The first Flaviviridae symposium

The first annual Flaviviridae Symposium, sponsored by ICN Pharmaceuticals Inc., was held in Lyon, France, on 9 October, 1997, to communicate current understanding on the Flaviviridae. This multidisciplinary symposium attracted over 300 international delegates and presentations covered virology, viral pathogenesis, potential therapies and strategies for vaccine development. The symposium reviewed the research area that may lead to the discovery and design of human and veterinary medicines against members of this virus family.     

Safety and cost-effectiveness of MIDCABG in high-risk CABG patients

BACKGROUND: Myocardial revascularization without cardiopulmonary bypass has been proposed as a potential therapeutic alternative in high-risk patients undergoing coronary artery bypass grafting. To evaluate this possibility we compared 15 high-risk (HR) patients in whom minimally invasive direct coronary artery bypass grafting was used as the method of revascularization with 41 consecutive patients who underwent conventional coronary artery bypass grafting during 1 month. METHODS: Patients undergoing myocardial revascularization without cardiopulmonary bypass were significantly older than their low-risk (LR) counterparts (72.2 +/- 11.6 versus 63.3 +/- 9.7 years, p = 0.006). The demographic profile for HR versus LR patients was as follows: female patients, 60.0% versus 26.8%, p = 0.02; diabetes, 20.0% versus 24.4%, p = 0.7; prior stroke, 33.3% versus 7.4%, p = 0.03; chronic obstructive pulmonary disease, 60.0% versus 9.8%, p < 0.0001; peripheral vascular disease, 33.3% versus 12.2%, p = 0.03, congestive heart failure, 26.6% versus 9.8%, p = 0.09; impaired left ventricular (ejection fraction < 0.40), 40.0% versus 17.0%, p = 0.07; urgent operation, 86.6% versus 46.3%, p < 0.0001; and redo operation, 20.0% versus 0%, p = 0.003. RESULTS: There were no deaths in the HR group and one death in the LR group. The average intensive care unit stay was 1.1 +/- 0.5 days in HR patients versus 1.6 +/- 1.6 days in LR individuals (p = 0.2), and the average hospital stay was 6.1 +/- 1.8 versus 7.3 +/- 4.4 days, respectively (p = 0.3). We used an acuity risk score index developed by the Adult Cardiac Care Network of Ontario to predict outcome in the HR group. The expected intensive care unit stay in HR patients was 4.1 +/- 1.2 days (versus the observed stay of 1.1 +/- 0.5 days, p < 0.0001), and the expected hospital stay was 12.5 +/- 1.5 days (versus the observed stay of 6.1 +/- 1.8 days, p < 0.0001). The expected mortality in the HR group was 6.1% versus 0%, p = 0.3. A cost regression model was used to examine predicted versus actual cost (in Canadian dollars) for the HR patient cohort (based on Ontario Ministry of Health funding). The expected cost for the HR cohort would have been $11,997 per patient. In contrast, the average cost for these 15 patients was $5,997 per patient, an estimated cost saving of 50%. CONCLUSIONS: Myocardial revascularization without cardiopulmonary bypass appears to be a safe and cost-effective therapeutic modality for HR patients requiring myocardial revascularization.     

Hypofunction of the stress axis in Sj?gren's syndrome

OBJECTIVE: To examine the functional integrity of the hypothalamic-pituitary-adrenal (HPA) and thyroid axes in Sj?gren's syndrome (SS) via the assessment of basal and stimulated adrenocorticotropin (ACTH), cortisol, thyroid stimulating hormone (TSH), and prolactin levels. METHODS: Pituitary function of the HPA axis was assessed by determining the basal plasma levels of ACTH in the late afternoon, as well as the ACTH released to ovine corticotropin releasing hormone (oCRH) stimulation; adrenal function was assessed by measuring plasma cortisol levels in the late afternoon at baseline and after release of the endogenous ACTH during oCRH stimulation. Basal and thyrotropin releasing hormone (TRH) stimulated levels of TSH and prolactin were also assessed. Healthy volunteers were used as controls. RESULTS: Patients with SS, compared to controls, were characterized by significantly lower ACTH levels (pg/ml), (5.1 +/- 0.5 vs 11.4 +/- 1.5, respectively; p < 0.05) and cortisol levels (microg/ml), (2.4 +/- 0.6 vs 5.9 +/- 1.2, respectively; p < 0.05). Furthermore, a blunted pituitary and adrenal response to oCRH compared to controls was observed: peak plasma ACTH and cortisol levels for patients with SS were 46.2 +/- 5.4 pg/ml and 15.7 +/- 1.6 microg/ml, respectively, and for controls 61.5 +/- 3.8 and 19.6 +/- 0.7, respectively (p < 0.05). Basal TSH levels were significantly elevated in patients (1.3 +/- 0.3 microIU/ml vs 0.9 +/- 0.05 microIU/ml; p < 0.05). CONCLUSION: The above findings indicate hypoactivity of the HPA axis in patients with SS. Further studies are needed to definitively identify the locus of the defects and assess the significance of the pattern of the perturbations to the pathogenesis and expression of SS.     

Somatic von Hippel-Lindau mutation in clear cell papillary cystadenoma of the epididymis

Papillary cystadenoma of the epididymis is an uncommon benign lesion that may occur sporadically or as a manifestation of von Hippel-Lindau (VHL) disease. Neither immunohistochemical studies nor molecular genetic analyses of the VHL gene have been reported previously for this lesion. The authors describe two cases of clear cell papillary cystadenoma of the epididymis, both of which were initially confused with metastatic renal cell carcinoma. Both lesions showed positive immunohistochemical staining for low and intermediate molecular weight keratins (Cam 5.2 and AE1/AE3), EMA, vimentin, alpha 1-antitrypsin, and alpha 1-antichymotrypsin. Each was negative for CEA. Because clear cell papillary cystadenoma is similar to renal cell carcinoma histologically, and because both occur as components of the von Hippel-Lindau disease complex, the authors analyzed both cases for the presence of mutations in the VHL gene. A somatic VHL gene mutation was detected in one of the two tumors by polymerase chain reaction followed by single-strand conformation polymorphism analysis. Direct sequencing revealed a cytosine to thymine transition at nucleotide 694, resulting in the replacement of an arginine with a stop codon after the sixth amino acid of exon 3. As the VHL gene is believed to function as a tumor suppressor gene, VHL gene mutations may play a role in the initiation of tumorigenesis in sporadic cystadenomas of the epididymis.     

Analysis of the axial flow field in stenosed carotid artery bifurcation models--LDA experiments

Laser Doppler anemometer (LDA) experiments were performed to gain quantitative information on the differences between the large-scale flow phenomena in a non-stenosed and a stenosed model of the carotid artery bifurcation. The influence of the presence of the stenosis was compared to the effect of flow pulse variation to evaluate the feasibility of early detection of stenosis in clinical practice. Three-dimensional Plexiglass models of a non-stenosed and a 25% stenosed carotid artery bifurcation were perfused with a Newtonian fluid. The flow conditions approximated physiological flow. The results of the velocity measurements in the non-stenosed model agreed with the results from previous hydrogen-bubble visualization. A shear layer separated the low-velocity area near the non-divider wall from the high-velocity area near the divider wall. In this shear layer, vortex formation occurred during the deceleration phase of the flow pulse. The instability of this shear layer dictated the flow disturbances. The influences of the mild stenosis, located at the non-divider wall, was mainly limited to the stability of the shear layer. No disturbances were found downstream of the stenosis near the non-divider wall. Using a pulse wave with an increased systolic deceleration time, the velocity distribution showed an extended region with reversed flow, a more pronounced shear layer and increased vortex strength. From these measurements it is obvious that the influence of the presence of a mild stenosis, mainly limited to the stability of the shear layer, can hardly be distinguished from the effects of a variation of the flow pulse. From this it can be concluded that methods for detection of mild stenosis, using solely the large-scale flow phenomena, as can be measured by ultrasound or MRI techniques, will hardly have any clinical relevance.     

Rapid assessment of drug abuse in Cameroon

The present paper describes a rapid assessment that was carried out in Cameroon from March to November 1994 and presents a summary of the findings and recommendations. It was the first rapid assessment study conducted by Cameroon in collaboration with the Economic Community of Central African States, with technical assistance from the World Health Organization and the support of the United Nations International Drug Control Programme. It was hoped that the study would help to fill gaps in the information available on drug abuser profiles, the types of drugs abused and the response of the community to drug abuse in Cameroon. In focus group discussions, key informant interviews and interviews with drug abusers, it was revealed that Cameroon was not only used by drug traffickers as a transit country, but was also a drug-consuming country. The drug consumers were both males and females from all age groups. The drugs consumed ranged from traditional drugs to imported cocaine and heroin. Cannabis was the most frequently consumed drug, followed by amphetamine-type tablets and a broad range of pharmaceuticals. Solvents were mainly consumed by street children in northern Cameroon. Local beer and gin also held a special place in society. In order to tackle the existing problems, programmes offering preventive education and alternative forms of recreation for youth were necessary, and national policies on demand and supply reduction should be harmonized.     

Planar MESFET grid oscillators using gate feedback

A method for quasi-optically combining the output power of MESFETs in which drain and source leads couple directly to the radiated field is introduced. The design consists of a planar grid of devices placed in a Fabry-Perot cavity. Capacitive feedback is provided to the gate, allowing oscillation at much higher frequencies than previous grids. The oscillation frequency is dependent on the device characteristics, the resonator cavity, and the symmetries of the grid. A transmission-line model for the grid is discussed and used to design two oscillator arrays. A 16-element grid has produced 335 mW of power at 11.6 GHz with a DC-to-RF conversion efficiency of 20%. This design was scaled to produce a 36-element grid oscillator with output power of 235 mW at 17 GHz. These results represent a significant improvement in the performance of planar grid oscillators. The planar configuration of the grid is very convenient for monolithic integration and is easily scalable to millimeter-wave frequencies     

Heparin-binding protein (CAP37) is internalized in monocytes and increases LPS-induced monocyte activation

Previous studies have shown that the neutrophil-derived heparin-binding protein (HBP), also known as CAP37 or azurocidin, potentiates the LPS-induced release of proinflammatory cytokines (TNF-alpha, IL-1, and IL-6) from isolated human monocytes. To date, the mechanisms by which HBP enhances LPS-induced monocyte activation have not been elucidated, and it is not known whether HBP also increases the LPS-induced production of other bioactive substances. We studied human monocytes activated by recombinant human HBP and LPS and their interaction with the LPS receptor CD14. We hypothesized that the stimulatory effect of HBP on the LPS-induced release of proinflammatory mediators from monocytes was mediated by specific binding of HBP to monocytes, which resulted in an up-regulation of CD14. Our results demonstrated that HBP alone (10 microg/ml) stimulated the production of TNF-alpha from isolated monocytes. In addition, HBP had an additive effect on LPS-induced production of TNF-alpha and PGE2, suggesting a generalized monocyte activation. We used flow cytometry to demonstrate that HBP had a high affinity to monocytes but not to the LPS receptor CD14, and experiments performed at 4 degrees C indicated an energy-dependent step in this process. Confocal microscopy showed that monocytes internalize HBP within 30 min. These data suggest that mechanisms other than increased CD14 expression are responsible for the enhanced release of TNF-alpha or PGE2 in response to HBP and LPS.