Emerging Salmonella Enteritidis anaerogenic phage type 14b: outbreak in Norwegian, Swedish and Finnish travellers returning from Greece.

In July 2001, the Norwegian Institute of Public Health (Folkehelseinstituttet, FHI) reported a cluster of Salmonella Enteritidis of phage type 14b infections in Norwegian travellers returning from Greece. An increase in the same uncommon phage type was also registered in Sweden and Finland at the same time. Cases of S. Enteritidis PT 14b in patients returning from Greece were reported in these three Nordic countries in 2001 (303 cases), 2002 (164 cases) and 2003 (199 cases). Case-control studies performed in 2001 in Norway and Sweden indicated that consumption of chicken was associated with illness. In 2002 and 2003, continuing case reports indicated that this uncommon phage type had probably become established in the Greek food chain. Tour operators were informed and contacts were made with Greek public health authorities. Because place of infection is not systematically included in most Salmonella notification systems, the S. Enteritidis phage type 14b outbreak reported here may represent only part of a larger outbreak among travellers visiting Greece. Infections are often reported only in the tourists' home countries and public health authorities in the tourist destinations may not be aware of the problem. Further collaboration between national institutes of public health in Europe is needed to detect outbreaks occurring among tourists.

Emerging Salmonella Enteritidis anaerogenic phage type 14b: Outbreak in Norwegian, Swedish and Finnish travellers returning from Greece.

In July 2001, the Norwegian Institute of Public Health (Folkehelseinstituttet, FHI) reported a cluster of Salmonella Enteritidis of phage type 14b infections in Norwegian travellers returning from Greece. An increase in the same uncommon phage type was also registered in Sweden and Finland at the same time. Cases of S. Enteritidis PT 14b in patients returning from Greece were reported in these three Nordic countries in 2001 (303 cases), 2002 (164 cases) and 2003 (199 cases). Case-control studies performed in 2001 in Norway and Sweden indicated that consumption of chicken was associated with illness. In 2002 and 2003, continuing case reports indicated that this uncommon phage type had probably become established in the Greek food chain. Tour operators were informed and contacts were made with Greek public health authorities. Because place of infection is not systematically included in most Salmonella notification systems, the S. Enteritidis phage type 14b outbreak reported here may represent only part of a larger outbreak among travellers visiting Greece. Infections are often reported only in the tourists' home countries and public health authorities in the tourist destinations may not be aware of the problem. Further collaboration between national institutes of public health in Europe is needed to detect outbreaks occurring among tourists.

Risk factors associated with typhoid fever in Son La province, northern Vietnam.

Between July and December 2002, we undertook a hospital-based case-control study to identify risk factors associated with typhoid fever in Son La province, northern Vietnam. Among 617 suspected cases, 90 cases of typhoid fever were confirmed by blood or stool culture. One hundred and eighty controls (neighbours of typhoid cases matched for gender and age) were chosen. Participants were interviewed at home using a standardized questionnaire. Seventy-five per cent of cases were aged 10-44 years. No cases in patients aged less than 5 years were recorded in this study. In a conditional logistic regression analysis recent contact with a typhoid patient (OR = 3.3, 95% CI 1.7-6.2, P < 0.001), no education (OR = 2.0, 95% CI 1.0-3.7, P = 0.03) and drinking untreated water (OR = 3.9, 95% CI 2.0-7.5, P < 0.001) were independently associated with typhoid fever. Improving quality of drinking water must be a priority and health education strategies targeted at individuals with no schooling, and contacts of patients, would be expected to decrease the burden of typhoid fever.

Waterborne outbreak of gastroenteritis in a religious summer camp in Norway, 2002.

In July 2002 an outbreak of acute gastroenteritis occurred in a camp facility in western Norway during a 10-day seminar, with around 300 guests staying overnight and several day-time visitors. Environmental and epidemiological investigations were conducted to identify and eliminate the source of the outbreak, prevent further transmission and describe the impact of the outbreak. Of 205 respondents, 134 reported illness (attack rate, 65%). Multivariate analysis showed drinking water and taking showers at the camp-site to be significant risk factors. Secondary person-to-person spread among visitors or outside of the camp was found. Norovirus was identified in 8 out of the 10 stool samples analysed. Indicators of faecal contamination were found in samples from the private untreated water supply, but norovirus could not be identified. This outbreak investigation illustrates the importance of norovirus as a cause of waterborne illness and the additional exacerbation through person-to-person transmission in closed settings. Since aerosol transmission through showering contributed to the spread, intensified hygienic procedures such as isolation of cases and boiling of water may not be sufficient to terminate outbreaks with norovirus.

Association between environmental risk factors and campylobacter infections in Sweden.

Campylobacter sp. is the most common cause of acute bacterial gastroenteritis in Sweden and the incidence has been increasing. Case-control studies to identify risk factors have been conducted in several countries, but much remains unexplained. The geographical distribution of campylobacter infections varies substantially, and many environmental factors may influence the observed pattern. Geographical Information Systems (GIS) offer an opportunity to use routinely available surveillance data to explore associations between potential environmental risk factors showing a geographical pattern and disease incidence, complementing traditional approaches for investigating risk factors for disease. We investigated associations between campylobacter incidence and environmental factors related to water and livestock in Sweden. Poisson regression was used to estimate the strength of the associations. Positive associations were found between campylobacter incidence and average water-pipe length per person, ruminant density, and a negative association with the percentage of the population receiving water from a public water supply. This indicates that drinking water and contamination from livestock may be important factors in explaining sporadic human campylobacteriosis in Sweden, and that contamination occurring in the water distribution system might be more important than previously considered.

Global, synchronous oscillations in cytosolic calcium and adherence in bradykinin-stimulated Madin-Darby canine kidney cells.

AIMS AND METHODS: Intercellular Ca2+ oscillations are a universal mode of signalling in both excitable and non-excitable cells. Here, we study the relationship between Ca2+ signalling and coherent changes in adhesion properties by measuring the transepithelial impedance across bradykinin-stimulated Madin-Darby canine kidney (MDCK) cell layers grown on a microelectrode. During hormone stimulation, the impedance is found to oscillate, reflecting that the cells undergo morphological/adhesive alterations with high spatio-temporal organization. The experiments are supplemented with parallel, digital imaging fluorescence microscopy of bradykinin-induced single-cell Ca2+ oscillations. RESULTS: In agreement with previous experiments, MDCK cells are found to elicit synchronous, multicellular Ca2+ oscillations in response to hormone stimulus. The periods of the Ca2+ oscillations and the electrical fluctuations are found to coincide. Further, blocking of gap junctions by 18alpha-glycyrrhetinic acid causes a loss of synchrony in Ca2+ signals and inhibition of impedance oscillations, emphasizing the importance of gap junctions in the signal transduction process. CONCLUSION: Based on these observations it is concluded that the co-ordinated adhesive changes in MDCK cells are a direct consequence of synchronized Ca2+ oscillations. Calcium signalling represents an efficient way of organizing physiological responses in a tissue. A possible functional implication of the structural changes might be to modulate transportation of various substances across the cell sheet.

Definition and estimation of an actual reproduction number describing past infectious disease transmission: application to HIV epidemics among homosexual men in Denmark, Norway and Sweden.

Prevalence and incidence measures are the common way to describe epidemics. The reproduction number supplies information on the potential for growth or decline of an epidemic. We define an actual reproduction number for infectious disease transmission that has taken place. An estimator is suggested, based on the number of new infections observed in a given time-interval, the number of those infected at the start of the interval, and the length of the infectious period. That estimator is applied to HIV among men having sex with other men over the period, 1977-1995, in Scandinavia. The actual reproduction number was estimated with acceptable certainty from the period, 1981-1982, yielding a value of 15 secondary cases. A value of less than one secondary case was assessed for the period, 1988-1995, in Denmark and Sweden. The actual reproduction number gives us some additional understanding of the dynamics of epidemics, compared with prevalence and incidence curves.

Rocuronium and anaphylaxis--a statistical challenge.

Drug induced anaphylaxis is frequently attributed to the use of muscle relaxants during anaesthesia. Recently The Norwegian Medicines Agency recommended that rocuronium bromide (Esmeron) be withdrawn from routine practice due to frequent reports of anaphylaxis. Over a period of two and a half years approximately 150,000 patients received rocuronium as part of their anaesthesia. In this period the Norwegian drug authorities received 29 reports of anaphylaxis or anaphylactoid reactions in patients treated with rocuronium. This is in stark contrast to the situation in other Nordic countries where a total of only seven cases of anaphylaxis in approximately 800,000 patients treated with rocuronium had been recorded by December 2000. This situation highlights the many potential problems of the surveillance of adverse drug reactions: reporting bias may lead to an over-estimate of the risk of one drug compared to another, and the possibility of under-reporting of adverse events (due to a weak reporting culture) further limit the validity of such comparisons. The surveillance of adverse drug reactions also represents a statistical challenge. While adverse event reports may help us to estimate the anaphylaxis rate we need to appreciate the uncertainty of such estimates. Adverse reactions are rare, random, and mostly independent events, resulting from the successive exposure of patients to a low risk intervention. The frequency distribution of adverse events will therefore conform to that of a Poisson process. The resulting Poisson distribution may inform us about the variability of adverse event data. An understanding of these methodological problems and statistical challenges will allow anaesthesiologists to make informed decisions concerning the use of muscle relaxants and other drugs associated with severe adverse reactions.

A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: how much really is known?

BACKGROUND: Many studies have explored the role of "classic" sexually transmitted diseases (STDs) in determining the pattern of HIV epidemics. However, the many different STDs may contribute in different ways, at different magnitudes. GOAL: To review available studies on the bidirectional interactions of HIV and STDs to explore the extent of current knowledge on the different influences of the varied STDs in heterosexual HIV epidemics. METHODS: Longitudinal studies on susceptibility and controlled studies on infectiousness and duration of disease identified on electronic databases through reference lists and citation indices up to the end of 1999 were systematically reviewed, including meta-analyses assessing the influence of STDs on susceptibility to HIV. RESULTS: Studies have a clear publication bias with a significant result that hinders robust interpretation. However, genital ulcerative disease appears to have a greater impact than nonulcerative disease, and men are more affected than women by the effects of STDs on susceptibility to HIV. There is evidence that STDs increase the infectiousness of HIV from men to women, whereas the evidence is more equivocal for the infectiousness of women. Few studies identify the impact of different STDs, and there is a marked lack of studies investigating the impact of HIV infection on the transmission of other STDs. CONCLUSIONS: A large body of work has measured the association between STDs and HIV. However, publication bias and gaps in the focus of studies mean that a detailed, quantitative understanding of the interaction requires much more attention.

Phagocytic dendritic cells from myelomas activate tumor-specific T cells at a single cell level.

Antigen-presenting cells (APCs) from subcutaneous mouse MOPC315 plasmacytoma phagocytosed immunoglobulin G-coated magnetic beads, enabling efficient isolation within 2 hours by magnetic separation (APC-MB). Cell morphology was heterogeneous, with some of the cells having dendrites. The surface phenotype of purified tumor APCs-MB was CD11b(+), CD11c(+), CD40(+), CD80(+), CD86(+), and MHC class II(+). Tumor APCs-MB expressed messenger RNA for fractalkine and ABCD-1 chemokines, and for CC-type chemokine receptors CCR5 and CCR7, indicating the presence of mature dendritic cells (DCs). Visualized at a single cell level within 4 hours after disruption of the tumor, APCs-MB induced rapid Ca(++) mobilization in MHC class II-restricted tumor idiotype (Id)-specific cloned CD4(+) T cells. In long-term assays, tumor APCs-MB induced proliferation of naive T cells from Id-specific T-cell receptor transgenic mice. The results suggest that tumor APCs-MB represent a heterogeneous cell population that includes myeloid-derived DCs of various stages of maturation. A considerable fraction (> or = 15%) of DCs is spontaneously primed with tumor-specific antigen.

T cell-specific adapter protein inhibits T cell activation by modulating Lck activity.

We previously reported the isolation of a cDNA encoding a T cell-specific adapter protein (TSAd). Its amino acid sequence contains an SH2 domain, tyrosines in protein binding motifs, and proline-rich regions. In this report we show that expression of TSAd is induced in normal peripheral blood T cells stimulated with anti-CD3 mAbs or anti-CD3 plus anti-CD28 mAbs. Overexpression of TSAd in Jurkat T cells interfered with TCR-mediated signaling by down-modulating anti-CD3/PMA-induced IL-2 promoter activity and anti-CD3 induced Ca2+ mobilization. The TCR-induced tyrosine phosphorylation of phospholipase C-gamma1, SH2-domain-containing leukocyte-specific phosphoprotein of 76kDa, and linker for activation of T cells was also reduced. Furthermore, TSAd inhibited Zap-70 recruitment to the CD3zeta-chains in a dose-dependent manner. Consistent with this, Lck kinase activity was reduced 3- to 4-fold in COS-7 cells transfected with both TSAd and Lck, indicating a regulatory effect of TSAd on Lck. In conclusion, our data strongly suggest an inhibitory role for TSAd in proximal T cell activation.

Ruled by waves? Intracellular and intercellular calcium signalling.

The field of calcium signalling has evolved rapidly the last 20 years. Physiologists had worked with cytosolic Ca2+ as the coupler of excitation and contraction of muscles and as a secretory signal in exocrine glands and in the synapses of the brain for several decades before the discovery of cellular calcium as a second messenger. Development of powerful techniques for measuring the concentration of cytosolic free calcium ions in cell suspensions and later in single cells and even in different cellular compartments, has resulted in an upsurge in the knowledge of the cellular machinery involved in intracellular calcium signalling. However, the focus on intracellular mechanisms might have led this field of study away from physiology. During the last few years there is an increasing evidence for an important role of calcium also as an intercellular signal. Via gap junctions calcium is able to co-ordinate cell populations and even organs like the liver. Here we will give an overview of the general mechanisms of intracellular calcium signalling, and then review the recent data on intercellular calcium signals. A functional coupling of cells in different tissues and organs by the way of calcium might be an important mechanism for controlling and synchronizing physiological responses

Coagulation factors VIIa and Xa induce cell signaling leading to up-regulation of the egr-1 gene.

Intracellular signaling induced by the coagulation factors (F) VIIa and Xa is poorly understood. We report here studies on these processes in a human keratinocyte line (HaCaT), which is a constitutive producer of tissue factor (TF) and responds to both FVIIa and FXa with elevation of cytosolic Ca(2+), phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38(MAPK), and c-Jun N-terminal kinase, and up-regulation of transcription of the early growth response gene-1 (egr-1). Using egr-1 as end point, we observed with both agonists that phosphatidylinositol-specific phospholipase C and the mitogen-activated protein kinase/Erk kinase/Erk pathway were mediators of the responses. The responses to FVIIa were TF-dependent and up-regulation of egr-1 mRNA did not require presence of the TF cytoplasmic domain. Antibodies to EPR-1 and factor V had no effect on the response to FXa. We have provided evidence that TF is not the sole component of the FVIIa receptor. The requirement for proteolytic activity of both FVIIa and FXa suggests that protease-activated receptors may be involved. We now report evidence suggesting that protease-activated receptor 2 or a close homologue may be a necessary but not sufficient component of this particular signal transduction pathway. The up-regulation of egr-1 describes one way by which the initiation of blood coagulation may influence gene transcription. The ability of these coagulation proteases to induce intracellular signals at concentrations at or below the plasma concentrations of their zymogen precursors suggests that these processes may occur also in vivo.

[Medical research at Norwegian universities]. / Medisinsk forskning ved norske universiteter.

This study shows that Norwegian medical research suffers from lack of both public funds and recruitment, as well as being affected by the following major factors. Norway uses less of its GNP on R&D than other Western countries and less than the OECD average. Medical research in particular receives less financial support than in any of the other Nordic countries. Norwegian medical researchers publish less material and are cited less often than their colleagues in comparable countries. More than half of the medically trained scientific staff in Norway's four medical faculties will retire during the next decade and today there are many vacant positions in academic medicine because there are not enough competent applicants to fill them. The percentage of M.D.s among professors and lecturers has fallen, and a continued decline in preclinical and laboratory medicine and in public health is predicted. This percentage has also decreased among Ph.D. students, while the age at which medical doctors dissertate has increased and is higher than for other Ph.D.s. The number of medical students doing research has fallen in recent years, and the number of doctoral theses has not increased as much in medicine as in other fields. There are significant differences between the salaries paid in medical science and those paid in clinical medicine. Lack of resources and low salaries keep doctors from pursuing a career in academic medicine. In conclusion, if Norway is to be visible in the field of international medical science, this negative trend must be reversed and medical research and academic medicine revitalised.