Sustainability of vaginal estrogens for genitourinary syndrome of menopause - a systematic review.

Genitourinary syndrome of menopause (GSM) is a highly prevalent, not self-limiting condition displaying a major negative impact on sexual function and emotional well-being. Various non-hormonal and hormonal treatment options are available. Many women consider GSM treatment to be a short-term interval cure rather than a long-term or lifelong treatment. The aim of this systematic literature search was to assess the sustainability of vaginal estrogens for GSM treatment after treatment cessation. We found that objective GSM signs mostly deteriorated within approximately 4 weeks after vaginal estrogen treatment cessation, while vaginal estrogens had a more sustainable impact on subjective GSM symptoms up to 3-6 months. However, overall, scientific evidence on sustainability of vaginal estrogens was low. Thus, GSM treatment should not be considered a short-term interval cure but long-term therapy. Further studies in an internationally harmonized setting (Core Outcomes in Menopause [COMMA]) are needed.

Estimating healthcare costs of acute gastroenteritis and human campylobacteriosis in Switzerland.

Rising numbers of campylobacteriosis case notifications in Switzerland resulted in an increased attention to acute gastroenteritis (AG) in general. Patients with a laboratory-confirmed Campylobacter infection perceive their disease as severe and around 15% of these patients are hospitalized. This study aimed at estimating healthcare costs due to AG and campylobacteriosis in Switzerland. We used official health statistics, data from different studies and expert opinion for estimating individual treatment costs for patients with different illness severity and for extrapolating overall costs due to AG and campylobacteriosis. We estimated that total Swiss healthcare costs resulting from these diseases amount to €29-45 million annually. Data suggest that patients with AG consulting a physician without a stool diagnostic test account for €9·0-24·2 million, patients with a negative stool test result for Campylobacter spp. for €12·3 million, patients testing positive for Campylobacter spp. for €1·8 million and hospitalized campylobacteriosis patients for €6·5 million/year. Healthcare costs of campylobacteriosis are high and most likely increasing in Switzerland considering that campylobacteriosis case notifications steadily increased in the past decade. Costs and potential cost savings for the healthcare system should be considered when designing sectorial and cross-sectorial interventions to reduce the burden of human campylobacteriosis in Switzerland.

Testing for Chlamydia trachomatis: time trends in positivity rates in the canton of Basel-Stadt, Switzerland.

National health statistics report a 2·5-fold increase in laboratory-confirmed Chlamydia trachomatis (CT) cases over the last decade in Switzerland where no CT screening programme exists. We obtained essential denominator information to describe the epidemiology of CT in the canton of Basel-Stadt, an urban canton in north-western Switzerland. Laboratories reporting at least two CT infections from Basel-Stadt residents to the SFOPH in 2010 provided demographic and test-related data. CT positivity rates were calculated for 2002­2010. The influences of test year, age, sex and laboratory on CT positivity were investigated in a multivariable model. Positivity differed between sexes and age groups. In our sample of 32 034 records, female and male CT positivity rates were 4·7% and 11·1%, respectively. Test year was significantly associated with test outcome in the multivariable analysis but no time trend was observed. CT positivity did not change over the past 9 years in Basel-Stadt. In contrast to other European countries without CT screening, we found no evidence that the observed increase of Chlamydia cases in the national notification system represents an epidemiological trend, but rather results from an increased testing frequency.

Release of extracellular particles by recombinant vaccinia virus over-expressing the major envelope protein p37K.

During the replication cycle of vaccinia virus, four different forms of viral particles are produced. The two extracellular enveloped forms, cell-associated enveloped virus and extracellular enveloped virus, are responsible for cell-to-cell transmission and long-range spread of infection both in vivo and in vitro. Despite the biological importance of the enveloped forms, the mechanism of envelopment and the components involved in this process have been analysed only recently. Therefore the individual steps and the rate-limiting factors of the envelopment process are still unknown. The protein p37K, an unglycosylated but acylated envelope protein of molecular mass 37 kDa, has been shown to be essential for envelopment. However, this study shows that over-expression of p37K by vaccinia virus recombinants reduces rather than increases the yield of infectious enveloped virus which is mainly due to the enveloped virions exhibiting a strongly diminished specific infectivity.

Stability of succinylcholine chloride injection.

The stability of succinylcholine chloride injection prepared by a hospital pharmacy was studied under a wide variety of conditions. Batches of succinylcholine chloride injection 10 mg/mL containing sodium chloride, methyl-4-hydroxybenzoate, hydrochloric acid, and water were prepared. Samples were tested for the effect of initial pH (3.0 and 4.2) and sterilization (steam treatment at 100 degrees C for 30 minutes and 121 degrees C for 20 minutes) on stability after three weeks; long-term stability under refrigeration (12, 17, and 23 months of storage at 4 degrees C); and the effect of storage temperature (4-6 degrees C, 20-26 degrees C, 35 degrees C, and 70 degrees C) and light exposure at various intervals up to 12 months. Samples were analyzed by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Unlike heating at 121 degrees C, heating at 100 degrees C produced no significant loss of succinylcholine chloride, independent of the initial pH. Succinylcholine chloride was hydrolyzed only minimally over 23 months if the solution was stored at 4-6 degrees C. A 10% loss of drug content occurred if solutions were kept at 20-26 degrees C for five months, at 35 degrees C for one month, or at 70 degrees C for one day. Initial degradation was slowed if the solution was protected from light. The assessments by TLC proved to be more sensitive than the HPLC measurements. Succinylcholine chloride injection sterilized at 100 degrees C for 30 minutes can be stored for up to five months at room temperature if protected from light. The preparation is stable for at least two years under refrigeration.

A mutation in the gene encoding the vaccinia virus 37,000-M(r) protein confers resistance to an inhibitor of virus envelopment and release.

Plaque formation in vaccinia virus is inhibited by the compound N1-isonicotinoyl-N2-3-methyl-4-chlorobenzoylhydrazine (IMCBH). We have isolated a mutant virus that forms wild-type plaques in the presence of the drug. Comparison of wild-type and mutant virus showed that both viruses produced similar amounts of infectious intracellular naked virus in the presence of the drug. In contrast to the mutant, no extracellular enveloped virus was obtained from IMCBH-treated cells infected with wild-type virus. Marker rescue experiments were used to map the mutation conferring IMCBH resistance to the mutant virus. The map position coincided with that of the gene encoding the viral envelope antigen of M(r) 37,000. Sequence analysis of both wild-type and mutant genes showed a single nucleotide change (G to T) in the mutant gene. In the deduced amino acid sequence, the mutation changes the codon for an acidic Asp residue in the wild-type gene to one for a polar noncharged Tyr residue in the mutant.

Biochemical analysis of the major vaccinia virus envelope antigen.

The major envelope antigen of vaccinia virus is an acylated protein of M(r) 37,000 (p37K) which is required for the formation of extracellular enveloped virions (EEV). Despite its important role in the wrapping process, p37K has not been studied in much detail. In order to better characterize this protein we have undertaken a detailed biochemical analysis. Sodium carbonate treatment showed that p37K is tightly bound to the viral envelope. Its resistance to proteinase K digestion indicates that it is not exposed on the surface of EEV but lines the inner side of the envelope. Since p37K does not contain a signal peptide characteristic of most membrane proteins, we examined the possibility that the protein acquires its membrane affinity through the addition of fatty acids. Indeed, Triton X-114 phase partitioning experiments demonstrated that p37K is hydrophobic when acylated, but hydrophilic in the absence of fatty acids. Three other viral proteins have been shown to be required for virus envelopment and release from the host cell and we therefore tested whether p37K interacts with viral proteins. In EEV and in absence of reducing agents, an 80-kDa complex reacting with an anti-37K antiserum was found. Analysis of this complex showed that it most likely consists of a p37K homodimer. Interestingly, only a small amount of p37K occurs as a complex, most of it is present in the viral envelope as monomers.

Granulocyte-macrophage colony-stimulating factor as an autocrine survival factor for mature normal and malignant B lymphocytes.

The role of GM-CSF in B cell (patho)physiology is unclear. Although B cells can respond to GM-CSF, there is controversy concerning the extent to which various resting and activated B cell types can themselves produce this cytokine, and the possibility that it can function in an autocrine fashion has not previously been considered. The aim of the present study was to address these issues using hairy cells (HCs) and chronic lymphocytic leukemia cells, two intrinsically activated mature malignant B cell types (with activation being more uniform and more pronounced in HCs). Normal B cells were used for comparison. Using a number of techniques, we demonstrated the constitutive production of GM-CSF by all three cell types and showed that the cytokine was biologically active. GM-CSF mRNA and protein were increased after cell activation by PMA, and constitutive production of the cytokine was highest in HCs, suggesting that the level of GM-CSF production is influenced by cell activation. Because GM-CSF is known to be antiapoptotic for myeloid cells, we used blocking anti-GM-CSF Abs to examine the contribution of autocrinely produced cytokine to cell survival. The Abs produced marked reduction in the in vitro survival of HCs, chronic lymphocytic leukemia cells, and normal B cells by promoting apoptosis. Taken together, these findings suggest that, in combination with other known rescue factors, autocrinely produced GM-CSF may contribute to normal and malignant B cell survival in vivo.