Medical adherence in patients with systemic lupus erythematosus in Germany: predictors and reasons for non-adherence - a cross-sectional analysis of the LuLa-cohort.

Objective Adherence to medication has a major impact on treatment control and success especially in chronic diseases but often remains unrecognized. Besides clinical, socioeconomic, disease-related and treatment-related parameters, general and personal health beliefs, as well as perception of health, can affect adherence. Our aim was to investigate the adherence to lupus-specific medications in German lupus patients and to assess influencing factors including detrimental or beneficial effects of health perceptions and beliefs. Methods The Lupus Erythematosus (LE) Long-Term Study (LuLa-study) is a nationwide longitudinal study among German Caucasian patients with systemic lupus erythematosus who have been assessed annually using a self-reported questionnaire since 2001. In 2013, we included questions concerning medical adherence (Morisky Medication Adherence Scale; MMAS-4), beliefs about medication prescribed (BMQ), illness perception and about the patients' health locus of control (HLC). We present a cross-sectional analysis to assess predictors of adherence using a multivariable stepwise logistic regression. Results Five hundred and seventy-nine patients participated, 81 of whom did not take any lupus-specific medication and 40 of whom did not complete the MMAS-4 and were therefore omitted. Only 62.7% reported high adherence. Unintentional behaviour for low medical adherence exceeded the intentional behaviour by far. The use of azathioprine (OR: 1.85; 95% CI: 1.02-3.34), prednisone <7.5 mg (OR: 1.56; 95% CI: 0.97-2.49), a higher age (OR: 1.06; 95% CI: 1.03-1.08) and higher external HLC (OR: 1.15; 95% CI: 1.01-1.30) proved conducive for high adherence in our multivariable model. On the contrary, the general perception of medication being harmful or addictive (OR: 0.89; 95% CI: 0.82-0.97) was detrimental. Conclusion A low belief that one's own health is determined by healthcare providers (external HLC) and the belief of the harmfulness of medication were independent predictors of low adherence besides age and the choice of the medical agent. The recognition of these potential obstacles in physician-patient relationships is essential to ameliorate adherence. Provision of sufficient information and education might help to reach the best possible outcome.

Foveolar gastric metaplasia of the duodenum: a frequent, so far neglected type of duodenal polyp.

Foveolar gastric metaplasia of the duodenum (FGM) is considered as imperfect mucosal healing in the context of H. pylori gastritis and intake of NSAIDs or ASS.  Typical endoscopic findings are redness of the mucosa, erosion/ulcer and loss of mucosal folds. During diagnostic histological examinations we observed a frequent so far not described association of FGM with endoscopically observed duodenal polyps. The archives of two institutes of pathology with high gastroenterological workload (approximately 100 000 patients per year) were investigated for an association between "duodenal polyp" and "foveolar gastric metaplasia". In Institute 1, of 481 duodenal polyps 41 % were classified as FGM, 9 % as adenoma and 2 % as heterotopic gastric mucosa. In 48 % no histological correlate was present. In Institute 2, 217 cases of FGM were diagnosed. Of these, in 69 cases the endoscopic finding was "polyp" (32 %). In the other cases, the endoscopic findings were mucosal defect (18 %), redness/inflammation (16 %), suspicion for gastric heterotopia (5 %) and scar (3 %). In 26 % of cases no pathologic endoscopic finding was reported. Both groups of patients with FGM showed a similar distribution of age ranges (24 - 83 years and 16 - 88 years), median age (62 years and 61 years, respectively) and a dominance of male sex (both 1.5:1). In conclusion, foveolar gastric metaplasia is a frequent, so far neglected correlate of endoscopically detected duodenal polyps.

Value of ultrasound in preoperative local staging in early breast cancer.

PURPOSE: The purpose of this study was to determine the precision of breast ultrasound for the measurement of breast lesions compared to the histological measurement. A number of other dependent variables were also analyzed. MATERIAL AND METHODS: 460 patients with 445 malignant lesions were examined using breast ultrasound and the lesions were measured and compared to the histologically measured size. The data was further analyzed according to histology, tumor stage, age, grading and therapy. RESULTS: Metric comparison showed good correlation between sonography and the pathologically measured size of breast lesions, especially in tumor stage T 1 and T 2 and within ductal invasive carcinomas. Higher tumor stages lead to imprecise measurements and the histological type of lobular invasive carcinoma also results in imprecise measurements. Age and grading do not influence measurement precision. CONCLUSION: Breast ultrasound allows precise measurement of breast lesions especially at lower tumor stages. The higher the tumor stage, the more imprecise the measurement becomes. Multivariate analysis shows no cross impact between tumor stage and histological type with respect to the quality of measurement.

Lambda transition in liquid sulfur.

Density measurements on liquid sulfur near the transition at 160 degrees C show a logarithmic singularity and discontinuous density. The transition shows the kinetic behavior of a zero-order reaction. The transition is expected to have a latent heat characteristic of a first-order phase transition but is of the cooperative nature associated with second-order transitions such as the lambda point in liquid helium.

[Pathophysiology of bone metastases in urologic carcinomas]. / Pathophysiologie der Skelettmetastasierung urologischer Karzinome.

The skeletal system is the most frequent metastatic site of hematogenous spread of urologic carcinomas. Osseus metastases are classified as osteoneutral, osteolytic, osteoblastic and combinations thereof. Osteolytic metastases lead to bone resorption by activating osteoclasts, while osteoblastic metastases stimulate osteoblasts by paracrine mechanisms. The local osteoblastic effect is associated with secondary systemic bone resorption. The use of bisphosphonates is now an established supportive therapy and newer treatment strategies including targeted intervention in the pathophysiology of bone metastases and radioimmunotherapy are being applied or will be coming soon.

Random cleavage of superhelical SV 40 DNA S1 nuclease.

SV40 DNA FO I is randomly cleaved by S1 nuclease both at moderate (50 mM) and higher salt concentrations (250 mM NaC1). Full length linear S1 cleavage products of SV40 DNA when digested with various restriction endonucleases revealed fragments that were electrophoretically indistinguishable from the products found after digestion of superhelical SV40 DNA FO I with the corresponding enzyme. Concordingly, when the linear S1 generated duplexes were melted and renatured, circular duplexes were formed in addition to complex larger structures. This indicated that cleavage must have occurred at different sites. The double-strand-cleaving activity present in S1 nuclease preparations requires circular DNA as a substrate, as linear SV40 DNA is not cleaved. With regard to these properties S1 nuclease resembles some of the complex type I restriction nucleases from Escherichia coli which also cleave SV40 DNA only once, and, completely at random.

The extraction of high-molecular-mass DNA from hair shafts.

A simple and efficient method is presented for the extraction of DNA from hair shafts. DNA preparations obtained by this approach can be made amenable to restriction enzyme digestion, thereby allowing further molecular biological analysis.

Voltage and substrate dependence of the inverse transport mode of the rabbit Na(+)/glucose cotransporter (SGLT1).

Properties of the cytoplasmic binding sites of the rabbit Na(+)/glucose cotransporter, SGLT1, expressed in Xenopus oocytes were investigated using the giant excised patch clamp technique. Voltage and substrate dependence of the outward cotransport were studied using alpha-methyl D-glucopyranoside (alphaMDG) as a substrate. The apparent affinity for alphaMDG depends on the cytoplasmic Na(+) concentration and voltage. At 0 mV the K(M) for alphaMDG is 7 mM at 110 mM Na(+) and 31 mM at 10 mM Na(+). The apparent affinity for alphaMDG and Na(+) is voltage dependent and increases at positive potentials. At 0 mV holding potential the outward current is half-maximal at about 70 mM. The results show that SGLT1 can mediate sugar transport out of the cell under appropriate concentration and voltage conditions, but under physiological conditions this transport is highly improbable due to the low affinity for sugar.

Selective killing of tumor cells by xanthates.

Xanthate derivatives of primary alcohols with antiviral properties exert, in combination with monocarboxylic C11 or C12 acids a pronounced anti-tumor activity in vitro and in vivo. Tricyclodecan-9-yl-xanthogenate (D609) or cyclododecyl xanthogenate (D435) when administered together with either undecanoic or dodecanoic acid to various transformed animal and human tumor cells (displaying low serum requirement) cause cell death. In contrast, normal cells from which transformed derivatives arose, were unaffected.

Systemic treatment of a human epidermoid non-small cell lung carcinoma xenograft with a xanthate compound causes extensive intratumoral necrosis.

Therapeutic effects were obtained after systemic treatment of athymic mice bearing an epidermoid non-small cell human lung carcinoma (NSCLC) xenograft with tricyclodecan-9-yl xanthogenate (D609) and the potassium salt of a fatty (dodecanoic) acid. Extensive intratumoral necrosis was observed 3 days after the treatment.

Antitumoral activity of a xanthate compound. I. Cytotoxicity studies with neoplastic cell lines in vitro.

Xanthate derivatives were shown previously to display antitumor activity against transformed fibroblasts and lymphoma cells in combination with monocarboxylic acids [1]. Various malignant cell lines of human origin were treated in vitro to explore the range of antitumoral activity of the compounds. The combination of tricyclodecan-9-yl-xanthogenate (D 609) with undecanoic acid (C11) exerted dose dependent cytotoxic and antiproliferative effects on cell lines both from solid tumors (glioblastomas, colon-carcinomas) and hematological diseases (lymphomas, CML/BC). Additionally, the combination of D 609/C11 was able to kill both methotrexate- and adriamycin-resistant L 1210 and S 180 cells, indicating that there is no cross-resistance for these drugs and D 609/C11 in vitro.

Antitumoral activity of a xanthate compound. II. Therapeutic studies in murine leukemia and tumor models in vivo.

The combinations of tricyclodecan-9-yl-xanthogenate (D 609) with undecanoic acid (C11) and D 609 with myristic acid (C14) were tested in 3 rodent tumor models in vivo. D 609 in combination with C11 or C14 did not show antitumoral efficacy in 3-Lewis lung carcinoma (3-LL) growing in syngeneic C57BL6-mice (primary tumor and metastasis) or in WEHI-3B myelomonocytic leukemia growing in Balb/c mice, when given in a dose range lower than the lethal dose for 10% of the treated animals (LD10). In L 1210 mouse lymphoid leukemia growing in CD2F1 mice the combination of D 609/C11 given intraperitoneally in a concentration of 100 mg/kg for more than 1 day effected a significant difference in the survival curves between the control and therapeutic groups in 1 out of 2 experiments. In conclusion, the treatment schedules of D 609/C11 or D 609/C14 used in this study has not revealed significant therapeutic effects in mouse tumors or leukemias in vivo.

Inhibition of HIV-1 replication by an antiviral xanthate compound in vitro.

The antiviral xanthate compound tricyclodecan-9-yl-xanthogenate (code name D609) is capable of inhibiting DNA and RNA viruses in vitro. It can also inhibit the shedding of infectious HIV into the tissue culture medium from chronically infected lymphoma cells (KE37-III) as shown by infectivity assays and Western blots of the supernatant. HIV-specific proteins, however, were accumulated intracellularly. The initiation of a de novo HIV replication after infection of permissive KE37-1 cells was completely inhibited at concentrations of D609 which still permitted mitotic divisions of the cells. Furthermore, the selective antiviral activity of the xanthate compound was evidenced by the absence of HIV replicative intermediate DNA. The expression of cellular genes, such as c-myc, remained unimpaired within these cells.

Binding of NF-kB to the HIV-1 LTR is not sufficient to induce HIV-1 LTR activity.

Human immunodeficiency virus type 1 (HIV-1) spends a significant part of its life cycle as latent provirus in nonactivated cells. It induction requires mitogen stimulation. TPA treatment induces HIV-1 transcription by protein kinase C (PKC)-mediated activation of the cellular transcription factor NF-kB. PKC activation induces the dissociation of NF-kB from its inhibitor protein (IkB). The liberated NF-kB then binds to its proviral recognition sequence in the HIV-1 long terminal repeat (LTR) sequence. This step, however, is not sufficient to augment transcription. We demonstrate that NF-kB-mediated HIV-1 LTR activation is regulated by an additional event that is not dependent on IkB. A further phosphorylation event is proposed, since this step could be blocked by an inhibitor of a phospholipase C (PLC) type reaction. This inhibitor precludes the formation of diacylglycerols, which are required for activation of PKC isoenzymes. As an alternative pathway that is not dependent on PLC reactions, high-level transcription from the HIV-1 LTR is shown to require binding of both NF-kB and TAT.

Medium chain length fatty acids stimulate triacylglycerol synthesis in tissue culture cells.

In the presence of undecanoic acid (C11) or lauric acid (C12) the synthesis of triacylglycerols was stimulated up to 10-fold both in tumor cell lines and in normal cell lines. Monocarboxylic acids of shorter or longer chain length either had no effect at all or were less effective. The increased triacylglycerol production was demonstrated, on the one hand, by the incorporation of radiolabeled glycerol into triacylglycerols and, on the other, by the incorporation of radiolabeled monocarboxylic acids, the incorporation of all (1-14C)-labeled monocarboxylic acids (C6, C12, C16, C18) regardless of their chain length, being preferentially enhanced by C11 and C12. C12 stimulated the de novo synthesis of triacylglycerols to such a degree that a 7-fold increase in the total amount of triacylglycerols per cell was observed during the first 10 hr of incubation. After removal of C12 from the tissue culture medium levels of triacylglycerols reach initial values again within 6 hr, indicating that the stimulatory effect of C12 is dependent on its continued presence. This led to the speculation that medium chain length monocarboxylic acids might be involved in the control of triacylglycerol synthesis.

Mechanistic aspects of the synergistic antiviral effect of xanthates and monocarbonic acids.

The xanthate tricyclodecan-9-yl-xanthogenate (D609) displays antiviral and antitumoral properties that are inversely proportional in vitro to the serum concentration. Accordingly, it has been found that D609 binds to serum albumin. Recently, we have reported that D609, in combination with undecanoic acid, has a synergistic antiviral effect, which appears, as shown here, to be due to competition for the same binding domain on serum albumin. Furthermore, undecanoic acid fosters the binding of D609 to the cell. Both the competition of D609 with monocarbonic acid for binding on serum albumin and the enhanced binding of xanthate to the cell are dependent, in accordance with previously reported results, on the chain length of the fatty acids. Eleven to 14 C-atoms (undecanoic, lauric and myristic acid) were found to be appropriate while shorter (C6) and larger (C18) monocarbonic acids were shown to lack synergistic properties.

Synergistic antiviral effect of xanthates and ionic detergents.

Xanthate compounds have been shown to exhibit antiviral activity against various DNA and RNA viruses under acidic pH conditions. It is now possible to utilize the unique broad range antiviral spectrum of these compounds under physiological pH conditions (pH 7.4) by simultaneous administration of certain ionic detergents. When used in conjunction with tricyclodecan-9-yl-xanthate (D609), sodium deoxycholate, sodium dodecylsulfate and certain fatty acids, which have no antiviral activity of their own, inhibit the replication of various DNA and RNA viruses (such as herpes simplex, vesicular stomatitis and Coxsackie B 4) in vitro at pH 7.4. Among saturated fatty acids of various chain lengths there was a marked size restriction in that the efficiency of undecanoic acid (11 C atoms) was three orders of magnitude greater than that of shorter (6 C atoms) or longer (18 C atoms) monocarbonic acids. Dose-response kinetics revealed a synergistic interaction between the xanthate and the monocarbonic acid. A dose that inhibited the replication of herpesvirus by a factor of 1000 still permitted mitotic activity in uninfected growing control cultures.

Measurement of hypoxia using the comet assay correlates with preirradiation microelectrode pO2 histography in R3327-AT rodent tumors.

Polarographic determination of tumor oxygenation by Eppendorf histography is currently under investigation as a possible predictor of radiotherapy outcome. Alternatively, the alkaline comet assay has been proposed as a radiobiological approach for the detection of hypoxia in clinical tumor samples. Direct comparisons of these methods are scarce. One earlier study with different murine tumors could not establish a correlation, whereas a weak correlation was reported for a variety of human tumors. Considering the different end points and spatial resolution of the two methods, a direct comparison for a single tumor entity appeared desirable. Anaplastic R3327-AT Dunning prostate tumors were grown on Copenhagen rats to volumes of 1-6 cm(3). Eppendorf histography (100-200 readings in 5 parallel tracks) for 8 different tumors revealed various degrees of oxygenation, with median pO(2) values ranging from 1.1 to 23 mmHg. Within 5 min after an acute exposure to 8 Gy (60)Co gamma rays, tumors were excised from killed animals and rapidly cooled to limit repair, and a single cell suspension was prepared for use with the comet assay. The resulting comet moment distributions did not exhibit two subpopulations (one hypoxic and the other aerobic), and a hypoxic fraction could not be calculated. Instead, the average comet moment distribution was taken as a parameter of overall strand break induction. Corresponding experiments with tumor cells grown in vitro allowed us to derive the relationship between the oxygen enhancement ratio (OER) for the average comet moment and oxygen partial pressure (Howard-Flanders and Alper formula). The validity of this relationship was inferred for cells exposed in situ, and the convolution of a pO(2) distribution with the formula of Howard-Flanders and Alper yielded an array of expected OER values for each tumor. The average expected OER correlated well with the average comet moment (r = 0.89, P < 0.01), and the in situ comet moment distributions could be predicted from the Eppendorf data when 50% repair was taken into account, assuming a 5-min damage half-life. The findings confirm the potential of interstitial polarography to reflect radiobiologically relevant intracellular oxygenation, but also underscore the confounding influence of differences in repair that may occur when cells are prepared from irradiated tissues for use with the comet assay.

Safety of long-term tetracycline therapy for acne.

Results of blood chemistry studies using an automated multiple analysis system and blood cell counts for 325 patients receiving long-term low-dosage tetracycline hydrochloride therapy continuously for three years or longer revealed minimal changes in all but one patient. This patient developed a transient hyperbilirubinemia with mild juandice while taking 500 mg of tetracycline daily.

Binding studies in the Lurcher mutant suggest an uneven distribution of putative benzodiazepine receptor subclasses in the mouse cerebellum.

Binding studies using [3H]flunitrazepam in the cerebellum of normal and Lurcher mutant mice indicate that about 90% of the total benzodiazepine receptor population reside on the Purkinje and granule cells. Moreover, the specific binding of the BZ1 receptor subclass specific ligand [3H]propyl-beta-carboline-3-carboxylate suggests that neuronal elements of the mouse cerebellum other than the Purkinje and granule cells contain about 18% of the BZ1 receptors but only about 7% of the BZ2 receptors of the mouse cerebellum.