The temporal association between incident late-life depression and incident dementia.

OBJECTIVE: There is an established association between depression and subsequent dementia. The present study examined temporal associations between incident late-life depression and subsequent dementia, also considering age and sex. METHODS: We used longitudinal health claims data from the largest German health insurance provider ('Allgemeine Ortskrankenkasse') considering up to 9 follow-up years in piecewise exponential models. ICD-10 codes were used to define incident depression and dementia in individuals ≥65 years (n = 97 110). RESULTS: Incident depression was associated with a higher risk of subsequent dementia (incidence rate ratios (IRR) adjusted for age and sex: IRR = 1.58, 95% CI = 1.51-1.64). The strongest association was found for the shortest interval of 1 quarter (IRR = 2.04, 95% CI = 1.88-2.21), with significant associations up to an interval of roughly 3 years. The association was more pronounced and lasted for more quarters in the younger portion of this study group (ages from 65-74: IRR = 2.00, 95% CI = 1.83-2.18; 75-84: IRR = 1.64, 95% CI = 1.55-1.73; ≥85: IRR = 1.19, 95% CI = 1.08-1.31). It was stronger among men than women (men: IRR = 1.98, 95% CI = 1.84-2.14; women: IRR = 1.44, 95% CI = 1.37-1.51) with no sex-specific temporal association. CONCLUSION: This large claims data study confirmed that incident late-life depression is associated with a higher risk of dementia within the 3 years following diagnosis. Hence, incident late-life depression should prompt further cognitive examinations and referrals to specialists. This might apply especially to younger seniors and men.

Portable through-metal ultrasonic power transfer using a dry-coupled detachable transmitter.

Ultrasonic waves can be used to transfer power and data efficiently through metallic enclosures when feedthroughs are not practical due to structural or electromagnetic shielding considerations. Previous implementations of ultrasonic power transfer (UPT) used a piezoelectric transducer permanently bonded to the metal for efficient ultrasonic coupling. For portable operation, it is essential to have a detachable transmitter (charger) that is only attached to the enclosure while transferring power. This requirement presents several design challenges; notably, detachable ultrasonic coupling typically relies on liquid or gel couplant, which may become inconvenient or less robust during repeated attachment and detachment. Thus, this work develops a dry-coupled detachable UPT system to transfer power efficiently through a metallic enclosure without the need for a liquid couplant. Low attenuation soft elastomers are experimentally tested with a magnetic setup to evaluate their dry-coupled efficiency. Samples with different materials and thicknesses are experimentally tested to select the best configuration for dry ultrasonic coupling. The softest elastomer tested yielded the best ultrasonic efficiency (AC-to-AC) of 68% at 1 MHz. A full DC-to-DC portable (battery-operated) UPT system was then developed and experimentally characterized. The system was capable of delivering up to 3 W of DC power to a resistive load with a total efficiency of 50%.

Effect of insurance status on patients admitted for acute diverticulitis.

AIM: The study aimed to evaluate the relationship between insurance status and the management and outcome of acute diverticulitis in a nationally representative sample. METHOD: A retrospective cohort analysis of a nationally representative sample of 1 031 665 hospital discharges of patients admitted for acute diverticulitis in the 2006-2009 Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project data set. The main outcome measures included state at presentation (complicated/uncomplicated), management (medical/surgical), time to surgical intervention, type of operation and inpatient death. RESULTS: In total, 207 838 discharges were identified (including 37.0% with private insurance, 49.3% in Medicare, 5.6% in Medicaid and 5.8% uninsured) representing 1 031 665 total discharges nationally. Medicare patients were more likely to present with complicated diverticulitis compared with private insurance patients (23.8% vs 15.1%). Time to surgical intervention differed by insurance status. After adjusting for patient, hospital and treatment factors, Medicare patients were less likely than those with private insurance to undergo a procedure (Medicare OR = 0.86, 95% CI: 0.82-0.91), while the uninsured were more likely to undergo drainage (OR = 1.30, 95% CI: 1.16-1.46) or a colostomy only (OR = 1.70, 95% CI: 1.24-2.33). All patients without private insurance were more likely to die in hospital (Medicare OR = 1.29, 95% CI: 1.09-1.52; Medicaid OR = 1.55, 95% CI: 1.22-1.97; uninsured OR = 1.41, 95% CI: 1.07-1.87). CONCLUSION: In a nationally representative sample of patients with acute diverticulitis, patient management and outcome varied significantly by insurance status, despite adjustment for potential confounders. Providers might need to heighten surveillance for complications when treating patients without private insurance to improve outcome.

All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages.

All-trans retinoic acid (ATRA) is controversially discussed in emphysema therapy. We re-evaluated ATRA in the elastase model and hypothesised that beneficial effects should be reflected by increased alveolar surface area, elastin expression and downregulation of inflammatory mediators and matrix metalloproteinases (MMPs). Emphysema was induced by porcine pancreatic elastase versus saline in Sprague-Dawley rats. On days 26-37, rats received daily intraperitoneal injections with ATRA (500 µg · kg(-1) body weight) versus olive oil. Lungs were removed at day 38. Rat alveolar epithelial L2 cells were incubated with/without elastase followed by ATRA- or vehicle-treatment, respectively. ATRA only partially ameliorated structural defects. Alveolar walls exhibited irregular architecture: increased arithmetic mean thickness, reduction in surface coverage by alveolar epithelial cells type II. ATRA only partially restored reduced soluble elastin. It tended to increase the ratio of ED1(+):ED2(+) macrophages. Bronchoalveolar lavage (BAL) cells exhibited a proinflammatory state and high expression of interleukin-1ß, cytokine-induced neutrophil chemoattractant-1, tumour necrosis factor-α, nuclear factor-κB, MMP-2, MMP-9, MMP-12, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in emphysema, with ATRA exerting only few effects. MMP-7 was highly induced by ATRA in healthy but not in emphysematous lungs. ATRA reduced both MMP-2 and TIMP-1 activity in BAL fluid of emphysematous lungs. ATRA-therapy may bear the risk of unwanted side-effects on alveolar septal architecture in emphysematous lungs.

A role for actin, Cdc1p, and Myo2p in the inheritance of late Golgi elements in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, Golgi elements are present in the bud very early in the cell cycle. We have analyzed this Golgi inheritance process using fluorescence microscopy and genetics. In rapidly growing cells, late Golgi elements show an actin-dependent concentration at sites of polarized growth. Late Golgi elements are apparently transported into the bud along actin cables and are also retained in the bud by a mechanism that may involve actin. A visual screen for mutants defective in the inheritance of late Golgi elements yielded multiple alleles of CDC1. Mutations in CDC1 severely depolarize the actin cytoskeleton, and these mutations prevent late Golgi elements from being retained in the bud. The efficient localization of late Golgi elements to the bud requires the type V myosin Myo2p, further suggesting that actin plays a role in Golgi inheritance. Surprisingly, early and late Golgi elements are inherited by different pathways, with early Golgi elements localizing to the bud in a Cdc1p- and Myo2p-independent manner. We propose that early Golgi elements arise from ER membranes that are present in the bud. These two pathways of Golgi inheritance in S. cerevisiae resemble Golgi inheritance pathways in vertebrate cells.

[Wheezing during normal breathing as a sign of bronchial obstruction]. / Giemen bei Ruheatmung als Zeichen bronchialer Obstruktion.

Wheezing is a clinical feature in patients with chronic obstructive airway diseases. Long-term monitoring of wheezing could provide a new dimension of diagnostic information as compared to lung function if wheezing really does represent airway obstruction. Patients with wheezing who were part of our Marburg Respiratory Sound Database (MARS) were studied. 20 patients with asthma and 17 patients with chronic obstructive pulmonary disease (COPD) were analysed with respect to pathological changes of lung function parameters. The patients were matched with persons without wheezing in regard to age, diagnosis and sex. Additionally, 58 healthy persons with normal lung function tests were analysed for the occurrence of spontaneous wheezing during normal breathing. In patients with wheezing, at least one parameter of lung function was pathological. For asthmatic patients significant differences for MEF (50) (p = 0.011), R (tot) (p = 0.002) and Tiffeneau (p = 0.001) were found. In patients with COPD significant differences for FEV (1) (p = 0.002) and MEF (50) (p = 0.030) were found. In none of the healthy persons with normal lung function did we find wheezing. Wheezing as a clinical sign of bronchial obstruction is useable for long-term monitoring. The method provides additional information that can help to monitor nocturnal asthma.

["Malignant" ARDS]. / "Malignes" ARDS.

Acute respiratory failure and the "acute respiratory distress syndrome" (ARDS) are frequent medical conditions in critically ill patients. Various causes can potentially result in the development of ARDS. Two cases are presented, in which malignant diseases were identified as causes of the respiratory failure. The first patient was diagnosed with an acute myeloic leukemia M5 (FAB). In the second patient, lung histology revealed an adenocarcinoma of the lung. These case reports show that in addition to the classical causes of ARDS, specific disease entities can mimic this form of respiratory failure. Beside solid cancers and lymphomas, acute and progressive forms of inflammatory, parenchymal lung diseases (such as acute interstitial pneumonitis, acute eosinophilic pneumonia, diffuse alveolar hemorrhagia, and acute hypersensitivity pneumonitis) can manifest with this picture. As a consequence, the diagnostic workup of respiratory failure of unknown cause should include these entities.

DNA polymerase in nuclei isolated from herpes simplex virus type-2-infected cells. Characterization of the reaction product and inhibition by substrate analogs.

Nuclei isolated from herpes simplex virus (HSV) type 2-infected KB cells were examined for their capacity to serve as an in situ source of herpes DNA polymerase. In contrast to purified enzymes with added template, approx. 80% of the DNA synthesized in isolated nuclei was viral. The average size of DNA fragments labeled in vitro was 3.2 X 10(6) Da. Based on an increase in DNA density when nuclei were incubated in the presence of BrdUTP rather than dTTP, 16% of the nucleotides were added during the in vitro reaction. Sucrose gradient analysis of DNA polymerase activity in extracts of isolated nuclei demonstrated the nearly exclusive presence of herpes DNA polymerase. Km concentrations for the four dNTPs were from 0.14 to 0.55 microM. DNA synthesis was inhibited competitively by the 5'-triphosphates of ara-A and ara-C (Ki = 0.03 and 0.22 microM, respectively) but not by the 5'-triphosphate of dideoxythymidine. aATP also served as a substrate (Km = 0.014 microM) for the reaction. We conclude that nuclei from HSV-infected cells have significant advantages for the detailed study of inhibitors of herpesvirus replication.

An evaluation of certain chain-extended analogues of 9-beta-D-arabinofuranosyladenine for antiviral and cardiovascular activity.

Several nucleosides modified and chain extended at the 5'-position have been synthesized as follows: N6-benzamido- 9-(2,3-di-O-benzoyl-beta-D-arabino-pentodialdo-1,4-furanosyl)adenine, O=CHR, a leads to (E)-EtOCOCH=CHR (2) b leads to EtOCOCH2CH2R (3) c leads to H2NCOCH2CH2R (6) d leads to 1-(adenin-9- yl)-1,5,6-trideoxy-beta-D-arabino-hepto-1,4-furanuronamide (8); 3 e leads to ethyl 1-(adenin-9-yl)-1,5,6-trideoxy-beta-D-arabino-hepto-1, 4-furanuronate (5) f leads to 1-(adenin-9-yl)-1, 5,6-trideoxy-beta-D-arabino-hepto-1,4-furanuronic acid (4); 5 g leads to 9-(5,6-dideoxy-beta-D-arabino-hepto-1,4-furanosyl)adenine (7) [where a = EtOCOCH=PPh3; b = H2, Pd/C; c = Me2A1NH2; d = NH3/MeOH; e = NaOEt/EtOH; f = NaOH/MeOH; g = LiA1H4]. Both 7 and 8 show activity against herpes simplex virus type 1. The mechanism for such activity is unknown. Compounds 5 and 8 exhibited weak coronary vasodilation effects in dogs.

Inhibition of herpes simplex virus DNA replication by ara-tubercidin.

Preliminary studies of the biochemical basis for the antiviral activity of the pyrrolo[2,3-d]pyrimidine nucleoside ara-tubercidin were conducted. Herpes simplex virus DNA synthesis was 3-fold more sensitive to inhibition by ara-tubercidin than was cellular DNA synthesis. Partially purified herpes DNA polymerases were more sensitive to inhibition by ara-tubercidin 5'-triphosphate than were cellular polymerases alpha and beta. Inhibition of viral DNA polymerase was competitive with dATP and noncompetitive with dTTP. The results suggest that the viral DNA polymerase plays a significant role in the antiviral activity of ara-tubercidin.

A sensitive fluorescent assay for N-acetyltransferase activity in human lymphocytes from newborns and adults.

We have developed a simplified assay for the enzyme N-acetyltransferase, based upon the loss of fluorescence after acetylation of the substrate p-aminobenzoic acid. This method is sufficiently sensitive to permit the quantitation of N-acetyltransferase activity in 10(5) human lymphocytes. Using this method, we have compared the level of N-acetyltransferase activity in lymphocytes from adult peripheral blood and from cord blood samples.

Reduction of fecal shedding and egg contamination of Salmonella enteritidis by increasing the number of heterophil adaptations.

Serial passage of Salmonella enteritidis (SE) in chicken heterophils resulted in heterophil-adapted SE (HASE). We now report that an additional five heterophil passages have further reduced the number and frequency of fecal shedding of HASE. Eleven-times HASE (11 x HASE) given to 12 laying hens for three consecutive days reduced fecal shedding of 11 x HASE to three isolations from fecal samples during the 70-day postexposure observation period. Hens were exposed to challenge SE 74 days after treatment with 11 x HASE. Three of 12 11 x HASE-treated hens were positive for challenge SE (11/396 fecal samples, or 2.8%) between days 5 and 40 postchallenge, whereas all 12 challenge control birds were positive (118/420 fecal samples, or 28.1%) for SE. None of 12 11 x HASE-treated hens was fecal positive from day 9 postchallenge, whereas 10 of 12 challenge control hens (82/372 fecal samples, or 22.0%) remained positive until day 40, the termination of the experiment. None of 525 eggs and eggshells cultured after 11 x HASE exposure was positive for Salmonella, and none of 422 eggs and eggshells cultured after challenge SE exposure was positive for Salmonella. Eggs or eggshells from challenge control hens were positive for Salmonella in 12/479 (2.5%) cases after challenge SE exposure.

Flow-cytometric investigation of cellular metabolism during oxidative stress and the effect of tocopherol.

Many studies and scientific publications report on potentially beneficial effects of the lipophilic anti-oxidant vitamin E on cellular metabolic pathways. The present work presents data on the influence of tocopherol on different intracellular parameters of intact and living human skin fibroblasts by flow-cytometric measurements. The parameters analysed were the intracellular pH, representing cell metabolism and cell function, intracellular glutathione, representing one of the cell's own radical scavenger enzyme systems, membrane potential and cell viability. In order to cause large numbers of free radicals cells were UVB-irradiated prior to measurement. The results of the flow-cytometric measurements indicate that vitamin E has significant protecting effects on the measured biochemical parameters during oxidative stress. In the presence of the lipophilic radical scavenger a significant stabilizing effect on pH, intracellular glutathione levels and membrane potential could be observed. Furthermore, vitamin E administration was associated with increased cell viability after UVB irradiation.

The ultimate birth center: a collaborative model for innovation.

Lest these descriptions sound too good to be true, Virginia Mason Birth Center is not utopia. It is a real place with real problems and struggles. Implementing and maintaining personalized, high-quality obstetric care to the childbearing woman and her family has not come easily. Innovations continue to be developed in response to patients' and providers' desire for birth services that are flexible, sensitive, and designed around families' preferences and needs. A common philosophy continues to guide a dedicated staff, administration, and provider group within a framework of collaboration, innovation, and quality to enable a wonderful professional practice to evolve.

[Effect of subcutaneous fatty tissue on normal respiratory sounds]. / Der Einfluss der subkutanen Fettschicht auf die normalen Atemgeräusche.

Auscultation is an important, non-invasive and simple measure in the diagnosis of lung diseases that can detect sometimes pathological processes prior to radiography. Attempts have already been made to automatically detect characteristic pathological sounds, but a knowledge of potential influencing factors is a must for correct interpretation. In this study we have investigated the effect of the subcutaneous fat layer on normal lung sounds. This is of importance to determine corrective factors for the automatic detection of bronchial breathing in pneumonia. The lung sounds of 125 healthy people (55f, 70m) were digitally recorded at four different positions of the thorax (3. ICR paravertebral, 7. ICR medioscapular, all left and right). Evaluation was done separately for gender. The subcutaneous fat layer was measured with a Holtain Skinfold Caliper at the identical four recording positions. For a quantitative evaluation of the sounds we calculated the relative power of frequency bands 330-600 Hz and 60-330 Hz and their ratio. The relation between these parameters and the subcutaneous fat layer was analyzed with the Pearson correlation. The results of this study show that the influence of subcutaneous fat layer is negligible and can be ignored in the automatic detection of lung sounds.

[Dependence of nocturnal bronchial obstruction on sleep position]. / Abhängigkeit Nächtlicher Bronchialobstruktionen von der Schlafposition.

Patients with bronchial obstructions often have problems to stay asleep at night. The interaction between sleep position and bronchial obstructions has not been investigated until now. A total of 20 patients was included in this study. All patients were recorded one night in our sleep laboratory with a parallel recording of lung sounds using a commercial Pulmotrack 1010 system. The bronchial obstructions were lower in lateral position than in supine position for both tracheal and chest sounds (p = 0,083 and p = 0,036; n.s.). This effect seemed to be especially high in patients with many obstruction episodes. From our results we can conclude that there is a small dependence of bronchial obstructions from sleep position. Further investigations are needed to verify this result.

Apparent hemolysis in an AIDS patient receiving trimethoprim/sulfamethoxazole: case report and literature review.

OBJECTIVE: To describe a case of acute hemolysis associated temporally with administration of trimethoprim/sulfamethoxazole (TMP/SMX) in a patient with AIDS, review the available literature on TMP/SMX-induced hemolytic anemia, and discuss possible drug- and disease-related factors that may have contributed to the episode of hemolysis. CASE SUMMARY: A precipitous decrease in red blood cell count, hemoglobin, and hematocrit occurred shortly after a black woman with AIDS received a single intravenous dose of TMP/SMX for Pneumocystis carinii pneumonia. Following drug discontinuation and repeated transfusions, the patient's hematologic indices returned to baseline. LITERATURE SOURCES: References were obtained using MEDLINE searches, the bibliographies of articles identified during the searches, review articles, and standard textbooks. DATA SYNTHESIS: Of the two different mechanisms of TMP/SMX-induced hemolytic anemia, the reaction is most likely to occur via dose-related oxidative disruption of the erythrocyte membrane in subpopulations deficient in glucose-6-phosphate dehydrogenase (G6PD) activity. In the US, G6PD deficiency most frequently is encountered among blacks. The potential for hemolysis may be further increased in G6PD-deficient AIDS patients, who also appear to lack adequate intracellular glutathione, which is essential for protecting the erythrocyte membrane from oxidative damage. Although an assay for G6PD activity was not conducted, the case circumstances were consistent with TMP/SMX-induced hemolysis in a G6PD-deficient patient. CONCLUSIONS: Black patients with AIDS who are receiving relatively high (greater than or equal to 50 mg/kg/d) dosages of TMP/SMX should be monitored closely for signs and symptoms of hemolytic anemia.

[Autonomic dysfunction and cardiac arrhythmia in patients with obstructive and central sleep apnea]. / Autonome Dysregulation und kardiale Arrhythmien bei Patienten mit obstruktiver und zentraler Schlafapnoe.

Obstructive sleep apnea and central sleep apnea with Cheyne-Stokes respiration are associated with an increased risk of cardiac arrhythmia. Apnea- associated arrhythmia may contribute to sudden cardiac death and premature mortality in those patients. Both forms of sleep apnea excert strong modulatory effects on the autonomic system with a special autonomic profile. Profound vagal activity is leading to bradyarrhythmias, and sypathico-excitation to tachyarrhythmias. Atrial fibrillation and ventricular arrhythmias in obstructive and central sleep apnea patients are mainly found in combination with cardiovascular comorbidity (coronary heart disease, hypertensive heart disease, chronic heart failure). Bradyarrhythmias in OSA are induced by a cardioinhibitory vagal reflex due to obstructed airway. CPAP-therapy has been demonstrated to reduce arrhythmias.

Comparison of the effects of nebivolol and valsartan on BP reduction and sleep apnoea activity in patients with essential hypertension and OSA.

OBJECTIVES: To investigate the effect of nebivolol, a third generation beta-blocker, on blood pressure (BP) reduction and polysomnographic parameters in hypertensive patients with mild-to-moderate obstructive sleep apnoea (OSA). METHODS: In this double-blind, parallel group study, patients were randomized to nebivolol 5 mg or valsartan 80 mg once daily following a 14-day, placebo run-in period during which any antihypertensive medication were discontinued. BP and heart rate measurements and overnight polysomnography were performed at baseline and after 6 weeks of treatment. Safety and tolerability were assessed. RESULTS: Thirty-one patients were randomized to nebivolol (n = 16) or valsartan (n = 15). After six weeks both systolic and diastolic BP were effectively reduced by both treatments. Reductions in BP were not statistically significant different between agents, but mean heart rate was significantly decreased with nebivolol (compared with valsartan (p < 0.001). There was no statistically significant difference between both treatments for the change from baseline to treatment end for mean (+/-SD) Apnoea Hypopnoea Index (AHI) (nebivolol: 23.0 +/- 9.2 to 27.9 +/- 21.2 events/h; valsartan: 23.8 +/- 6.6 to 22.5 +/- 18.0 events/h; p = 0.48) or for any other sleep-related parameters. Both agents were well tolerated. CONCLUSION: Nebivolol has a significant BP reduction effect in patients with OSA that is similar to valsartan and reduces heart rate to a greater extent which may prove beneficial in selected patients.