Implicit Partitioned Cardiovascular Fluid-Structure Interaction of the Heart Cycle Using Non-newtonian Fluid Properties and Orthotropic Material Behavior.

Although image-based methods like MRI are well-developed, numerical simulation can help to understand human heart function. This function results from a complex interplay of biochemistry, structural mechanics, and blood flow. The complexity of the entire system often causes one of the three parts to be neglected, which limits the truth to reality of the reduced model. This paper focuses on the interaction of myocardial stress distribution and ventricular blood flow during diastole and systole in comparison to a simulation of the same patient-specific geometry with a given wall movement (Spiegel, Strömungsmechanischer Beitrag zur Planung von Herzoperationen, 2009). The orthotropic constitutive law proposed by Holzapfel et al. (Philos. Trans. R. Soc. Lond. Ser. A, 367:3445-3475, 2009) was implemented in a finite element package to model the passive behavior of the myocardium. Then, this law was modified for contraction. Via the ALE method, the structural model was coupled to a flow model which incorporates blood rheology and the circulatory system (Oertel, Prandtl-Essentials of Fluid Mechanics, 3rd edn, Springer Science + Business Media, 2010; Oertel et al., Modelling the Human Cardiac Fluid Mechanics, 3rd edn, Universitätsverlag Karlsruhe, 2009). Comparison reveals a good quantitative and qualitative agreement with respect to fluid flow. The motion of the myocardium is consistent with physiological observations. The calculated stresses and the distribution are within the physiological range and appear to be reasonable. The coupled model presented contains many features essential to cardiac function. It is possible to calculate wall stresses as well as the characteristic ventricular fluid flow. Based on the simulations we derive two characteristics to assess the health state quantitatively including solid and fluid mechanical aspects.

Effects of teriparatide in postmenopausal women with osteoporosis pre-treated with bisphosphonates: 36-month results from the European Forsteo Observational Study.

OBJECTIVES: To describe fracture rates, back pain, and health-related quality of life (HRQoL) in postmenopausal women with osteoporosis and prior bisphosphonate therapy, treated with teriparatide for up to 18 months and followed up for a further 18 months. DESIGN: Prospective, multinational, and observational study. METHODS: Data on prior bisphosphonate use, clinical fractures, back pain visual analog scale (VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed using a repeated measures model. RESULTS: Of the 1581 enrolled patients with follow-up data, 1161 (73.4%) had a history of prior bisphosphonate use (median duration: 36 months). Of them, 169 (14.6%) sustained ≥1 fracture during 36-month follow-up. Adjusted odds of fracture were significantly decreased at each 6-month interval compared with the first 6 months of teriparatide treatment: 37% decrease in the 12 to <18 months period during teriparatide treatment (P=0.03) and a 76% decrease in the 12- to 18-month period after teriparatide was discontinued (P<0.001). Significant reductions in back pain and improvement in HRQoL were observed. CONCLUSIONS: Postmenopausal women with severe osteoporosis previously treated with bisphosphonates had a significant reduction in the incidence of fractures compared with the first 6 months of therapy, a reduction in back pain and an improvement in HRQoL during up to 18 months of teriparatide treatment. These outcomes were still evident for at least 18 months after teriparatide was discontinued. The results should be interpreted in the context of an uncontrolled, observational study in a routine clinical setting.

Changes in cross-sectional area of spinal canal and vertebral body under 2 years of teriparatide treatment: results from the EUROFORS study.

The treatment of osteoporotic patients with teriparatide is associated with a significant increase in bone formation and gain of bone mass. The purpose of this post hoc analysis was to determine if the cross-sectional area (CSA) of the spinal canal and the vertebral body is affected by teriparatide treatment. Narrowing of the spinal canal might represent a safety problem, while widening of the vertebral CSA might improve mechanical stability. High-resolution computed tomography (HRCT) scans of vertebra T12 were obtained at baseline and after 6, 12, and 24 months of teriparatide treatment (20 microg/day) from 44 postmenopausal women with established osteoporosis participating in the prospective, randomized EUROFORS study. The CSA of the spinal canal did not decrease but increased marginally by 0.9% (2.6 mm(2)) over 24 months (P < 0.001), with a range from -0.5% (-2 mm(2)) to 3.1% (+8 mm(2)). Even when analyzing the spinal CSA on a slice-by-slice basis, no clinically relevant narrowing of the spinal canal was observed. For vertebral bodies, the CSA increased by 0.7% (5.7 mm(2)) over 24 months (P < 0.001), with a range from -0.4% (-3 mm(2)) to 1.6% (+14 mm(2)). Our data do not provide evidence for safety concerns regarding spinal canal narrowing. On the other hand, the increases observed for vertebral CSA apparently also only minimally contribute to the mechanical strengthening of the vertebral body under teriparatide treatment.

Skeletal pain in postmenopausal women with osteoporosis: prevalence and course during raloxifene treatment in a prospective observational study of 6 months duration.

OBJECTIVE: To assess the prevalence of skeletal pain in postmenopausal women before the onset of raloxifene treatment and the further course of pain during treatment in a naturalistic setting. RESEARCH DESIGN AND METHODS: Prospective, uncontrolled, multicentre, 6-month, observational study in Germany. Clinical, diagnostic and pain data were collected at baseline, 6 weeks and 6 months of raloxifene treatment from 3299 female outpatients with postmenopausal osteoporosis. Physicians assessed the presence or absence of back pain, joint pain and diffuse bone pain at each visit, perceived sleep quality and the use of analgesics. Patients assessed intensity and frequency of pain using a 100 mm visual analogue scale (VAS) and a 5-point scale (from 'rarely' to 'permanently'), respectively. RESULTS: At baseline, patients had mean (SD) age 67.6 (9.3) years, 89.4% were reported to have reduced bone mineral density, 39.8% had pre-existing fractures and 93.4% had skeletal pain (physician assessment): 85.1% had back pain, 41.8% joint pain and 32.5% diffuse bone pain. Median pain intensity on VAS was 66.0 mm. After 6 months of raloxifene treatment, the frequency and intensity of pain and use of analgesics for skeletal pain decreased consistently by approximately 50%. Pain frequency decreased in 58.2% and increased in 2.3% of patients. The median decrease in pain intensity from baseline to 6 months was 27.0 mm (46%). Patients' subjective quality of sleep improved: the proportion of patients who were reported to sleep well increased from 21.3% at baseline to 46.7% at 6 months. The decrease in relative pain frequency was greatest with diffuse pain (67.6%) followed by joint pain (36.9%) and back pain (32.5%). CONCLUSION: Raloxifene treatment in postmenopausal women with osteoporosis was associated with a marked reduction of skeletal pain and analgesic consumption and an improvement in subjective sleep quality. Further investigation in a randomised, placebo-controlled trial is warranted.

The effect of growth hormone substitution on cognitive performance in adult patients with hypopituitarism.

OBJECTIVE: Adult hypopituitary patients with growth hormone deficiency, though on adequate adrenal, thyroid or sex hormone replacement therapy, complain of attention and memory disabilities. During the past years several studies have evidenced that growth hormone (GH) may exert distinctive effects on the central nervous system and induce beneficial effects on psychological capabilities. The aim of our study was to determine whether a long-term replacement therapy of recombinant human growth hormone (rhGH) affects cognitive performance in adults with GH deficiency. DESIGN: A double-blind, randomized placebo controlled trial over 6 months, followed by an open period of 6 months of rhGH treatment. MEASUREMENTS: The assessment of cognitive performance comprised attention, verbal memory and non-verbal intelligence and was examined at baseline (0), at 3, 6, 9, and 12 months. In addition, emotional well-being and energy were assessed using the Nottingham Health Profile self rating questionnaire. PATIENTS: Eighteen hypopituitary patients, mean age 41.6 (range 21-63) years with adult onset GH deficiency were evaluated. Patients were on adequate and stable adrenal, thyroid, gonadal and desmopressin replacement therapy where necessary, but not substituted for GH deficiency. RESULTS: After 3 and 6 months of rhGH treatment in the closed label phase a significant improvement of attentional performance was observed compared to baseline in the rhGH group but not in the placebo group. After 6 months scores of attention were significantly different between rhGH and placebo treatment for the digit cancellation test and marginally different for the trail-making test. In contrast, long-term verbal memory and non-verbal intelligence did not improve compared to baseline during therapy and short-term memory improved both in the GH and the placebo group after 3 and 6 months. This was considered as a placebo or practice effect. In the open-label phase a further improvement of attention was found in the GH group and subsequent treatment with rhGH for 3 and 6 months in the placebo group also significantly improved attentional performance supporting the results of the rhGH group in the first 6 months of the double-blind phase. CONCLUSION: RhGH treatment appears to have a beneficial effect on attentional performance in adult hypopituitary patients with GH deficiency when treated for at least 3 months. Our study does not support a role for GH in influencing verbal memory or non-verbal intelligence.

Effects of Psoroptes ovis infection and its control with an ivermectin controlled-release capsule on growing sheep. 2. Evaluation of wool production and leather value.

To evaluate the prophylactic and therapeutic effects of an ivermectin controlled-release capsule (IVM-CRC) on the productivity of growing sheep infested with Psoroptes ovis 24 male and 24 female Merino landrace lambs, 5-6 months old and weighing 21.2-35.0 kg, were used. Sixteen replicates of three animals were formed based on sex and Day 0 body weight. Within each replicate animals were randomly allocated to one of three groups: untreated control; IVM-CRC on Day 0; IVM-CRC on Day 84. For treatment an IVM-CRC for sheep weighing 20-45 kg was used which is designed to deliver ivermectin at a minimum dose of 20 microg/kg/day for 100 days. The lambs were infested with 50-60 P. ovis mites each on days 14 and 21. The animals were shorn on Day 126. After slaughter on Day 127 the quality of the leather produced from their skins was evaluated. The IVM-CRC treatment on Day 0 prevented the establishment of P. ovis. All untreated lambs became infested. The lambs treated with an IVM-CRC on Day 84 became mite-free from Day 112 onwards. The lambs which were treated on Day 0 had significantly (p<0.05) greater clean fleece weight (1.5 kg) and fleece yield (52.1%) than the untreated controls (0.9 kg and 34.1%, respectively) or than lambs treated on Day 84 (1.0 kg and 47.8%, respectively). Clean fleece weight and fleece yield were in the tendency (p=0.055) or significantly (p<0. 001) greater, respectively, for lambs treated on Day 84 than for the untreated controls. The chrome tanned dried crust leather of all untreated controls and six of the 16 lambs treated on Day 84 showed grain surface defects such as discolourations, indurations and coarse, pitted grain. The useful (defect-free) leather size was significantly (p<0.01) higher for the lambs treated on Day 0 (100%) than for the lambs treated on Day 84 (82.7%) and the untreated controls (7.8%). The physical testing revealed that the leather of sheep treated on Day 0 had significantly (p<0.05) higher thickness, elongation break and tear resistance than the leather of both untreated controls and sheep treated on Day 84. There were no significant differences in the physical characteristics of the leather of the untreated controls and the sheep treated on Day 84.

Spontaneous regression of hepatocellular carcinoma.

Spontaneous regression of cancer is a rare phenomenon seldom described in patients with hepatocellular carcinoma. A case of spontaneous regression of hepatocellular carcinoma is reported and compared with the reports published in the English literature. A 52-yr-old man presented with biopsy-proven hepatocellular carcinoma, which was considered to be unresectable at initial laparotomy. The tumor subsequently regressed without specific treatment, as assessed radiologically and by normalization of a previously elevated alpha-fetoprotein level. At repeat laparotomy 14 months after initial diagnosis, intraoperative ultrasound failed to disclose a hepatic mass, and multiple biopsies showed no evidence of malignancy. To date, only nine case reports of apparently spontaneous regression of hepatocellular carcinoma have been published in the English literature. Clinical characteristics discriminating these patients from less fortunate patients with hepatocellular carcinoma could not be identified. The mechanisms underlying this intriguing phenomenon remain unknown.

Difference in expression of Helicobacter pylori gastritis in antrum and body.

Seven hundred seventy biopsy specimens obtained from 10 different sites in stomachs of 77 patients were examined for the presence of active chronic gastritis (ACG) and Helicobacter pylori to investigate the characteristics of gastritis in the antrum and body. Forty-eight patients with ACG at one or more sites were all H. pylori positive. H. pylori was not found in 20 patients who had chronic gastritis with no activity or in 9 patients who had histologically normal mucosa. In patients with ACG in at least one biopsy site, a strong positive topographic association between H. pylori colonization and ACG was seen in the Warthin-Starry stain. The frequency of H. pylori colonization was similar in the antrum and body. However, the incidence of ACG declined significantly proximal to the borderline between the antrum and body (P less than 0.001). The average grade of gastritis at the individual biopsy sites was distributed evenly throughout the antrum but decreased markedly in the body (P less than 0.0001). In the same manner, the average grade of H. pylori colonization decreased in the body (P less than 0.0027). The grade of H. pylori colonization in the individual biopsy specimens was closely related to the grade of gastritis (r = 0.51); also, the grade of neutrophil infiltration was related to the grade of gastritis (r = 0.79). A good correlation existed between the grade of H. pylori colonization and the grade of neutrophil infiltration (r = 0.70). The results of this study show a different expression of H. pylori gastritis in the antrum and body, which is the main subtype of chronic type B gastritis. The close topographic and graded association between the presence of H. pylori and the activity and grade of gastritis lend further support to the major pathogenic role of H. pylori in active chronic gastritis. The different expression of gastritis in antrum and body is suggested to be increased reactivity of the antral mucosa to the infection, possibly on the basis of an enhanced immunologic response to H. pylori in this region.

Topographic association between active gastritis and Campylobacter pylori colonisation.

One thousand biopsy specimens obtained from 10 sites in the stomachs of 50 patients were examined for the presence of active chronic gastritis and Campylobacter pylori. All 32 patients with active chronic gastritis at 234 out of 320 sites were positive for C pylori: 227 showed colonisation with C pylori by the Warthin-Starry stain; and 222 were positive by culture. C pylori was not found in 18 patients with inactive chronic gastritis or histologically normal mucosa. The area of C pylori colonisation was larger than the area of active chronic gastritis in 289 positive specimens on culture and 261 on staining, respectively, suggesting that C pylori colonisation may precede the development of active chronic gastritis. It is concluded that patchy distribution of active chronic gastritis and C pylori colonisation must be considered, particularly in serology or breath test studies where the histological examination serves as a reference. Furthermore, it may have important implications for the follow up of patients after antibacterial treatment. The topographic and specific association of C pylori and active chronic gastritis provides further evidence for the pathogenic role of C pylori in active chronic gastritis.

The biologic activity of mast cell granules. VI. The effect of vinblastine-induced neutropenia on rat cutaneous late phase reactions.

Type I immediate hypersensitivity reactions in human and rat skin may be followed by late phase reactions (LPR). A consistent feature of both human and rat LPR is the early histologic appearance of neutrophils, which, in rats, is followed by the later appearance (8 to 24 hr) of mononuclear cells. To determine the importance of the neutrophil in the development of LPR, rats were depleted of neutrophils using parenteral injections of vinblastine sulfate (VS). VS produced a dose-dependent neutropenia, with the maximal effect on day 4. LPR that were induced with anti-IgE, isolated mast cell granules (MCG), or purified high (greater than 10,000 daltons) and low (500 to 10,000 daltons) m.w. fractions obtained from MCG were significantly abrogated in VS-treated rats. In neutropenic rats previously immunized with complete Freund's adjuvant, the intensity of inflammatory reactions produced by skin testing with purified protein derivatives was also significantly reduced. Administration of exogenous neutrophils to neutropenic animals partially reconstituted the reduced LPR. These data confirm and extend previous observations on the contribution of neutrophils to delayed hypersensitivity reactions and provide evidence that the neutrophil is critical for the development of rat cutaneous LPR as well.