[Development of a real-time RT-PCR for detection of equine influenza virus]. / Entwicklung einer real-time RT-PCR zum Nachweis von equinem Influenzavirus.

Equine influenza is a highly contagious respiratory disease in horses caused by influenza A viruses. In this work a real-time RT-PCR for fast and sensitive diagnosis of equine influenza viruses (EIV) targeting a highly conserved region of the matrix gene was developed. In addition two RT-PCR methods for the amplification of large parts of the matrix- and HA gene were adapted for molecular-epidemiological characterization of viruses. The primers of the real-time RT-PCR had homologies of 99.4% to EIV- and 97.7% to all influenza A viral sequences, whereas the minor groove binder (MGB) probe showed homologies of 99.3% and 99.6%, respectively. These high values allow application of the assay for influenza viruses in other species. Using 20 equine, 11 porcine and 2 avian samples, diagnostic suitability of the assay was confirmed. High specificity for influenza viruses was shown both experimentally and by software simulation. The assay analytical sensitivity was at 10(2)-10(3) copies of RNA and 10(0)-10(1) copies of DNA, respectively. This allows virus detection also in circumstances of minor viral shedding. All amplified EIV sequences were classified phylogenetically within the known lineages.

Sheep persistently infected with Border disease readily transmit virus to calves seronegative to BVD virus.

Bovine viral diarrhea- and Border disease viruses of sheep belong to the highly diverse genus pestivirus of the Flaviviridae. Ruminant pestiviruses may infect a wide range of domestic and wild cloven-hooved mammals (artiodactyla). Due to its economic importance, programs to eradicate bovine viral diarrhea are a high priority in the cattle industry. By contrast, Border disease is not a target of eradication, although the Border disease virus is known to be capable of also infecting cattle. In this work, we compared single dose experimental inoculation of calves with Border disease virus with co-mingling of calves with sheep persistently infected with this virus. As indicated by seroconversion, infection was achieved only in one out of seven calves with a dose of Border disease virus that was previously shown to be successful in calves inoculated with BVD virus. By contrast, all calves kept together with persistently infected sheep readily became infected with Border disease virus. The ease of viral transmission from sheep to cattle and the antigenic similarity of bovine and ovine pestiviruses may become a problem for demonstrating freedom of BVD by serology in the cattle population.

Mucosal lesions in a sheep infected with the Border Disease Virus (BDV).

A 28-week-old sheep was presented at the animal hospital because of chronic emaciation, anemia and slight diarrhea. Due to poor general condition and bad prognosis the animal was euthanized and submitted for postmortem investigation. Multiple erosions and ulcerations were found in the dorsal region of the tongue, the pharynx, the hard palate, in the esophagus and the ruminal pillars. Histologically, these lesions consisted of necrosuppurative inflammation. The animal was tested positive for pestivirus antigen both by immunohistochemical and by virological examination (cell culture, antigen capture ELISA and RT-PCR). A non-cytopathic Border Disease Virus was identified, and sequencing revealed a virus belonging to the BDV-3 cluster. Based on the macroscopical, histological, immunohistological and virological results this case was diagnosed as Border Disease with mucosal lesions. This is the first report of such a case in Switzerland.

Missed appointments at a Swiss university outpatient clinic.

OBJECTIVE: To assess the appointment conditions and characteristics of patients who miss their appointments ('no-shows'); this will aid in the formulation of intervention methods to reduce no-show rates. METHODS: During a one-month period, data on all no-shows at the general internal medicine outpatient clinic of the Geneva University Hospitals were collected. Control patients were matched for appointment time and gender. Patient and appointment characteristics were collated on 13 parameters, and these were compared between no-shows and controls. RESULTS: Two hundred and six of 1296 appointments were no-shows (15.8%). Compared with controls, no-shows were younger, born earlier in the year, more often were not Europeans, more often had a common language with the physician or translator (no communication problems), and more often had a follow-up (not first) appointment. Other parameters were not significant (appointment day of week and time of day, gender, residency status, insurance coverage, family physician, medical consequences, covert addiction). CONCLUSIONS: The no-show rate was within the range for comparable settings. Several parameters associated with no-shows reflected specifics of a hospital-based adult outpatient clinic that mainly serves middle-to-low socio-economic classes and is a referral clinic for refugees in a middle-sized European city with a high percentage of foreigners with different backgrounds and languages. Planned interventions should consider local factors.

[Fever and weight loss in a 57-year-old patient]. / Fièvre et perte de poids chez une patiente de 57 ans.

Presentation of a 57-year-old female patient with fever of unknown origin, asthenia, and weight loss for I month. History and examination were unremarkable. Blood analysis showed an important inflammatory syndrome. Other paraclinic tests were all normal. Finally, sophisticated exams (CT-scan, and FDG PET-scan) allowed the diagnosis of giant cell arteritis, confirmed by biopsy of the temporal arteries. Differential diagnosis and treatment are discussed.

[General practice--linear thinking and complexity]. / Médecine générate--pensée Linéaire et complexité.

As physicians, we apply and teach linear thinking. This approach permits to dissect the patient's problem to the molecular level and has contributed enormously to the knowledge and progress of medicine. The linear approach is particularly useful in medical education, in quantitative research and helps to resolve simple problems. However, it risks to be rigid. Living beings (such as patients and physicians!) have to be considered as complex systems. A complex system cannot be dissected into its parts without losing its identity. It is dependent on its past and interactions with the outside are often followed by unpredictable reactions. The patient-centred approach in medicine permits the physician, a complex system himself, to integrate the patient's system and to adapt to his reality. It is particularly useful in general medicine.

[Quality care in primary care: the importance of patients' reports]. / Qualité des soins en médecine de premier recours: "a l'ecoute de nos patients".

Patients' evaluation of care is an important element of quality of care, especially for patients with chronic conditions. Our objective was to expose physicians in training to a quality improvement program and study how continuity of care could influence patients' experience of care. Physicians in training valued this approach, but deplored no to be actively involved in its planning. They also underlined the importance of keeping physicians' individual results absolutely confidential. Positive patients' reports toward communication and physician-patient relationship were associated with longer duration of follow-up at the medical outpatient clinic. Following this project, several changes have been made to improve aspects of care that were problematic.

[Preparing a drug list for primary care]. / Prescription en médecine de premier recours: l'intérêt d'une liste de médicaments.

To limit drug adverse effects, the use of a limited choice of drugs is desirable. We identified 29 frequent health problems and selected first and second choice medication based on the following criteria: clinical efficacy based on medical evidence or expert consensus, safety profile, and costs. For each substance, adverse effect, contraindication, interaction risk, specific dosing, and safety use during pregnancy and lactation were reviewed. More than seventy substances were identified. This list is available for download at the following address (in French): http://www.hcuge.

Genetic heterogeneity of pestiviruses of ruminants in Switzerland.

We have genetically analyzed ruminant pestiviruses. All >150 bovine viral diarrhea (BVD) viruses isolated from cattle in Switzerland belonged to genotype 1, with subgenogroups e, h, k and b found in decreasing frequency. To date, representatives of subgenogroup k have been detected in Switzerland only. Despite serological evidence of Border disease in sheep, only few Border disease viruses have been isolated, all of which belong to the novel group 3. Serological evidence suggested that pestivirus infections may occur also in wild ruminants in Switzerland but no isolates are available for analysis. In addition, we describe two pestiviruses, one a cell culture contaminant and the other isolated from a buffalo, that cluster with a recently proposed novel pestivirus species.

[Sociocultural diversity and medical education]. / Diversité socioculturelle et formation médicale.

Global migration patterns have led to increasingly diverse populations, and physicians must learn to work effectively with patients from diverse backgrounds. However, some aspects of medical education may actually reinforce the idea that physicians do not need to take social and cultural differences into consideration in their work. In order to train physicians who are capable of providing quality care to patients from diverse backgrounds, it will be important to integrate the concept of cultural competence into all aspects of medical training, such that it will cease to be perceived as an "optional" aspect of medicine.

[Social inequalities and health: experiences of a mobile health care unit in Geneva]. / Inégalités sociales et santé: l'expérience de l'unité mobile de soins communautaires a Genève.

Health care professionals are in contact with patients of all social horizons. Healthcare professionals come into contact with patients from all social backgrounds. Low socio-economic status is a well-known determinant of morbidity and mortality. A mobile community health care unit ("Umsco") was created in Geneva in 1996 with the aim of providing health care to very low-income patients who aren't catered for by the traditional healthcare system in Switzerland. The Mobile Unit's patients are mainly female South American illegal immigrants, but also the city' homeless. This article explains how the Unit functions on a day-to-day basis. We describe socio-demographic characteristics of the patients and their main presenting complaints. We also discuss how health care professionals in general can adapt to the specific needs of socially deprived and vulnerable patients.

[The Geneva experience: the Department of Community Medicine]. / L'expérience genevoise: le Département de Médecine Communautaire.

The mission of the Department of Community Medicine at the Geneva University Hospitals is to offer the underserved and marginalised populations guaranteed access to the health system and to promote education and research in general and internal medicine (primary care). The activity with a two-fold focus--medical-social and academic--demonstrated by the type of care offered to homeless people and other clandestine groups allows for the achievement of a number of objectives of the Towards Unity for Health programme. However, evidence to date emphasises that such a structure remains fragile.

[Border disease in a flock of sheep]. / Border Disease in einem Schafbetrieb.

This report describes border disease in a flock of sheep in Switzerland. In April 2001, three ewes in a flock of 41 sheep gave birth to lambs that had generalized tremors and excessively hairy fleece. One of these, a three-week-old female lamb, was referred to our clinic for further diagnostic work-up. The lamb was very nervous, bleated constantly and had generalized muscle tremors, which were more pronounced in the head region. Hind end ataxia was observed, and the lamb was slow to correct its posture when the hind limbs were abducted, adducted or crossed. Blood samples were collected every six weeks to determine antibody titres to pestivirus and for virus isolation via cell culture. A skin biopsy sample was also collected and examined immunohistochemically for pestivirus antigen. Antibody titres in the first tests were suspicious and those of the second were negative. Pestivirus was identified in cell culture, and the skin biopsy sample was positive for pestivirus antigen. Blood samples were collected from all of the ewes and lambs and the buck for virus isolation via cell culture and determination of pestivirus antibody titres. Thirty-one animals were seropositive, six had borderline antibody titres and four were seronegative. Pestivirus was isolated from eight animals, which included the lamb described in this report. Of the virus-positive animals, three were seronegative, three others had borderline titres and two were seropositive. Six of the eight viruses isolated from cell culture were further characterized genetically via retrotranscription and polymerase chain reaction and subsequent sequencing. The phylogenetic analysis revealed that the causative agent was border disease virus. This is the first time that border disease virus has been isolated in Switzerland. The lamb referred to our clinic was observed for three months; it was then euthanatised and a postmortem examination was performed. Immunohistochemical examination of numerous organs revealed pestivirus antigen. The source of infection was though to be infected sheep from another flock, which shared a pasture. All antigen-positive animals were slaughtered.

Role of nasopharyngeal culture in antibiotic prescription for patients with common cold or acute sinusitis.

The aim of the present study was to assess the hypothesis that, when present in nasopharyngeal secretions, Streptococcus pneumoniae. Haemophilus influenzae, and Moraxella catarrhalis play a pathogenic role early in the course of an upper respiratory tract infection. Adults with a clinical diagnosis of acute sinusitis or common cold were enrolled. Participants were randomly assigned in a double-blind manner to receive azithromycin 500 mg daily or placebo for 3 days. The effect of treatment on symptom evolution in the predefined subset of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis in their nasopharyngeal secretions was assessed. Of 265 patients enrolled, 132 received placebo and 133 azithromycin. Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis was identified in nasopharyngeal secretions of 77 patients (29%). In this predefined subgroup of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 occurred in 73% of those treated with azithromycin compared with 47% of those who received placebo (P=0.007). The median time before resolution of symptoms was 5 days in the azithromycin group compared to 7 days in the placebo group. Respiratory complications requiring antibiotic treatment occurred in 19% of patients in the placebo group and in 3% of the azithromycin group (P=0.025). In the remaining 188 patients without Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 was similar in both groups (69% in the placebo group vs. 64% in the azithromycin group [P=0.75]). Antibiotic treatment is of clinical benefit for patients with acute sinusitis or common cold when Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis is present in nasopharyngeal secretions. This observation provides new insights into the pathogenic role of these bacteria in the early stage of the common cold.

2-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)- and 2-(2,2-dioxo-1,4-dihydro-2H-2lambda6-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamides as potent and selective peptide deformylase inhibitors.

Potent, selective, and structurally new inhibitors of the Fe(II) enzyme Escherichia coli peptide deformylase (PDF) were obtained by rational optimization of the weakly binding screening hit (5-chloro-2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-acetic acid hydrazide (1). Three-dimensional structural information, gathered from Ni-PDF complexed with 1, suggested the preparation of two series of related hydroxamic acid analogues, 2-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-N-hydroxy-acetamides (A) and 2-(2,2-dioxo-1,4-dihydro-2H-2lambda(6)-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamides (B), among which potent PDF inhibitors (37, 42, and 48) were identified. Moreover, two selected compounds, one from each series, 36 and 41, showed good selectivity for PDF over several endoproteases including matrix metalloproteases. However, these compounds showed only weak antibacterial activity.

Blood pressure and renal haemodynamic response to salt during the normal menstrual cycle.

The purpose of the present study was to evaluate prospectively blood pressure and the renal haemodynamic response to salt during the normal menstrual cycle. A total of 35 healthy normotensive young women not on oral contraceptives were enrolled; 17 were studied in the follicular phase and 18 in the luteal phase of the menstrual cycle. The women in each group were then randomly allocated to receive a low-sodium (40 mmol/day) or a high-sodium (250 mmol/day) diet for a 7-day period in two consecutive menstrual cycles. At the end of each dietary period, 24 h ambulatory blood pressure, urinary sodium excretion, plasma renin activity, plasma catecholamine levels and renal haemodynamics were measured. Our results show that the blood pressure response to salt is comparable during the luteal and the follicular phases of the normal menstrual cycle and is characterized by a salt-resistant pattern. In the kidney, effective renal plasma flow was significantly greater and the filtration fraction lower (P<0.05) after salt loading in women studied in the luteal phase compared with women investigated in the follicular phase. This study thus demonstrates that the female hormone status does not affect the blood pressure response to sodium in young normotensive women. However, in contrast with systemic haemodynamics, the renal response to salt varies during the normal menstrual cycle, suggesting that female sex hormones play a role (direct or indirect) in the regulation of renal haemodynamics.

Stress fracture of the cuboid in an 8-year-old boy: a characteristic magnetic resonance imaging diagnosis.

A stress fracture of an 8-year-old boy diagnosed on magnetic resonance (MR) images is presented. Stress fractures of the cuboid are probably more common than previously reported. The diagnosis should be considered even when a history of trauma or chronic overload is absent. The MR appearance of the stress fracture was characteristic.

[Symptoms and clinical and radiological signs predicting the bacterial origin of acute rhinosinusitis]. / Symptômes, signes cliniques et radiologiques prédictifs de l'origine bactérienne des rhino-sinusites aiguës.

A minority of patients with common cold and upper respiratory tract infections have a bacterial infection and may benefit from antibiotic therapy. The present analysis set out to determine whether there were clinical symptoms or signs which could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis who are infected with pathogenic bacteria. Detailed clinical history and medical examination were obtained from 265 patients (mean age 35 years, 138 females and 127 males) presenting symptoms of upper respiratory tract infections but no fever above 38 degrees C. The presence of three pathogenic bacteria (S. pneumoniae, H. influenzae or M. catarrhalis) was determined in all patients by culture of nasopharyngeal secretions. Aggravating factors for severity of rhinosinusitis, such as severe nasal obstruction, inferior and/or middle turbinate hypertrophy, oedema of the middle meatus mucosa and septal defects, were not associated with the presence of bacteria. Pathogenic bacteria were found in 77 patients (29%). The clinical signs and symptoms which were significantly associated in a multivariate model with the presence of bacteria included facial pain (p < 0.003), coloured nasal discharge (p < 0.003) and radiological maxillary sinusitis (complete opacity, air-fluid level or mucosal thickening greater than 10 mm) (p < 0.002). This, the best predictive model, had a sensitivity of 69% and a specificity of 64% and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis. We conclude that signs and symptoms of acute rhinosinusitis in patients with a mild to moderate clinical presentation are poor predictors of the presence of bacteria. In agreement with previous studies, culture of nasopharyngeal secretions may identify patients who would benefit from antibiotic treatment. Thus, antibiotic therapy should not be prescribed in the absence of bacteriological evidence.