[Management of patients with the cardinal symptom dizziness or vertigo]. / Versorgungssituation von Patienten mit dem Leitsymptom Schwindel.

BACKGROUND: Vertigo and dizziness are common symptoms leading patients to consult a physician. The nationally representative "2003 Health Survey" depicts the epidemiology of the symptoms vertigo and dizziness across all of Germany. A breakdown of the data by region is not available. METHODS: Routine data of the Bavarian Association of Statutory Health Insurance Physicians accounting centre ("Kassenärztliche Vereinigung Bayerns", KVB) from 2008 were analysed using multilevel models to investigate individual and regional factors and the relevance of nonspecific regional heterogeneity. RESULTS: Altogether, 866,086 of 9,269,729 (9.34%) inhabitants received an ambulatory diagnosis of vertigo or dizziness, including 1.77 times as many women as men. Visits to the doctor because of vertigo or dizziness increased with age. After adjustments for age and sex, a North-South divide and a higher prevalence in the urban centres were apparent within Bavaria. The majority of patients were seen by their GP and nearby doctors. This held especially true for women. Also older patients were less likely to go to specialists further afield. CONCLUSION: This analysis of the KVB data of patients with vertigo or dizziness underlines the central role that is played by GPs in diagnosis and treatment. In order to correctly diagnose the underlying causes, treat patients or send them to specialists effectively, all doctors need to be trained about this relevant clinical symptom. The insufficient representation of clinically established vertigo disorders by the ICD-10 was problematic. The most frequently coded diagnosis was N95.1 "postmenopausal dizziness".

New antifolate inhibitors for Mycobacterium avium.

The present study extends our previous work regarding new antifolates for Mycobacterium avium (MAC) dihydrofolate reductase (DHFR). The objectives of this study were to synthesize and test new derivatives in the general class of 2,4-diamino-5-methyl-5-deazapteridines in an effort to improve solubility and selectivity for the MAC DHFR, while maintaining lack of selectivity for the human DHFR. New 6-[2', 5'-dialkoxyphenyl) methyl]-substituted DMDP analogs were synthesized as previously described. Three clinical isolates of MAC (NJ211, NJ3404, and NJ168) and M. tuberculosis H37Ra (MTB) were used to evaluate the new derivatives. A previously described colorimetric (alamarBlue(R)) microdilution broth assay was used to determine minimal inhibitory concentrations (MIC). Purified recombinant human (rDHFR), MAC rDHFR, and MTB rDHFR were used in a validated enzyme assay to obtain IC(50) values and to determine selectivity ratios (SR) for the derivatives. For the MAC strains, the MICs ranged from < 0.25 to > 16 microg/mL. The most active derivative against MAC was SRI-20920 which had MICs of 0.25, 0.25, and 8 microg/mL for the three strains, respectively. The most selective derivative was SRI-20730 with IC(50s) of 29 and 67,781 nM for MAC rDHFR and hDHFR, respectively, and a SR of 2,337. MICs for MTB ranged from 4 to >64 microg/mL and the SR, in general, ranged from 0.32 to 2.5. These results further substantiate the utility of this group of DMDP derivatives for selective activity against MAC.

The rad9 gene of Coprinus cinereus encodes a proline-rich protein required for meiotic chromosome condensation and synapsis.

The rad9 gene of Coprinus cinereus is essential for the normal completion of meiosis. We examined surface-spread preparations of wild-type and rad9-1 nuclei from the meiotic stages of karyogamy through metaphase I, and we determined the primary sequence, structure, and meiotic expression of the rad9 gene. In wild-type C. cinereus, karyogamy is followed by condensation and alignment of homologous chromosomes. Condensation and axial core development largely precede synapsis, which often initiates at telomeres. A diffuse diplotene phase coincides with dissolution of the synaptonemal complex, and subsequently chromosomes further condense as the cells progress into metaphase I. In contrast, although karyogamy and nucleolar fusion are apparently normal in rad9-1 basidia, only short stretches of synaptonemal complex form. These correlate with stretches of condensed chromatin, mostly at apparent chromosome ends, and regions of presumptive triple synapsis are numerous. rad9-1 basidia enter the diffuse stage of early diplotene, and then 50% of these cells enter metaphase I by the criteria of nucleolar elimination and at least some chromatin condensation. rad9 gene expression is induced after gamma irradiation and during meiosis. The gene has 27 exons and encodes a predicted protein of 2157 amino acids, with a proline-rich amino terminus.

Encrypted storage of medical data on a grid.

OBJECTIVES: In this article we present grids as an architecture for medical image processing and health-care networks. We argue that confidential patient data should not be stored unprotected on a grid and explain why access control systems alone do not offer sufficient protection. The objective of our work is to propose a method that complements access control systems on a grid architecture and thus makes the storage of confidential data more secure. METHODS: Effective protection can be achieved by storing confidential data in encrypted form. This raises the problem of how authorized users get access to the data, since they need to have the decryption keys. RESULTS: Our proposal details a key management architecture, that allows encrypted storage and still enables users to access decryption keys for data they are authorized to see. To achieve this functionality we use distributed keyservers storing redundant shares of the keys. CONCLUSIONS: The resulting architecture achieves our primary objective of making the storage of confidential data more secure without loosing the data sharing properties of the grid architecture. Furthermore our architecture is robust against breakdowns and denial of service attacks. It scales well with the number of users and does not introduce a single point of failure into the system.

Defective monocyte chemotaxis in mycosis fungoides.

Monocyte-macrophage function was studied in 14 patients with histologically confirmed mycosis fungoides. Three component parts of the monocyte-macrophage system were examined. Monocyte bacterial phagocytosis and bacterial killing were normal. However, a defect in directional mobility (chemotaxis) was found in patients with mycosis fungiodes (P less than .0025) when compared to 35 healthy controls. Defective chemotaxis was present regardless of disease stage or therapy. This defect in monocyte chemotaxis represents a previously unrecognized immune deficiency and may help explain the frequent infections found in patients with mycosis fungoides.

Altered immunomodulating and toxicological properties of degraded Quillaja saponaria Molina saponins.

Quillaja saponins are readily hydrolyzed under physiological conditions, yielding deacylated forms that are significantly less toxic than their precursors. Yet, deacylated saponins are unable to stimulate a strong primary immune response. Although deacylated saponins elicit a strong total IgG response, their capacity to stimulate a Thl type IgG isotype profile (i.e. high levels of IgG2a and IgG2b) has been significantly diminished. Instead, an IgG profile closer to that of a Th2 immune response is stimulated (i.e. high IgG1 levels). Deacylated saponins have also lost their capacity to elicit an effective T cell immunity, as shown by their stimulation of a marginal lymphoproliferative response and their inability to elicit the production of cytotoxic lymphocytes (CTL). Modification of the immune-modulating properties brought by the degradation of quillaja saponins during vaccine storage may change the intended immune response from a Th1 to a Th2 type. This alteration would have negligible effects on vaccines depending on Th2 immunity mediated by neutralizing antibodies. However, the performance of vaccines directed against intracellular pathogens as well as therapeutic cancer vaccines may be seriously affected by the loss of their capacity to stimulate both a Th1 immune response and the production of CTL.

Volatile methoxybenzene compounds in grains with off-odors.

More than 20 volatile methoxybenzene compounds were found in a set of 745 corn, sorghum, soybean, and wheat samples obtained from official grain inspectors. Most samples containing methoxybenzenes were off-odor. By using an autosampler, volatiles were purged from whole grain at 80 degrees C, collected on Tenax, and then thermally desorbed and transferred to a gas chromatograph-mass spectrometer for separation and identification. Use of an infrared detector aided identification of some compounds, especially isomers with similar mass spectra. Samples with insect odor had 1,4-dimethoxybenzene and its 2-methyl, 2-ethyl, and 2-methoxy derivatives that appeared to be derived from 1,4-quinones, which are known (except for 2-methoxy) defensive secretions of Tribolium insects. Samples with mostly musty, sour, and/or smoke odors commonly contained methoxybenzene and 1, 2-dimethoxybenzene along with their 4-ethyl and 4-ethenyl derivatives, 4-chloro-1-methoxybenzene, and/or 2-methoxyphenol and its 4-ethyl derivative. Other methoxybenzenes were also found, including methoxy derivatives of other phenols and N-heterocyclic compounds. Co-occurrences and correlations of levels of some compounds were also reported to indicate relationships with odors and inter-relationships among compounds.

Volatiles obtained from whole and ground grain samples by supercritical carbon dioxide and direct helium purge methods: observations on 2,3-butanediols and halogenated anisoles.

Volatile compounds were obtained from whole and ground grain samples by two methods. In the supercritical fluid extraction (SFE) method, volatiles were extracted from the grain with supercritical carbon dioxide, trapped at -78 degrees C, and then transferred via a purge-and-trap instrument to a gas chromatograph with mass and infrared detectors (GC-MS/IR) for separation and identification. In the direct-helium-purge method (DHP), volatiles were purged directly from the grain into the purge-and-trap instrument for subsequent transfer to the GC-MS/IR system. With SFE, extraction of volatiles was favored by ground grain, low pressures (

Use of an autosampler for dynamic headspace extraction of volatile compounds from grains and effect of added water on the extraction.

An autosampler attached to a purge and trap instrument was used to aid routine analyses of grain samples for volatile compounds associated with off-odors. Trapped volatiles were transferred to a gas chromatograph/mass spectrometer instrument for separation and detection. Dynamic extraction of volatiles from approximately 18 g of whole grain at 80 degrees C was accomplished by purging helium through a sample vial with a Teflon-lined septum on each end. The autosampler automatically added internal standard to the sample before purging began, which required the addition of 1 mL of water for complete transfer of the standard to the sample. The added water enhanced extraction of 1-octen-3-ol, 1-octen-3-one, and some other compounds from soybeans but not from starchy grains such as corn and wheat. Addition of a free radical scavenger, such as citric acid, greatly diminished the recovery of 1-octen-3-ol and 1-octen-3-one from soybeans.

Deoxynivalenol-contaminated wheat in swine diets.

Two studies were conducted using Fusarium graminearum-infected (scabby) wheat containing 6.8 ppm deoxynivalenol (DON), commonly called vomitoxin, substituted for normal wheat in starter pig diets to give varying levels of DON. After 3 wk on experimental treatments, one-half of the pigs in trial one were sacrificed to evaluate the effects of DON on heart, kidney, spleen and liver. Analyses for DON residues in these tissues were also performed. The remaining 16 pigs were placed on a conventional diet for 4 wk to evaluate effects of DON on subsequent animal performance. A different sample of scabby wheat containing 4.9 ppm of DON was substituted for sorghum grain in growing-finishing pig diets to give varying concentrations of DON. At the end of the 42-d feeding period, eight pigs were slaughtered to evaluate the effects of DON on selected tissues. Results of the three trials suggest that feed intake was reduced when DON concentrations in the swine diets neared or exceeded 1 ppm. No apparent signs of disease, including vomiting, were observed in experimental animals. Histological evaluation revealed no significant lesions or abnormalities related to DON ingestion in tissues examined. Traces of DON (8 to 28 ppb, wet weight) were found in kidney, liver, spleen and heart of starter pigs consuming the diets containing DON up to time of slaughter. No DON was found in tissues of growing-finishing pigs that were withdrawn from feed about 12 h before slaughter.

Real-world patient-reported rates of non-severe hypoglycaemic events in Germany.

AIMS: Hypoglycaemia is a common side effect of insulin therapy in diabetes patients, with negative physical and emotional impacts. Despite this, there are few studies investigating the frequency of non-severe hypoglycaemic events from the perspective of patients in the real-world setting. We investigated self-reported NSHE frequency and levels of hypoglycaemia awareness in Germany. METHODS: Respondents > 15 years with Type 1 or insulin-treated Type 2 diabetes (receiving basal only, basal-bolus or other insulin regimens) were recruited using online panels to complete ≤ 4 questionnaires. Questionnaires collected demographics, non-severe hypoglycaemic event rates and patient-reported level of hypoglycaemia awareness. Non-severe hypoglycaemic event rates are reported as respondent-week records and calculated using data from all respondents completing at least one questionnaire. RESULTS: A total of 1,771 respondent-week records were obtained from 614 participants. Mean non-severe hypoglycaemic event rates per respondent-week were 1.6 for Type 1 and 0.6-0.8 for Type 2, with estimated annual rates of 83 and 31-42 respectively. Two-thirds of Type 1 (65%) and Type 2 (61-72%) respondents reported impaired levels of awareness or unawareness of hypoglycaemic events (inability or impaired ability to recognise the symptoms of hypoglycaemia). Respon­dents' self-reported hypoglycaemia-awareness was significantly associated with the proportion of asymptomatic non-severe hypoglycaemic events; respondents classified as being unaware of hypoglycaemia had a higher proportion of asymptomatic non-severe hypoglycaemic events than aware respondents. CONCLUSION: Non-severe hypoglycaemic events are common in people with Type 1 or insulin-treated Type 2 diabetes in the real-world setting in Germany but may still be underestimated due to an inability to recognise the symptoms of hypoglycaemia.

Health economics analysis of insulin aspart vs. regular human insulin in type 2 diabetes patients, based on observational real life evidence from general practices in Germany.

BACKGROUND: A retrospective analysis of German general practice data demonstrated that insulin aspart (IA) was associated with a significantly reduced incidence of macrovascular events (MVE: stroke, myocardial infarction, peripheral vascular disease or coronary heart disease) vs. regular human insulin (RHI) in type 2 diabetes patients. Economic implications, balanced against potential improvements in quality-adjusted life years (QALYs) resulting from lower risks of complications with IA in this setting have not yet been explored. METHODS: A decision analysis model was developed utilizing 3-year initial MVE rates for each comparator, combined with published German-specific insulin and MVE costs and health utilities to calculate number needed to treat (NNT) to avoid any MVE, incremental costs and QALYs gained/ person for IA vs. RHI. A 3-year time horizon and German 3(rd)-party payer perspective were used. Probabilistic sensitivity analysis was performed, sampling from distributions of key parameters. Additional sensitivity analyses were performed. RESULTS: NNT over a 3 year period to avoid any MVE was 8 patients for IA vs. RHI. Due to lower MVE rates, IA dominated RHI with 0.020 QALYs gained (95% confidence interval: 0.014-0.025) and cost savings of EUR 1 556 (1 062-2 076)/person for IA vs. RHI over the 3-year time horizon. Sensitivity analysis revealed that IA would still be overall cost saving even if the cost of IA was double the cost/unit of RHI. CONCLUSIONS: From a health economics perspective, IA was the superior alternative for the insulin treatment of type 2 diabetes, with lower incidence of MVE events translating to improved QALYs and lower costs vs. RHI within a 3-year time horizon.

Pharmacokinetic and pharmacodynamic evaluation of the novel CCR1 antagonist CCX354 in healthy human subjects: implications for selection of clinical dose.

The safety and pharmacokinetic (PK)/pharmacodynamic (PD) profile of the novel CCR1 antagonist CCX354 was evaluated in double-blind, placebo-controlled, single- and multiple-dose phase I studies (1-300 mg/day oral doses). CCX354 was well tolerated and displayed a linear dose-exposure profile, with half-life approaching 7 h at the 300-mg dose. The extent of CCR1 receptor blockade on blood monocytes, which correlated well with plasma concentrations of the drug, was assessed using fluorescently labeled CCL3 binding in whole blood from phase I subjects. High levels of receptor coverage at the 12-h time point were achieved after a single dose of 100 mg CCX354. Preclinical studies indicate that effective blockade of inflammatory cell infiltration into tissues requires ≥90% CCR1 inhibition on blood leukocytes at all times. The comparison of the properties of CCX354 with those published for other CCR1 antagonists has informed the dose selection for ongoing clinical development of CCX354 in rheumatoid arthritis (RA).

New Mycobacterium avium antifolate shows synergistic effect when used in combination with dihydropteroate synthase inhibitors.

Mycobacterium avium complex (MAC) is resistant to trimethoprim, an inhibitor of bacterial dihydrofolate reductase (DHFR). A previously identified selective inhibitor of MAC DHFR, SRI-8858, was shown to have synergistic activity in combination with dapsone and sulfamethoxazole, two drugs that inhibit bacterial dihydropteroate synthase.

Comparison of methods for aflatoxin analysis by high-pressure liquid chromatography.

Reversed-phase columns packed with octadecyl and phenyl reversed phases did not provide adequate separation of aflatoxins. A peculiar adsorption column provided partial separation, i.e. B1 and B2 from G1 andG2, but not B1 from B2 nor G1 from G2. A microparticulate adsorption (7icro-A) column completely separated aflatoxins B1, B2, G1, and G2. Detection was more selective at 350 nm (or 365 nm) than at 254 nm. A Fluoro Monitor Model 1209 detector (Laboratory Data Control Corp.) was more sensitive for aflatoxins G1 and G2 than for B1 and B2. Aflatoxin B1 at the 30-ppb level in yellow corn was detected with the Micro-A column and the 350-nm photometer. The limit of detection was estimated at about 10 ppb.

Simple method for simultaneous detection of aflatoxin and zearalenone in corn.

A method is described for the simultaneous detection of alfatoxin and zearalenone in corn at 5 and 200 ppb, respectively. No evaporation of solvent is required and the procedure is simple enough to be considered for use at marketing locations. The presence of absence of these myocotoxins can be determined in 10-20 min/sample. The procedure involves an initial blender extraction with methanol, partitioning of fat and pigments into 1-1,2-trichlorotrifluoroethane (Freon-113) from an aqueous ammonium sulfate layer, followed by extraction of aflatoxin from the aqueous layer with chlorobenzene. The chlorobenzene extract can be spotted directly onto a thin layer chromatographic plate which requires only 4 min development. Concentrations of aflatoxin and zearalenone can be estimated by visual comparison of sample spots with standards.

Genetic analysis of mecillinam-resistant mutants of Caulobacter crescentus deficient in stalk biosynthesis.

Stalk synthesis in Caulobacter crescentus is a developmentally controlled and spatially restricted event that requires the synthesis of peptidoglycan at the stalk-cell body junction. We show that the beta-lactam antibiotic mecillinam prevents stalk synthesis by inhibiting stalk elongation. In addition, mecillinam causes an increase in the diameter of the stalk at the stalk-cell body junction. We describe two mutations that confer resistance to mecillinam and that prevent stalk elongation. These mutations are probably allelic, and they map to a locus previously not associated with stalk synthesis.