Clinical Evaluation of All Ceramic Zirconia Framework Resin Bonded Bridges.

OBJECTIVE: To evaluate the clinical longevity of 58 adhesively bonded single unit yttria-stabilized tetragonal zirconia polycrystalline (Y-TZP) ceramic Resin Bonded Bridges (RBB). MATERIALS AND METHODS: Twenty six consecutive patients with at least one congenitally missing tooth in the maxilla or mandible were provided with 58 single unit Y-TZP RBBs. The cantilever RBBs were designed and milled using a CAD-CAM system to produce frameworks which were veneered using a glass-ceramic material and cemented with a self-etching dual-cure resin cement. RESULTS: Following a mean follow up period of 36.2 months (maximum 62.3 months, minimum 25.4 months), 48 restorations remain in service with a survival rate of 82.7%. One anterior retainer fracture was encountered and no fractures of the posterior framework or ceramic were noted within the time frame reported. CONCLUSIONS: All ceramic Y-TZP RBBs replacing maxillary and mandibular teeth in the anterior and posterior areas demonstrated an 82.7% Kaplan Meier survival rate over 3 years, which was comparable to previously published survival rates for the non-perforated metal framework RBBs. CLINICAL IMPLICATIONS: Replacement of anterior or posterior teeth using single unit cantilevered RBBs using Y-TZP ceramics should be considered a viable restorative option with a high survival rate.

A structured, group-based diabetes self-management education (DSME) programme for people, families and whanau with type 2 diabetes (T2DM) in New Zealand: an observational study.

BACKGROUND: Group-based diabetes self-management education (DSME) programmes have been shown to be effective. A programme tailored for the unique social and ethnic environment of New Zealand (NZ) was developed using concepts from internationally developed programmes. AIM: To assess the effectiveness of a 6 week New Zealand specific DSME programme. METHODS: In this observational study people with type 2 diabetes (aged 18-80 years) from diverse cultural backgrounds were recruited from primary care. Seventeen groups of six education sessions were run. Clinical data were collected from primary care at baseline, 3, 6 and 9 months. Participants also completed a self-administered questionnaire on diabetes knowledge, and self-management behaviours. RESULTS: 107 participants, mean age 56.7±11.3 years and mean duration of diabetes 7.5±7 years (NZ European (44%), Maori (24%), Pacific (16%) and Indian (16%)), were enrolled. Confidence in self-managing diabetes, regular examination of feet, physical activity levels and smoking rates all improved. Glycaemic control improved between baseline and 6 months (HbA1C 64.9±20.0 mmol/mol to 59.9±13.9 mmol/mol (p<0.05) (baseline 8.07%±1.80, 6 months 7.62%±1.25)), but was no different to baseline at 9 months. Systolic BP reduced from 131.9±16.4 to 127.4±18.2 mmHg (p<0.05) at 6 months, but increased to baseline levels by 9 months. Diastolic BP, triglycerides and urine microalbumin:creatinine ratio were significantly reduced at 3, 6 and 9 months. CONCLUSION: A group-based DSME programme designed specifically for the NZ population was effective at improving aspects of diabetes care at 6 months. The attenuation of these improvements after 6 months suggests a refresher course at that time may be beneficial.

Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis.

Bronchial biopsy specimens from chronic obstructive pulmonary disease (COPD) patients demonstrate increased numbers of CD8+ T-lymphocytes, macrophages and, in some studies, neutrophils and eosinophils. Smoking cessation affects the rate of forced expiratory volume in one second (FEV(1)) decline in COPD, but the effect on inflammation is uncertain. Bronchial biopsy inflammatory cell counts were compared in current and ex-smokers with COPD. A pooled analysis of subepithelial inflammatory cell count data from three bronchial biopsy studies that included COPD patients who were either current or ex-smokers was performed. Cell count data from 101 subjects, 65 current smokers and 36 ex-smokers, were analysed for the following cell types: CD4+ and CD8+ T-lymphocytes, CD68+ (monocytes/macrophages), neutrophil elastase+ (neutrophils), EG2+ (eosinophils), mast cell tryptase+ and cells mRNA-positive for tumour necrosis factor-alpha. Current smokers and ex-smokers were similar in terms of lung function, as measured by FEV(1) (% predicted), forced vital capacity (FVC) and FEV(1)/FVC. The results demonstrate that there were no significant differences between smokers and ex-smokers in the numbers of any of the inflammatory cell types or markers analysed. It is concluded that, in established chronic obstructive pulmonary disease, the bronchial mucosal inflammatory cell infiltrate is similar in ex-smokers and those that continue to smoke.

Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design.

There is variability in the distribution of inflammatory cells in bronchial tissue in chronic obstructive pulmonary disease (COPD). Better strategies for biopsy sampling of the airway mucosa may improve the capacity to show a difference between study populations where variability in distribution exists. The current authors have examined sources of biological variability in the quantification of inflammatory cells in endobronchial biopsies using immunostained samples taken from 51 subjects with COPD, with a mean forced expiratory volume in one second of 1.71 L, 55% predicted. The distribution of variance contributed by different sources was similar for different inflammatory cell types. For CD8+ cells, a key inflammatory cell in COPD, the largest contribution to intra-subject variability (39%) was time (i.e. 10 weeks between biopsies of placebo-treated subjects), followed by airway generation (23%), biopsy (2.5%), zone (within section; 1.4%) and section (0.4%). Power calculations demonstrated that examining one section from one biopsy, from each of two airway generations, would require a sample size of 32 subjects per group to show a difference of one doubling or halving in CD8+ cells, compared with 47 subjects per group if only one airway generation was sampled. Therefore, biopsies from more than one airway generation should be examined in order to maximise statistical power to detect a difference between study groups.

Variation of CD8+ T-lymphocytes around the bronchial internal perimeter in chronic bronchitis.

The variation of CD8+ cells has been determined around the internal perimeter of intrapulmonary bronchi in smokers with chronic bronchitis (CB), and the amount of tissue required to confidently estimate the true mean has been calculated. Lung specimens were obtained from 10 smokers with CB. Paraffin sections of intrapulmonary bronchi were immunostained and CD8+ cells counted in the epithelium and subepithelium in up to 10 sequential 1-mm segments around the internal perimeter of each airway. The percentage of counts falling between +/-20% of the final mean was 43.0% for epithelium and 40.9% for subepithelium. In 90% of subjects, the cumulative mean was stable after examination of subepithelial tissue associated with 5 mm of reticular basement membrane. There is considerable variation in the counts of CD8+ cells between adjacent 1-mm airway mucosal segments in chronic bronchitis. In order to achieve a representative count and to maximise statistical power to detect differences between study populations, subepithelial tissue including a minimum of 5 mm of reticular basement membrane length should be examined.

Nonspiking and spiking proprioceptors in the crab: white noise analysis of spiking CB-chordotonal organ afferents.

The proprioceptors that signal the position and movement of the first two joints of crustacean legs provide an excellent system for comparison of spiking and nonspiking (graded) information transfer and processing in a simple motor system. The position, velocity, and acceleration of the first two joints of the crab leg are monitored by both nonspiking and spiking proprioceptors. The nonspiking thoracic-coxal muscle receptor organ (TCMRO) spans the TC joint, while the coxo-basal (CB) joint is monitored by the spiking CB chordotonal organ (CBCTO) and by nonspiking afferents arising from levator and depressor elastic strands. The response characteristics and nonlinear models of the input-output relationship for CB chordotonal afferents were determined using white noise analysis (Wiener kernel) methods. The first- and second-order Wiener kernels for each of the four response classes of CB chordotonal afferents (position, position-velocity, velocity, and acceleration) were calculated and the gain function for each receptor determined by taking the Fourier transform of the first-order kernel. In all cases, there was a good correspondence between the response of an afferent to deterministic stimulation (trapezoidal movement) and the best-fitting linear transfer function calculated from the first-order kernel. All afferents also had a nonlinear response component and second-order Wiener kernels were calculated for afferents of each response type. Models of afferent responses based on the first- and second-order kernels were able to predict the response of the afferents with an average accuracy of 86%.

Exacerbations of Bronchitis: bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants.

Eosinophilia has been reported during exacerbations of bronchitis, but the mechanisms of tissue recruitment of eosinophils are unclear. We quantified eosinophils and the concurrent expression of cytokines and chemokines probably responsible for the tissue eosinophilia in bronchial biopsies obtained from three groups of nonatopic subjects: (1) healthy nonsmokers (n = 7; FEV1 % predicted = 108 +/- 4 [mean +/- SEM]); (2) nonasthmatic smokers with chronic bronchitis (CB) in a stable phase of their disease (n = 11; FEV1 % predicted: 75 +/- 5); and (3) nonasthmatic subjects with CB who sought medical advice for an exacerbation of their condition (n = 9; FEV(1) % predicted: 61 +/- 8). We applied anti-EG2 antibody and immunostaining to detect and count eosinophils. We performed in situ hybridization to visualize and enumerate cells expressing the genes for interleukin (IL)-4 and IL-5 and the eosinophil chemokines eotaxin, monocyte chemoattractant protein (MCP)-4, or regulated on activation, normal T-cell expressed and secreted (RANTES). We confirmed an increase in EG2-positive eosinophils in patients with CB in exacerbation. We found messenger RNA (mRNA) positivity for IL-4 and IL-5 in CB, but the between-group differences were not statistically significant. However, the numbers of lymphomononuclear cells expressing eotaxin mRNA were significantly greater in the smokers with CB than in the healthy nonsmokers without CB (p < 0.01). Following an exacerbation, RANTES expression was upregulated and this chemokine was strongly expressed in both the surface epithelium and in subepithelial lymphomononuclear cells: only RANTES showed a significant positive correlation with the increasing number of EG2-positive cells (r = 0.51; p < 0.03). In conclusion, an allergic profile of inflammation can also occur in CB: the marked upregulation of RANTES in the epithelium and subepithelium most likely accounts for the increased eosinophilia associated with an exacerbation of bronchitis.

Transverse myelopathy and radiculomyelopathy associated with pulmonary atypical Mycobacterium infections.

Myelopathy is a well recognised but rare association with Mycobacterium tuberculosis infection, but has not been described with atypical mycobacteria. We report two cases of disabling myelopathy in association with pulmonary infection by Mycobacterium kansasii and Mycobacterium malmoense; the myelopathy is presumed to be a para-infectious phenomenon.

The availability of smoking cessation advice from health professionals--a census from one East London District.

A survey of 382 hospital inpatients and a survey of 500 adults attending a GP open access chest X-ray service showed that 18% and 25% respectively were current smokers. Sixty per cent of the inpatient smokers and three quarters of the community smokers expressed a wish to stop smoking, and 44% of the inpatient smokers and 62% of the community smokers reported having received advice from their primary care physician to stop smoking. However, when the community smokers were asked about more specific advice they had received to help them stop smoking, only 13% had received advice regarding nicotine replacement therapies and under 5% had been given the telephone number of a smoking cessation support service (Smokers Quitline). Use of nicotine replacement therapies nearly doubles the success rate for smoking cessation, and it is essential for all health professionals to be able to give specific advice as to how smokers may be able to quit.

Long-term storage of sediments: Implications for sediment toxicity testing.

Juvenile Nereis (Neanthes) arenaceodentata survival and growth were used to evaluate the effect of storage time on the toxicity of sediments with moderate PAH and metal contamination. Seven San Francisco Bay area sediments and a clean control sediment were stored (4 degrees C) and then periodically evaluated (up to two years after collection). During each test, juvenile worms (2-3 weeks post emergence) were exposed for 21 days. Test endpoints were survival and growth rate (mg dry weight/day). In general, survival was high (>75%) and long-term cold storage (740 days) did not significantly alter growth or survival. In half of the sediments a cyclical phenomenon was observed associated with the appearance of ammonia in the overlying water of bioassay beakers. The periodicity of this phenomenon was approximately one year. It was not associated with any geophysical characteristic of the test sediments (i.e. grain size, % TOC, % TKN). Significant mortality (0% survival on day 427) was associated with the largest of these peaks in overlying water ammonia concentration. Results of this study suggest that ammonia in stored sediments is an important, potentially confounding factor in sediment toxicity tests.

Anticonflict and discriminative stimulus effects in the pigeon of a new methoxy-chroman 5-HT1A agonist, (+)S 20244 and its enantiomers (+)S 20499 and (-)S 20500.

The present experiments examined the behavioral and receptor binding characteristics of new 5-HT1A methoxy-chroman derivatives in procedures known to be sensitive to the activity of 5-HT1A compounds. Key peck responding of pigeons was maintained by a 30-response fixed-ratio schedule of food delivery. In studies involving punished responding, every 30th response during one keylight stimulus also produced shock ("conflict" procedure). In drug discrimination studies, pigeons were trained to discriminate injections of the 5-HT1A agonist 8-OH-DPAT (0.3 mg/kg) from saline. Three forms of the methoxy-chroman compounds were tested: the enantiomers (+)S 20499 (0.01-3.0 mg/kg) and (-) S 20500 (0.3-5.6 mg/kg), as well as the racemic mixture (+)S 20244 (0.03-5.6 mg/kg). (+)S 20499 was approximately 10-fold more potent than (-)S 20500 in producing maximal increases in punished responding. (+)S 20244 was comparable in potency to (-)S 20500 in producing maximal increases in punished responding, but increases also occurred at much lower doses with (+)S 20244 and the magnitude of the effect with (-)S 20500 was less than that of the two other compounds. While increases in punished responding were observed with all three drugs at doses that did not affect unpunished responding, the highest doses of all drugs decreased unpunished responding. All compounds substituted for 8-OH-DPAT in the drug discrimination procedure, suggestive of 5-HT1A agonist activity. (+)S 20499 was approximately 30-fold more potent than (-)S 20500 in substituting for 8-OH-DPAT and 3-fold more potent than the racemate. All three compounds bound with high affinity to pigeon cerebrum receptor sites labelled by [3H]8-OH-DPAT. As in behavioral studies, (+)S 20499 was approximately 10-fold more potent than (-)S 20500 in displacing [3H]8-OH-DPAT (IC50 = 2.79 versus 20.3 nM). These studies demonstrate that the enantiomers of this compound, as well as the racemic mixture, are effective 5-HT1A compounds and that (+)S 20499 in particular is likely to be a clinically effective anxiolytic and/or antidepressant.

Anxiolytic and antidepressant mechanisms of 5-HT1A drugs in the pigeon: contributions from behavioral studies.

The discovery that compounds acting through 5-hydroxytryptamine (5-HT) receptor subtypes can produce anxiolytic and/or antidepressant therapeutic effects in humans has resulted in considerable interest in the role of the 5-HT receptor system in both anxiety and depressive disorders. Because many of the clinically efficacious 5-HT1A anxiolytic drugs are either ineffective or produce inconsistent results in traditional or standard types of preclinical punishment or conflict procedures with rodents and other nonhuman mammals, there is considerable need for alternative behavioral assays sensitive to and selective for these compounds. In contrast to data with nonhuman mammals, 5-HT1A drugs are quite effective in pigeons studied under a punishment procedure. This paper reviews the use of the pigeon conflict procedure as a method for the detection and analysis of potential anxiolytic drugs acting through 5-HT1A receptors. Additionally, recent studies, also with the pigeon, have indicated that, in contrast to the rat, it is possible to establish an antidepressant such as imipramine as a discriminative stimulus, and then to use this procedure to evaluate the neuropharmacological bases for the behavioral and, presumably, therapeutic actions of these drugs. Using the drug discrimination procedure, it has been possible to examine a number of selective compounds that substitute for imipramine, thereby clarifying specific substrates for the antidepressant activity of this and related drugs. The pigeon promises to be a useful species in the pharmacological analyses of novel anxiolytic drugs and provides new approaches to the analysis and understanding of traditional as well as the more recently introduced antidepressant drugs.

Knowledge, attitudes, and behavior of elderly persons regarding living wills.

The knowledge, attitudes, and behavior of elderly persons regarding living wills were explored in a rural county in eastern North Carolina. A questionnaire was administered to 75 ambulatory elderly persons by personal interview at community dining sites. Fifty-two percent (39) of these subjects said they were familiar with living wills and 64% (48 persons) correctly summarized what the North Carolina living will says. When asked about preferences for medical care in the setting of a terminal illness, 86% (65 persons) stated a desire to receive basic medical care or comfort care only. Although their preferences were consistent with the provisions of a living will, none had signed the living will document provided by the state of North Carolina, and only two (3%) had discussed a living will with their physician. Seventy (93%) wanted their family or spouse to make decisions about terminal care if they themselves were unable to participate, and discussions between these persons and their chosen proxies actually occurred 45% (34/75) of the time. Eighty-one percent (61 persons) stated a desire to discuss end-of-life care with their physicians, but a minority (eight [11%]) had actually talked with their physicians, and these discussions were usually initiated by the patient (five of eight). We conclude that living will legislation is congruent with the desire of many elderly persons to limit medical care in terminal illness. However, this elderly population did not make use of living wills as a means of indicating their wishes. Recommendations are made to improve physician-patient and patient-proxy communication regarding preferences for medical care at the end of life and living wills. Alternatives to the living will should also be explored.

Conditioned diastolic blood pressure: the effects of magnitude of acquired response and feedback schedules on resistance to extinction.

The purpose of this experiment was to examine the effects of: (a) training to two different response magnitude criteria, and (b) three different feedback schedules on the acquisition and subsequent extinction of diastolic blood pressure changes. Subjects were 20 male and female normotensive volunteer college students, ages 18-36 years. A 3 x 2 design was used in which 3 schedules of reinforcement (0, 50 and 100%) were factorially compared with two response magnitude training criteria (10% and 20% of resting basal diastolic blood pressure). The results indicated that while the partial reinforcement effect appears to hold for the acquisition of bidirectional diastolic blood pressure changes, different response magnitude training criteria seemed to have a greater influence in producing significant differences in acquisition rate during the training of diastolic blood pressure decreases. Resistance to extinction was notably weak across all conditions, with most subjects failing to exhibit previously acquired bidirectional diastolic blood pressure performance after the end of the first extinction session.

Parallel integration of vision modules.

Computer algorithms have been developed for several early vision processes, such as edge detection, stereopsis, motion, texture, and color, that give separate cues to the distance from the viewer of three-dimensional surfaces, their shape, and their material properties. Not surprisingly, biological vision systems still greatly outperform computer vision programs. One of the keys to the reliability, flexibility, and robustness of biological vision systems is their ability to integrate several visual cues. A computational technique for integrating different visual cues has now been developed and implemented with encouraging results on a parallel supercomputer.

The dynamics of free calcium in dendritic spines in response to repetitive synaptic input.

Increased levels of intracellular calcium at either pre- or postsynaptic sites are thought to precede changes in synaptic strength. Thus, to induce long-term potentiation in the hippocampus, periods of intense synaptic stimulation would have to transiently raise the levels of cytosolic calcium at postsynaptic sites--dendritic spines in the majority of cases. Since direct experimental verification of this hypothesis is not possible at present, calcium levels have been studied by numerically solving the appropriate electro-diffusion equations for two different postsynaptic structures. Under the assumption that voltage-dependent calcium channels are present on dendritic spines, free intracellular calcium in spines can reach micromolar levels after as few as seven spikes in 20 milliseconds. Moreover, a short, but high-frequency, burst of presynaptic activity is more effective in raising levels of calcium and especially of the calcium-calmodulin complex than sustained low-frequency activity. This behavior is different from that seen at the soma of a typical vertebrate neuron.