Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis.

Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo. INTRODUCTION: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies. MATERIALS AND METHODS: We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 microg or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial. RESULTS: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation. CONCLUSIONS: Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.     

Axonal transport and tissue contents of substance P in rats with long-term streptozotocin-diabetes. Effects of the aldose reductase inhibitor ‘statil’

This study examined the axonal transport of substance P-like immunoreactivity (SPLI) and its content in dorsal root ganglion, trigeminal ganglion, stomach and ileum of non-diabetic rats and two groups of rats with streptozotocin-induced diabetes of 9 months duration. One diabetic group received the aldose reductase inhibitor ‘Statil’ throughout the period of study. To reduce morbidity all diabetic animals were given twice-weekly injections of a long-acting insulin which restricted weight loss but did not prevent regular and severe hyperglycaemia. Axonal transport of SPLI was studied by measurement of accumulation at 12 h ligatures on the left sciatic nerve. There were no differences between the 3 groups either in the calculated anterograde and retrograde mean rates of accumulation (ranges 6.0 to 7.6 and 0.38 to 0.72 mm/h respectively) or mobile fractions of SPLI (means from 0.54 to 0.58). There were, however, marked reductions in anterograde and retrograde accumulations of SPLI in the constricted nerves of the ‘untreated’ diabetics (respectively 57 and 33% of controls;P < 0.01 for both). In the ‘Statil’-treated rats these deficits were attenuated (80 and 75% of controls). Diabetes also reduced the SPLI content of unligated sciatic nerve and trigeminal ganglion (65 and 75% of controls). ‘Statil’ prevented the deficit in the ganglion, but not in the nerve. ‘Statil’ treatment prevented themyo-inositol depletion and attenuated the sorbitol and fructose accumulation seen in the sciatic nerves of the untreated diabetic animals suggesting effective inhibition of aldose reductase in this tissue. The total SPLI content of the stomach and 1-cm segments of ileum were unaltered in the diabetic animals but due to the increased weights of these tissues the SPLI content per unit weight was reduced. These changes were unaffected by ‘Statil’.     

Mycoplasma pneumoniae Induces Chronic Respiratory Infection, Airway Hyperreactivity, and Pulmonary Inflammation: a Murine Model of Infection-Associated Chronic Reactive Airway Disease

Because chronic Mycoplasma pneumoniae respiratory infection is hypothesized to play a role in asthma, the potential of M. pneumoniae to establish chronic respiratory infection with associated pulmonary disease was investigated in a murine model. BALB/c mice were intranasally inoculated once with M. pneumoniae and examined at 109, 150, 245, 368, and 530 days postinoculation. M. pneumoniae was detected in bronchoalveolar lavage fluid by culture or PCR in 70 and 22% of mice at 109 and 530 days postinoculation, respectively. Lung histopathology was normal up to 368 days postinoculation. At 530 days, however, 78% of the mice inoculated with M. pneumoniae demonstrated abnormal histopathology characterized by peribronchial and perivascular mononuclear infiltrates. A mean histopathologic score (HPS) at 530 days of 5.1 was significantly greater (P < 0.01) than that for controls (HPS score of 0). Serum anti-M. pneumoniae immunoglobulin G was detectable in all of the mice inoculated with M. pneumoniae and was inversely correlated with HPS (r = -0.95, P = 0.01) at 530 days postinoculation. Unrestrained whole-body plethysmography measurement of enhanced pause revealed significantly elevated airway methacholine reactivity in M. pneumoniae-inoculated mice compared with that in controls at 245 days (P = 0.03) and increased airway obstruction at 530 days (P = 0.01). Murine M. pneumoniae respiratory infection can lead to chronic pulmonary disease characterized by airway hyperreactivity, airway obstruction, and histologic inflammation.     

Cardiac flow measurement by ultrafast CT: validation of continuous and pulsatile flow.

To gauge the accuracy of ultrafast CT in measuring cardiac output and myocardial perfusion in humans, measurements of continuous and pulsatile flow were made in a large asymmetrical phantom. The variation in the relationship between Hounsfield number and contrast concentration was assessed in a human thorax phantom. Radiopaque contrast medium was injected during perfusion of the phantom at a range of flow rates between 1.5 and 8 L/min. The phantom was scanned in two modes (50 and 100 ms) during continuous and pulsatile flow and with the phantom surrounded by air and by water. Flow in the tubes was calculated using indicator dilution theory, and flow in the tissue-equivalent chamber was calculated by applying first-pass distribution principles. The standard deviation of the difference between calculated and measured flow varied from 0.2 to 0.6 L/min, giving 95% limits of agreement from 0.4 to 1.2 L/min. The constant (K) relating Hounsfield unit number to iodine concentration varied widely both in different locations within the phantom and under different scan conditions (17.2-27.6 HU/mg I). Within a human thorax phantom, K varied from 14.15 to 23.18 HU/mg I and was dependent on location within the thorax phantom, the scan mode, and the cross-sectional diameter of the phantom. These data suggest that though the ultrafast CT scanner can measure continuous and pulsatile flow accurately in tubes, precise measurements of cardiac output in humans will require K to be assessed for each subject. Measurements of flow in tissue should be possible.     

Reductions in depressed mood and denial coping during cognitive behavioral stress management with hiv-positive gay men treated with haart

Background: Stress management interventions for HIV-positive persons have been designed to enhance coping skills and encourage health-promoting behaviors with the hope of decreasing distress and slowing disease progression.Purpose: We examined the efficacy of a cognitive behavioral stress management (CBSM) intervention in combination with medication adherence training (MAT) in 130 gay and bisexual men living with HIV infection.Methods: Participants were randomized to either a 10-week CBSM+MAT intervention (n = 76) or a MAT-only condition (n = 54). Measures of self-reported adherence, active cognitive coping (i.e., acceptance and positive reinterpretation), avoidant coping (i.e., denial and behavioral disengagement), and depressed mood were examined over the 10-week intervention period.Results: Men in CBSM+MAT reported reductions in depressed mood and denial coping during the 10-week intervention period, but no changes in active cognitive coping or self-reported adherence were observed. Using path analysis, greater reliance on denial coping at baseline was associated with decreased depressed mood at 10 weeks. We also determined that CBSM+MAT may decrease depressed mood by reducing reliance on denial coping over the 10-week intervention period.Conclusions: Although denial may be an effective means of distress reduction in the short term, reliance on this coping strategy may result in a decreased capacity to effectively manage a variety of disease-related stressors in the long term. CBSM+MAT addresses this potentially detrimental pattern by teaching stress reduction skills that may decrease depressed mood via reduced reliance on denial coping. This research was supported by National Institute of Mental Health Grants P01 MH49548 and T32 MH18917.     

The prevalent cohort study and the acquired immunodeficiency syndrome

The acquired immunodeficiency syndrome (AIDS) is caused by a retrovirus, the human immunodeficiency virus (HIV). A rapid and convenient method to identify additional cofactors or risk modifiers and markers of disease progression is to study a cohort prevalent with HIV antibody. However, because the time of viral infection is usually unknown in the cohort, there are several potential sources of bias. Three sources of bias in a prevalent cohort study are identified assuming a proportional hazards model: onset confounding, differential length-biased sampling, and frailty selection. A number of problems in the interpretation of results on markers from a prevalent cohort also are considered. It is concluded that risk estimates derived from a prevalent cohort are not directly comparable to risk estimates derived from an incident cohort.     

Pharmacological profile of the novel P2T-purinoceptor antagonist, FPL 67085 in vitro and in the anaesthetized rat in vivo.

1. We measured the ratio of ETA and ETB sub-types in the media (containing mainly smooth muscle) of human cardiac arteries (aorta, pulmonary and coronary), internal mammary arteries and saphenous veins. 2. In saturation experiments, [125I]-endothelin-1 ([125I]-ET-1) bound with high affinity to the media of each vessel (n = 3 individuals or homogenate preparations +/- s.e. mean): coronary artery, KD = 0.14 +/- 0.02 nM, Bmax = 71.0 +/- 21.0 fmol mg-1 protein; pulmonary artery, KD = 0.85 +/- 0.25 nM, Bmax = 15.2 +/- 10.3 fmol mg-1 protein; aorta, KD = 0.51 +/- 0.02 nM, Bmax = 9.4 +/- 4.4 fmol mg-1 protein; internal mammary artery. KD = 0.34 +/- 0.31 nM, Bmax = 2.0 +/- 0.5 fmol mg-1 protein and saphenous vein, KD = 0.28 +/- 0.05 nM, Bmax = 52.8 +/- 1.0 fmol mg-1 protein. In each vessel, over the concentration-range tested, Hill slopes were close to unity and a one site fit was preferred to a two site model. 3. In competition binding assays, the ETA selective ligand, BQ123 inhibited the binding of 0.1 nM [125I]-ET-1 to the media in a biphasic manner. In each case, a two site fit was preferred to a one or three site model: coronary artery, KDETA = 0.85 +/- 0.03 nM, KDETB = 7.58 +/- 2.27 microM, ratio = 89:11%; pulmonary artery, KDETA = 0.27 +/- 0.05 nM, KDETB = 24.60 +/- 5.34 microM, ratio = 92:8%; aorta, KDETA = 0.80 +/- 0.40 nM, KDETB = 2.67 +/- 2.60 microM ratio = 89:11%; saphenous vein, KDETA = 0.55 +/- 0.17 nM, KDETB = 14.4 +/- 0.26 microM, 85:15% (n = 3 individuals or homogenate preparations +/- s.e. mean). BQ123 showed up to 18000 fold selectivity for the ETA over the ETB sub-type. The ETA-selective ligand, [125I]-PD151242 labelled 85% of the receptors detected by a fixed concentration of [125I]-ET-1 in media of internal mammary artery, measured by quantitative autoradiography. In contrast, the density of ETB receptors detected with [125I]-BQ3020 was 7.0 +/- 1.5 amol mm-2, representing about 8% of [125I]-ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Communities coping with change: A conceptual model

Changing economic, political, environmental, and social conditions continue to have a cumulative impact on Australian regional communities, and in many instances, rural communities are being forced to initiate their own strategies in order to remain economically and socially viable. However, while communities respond in differing ways to similar change events, as do individuals, research examining the change process has largely been undertaken at the individual level. This article reports on an investigation of the characteristics that moderate a community's ability to manage change and the types of collective coping strategies communities employ to deal with change events. A model of community change process was used as the framework to examine the links between community characteristics, appraisal of change events (forest restructuring and tourism), and the use of collective strategies in three communities in Western Australia. Findings suggest that a community's mobilization of strategies is dependent on the collective assessment of the change event, the nature of the event, and the characteristics of the community. The implications for intervention through policy and community development are discussed briefly. © 2004 Wiley Periodicals, Inc. J Comm Psychol 32: 201–216, 2004.     

High intensity focused ultrasound: physical principles and devices.

High intensity focused ultrasound (HIFU) is gaining rapid clinical acceptance as a treatment modality enabling non-invasive tissue heating and ablation for numerous applications. HIFU treatments are usually carried out in a single session, often as a day case procedure, with the patient either fully conscious, lightly sedated or under light general anaesthesia. A major advantage of HIFU over other thermal ablation techniques is that there is no necessity for the transcutaneous insertion of probes into the target tissue. The high powered focused beams employed are generated from sources placed either outside the body (for treatment of tumours of the liver, kidney, breast, uterus, pancreas and bone) or in the rectum (for treatment of the prostate), and are designed to enable rapid heating of a target tissue volume, while leaving tissue in the ultrasound propagation path relatively unaffected. Given the wide-ranging applicability of HIFU, numerous extra-corporeal, transrectal and interstitial devices have been designed to optimise application-specific treatment delivery. Their principle of operation is described here, alongside an overview of the physical mechanisms governing HIFU propagation and HIFU-induced heating. Present methods of characterising HIFU fields and of quantifying HIFU exposure and its associated effects are also addressed.