Do patients with diabetes type 2 or chronic heart failure understand a medication plan?

A standardized medication plan (MP) was recently enacted into German law (§ 31a SGB V). The purpose of our study was to assess if patients with chronic diseases requiring polymedication understand the standardized MP and can transfer the given information into practice. 100 patients who took at least five medicines regularly were prospectively included in a cross-sectional study: 50 patients with the primary diagnosis chronic heart failure (CHF), and 50 with diabetes mellitus type 2 (DMT2). We performed a structured test-scenario studying the handling of a provided MP then evaluated the execution of the information on the MP by filling pill boxes and requested patients' opinion. An established weighted scoring system, the "Evaluation Tool to test the handling of the Medication Plan" (ET-MP) was applied to quantitate the ability of the patients to handle the MP. In addition, signs of depression, cognitive function and self-care behavior in chronic heart failure were characterized using the PHQ-9, Mini-Cog, and G9-EHFScB-9 questionnaires, respectively. The understanding of the MP was poor and irrespective of the underlying primary diagnosis. Only 32% of all patients were able to handle the MP without difficulties (ET-MP score >90%), the median ET-MP score was 83 [(IQR) 50-98]. Comprehension of the MP was better in patients aged <70 years compared to ≥70 years (p<0.01). Patients ≥10 years of education achieved higher ET-MP results than patients with <10 years of education (p<0.01). Patients with signs of cognitive impairment exhibited significantly lower ET-MP scores than patients without cognitive impairment (p<0.001). There were no significant correlations of the ET-MP score with number of daily medications, living situation, sex, the Charlson Comorbidity Index, the PHQ-9 score, and use of a dosing aid or possession of a medication list.

A computational model of a human single sinoatrial node cell.

For the investigation of the spontaneous rhythmical activity response in the application of cardiac neuromodulation, we formulated a human sinoatrial node (SAN) cell model. With the aim of decreasing elevated heart rate (HR), we want to establish a hardware-in-the-loop system including this model for the analysis of optimal stimulation patterns of the neurostimulation system. Base model structures are adopted from rabbit SAN cell models available in literature and conveyed with Hodgkin-Huxley-type model equations describing the complex time and voltage dependent activation and deactivation processes of individual ion channels. The resulting model consists of 15 currents which are currently known to be responsible for the generation of the membrane action potential (AP). The model reproduces AP frequencies equivalent to those measured in isolated human SAN cells with a resulting HR of 71.8 bpm. Model validation via simulation of the inhibitory effect of ivabradine showed accordance with experimental results obtained in human studies. Furthermore, we could validate the model in regard to its HR effects upon parasympathetic stimulation with results obtained in a human trial study.

Sperm retrieval outcomes with microdissection testicular sperm extraction (micro-TESE) in men with cryptozoospermia.

Several studies support of the use of testicular rather than ejaculated spermatozoa for intracytoplasmic sperm injection (ICSI) in couples with virtual azoospermia or cryptozoospermia, although this approach remains controversial. We sought to evaluate sperm retrieval outcomes with microdissection testicular sperm extraction (micro-TESE) in men with cryptozoospermia. We conducted a retrospective study of 24 consecutive micro-TESEs in men with cryptozoospermia. We also evaluated the outcomes of seven consecutive TESAs (testicular sperm aspiration) in cryptozoospermic men during the same time period (January 2007 and September 2014). Micro-TESE and TESA were performed on the day prior to ICSI. Final assessment of sperm recovery (reported on the day of ICSI) was recorded as (i) successful (available spermatozoa for ICSI) or (ii) unsuccessful (no spermatozoa for ICSI). The decision to perform a unilateral or bilateral micro-TESE was guided by the intra-operative evaluation of sperm recovery from the first testicle. A unilateral procedure was performed in 87.5% (21/24) and 57% (4/7) of the micro-TESE and TESA cohorts, respectively. Sperm recovery was successful in 96% (23/24) of the men who underwent micro-TESE and 43% (3/7) of the men who underwent TESA (p < 0.01). The ICSI pregnancy rates (per embryo transfer) in the micro-TESE and TESA groups were comparable [33% (6/18) and 50% (1/2), respectively]. The data indicate that micro-TESE is a highly successful sperm retrieval technique for men with cryptozoospermia and few of these men will require a bilateral procedure. Moreover, sperm retrieval rates are higher with micro-TESE than TESA in this group of men.

Effect of replacing solvent-extracted canola meal with high-oil traditional canola, high-oleic acid canola, or high-erucic acid rapeseed meals on rumen fermentation, digestibility, milk production, and milk fatty acid composition in lactating dairy cows.

The objective of this experiment was to investigate the effects of replacing conventional, solvent-extracted canola meal (control; CTRL) with high oil content; conventional, mechanically extracted canola meal (CMEC); high-oleic, low polyunsaturated fatty acid (FA) canola meal (HOLL); and high-erucic acid, low-glucosinolate rapeseed meal (RPS) on rumen function, digestibility, milk production, and milk FA composition in lactating dairy cows. The experimental design was a replicated 4×4 Latin square with 8 lactating dairy cows. Four of the cows were ruminally cannulated. All oilseed meals were included at approximately 12 to 13% of dietary dry matter (DM). Crude protein and fat concentrations (% of DM) of the meals were 43 and 3.1%, 32.8 and 16.1%, 45.2 and 13.7%, and 34.3 and 17.9% for CTRL, CMEC, HOLL, and RPS, respectively. All diets were formulated to supply net energy of lactation in excess of requirements. The CMEC and RPS diets were predicted to be about 1% deficient in metabolizable protein. Relative to the CTRL, inclusion of high-oil seed meals in the diet lowered ruminal acetate concentration and the molar acetate:propionate ratio and decreased DM intake. Milk yield generally followed DM intake and was lower for CMEC and RPS than the CTRL. Treatments had no effect on milk composition, other than an increase in milk urea nitrogen concentration for HOLL. Fat-corrected milk (3.5%) feed efficiency was increased by HOLL and RPS compared with CTRL. Urinary urea nitrogen losses were increased by HOLL, which, as a consequence, increased the ammonia-emitting potential of manure. The ratio of milk N-to-N intake was greater for CMEC and RPS. Replacing solvent-extracted canola meal with the high-oil meal decreased milk fat 12:0, 14:0, 16:0, and total saturated FA content and enhanced cis-9 18:1 and total monounsaturated FA concentrations. Relative to the CTRL, canola increased total trans FA in milk, whereas inclusion of HOLL in the diet increased trans-11 18:1 and cis-9, trans-11 CLA content. The RPS increased milk fat cis-13 22:1 content from 0.07 to 2.33 g/100g of FA. In conclusion, HOLL or RPS, which are likely to come from small-scale biodiesel plants where oil is cold pressed without hexane extraction, fed at levels at or above 12 to 13% of dietary DM may decrease feed intake and milk production, but can be used to alter milk FA composition in lactating dairy cows.

Novel insight into the regulation of GSH biosynthesis in higher plants.

In higher plants, the redox-active tripeptide glutathione (GSH) fulfills a plethora of functions. These include its pivotal role for maintaining the cellular redox poise and its involvement in detoxification of heavy metals and xenobiotics. Intimately linked to these functions, GSH also acts as a cellular signal, mediating control of enzyme and/or regulatory protein activities, either directly or via glutaredoxins. The redox potential of the GSH/GSSG couple is not only affected by the GSH/GSSG ratio but also by changes in GSH synthesis and/or degradation. As this couple operates as redox buffer in several cellular compartments, the regulation of GSH biosynthesis and transport (both intra- and intercellularly) are fundamental to the maintenance of cellular redox homeostasis during plant development and, even more so, when plants are exposed to biotic or abiotic stress. This review highlights novel aspects of GSH biosynthesis and transport with a focus on the regulation of the GSH1 (= gamma-glutamylcysteine synthetase) enzyme. Interestingly, GSH1 appears to be exclusively confined to the plastids, whereas the second biosynthetic enzyme, GSH2, is predominantly localized in the cytosol. GSH1 expression and enzyme activity are under multiple controls, extending from transcriptional regulation to post-translational redox control. Now that the plant GSH1 protein structure has been solved, the molecular basis of GSH1 function and redox regulation can be addressed. The review concludes with a discussion of the simultaneous changes observed for GSH synthesis, transport, and metabolism during Cd-induced phytochelatin accumulation.

[Münster age- and retina study (MARS). Association between risk factors for arteriosclerosis and age-related macular degeneration]. / Münsteraner Altern- und Retinastudie (MARS). Zusammenhang zwischen Risikofaktoren der Arteriosklerose und der altersabhängiger Makuladegeneration.

BACKGROUND: The association between arteriosclerosis and age-related macular degeneration (AMD) has only been examined in a few studies and the data is still very inconsistent. METHODS: A cross sectional study was initiated with 730 patients from the Münster age and retina study (MARS) which examines patients in the age range 60 to 80 years old who were referred by ophthalmologists from the Muenster area. Patients with narrow angle glaucoma were excluded. All patients underwent a standardized ophthalmoscopic examination und were classified into four groups: group 1 without AMD ( n=190), group 2 with unilateral or bilateral early forms of AMD ( n=340), group 3 with unilateral late forms of AMD ( n=139) and group 4 with bilateral late forms of AMD ( n=50). By means of these groups it was tested if there was a significant difference between the different risk factors for arteriosclerosis. RESULTS: The mean age was 72 years and 58% were women and the sex distribution within the different groups did not differ significantly (all trend tests with p>0.1). General risk factors for arteriosclerosis such as diabetes, body-mass-index and hypertension did not differ significantly (all trend tests with p>0.1). The number of smokers increased significantly with the severity of AMD ( p=0.02). Furthermore, various lipids were examined, adjusted for age and sex and showed significant decrease of HDL ( p=0.087) and significant increases of the HDL/LDL quotient ( p=0.0007) and the non-sober triglyceride values ( p=0.0058) correlated with the severity of AMD. CONCLUSIONS: There was a highly significant, direct association of indicators of dyslipidemia such as increasing HDL/LDL quotient and decreasing HDL with the severity of AMD. These results were underlined by increased triglyceride levels even if they were taken non-sober. The results must be interpreted with caution due to the explorative character of the evaluation.

The sialate-pyruvate lyase from pig kidney. Elucidation of the primary structure and expression of recombinant enzyme activity.

The first complete primary structure of a mammalian sialate-pyruvate lyase, namely of the enzyme from porcine kidney, was elucidated by a combination of different PCR techniques followed by sequencing of the resulting fragments. The primers used were either deduced from four porcine lyase peptides or from an alignment of human and mouse expressed sequence tags (ESTs), which were found to be homologous to already known microbial lyase sequences, and cDNA alone or after ligation with a plasmid vector served as a template. The lyase primary structure consists of 319 amino acids with a calculated protein molecular mass of approximately 35 kDa, which fits well to the value determined for the native enzyme. The porcine lyase sequence made it possible to assemble several ESTs from mouse and man in order to obtain the complete putative lyase genes. The three mammalian sequences reveal a high degree of homology both on the nucleotide (83% of the nucleotides are identical between all three sequences) and on the amino-acid level (72% of the amino acids are identical between all three sequences), and thus form a tightly related group. In contrast, the identity between the lyase primary structures from pig kidney and the microbial enzyme from Clostridium perfringens is much less pronounced (25%). Thirty-one amino acids were found to be absolutely conserved in all lyase sequences. Among them are two amino acids (lysine 173 and tyrosine 143 in the porcine lyase) that are most important for the catalytic reaction. After expression cloning, recombinant enzyme activity was expressed in Escherichia coli BL21(DE3)pLysS, which confirms the identity of the cloned sequence and verifies one of the putative human and murine sequences. After SDS/PAGE of a cell extract of the expression clone, a band of 35kDa was stained on the gel.

Blood flow velocities in the basal vein after subarachnoid haemorrhage. A prospective study using transcranial duplex sonography.

BACKGROUND: Early recognition of emerging delayed neurological deficits (DND) in patients after subarachnoid haemorrhage (SAH) is not always possible by transcranial Doppler sonography. Aim of this study was to investigate a) whether determination of blood flow velocities in deep cerebral basal veins can predict DND in these patients b) the correlation of venous flow velocity to cerebral blood flow (CBF). METHODS: a) We prospectively investigated the mean flow velocity in the basal vein (VBVR), in the middle cerebral artery (VMCA) and in the extracranial internal carotid artery (VICA) in 66 patients after spontaneous SAH. Examinations were performed daily during the first 10 days, using transcranial duplex sonography. Thirty-seven patients had VMCA exceeding 120 cm/s. They were categorised in three groups: 1: no delayed neurological deficit; II: transient DND; III: permanent DND or death associated with vasospasm. b) In another group of 14 patients, interdiane variations in global cerebral blood flow (CBF) measured by the Kety-Schmidt-method were correlated with variations in VBVR, VMCA, and VICA. FINDINGS: a) In patients without deficit, VBVR was significantly elevated above normal values the first day (p < 0.05), and days 5 and 6 (p < 0.1) after VMCA exceeding 120 cm/s. In group III (permanent deficit), flow velocities in the BVR were significantly below normal on day 5 (p < 0.05) and 9 (p < 0.1). b) The correlation between changes in VBVR to changes in CBF (r = 0.78, p < 0.001) was closer than between changes in VMCA to the changes in CBF (r = 0.54, p < 0.05). INTERPRETATION: In case of elevated VMCA, patients with higher VBVR seem to have a better outcome. Changes in CBF correlate better with VBVR than with arterial flow velocities.

Exposure of oncologic nurses to methotrexate in the treatment of osteosarcoma.

Methotrexate is a therapeutic agent used widely for osteosarcoma. We used an extremely sensitive high-performance liquid-chromatography assay to evaluate 112 urine samples obtained from 28 hospital employees during high-dose therapy with methotrexate and during routine care of patients. The highest cumulative urinary excretion was observed when methotrexate infusions were handled in a workbench from which a portion of filtered air was emitted into the room. Remarkable urine contaminations were identified for personnel, including 1 administrative employee who had "stood by" for 2 h in the room where infusions were prepared. Lower methotrexate concentrations were detected in the urine of nurses whose exclusive function was to care for patients. The urine burden in oncologic nurses decreased after a central pharmacy unit was installed. Methotrexate was excreted in the sweat of patients who were under high-dose therapy, and its elimination half-life was 11.1 h (mean maximal concentration = 1.7 micrograms/ml [n = 51). The maximal burden in spontaneous vomit from these patients was 441.5 micrograms/ml, and it declined to 0.24 micrograms/ml 19.5 h after infusion was completed. No methotrexate was detected in personnel who prepared 20-g methotrexate infusions in the central pharmacy unit. We demonstrated that occupational safety depended not only on technical precautions, but on the skills of specifically trained personnel.

Treatment of atopic dermatitis with alpha 1-proteinase inhibitor.

Alpha 1-proteinase inhibitor (alpha 1-PI), a serine protease inhibitor, was tested for its efficacy for the treatment of recalcitrant atopic dermatitis. Atopic dermatitis affects both children and adults and has no established etiology. We hypothesized that during inflammation there is an excess of serine proteases and a deficiency of their naturally occurring inhibitors at the local site of tissue injury, even though there is a normal serum level of serine protease inhibitors. This pilot study consisted of a nonblinded trial using alpha 1-PI at a concentration of 20 mg/mL in an aqueous solution in an alternate day schedule in conjunction with a 1% cream of alpha 1-PI (Stage I) and a 5% cream of alpha 1-PI for maintenance therapy (Stage II). Before enrollment in this trial all six patients failed to respond to high potency topical steroids. Safety was gauged by careful clinical monitoring of subjective complaints, objective findings of erythema, edema, and serial measurements of blood chemistries and complete blood counts. Wound healing was documented by serial photography. Written informed consent was obtained from each patient. All six patients showed significant clinical improvement within 6 to 21 days of initiation of alternate day therapy. Alpha 1-PI stopped pain, pruritus, and promoted tissue healing without scarring in all six patients. No adverse side effects of therapy were documented by clinical history, physical examination, or by blood studies after 120 days of therapy. Atopic dermatitis may be one example where inflammation is due to an imbalance of serine proteases and their naturally occurring inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Retinal phototrauma during intra-ocular lens-implantation.

The use of the operating microscope has become almost a necessity in the surgery of the anterior segment of the eye. However the coaxial light of the operating microscope is potentially hazardous for the retina, especially during intra-ocular lens implantation. The risk of producing a photic retinopathy increases if the duration of the surgical procedure is prolonged once the pseudophakos is in the eye and if high levels of illumination are used. We encountered our first case in a patient, whose intervention was filmed and where thus an increased illumination was needed. This complication is however also found in cases where no extra illumination was needed. As the clinical signs are usually very mild, the retinal lesions related to over-exposure to light are easily overlooked.

The effects of ritodrine on experimentally induced intra-uterine growth retardation in the rat.

The effects of oral ritodrine on artificially induced intra-uterine growth retardation in rats were tested in two animal models. In one model, foetal hypotrophy was induced by reduction of the uterine blood supply on ligating of the left uterine artery. In that experiment no significant inhibition of the foetal hypotrophy could be detected in the ritodrine treated animals, but the corresponding reduction of placental weight was inhibited. In the other model, hypotrophy was induced by hypothermia. Oral ritodrine, given twice daily in a dose of 50 mg/kg from day 7 to day 21 of the pregnancy, antagonized the decrease of the foetal weight produced by hypothermia.

Endocrine effects of two new retro-steroids in animal models and in women.

PIP: Endocrine effects of 2 new retrosteroids, DU 164 and DU 41 165, in a nimal models and in women are reported. Both retrosteroids exhibited hi gh progestational activity in the rabbit, their potency being 18 times that of the reference standard, chlormadinone acetate (CMA), when administered orally. Both retrosteroids maintained pregnancy in rabbits and rats with a potency of 6 and 11 times that of CMA for DU 41 164 and DU 41 165, respectively. In the pregnancy maintenance tests in rats the effective dose (ED) 50 of DU 41 164 and DU 41 165 was 2000 mcg/kg/day and 290 mcg/kg/day, respectively, whereas CMA could not maintain pregnancy in doses of 50,000 mcg/kg/day. Both retrosteroids were highly active as antifertility agents in rabbits and rats. Their potencies were 80 and 40 times that of CMA in rabbits and 100 and 300 times that of CMA in rats. In ovulation inhibition tests the ED 50 of oral DU 41 164 and DU 41 165 were .5 and .4 mcg/kg in rabbits, whereas the ED 50 of CMA was 40 mcg/kg. The retrosteroids were also more potent than CMA in ovulation inhibition and antiestrogenic activity. High doses of DU 41 165 induced a decrease in adrenal weight and exhibited some antiinflammatory effects. 23 volunteers treated with 50 or 200 mcg of the compounds/day revealed no consistent inhibition of ovulation and of corpus luteum function. Endometrial biopsy specimens obtained on Cycle Days 12-13 during treatment with 200 mcg of either retrosteroid revealed no signs of progestational effect.^ieng