozoite. It remains to be determined whether eimepsin has a catalytic function within the refractile body or whether the activated enzyme is stored in the refractile body so that it can be rapidly redistributed to the apical tip during parasite invasion.

Use of gas-liquid chromatography as a screening test for toxigenic Clostridium difficile in diarrhoeal stools.

In order to determine if gas-liquid chromatography (GLC) on concentrated stool extracts could be substituted to cell culture assay for cytotoxicity, we prospectively studied 154 diarrhoeal stools submitted for detection of Clostridium difficile toxin. Isocaproic-positive samples were cultured on egg yolk agar supplemented with cycloserine, cefoxitin and fructose for isolation of C difficile, and on egg yolk agar plus kanamycin for isolation of other clostridium species. Of the 154 samples, 129 were GLC-negative (height of the isocaproic peak less than 1.2 cm) and were toxin-negative. Twenty-five stools yielded isocaproic acid; C difficile isolated from 13 of them, six of which were also toxin-positive. Four other isocaproic-positive samples yielded C bifermentans and C sordellii; all were toxin-negative. These results indicate that a negative GLC is an excellent screening test for excluding C difficile infection; positive results must be checked by toxin testing and culture since they are not necessarily associated with the presence of C difficile or its toxin.

Detection of Bacteroides fragilis and Bacteroides melaninogenicus by direct immunofluorescence.

A new diagnostic kit, which contains a polyvalent antiserum for either Bacteroides fragilis or Bacteroides melaninogenicus, was tested for reliability and specificity on 146 clinical samples of different origin. A correlation between the culture and immunofluorescence was observed for B. fragilis in 87.39% of cases and for B. melaninogenicus in 81.48% of cases. When pure cultures were tested, aerobically as well as anaerobically, false-positive reactions were observed with staphylococci and Clostridium ramosum spores. The well-defined morphology of these bacteria and spores allows for the elimination of any diagnostic error. The method is rapid, and the margin for error is limited. The test gives a semiquantitative idea of the number of bacteroides organisms present in the clinical specimens even in the presence of a mixed flora.

The x-ray fovea, a device for reducing x-ray dose in fluoroscopy.

The x-ray fovea (U.S. patents pending) is a device for reducing x-ray dose to patients and operations during x-ray fluoroscopy. It consists of a semitransparent collimator with an open, circular, central hole. The fovea collimator is placed at the exit of the x-ray tube, and the attenuation of the peripheral x-ray beam reduces x-ray exposure to patients and operators. The shadow caused by the x-ray fovea can be compensated using real-time image processing hardware. Accurate compensation is demonstrated for both linearly and logarithmically acquired images using a model that accounts for beam hardening in the fovea collimator. The central fovea region has improved image quality due to reduced scatter and veiling glare from the periphery. From beam-stop measurements, a 40% reduction in scatter plus veiling glare is measured using the fovea. A contrast improvement ratio of 1.5 is measured throughout the central region. In the compensated periphery, noise is increased by a factor of 1.66 because fewer photons are detected, but a small amount of temporal filtering compensates this degradation. The Roentgen area product (RAP) exposure to patients is reduced by approximately 70%, while scattered exposure to operators is reduced by approximately 60%.

Purification of first-generation Eimeria tenella schizonts.

A rapid and simple method for purifying first-generation Eimeria tenella schizonts was developed with infected chicken cecal tissue. The schizonts were harvested from the tissue by treatment with a mixture of 3 enzymes: hyaluronidase, dispase, and collagenase. Subsequent purification of the parasites by filtration through gauze and centrifugation resulted in a clean final preparation compared with the starting material. Microscopical and biochemical examinations, performed to assess the quality of the schizont purification, showed a high degree of purity. This procedure may be used to obtain clean schizonts minimally contaminated with host-cell debris in order to study this parasitic stage.

[Longitudinal study of the functional capacity of aged persons in Upper Normandy, 1978-1985]. / L'enquête longitudinale de Haute-Normandie sur les capacités fonctionnelles des personnes âgées, 1978-1985.

A longitudinal study of 1,082 elderly persons was conducted by INSERM over a six-year period in order to identify risk factor in pathological ageing. Several functional capacities were selected for study on the basis of their relevance to independent daily living. This article describes the methodology and the extent to which research objectives were able to be fulfilled. The initial survey took place in 1978-79. A follow-up study targeted two distinct areas of interest: the monitoring of mortality rates and the re-evaluation of the performance of survivors at three and six year intervals. Re-evaluation of performance involved the exploration of the individual's mobility, capacity to carry out activities of daily living etc. The consistency of the entire data set assembled over the six-year period was assessed in various ways. At six year follow-up survival rate could be determined for 98.8% of the initial cohort, and 87.1% of the survivors were able to be reinterviewed. The different probabilities of healthy survival, by sex and age, are tabulated in the appendices.

[Gas-phase chromatography in the rapid bacteriological diagnosis of infections. Contributions and limitations of this technic]. / Contribution de la chromtographie en phase gazeuse au diagnostic bactériologique rapide des infections. Les apports et les limites de cette technique.

Gas-liquid chromatography has been used directly on clinical specimens as a method for presumptive diagnosis of anaerobic infections. This technique proved to be valuable and reliable. Combined with a Gram stain, it offers the possibility to differentiate in less than 1 hour aerobic from anaerobic infections by means of detection of volatile fatty acids (short chain monocarboxylic acids) others than acetic acid.

The reliability of urease tests, histology and culture in the diagnosis of Campylobacter pylori infection.

The accuracy of various staining techniques for immersion microscopy, of five media for culture and five urease test modalities for the detection of Campylobacter pylori infection is reported. It was found that 2% urea unbuffered gel preparation is the most accurate urease test (sensitivity: 89%, specificity: 98%) but a minimal amount of 10,000 CFU/ml is necessary to observe positivity and the sensitivity of urease tests drops to 52% in patients under antimicrobial treatment. For histological diagnosis, modified Giemsa staining was shown to be slightly superior to H&E. The most valuable diagnosis technique is culture when the biopsy specimen is transported and processed under appropriate conditions. A 94% sensitivity rate was observed with 'BCC agar', a new medium containing brain heart infusion, activated charcoal and horse serum.