Access to off-leash parks, street pattern and dog walking among adults.

We examined whether dog-walking among dog-owners correlated with street pattern and proximity to a park area designated for off-leash use. Dog-walking was associated with street pattern and with nearby off-leash areas, but these associations varied by the measure of dog-walking examined (participation versus frequency in a usual week). Interventions to increase dog-walking should be undertaken and evaluated. Demographic factors, urban design, and whether owners already walk their dogs should be taken into account in planning.

Associations between neighbourhood street pattern, neighbourhood socioeconomic status and sleep in adults.

Sleep duration is a risk factor for poor health and all-cause mortality. Evidence suggests that neighbourhood characteristics such as built environment and socioeconomic status (SES) may affect sleep duration in adults. This study examined the relationship between neighbourhood built environment (i.e., measured via the street pattern) and SES with sleep duration in adults (n = 797) from 12 neighbourhoods in Calgary (Canada). Covariate adjusted linear and multinomial logistic regression models estimated the associations between street pattern (grid, warped-grid, curvilinear), SES and sleep duration. We also tested if the interaction between street pattern and SES was associated with sleep duration. Although neighbourhood street pattern and neighbourhood SES were not independently associated with sleep, the interaction between street pattern and neighbourhood SES, was associated with mean sleep duration. Individuals living in curvilinear low SES neighbourhoods had the shortest sleep duration (6.93 h per day; 95% CI 6.68, 7.18), while those living in curvilinear high SES neighbourhoods slept the longest (7.43 h per day; 95% CI 7.29, 7.57). Neighbourhood street pattern and SES, as well as their interaction, were not associated with the odds of sleeping shorter or longer than 7 to 8 h per day. Our findings suggest that the combined effect of the neighbourhood built environment and SES is potentially important for influencing sleep duration. More research is needed to understand the complex interrelationships between the built environment, SES, and sleep.

The culturable mycobiota associated with three Atlantic sponges, including two new species: Thelebolus balaustiformis and T. spongiae.

Covering 70 % of Earth, oceans are at the same time the most common and the environment least studied by microbiologists. Considering the large gaps in our knowledge on the presence of marine fungi in the oceans, the aim of this research was to isolate and identify the culturable fungal community within three species of sponges, namely Dysidea fragilis, Pachymatisma johnstonia and Sycon ciliatum, collected in the Atlantic Ocean and never studied for their associated mycobiota. Applying different isolation methods, incubation temperatures and media, and attempting to mimic the marine and sponge environments, were fundamental to increase the number of cultivable taxa. Fungi were identified using a polyphasic approach, by means of morpho-physiological, molecular and phylogenetic techniques. The sponges revealed an astonishing fungal diversity represented by 87 fungal taxa. Each sponge hosted a specific fungal community with more than half of the associated fungi being exclusive of each invertebrate. Several species isolated and identified in this work, already known in terrestrial environment, were first reported in marine ecosystems (21 species) and in association with sponges (49 species), including the two new species Thelebolus balaustiformis and Thelebolus spongiae, demonstrating that oceans are an untapped source of biodiversity.

The cause of neuronal degeneration in Alzheimer's disease.

Alzheimer's disease is associated with a specific pattern of pathological changes in the brain that result in neurodegeneration and the progressive development of dementia. Pathological hallmarks common to the disease include beta-amyloid plaques, dystrophic neurites associated with plaques and neurofibrillary tangles within nerve cell bodies. The exact relationship between these pathological features has been elusive, although it is clear that beta-amyloid plaques precede neurofibrillary tangles in neocortical areas. Examination of the brains of individuals in the preclinical stage of the disease have shown that the earliest form of neuronal pathology associated with beta-amyloid plaques resembles the cellular changes that follow structural injury to axons. Thus, the development of beta-amyloid plaques in the brain may cause physical damage to axons, and the abnormally prolonged stimulation of the neuronal response to this kind of injury ultimately results in the profound cytoskeletal alterations that underlie neurofibrillary pathology and neurodegeneration. Therapeutically, inhibition of the neuronal reaction to physical trauma may be a useful neuroprotective strategy in the earliest stages of Alzheimer's disease.

Cyclophosphamide-cisplatin versus cyclophosphamide-carboplatin in stage III-IV ovarian carcinoma: a comparison of equally myelosuppressive regimens.

Between March 1985 and January 1987, 103 women with histologically proven stage III-IV ovarian carcinoma were randomly allocated to groups receiving monthly intravenous regimens of 1 g of cyclophosphamide/m2 plus either 60 mg of cisplatin (CDDP)/m2 or 150 mg of carboplatin (CBDCA)/m2 for 1 year unless disease progressed earlier. The groups were well balanced according to the stratification factors (age, histologic differentiation, extent of residual disease, and performance score), and both treatments were well tolerated and produced similar median first-course leukopenia (2,200 and 2,000 cells/microL) and thrombocytopenia (220,000 and 202,500 cells/microL). The CBDCA regimen was less emetogenic. After an interim analysis in January 1987 revealed superior progression-free survival for the group of 53 patients receiving CDDP (P = .005), the study was closed to further accrual. Those 24 patients still receiving CBDCA were encouraged to cross over to the CDDP-based regimen and 21 of them did. Following treatment crossover, the relative risk of death associated with original allocation to CBDCA receded from 1.79 to 0.97, indicating success of the salvage treatment using the CDDP-based regimen. This aborted study demonstrated the superiority of CDDP over CBDCA when the two platinum compounds were compared at equally myelosuppressive low doses in combination with 1 g of cyclophosphamide/m2. If CDDP is to be supplanted by CBDCA, larger, more myelosuppressive doses of CBDCA will be required. The platinum drug antitumor effect is a critically important therapeutic feature of this combination.

Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Cancer Treatment Group and the Mayo Clinic.

A total of 401 eligible patients with resected stages B and C colorectal carcinoma were randomly assigned to no-further therapy or to adjuvant treatment with either levamisole alone, 150 mg/d for 3 days every 2 weeks for 1 year, or levamisole plus fluorouracil (5-FU), 450 mg/m2/d intravenously (IV) for 5 days and beginning at 28 days, 450 mg/m2 weekly for 1 year. Levamisole plus 5-FU, and to a lesser extent levamisole alone, reduced cancer recurrence in comparison with no adjuvant therapy. These differences, after correction for imbalances in prognostic variables, were only suggestive for levamisole alone (P = .05) but quite significant for levamisole plus 5-FU (P = .003). Whereas both treatment regimens were associated with overall improvements in survival, these improvements reached borderline significance only for stage C patients treated with levamisole plus 5-FU (P = .03). Therapy was clinically tolerable with either regimen and severe toxicity was uncommon. These promising results have led to a large national intergroup confirmatory trial currently in progress.

Human metapneumovirus-associated respiratory tract infections in the Republic of Ireland during the influenza season of 2003-2004.

Human metapneumovirus (hMPV) is a newly identified paramyxovirus that has been associated with respiratory tract illness in children aged < 5 years, the elderly, and immunocompromised patients. This study determined the frequency of respiratory tract infections (RTIs) associated with hMPV in the Republic of Ireland. Bronchoalveolar lavage (BAL) samples from 168 adult patients and respiratory specimens from 122 children aged < 5 years were collected between September 2003 and May 2004. The virus was detected by reverse-transcription (RT)-PCR using hMPV polymerase (L) and matrix (M)-specific primers in four (2.4%) of 171 BAL specimens obtained from 168 adults. No other respiratory virus was detected in these specimens, and no hMPV RNA was detected in respiratory specimens from children during the same time period. In all four adult cases, two of whom had underlying disease, hMPV was associated with mild, self-limiting upper RTIs. The most common clinical findings included fever (3/4 patients), cough (4/4) and rhinorrhoea (3/4). No patient died as a result of these RTI episodes. Phylogenetic analysis was performed using the amplified regions of the M and fusion (F) genes of hMPV. The Irish isolates belonged to cluster 1B, and did not show a separate Irish sub-lineage.

Normal retinotopic mapping in human strabismus with anomalous retinal correspondence.

Burian proposed that a functional retinotopic remapping of the deviated eye on striate visual cortex may be the physiologic basis for the perceptual phenomenon of anomalous retinal correspondence (ARC) in human strabismus. This investigation searched for this type of retinotopic remapping in five esotropes and one exotrope with ARC by means of visual evoked potential (VEP) topographic mapping. Uniocular stimulation of the foveas (corresponding points) during binocular vision in a normal subject yielded identical VEP scalp topographies from each eye. Stimulation of anomalously corresponding points produced different VEP scalp topographies from each eye in the six strabismic subjects. Uniocular stimulation of the anatomic foveas of each eye (noncorresponding points) in a strabismic subject during binocular vision produced identical VEP scalp topographies. These results suggest that there is no significant functional binocular realignment of retinotopic mapping in the visual cortex of human strabismics with ARC.

Differences in tests of aniseikonia.

The New Aniseikonia Test (NAT), a hand-held direct-comparison test using red/green anaglyphs, has several potential advantages as a screener. We compared the validity of the NAT to that of the Space Eikonometer in three experiments: (1) aniseikonia was induced by calibrated size lenses in a double-blind study of 15 normal subjects; (2) habitual aniseikonia was measured with both instruments in four patients; and (3) eight of the normal subjects were retested with a computer-video simulation of the NAT. The NAT underestimated induced aniseikonia by a factor of 3 in the normal subjects and underestimated habitual aniseikonia in four patients. The Space Eikonometer correctly measured the magnitude of induced aniseikonia in the normal subjects. The simulation test did not show underestimation in the eight normal subjects. We could not attribute the NAT's underestimation of aniseikonia to the red/green anaglyph method, printing error, psychophysical method, or the direct-comparison test format. We speculate that the NAT induces a different sensory fusion response to aniseikonia than do the other tests, and that this altered sensory fusion response diminishes measured aniseikonia. We conclude that the NAT is not a valid measure of aniseikonia.

Infant VEP and preferential looking acuity measured with phase alternating gratings.

Previously, infants' grating acuity was found to be temporally tuned, but adults' grating acuity was not. In infants, acuity was higher for gratings phase alternating at 7.5 and 14 reversals/sec than for stationary gratings and gratings alternating at 2.5 or 23 reversals/sec. Also, when preferential looking (PL) and visually evoked potential (VEP) acuity were estimated with phase alternating gratings (14 reversals/sec), the acuity difference between the two techniques was smaller than that obtained when phase alternating gratings were used to estimate VEP acuity and stationary gratings were used to estimate PL acuity. In the present study, it was determined if PL grating acuity was tuned in older children and if the smaller difference between VEP and PL acuity found when infants were tested with phase alternating gratings was independent of temporal rate. Grating acuity in infants older than 2 yr was found to be not tuned, and the smaller difference between VEP and PL grating acuity in infants when both were measured with phase-alternating gratings was not rate dependent. VEP acuity and PL acuity for phase alternating gratings developed at different rates, converging to nearly equivalent levels by 12 mo of age.

A practical guide to the management of oesophageal varices.

Bleeding oesophageal varices are a frequent and sometimes fatal complication of portal hypertension. Prompt resuscitation and arrest of haemorrhage are the immediate short term priorities. Vasoactive therapy to reduce portal pressure is administered on presentation. Early endoscopy is necessary to make a definitive diagnosis and initiate appropriate therapy; usually emergency sclerotherapy or banding. After the acute bleeding episode, follow-up therapy is instituted either to obliterate the varices by sclerotherapy or banding, or to chronically lower portal pressure and hence reduce the risk of bleeding pharmacologically; a combination of both strategies may be also used. Active surveillance of those at risk of developing varices is advocated. Long term beta-blocker therapy has been demonstrated to be effective in both the primary prevention of variceal haemorrhage and the prevention of rebleeding in those who have already bled. Despite a multitude of therapeutic regimes and ongoing clinical trials, mortality from this condition remains disappointingly high.

Quinidine induced lupus syndrome.

Five patients with a lupus-like syndrome secondary to quinidine are described. Eleven other cases have previously been reported. The quinidine induced lupus syndrome is similar to that seen with procainamide and hydralazine treatment but occurs less frequently. The lower incidence may reflect a difference in the metabolism of quinidine. Quinidine should be considered as potentially responsible when multisystem disease appears in patients receiving this drug.

In-vitro cyclosporin sensitivity of proliferating lymphocytes is predictive of in-vivo therapeutic response in ulcerative colitis.

BACKGROUND: The efficacy of cyclosporin in the management of ulcerative colitis is recognized. Not all patients respond to this treatment. Existing clinical and laboratory parameters are of little use in identifying those most likely to respond. AIMS: To determine whether in-vitro sensitivity to cyclosporin as measured by a lymphocyte proliferation assay is predictive of in-vivo response to therapy. METHODS: The study comprised seven responders with ulcerative colitis, seven non-responders, and 14 healthy matched controls. A lymphocyte proliferation assay was carried out in the presence of a range of concentrations of cyclosporin and a dose-response curve constructed for each subject. The IC(50) value, the concentration of cyclosporin that resulted in 50% inhibition of proliferation, was calculated for each subject. IC(50) values for responders, non-responders and controls were compared using a Mann-Whitney test. RESULTS: There was a wide range of values obtained for the study group as a whole. IC(50) values for non-responders were significantly higher than those of responders (P < 0.05). CONCLUSIONS: There is a population-wide variation of in-vitro sensitivity to cyclosporin. This is reflected in in-vivo sensitivity as measured by clinical response to cyclosporin treatment. Future therapeutic strategies need to address this inherent variability of individual response to therapy.

Long-term results of low-dose intravenous ciclosporin for acute severe ulcerative colitis.

BACKGROUND: Intravenous ciclosporin for acute, severe colitis is usually administered in a dose of 4 mg/kg/day, with concurrent intravenous steroids. This is associated with considerable morbidity. We have been using a low-dose regimen, most commonly without concurrent steroids, for seven years, and present the outcome. METHODS: Records of all patients admitted for severe ulcerative colitis, treated by one physician over seven years, were reviewed. RESULTS: Thirty-one patients received low-dose intravenous ciclosporin (2 mg/kg/day) for a median 8 days. Eleven early patients received concurrent intravenous corticosteroids. Three patients had hypertension requiring dose reduction, one elevated creatinine and one elevated liver enzymes (all transient), and four experienced infection (two arm cellulitis, one perianal abscess, one post-operative wound infection). Twenty-four patients (77%) avoided urgent colectomy, and were discharged on oral ciclosporin and azathioprine. After a median 18 months (range 3-77), 14 patients (45% of total) avoided colectomy, of whom eight had flares responding to medical therapy and two had persistent, mildly active disease. CONCLUSIONS: Low-dose intravenous ciclosporin (2 mg/kg/day), usually used as a monotherapy and followed by azathioprine, achieves similar long-term efficacy to higher dose ciclosporin combined with steroids in severe acute ulcerative colitis. Morbidity appears to be low.

Oral fluid collection by post for viral antibody testing.

BACKGROUND: The objective of this study was to estimate the prevalence of hepatitis B virus exposure (HBV) in the population of the Republic of Ireland, by using oral fluid (saliva) collection by post for hepatitis B anti-core antibody (anti-HBc). This paper discusses the methodological approach used and the strategies that were adopted to improve response rates. METHODS: The sampling frame used was the Register of Electors for Irish parliamentary elections. A multistage stratified cluster sample was taken, and a total of 962 households were selected nationally. A four-letter approach was employed for sample collection. Households received an initial letter outlining the purpose of the study. This was followed by a letter containing six swabs for oral fluid collection, along with easy-to-follow instructions. Non-respondents received two reminder letters, and were also telephoned where possible. A telephone helpline was provided. All testing was anonymous and unlinked. RESULTS: The study achieved a good household response rate (60.4%), and more than 98% of the 1738 specimens received were suitable for testing. The prevalence of anti-HBc in the Irish population was estimated to be 0.51%. The observed design effect was 1.29. DISCUSSION: From a review of the literature, this is the first study where a representative sample of a national population was asked to self-collect oral fluid samples and return these by post for serological testing. The technique may have many future applications in epidemiological research.

Lung mechanics in papain-treated rabbits.

To further investigate the effects of airway cartilage softening on static and dynamic lung mechanics, 11 rabbits were treated with 100 mg/kg iv papain, whereas 9 control animals received no pretreatment. Lung mechanics were studied 24 h after papain injection. There was no significant difference in lung volumes, lung pressure-volume curves, or chest wall compliance. Papain-treated rabbits showed increased lung resistance: 91 +/- 63 vs. 39 +/- 22 cmH2O X l-1 X s (mean +/- SD; P less than 0.05), decreased maximal expiratory flows at all lung volumes, and preserved density dependence of maximal expiratory flows. We conclude that increased airway wall compliance is probably the mechanism that limited maximal expiratory flow in this animal model. In addition the increased lung resistance suggests that airway cartilage plays a role in the regulation of airway caliber during quiet tidal breathing.

Effect of intravenous papain on tracheal pressure-volume curves in rabbits.

To investigate the effects of airway cartilage softening on tracheal mechanics, pressure-volume (PV) curves of excised tracheas were studied in 12 rabbits treated with 100 mg/kg iv papain, whereas 14 control animals received no pretreatment. The animals were killed 24 h after the injection and the excised specimens studied 24 h later. Treated tracheas exhibited decreased ability to withstand negative transmural pressures, reflected in increased collapse compliance: 6.2 +/- 2.1 vs. 2.0 +/- 0.5% peak volume (Vmax)/cmH2O means +/- SD, P less than 0.001, (Vmax = extrapolated maximal tracheal volume), increased kc (exponential constant that reflects the shape of collapse limb of the PV curve): 0.244 +/- 0.077 vs. 0.065 +/- 0.015 (P less than 0.001). The distension limb of the PV curve greater than 2.5 cmH2O transmural pressure (Ptm) was no different. Compliance between 0 and 2.5 cmH2O Ptm was increased in papain-treated rabbits: 4.97 +/- 1.73 vs. 2.30 +/- 0.31% Vmax/cmH2O (P less than 0.001). Tracheal volume, and therefore mean diameter, was decreased at 0 Ptm: 2.7 +/- 0.26 vs. 3.2 +/- 0.27 mm (P less than 0.001). We conclude that airway cartilage softening increases the compliance of the trachea at pressures less than 2.5 cmH2O Ptm.

Effect of rioprostil on aspirin-induced gastrointestinal mucosal changes in normal volunteers.

Rioprostil, a 15-deoxy-16-methyl prostaglandin E1, was evaluated for its effect on aspirin-induced gastrointestinal mucosal changes in normal volunteers. Fifty-six normal male volunteers were evaluated by endoscopy in a double-blind, placebo-controlled study. Aspirin was given at a dose of 975 mg four times per day. Rioprostil was given at doses of 60, 120, and 300 micrograms four times per day. Rioprostil, at both antisecretory and subantisecretory doses, prevented or reduced aspirin-induced injury. Increased stool frequency was the most common side effect and appeared to be a dose-related effect of rioprostil occurring at only antisecretory doses.

Infant grating acuity is temporally tuned.

Studies of infant visual development have shown that acuity estimated with pattern visually evoked potential (VEP) techniques is higher than acuity estimated with preferential looking (PL) techniques. A major difference is that VEP stimuli are temporally modulated while PL stimuli are typically stationary. We measured PL acuity in 2-10-month-old infants for stationary gratings and for gratings phase alternating at 2.5, 7.5, 14 and 23 reversals/sec using a computer generated staircase method. The acuity functions were temporally tuned at 7.5 or 14 rev/sec for infants 3 months and older. Acuity for 7.5 and 14 rev/sec gratings was 0.5 to 1.0 octave higher than for stationary, 2.5 and 23 rev/sec gratings. When adults' grating acuity was measured foveally and 5 deg eccentrically, tuning occurred only for the eccentric targets, suggesting that the retinal area used by the infants to detect gratings acts like the adult perifovea. In a second experiment, VEP and PL acuity were both measured from the same infants using 14 reversals/sec gratings. The VEP/PL acuity difference was less for phase alternating gratings than for stationary gratings. The magnitude of the difference was age dependent, decreasing from 2 octaves at 2 months to 0.5 octave at 12 months. Even though the use of phase alternating gratings results in improved PL acuity, temporal modulation does not completely account for the difference between VEP and PL acuity.

Evaluation of trilostane plus hydrocortisone in women with metastatic breast cancer and prior hormonal therapy exposure.

Trilostane, which causes a perturbation of adrenal steroidogenesis, was studied in combination with hydrocortisone in 32 women with progressive metastatic breast cancer. Trilostane was administered orally at a dosage level of 240 mg four times daily after escalation over the first 10 days from 60 mg four times daily. Hydrocortisone was given orally at doses of 10 mg at 8 a.m. and 5 p.m. and 20 mg at bedtime. Patients must have been postmenopausal (81%) or previously castrated (19%), had a response to the hormonal treatment just prior to study (81%) or a positive estrogen receptor at time of entry on study (41%), and a measurable indicator lesion. The number of prior hormonal therapies was 1 in 19 patients (59%), 2 in 12 patients (38%), and 3 in 1 patient (3%), respectively. Twelve patients (38%) achieved an objective response, and a 95% confidence interval for this result is from 21 to 56%. The median time to disease progression was 140 days, median duration of response was 278 days, and median survival was 556 days. Common toxicities included lethargy, lightheadedness, diarrhea, and abdominal discomfort. Eleven patients required a dosage reduction, usually because of gastrointestinal side effects, and one additional patient had the trilostane discontinued because of leukopenia. We conclude that the combination of trilostane plus hydrocortisone appears to have definite antitumor activity in women with metastatic breast cancer who have characteristics favorable for response to hormonal therapy.