Disturbed glutathione metabolism and decreased antioxidant levels in human immunodeficiency virus-infected patients during highly active antiretroviral therapy--potential immunomodulatory effects of antioxidants

Oxidative stress has been implicated in the pathogenesis of human immunodeficiency virus (HIV) infection. We examined the effect of highly active antiretroviral therapy (HAART) on plasma levels of several antioxidants and intracellular glutathione-redox status in CD4+ T cells, in 20 HIV-infected patients. HAART was accompanied by both an improvement of glutathione-redox status and an increase in levels of antioxidant vitamins, without full normalization. Glutathione supplementation in vitro increases T cell proliferation and suppresses the spontaneous release of tumor necrosis factor-alpha from peripheral blood mononuclear cells, in HIV-infected patients receiving HAART. Our findings suggest that therapeutic intervention aimed at normalization of oxidative disturbances in HIV infection could be of interest, in addition to HAART.     

Saturday opening of alcohol retail shops in Sweden: an impact analysis

OBJECTIVE: The objective of this study was to assess the impact of Saturday opening of alcohol retail shops in Sweden. METHOD: An experimental design was applied. Prior to February 2000, all alcohol monopoly outlets we closed on Saturdays. After this date, stores in an experimental area (six counties) were open on Saturdays. In the control area (seven counties) the shops remained closed. To prevent biases resulting from border trade, the experimental and control areas were separated by a border area (seven counties). The outcome measures included alcohol sales and indicators of assaults and drunken driving. The pre-intervention period covered January 1995-January 2000, and the post-intervention period February 2000-June 2001 (17 months). The data were analyzed on a monthly basis through ARIMA-modeling according to the Box-Jenkins technique. RESULTS: The analysis uncovered a statistically significant increase in alcohol sales of 3.3%. There were no significant changes in any of the assault indicators. There was a statistically significant increase in drunken driving (8.3%) on Saturdays-Sundays; however, further analyses suggested this increase was due mainly to a change in the surveillance strategy of the police. CONCLUSIONS: The Saturday opening of alcohol retail shops seems to have increased consumption but not alcohol-related harm. The absence of a significant effect on harm indicators could signify either that no such effect is present or that the design has insufficient power to uncover effects of the expected magnitude.     

Complement activation and cytokine and chemokines release during mediastinitis

BACKGROUND: Mediastinitis after open heart operation is an infrequent, but life-threatening complication with a reported incidence rate between 1% and 4%. Hospital mortality is estimated at 10% to 35%. The aim of the present work was to study the systemic inflammatory reaction as judged by complement activation and cytokine and chemokines release in patients with mediastinitis after open heart operation. METHODS: Seven patients with clinical signs of mediastinitis were included. Three patients had undergone coronary artery bypass grafting, whereas 4 patients had combined coronary artery bypass grafting, valve replacement, or valvuloplasty. Blood samples were drawn before induction of anesthesia and at the time of reoperation, and thereafter daily during the hospital stay. Controls comprised similar patients with an uneventful postoperative course. RESULTS: The terminal SC5b-9 complement complex concentration in the mediastinitis patients was substantially higher compared with the controls (p < 0.001), and the terminal SC5b-9 complement complex values showed no overlap between the two groups. Interleukin-8, stromal cell-derived factor-1alpha and IL-6 concentrations were also significantly higher in the mediastinitis group than in the control group (p < 0.001), but with considerable overlap between the groups. Interleukin-1beta, interleukin-10, and monocyte chemoattractant protein-1 concentrations were slightly higher in the mediastinitis group, and no differences were seen for the tumor necrosis factor-alpha. CONCLUSIONS: During mediastinitis, the complement is activated and the cytokines and chemokines, interleukin-6, interleukin-8, and stromal cell-derived factor-1alpha are released. These proteins may be involved in the pathogenesis of this complication. Terminal SC5b-9 complement complex may be an indicator to discriminate mediastinitis patients from those with uneventful course.     

Prostate cancer--prevalence-based healthcare costs

OBJECTIVE: To calculate the total costs of in- and outpatient healthcare for patients with prostate cancer based on an episode-of-care approach. The cost analysis includes costs incurred during the first year of diagnosis, a longitudinal 3-year analysis and the incremental cost of prostate cancer during the first year of diagnosis. MATERIAL AND METHODS: Patients registered with prostate cancer between 1998 and 2000, according to the data files of the Southern Swedish Regional Tumour Registry, were given encrypted identifiers that could also be used in the Patient Administrative System of the Region Sk?ne County Council, making it possible to identify consumption of healthcare on an episode-of-care basis. Itemized costs for resources used by each individual patient were calculated from the complete accounting system of the County Council. RESULTS: Healthcare costs for prostate cancer during the first year varied between 45 000 and 51 000 SEK per patient. The second- and third-year costs were progressively lower, with an estimated total cost of 114 000 SEK over a period of 3 years. The age-standardized incremental cost of prostate cancer corresponded to 33 000 SEK during the first year, compared to the average cost per inhabitant. CONCLUSIONS: The episode-of-care approach, based on encrypted identifiers for the identification of the diagnoses of individual patients and their utilization of healthcare, gives a unique opportunity to estimate the healthcare costs of specific diseases. The incremental healthcare cost per patient with prostate cancer corresponded to 33 000 SEK during the first year.     

Raised plasma levels of tumor necrosis factor alpha in patients with depression: normalization during electroconvulsive therapy

OBJECTIVE: To examine whether electroconvulsive therapy (ECT) could modulate tumor necrosis factor (TNF)alpha levels in patients with depressive disorders. METHOD: Plasma levels of TNFalpha were analyzed in 23 depressed patients, mainly with severe depressive disorders, and in 15 sex- and age-matched healthy controls. Fifteen depressed patients were followed longitudinally with measurement of TNFalpha before, during, and after repeated ECT treatment. For comparison, TNFalpha levels were also analyzed longitudinally in the 8 depressed patients not receiving ECT. RESULTS: Patients with depressive disorders had markedly raised TNFalpha levels compared with healthy controls. The clinical improvement during repeated ECT was accompanied by a gradual and significant decline in TNFalpha level, reaching levels comparable with those in healthy controls at the end of the study. Such a decline was not seen in the depressed patients not receiving ECT, who instead showed raised TNFalpha levels throughout the study period. CONCLUSION: Our findings support an association between inflammation and TNFalpha in particular and severe depression, and suggest that ECT may down-regulate this immune activation.     

Inhibitory effect of zinc oxide on contact allergy due to colophony

Contact allergy to a wound dressing with an adhesive mass consisting of colophony, zinc oxide and rubber (Mezinc) was studied in 179 patients with a history of eczema. 12 patients were found to be allergic to colophony, whereas only 4 of these patients also showed a positive patch test reaction to the wound dressing. 14 patients with verified moderate contact allergy to colophony were patch tested with adhesive mass (10%), Portuguese colophony (10%), zinc oxide (10%), purified resin acids (10%), and Portuguese colophony (10%), in combination with zinc oxide. Only 3 patients reacted to the adhesive mass, whereas all patients showed a positive patch test reaction to Portuguese colophony. A combination of zinc oxide (10%) with Portuguese colophony (10%) provoked a positive patch test reaction in only 5 of these 14 patients. An allergic reaction to abietic acid (90-95% purity) was found in 7 patients and to neoabietic acid (99 + %) in 3 patients, whereas no reactions to dehydroabietic (99 + %), isopimaric (99 + %) or levopimaric acids (98 + %) were found.     

Correlations between initial cleft size and dental anomalies in unilateral cleft lip and palate patients after alveolar bone grafting

Objective To determine in individuals with unilateral cleft lip and palate the correlation between initial cleft size and dental anomalies, and the outcome of alveolar bone grafting.

Methods A total of 67 consecutive patients with non-syndromic unilateral complete cleft lip and palate (UCLP) were included from the cleft lip and palate-craniofacial center, Uppsala University Hospital, Sweden. All patients were operated by the same surgeon and treated according to the Uppsala protocol entailing: lip plasty at 3 months, soft palate closure at 6 months, closure of the residual cleft in the hard palate at 2 years of age, and secondary alveolar bone grafting (SABG) prior to the eruption of the permanent canine. Cleft size was measured on dental casts obtained at the time of primary lip plasty. Dental anomalies were registered on radiographs and dental casts obtained before bone grafting. Alveolar bone height was evaluated with the Modified Bergland Index (mBI) at 1 and 10-year follow-up.

Results Anterior cleft width correlated positively with enamel hypoplasia and rotation of the central incisor adjacent to the cleft. There was, however, no correlation between initial cleft width and alveolar bone height at either 1 or 10 years follow-up.

Conclusions Wider clefts did not seem to have an impact on the success of secondary alveolar bone grafting but appeared to be associated with a higher degree of some dental anomalies. This finding may have implications for patient counseling and treatment planning.     

Determinants of bone mass in end-stage renal failure patients at the time of kidney transplantation

Abstract: Background:  Patients with chronic renal failure (CRF) are at high risk of renal osteodystrophy. Our study aimed to identify predictors of bone mass and cumulative fracture rate at the time of renal transplantation (RTx). This is important since the patients experience further substantial bone loss the first month post-transplant.
Material and methods:  Altogether 133 renal transplant patients were examined for bone mineral density (BMD) using dual-energy X-ray absorptiometry shortly after RTx.
Results:  The patients' Z -scores were significantly lower at the time of RTx compared to the reference population (p < 0.05), 32% were osteopenic and 11% had osteoporosis. Independent predictors of low bone mass were age (p < 0.001), female sex (p < 0.001), intact parathyroid hormone (iPTH) level (p < 0.001), former transplantation (p = 0.001) and time on hemodialysis (HD) (p = 0.005). Body mass index (BMI) (p < 0.001) and physical activity (p = 0.027) were associated with high BMD. Cumulative fracture rate (29%) was associated with physical inactivity (p = 0.003), BMI (p = 0.036) and osteopenia (p < 0.001) at the time of RTx.
Conclusion:  In a representative CRF population, BMD was reduced. Independent predictors of BMD were as for the general population, and uremia associated predictors were time on HD, previous transplantation and serum iPTH level. Fracture rate was high, and physical inactivity had the strongest association with fractures.     

Angiopoietin-2 and angiopoietin-like 4 protein provide prognostic information in patients with suspected acute coronary syndrome

Background

Plasma levels of angiopoietin-2 (ANGPT2) and angiopoietin-like 4 protein (ANGPTL4) reflect different pathophysiological aspects of cardiovascular disease. We evaluated their association with outcome in a hospitalized Norwegian patient cohort (n = 871) with suspected acute coronary syndrome (ACS) and validated our results in a similar Argentinean cohort (n = 982).

Methods

A cox regression model, adjusting for traditional cardiovascular risk factors, was fitted for ANGPT2 and ANGPTL4, respectively, with all-cause mortality and cardiac death within 24 months and all-cause mortality within 60 months as the dependent variables.

Results

At 24 months follow-up, 138 (15.8%) of the Norwegian and 119 (12.1%) of the Argentinian cohort had died, of which 86 and 66 deaths, respectively, were classified as cardiac. At 60 months, a total of 259 (29.7%) and 173 (17.6%) patients, respectively, had died. ANGPT2 was independently associated with all-cause mortality in both cohorts at 24 months [hazard ratio (HR) 1.27 (95% confidence interval (CI), 1.08–1.50) for Norway, and HR 1.57 (95% CI, 1.27–1.95) for Argentina], with similar results at 60 months [HR 1.19 (95% CI, 1.05–1.35) (Norway), and HR 1.56 (95% CI, 1.30–1.88) (Argentina)], and was also significantly associated with cardiac death [HR 1.51 (95% CI, 1.14–2.00)], in the Argentinean population. ANGPTL4 was significantly associated with all-cause mortality in the Argentinean cohort at 24 months [HR 1.39 (95% CI, 1.15–1.68)] and at 60 months [HR 1.43 (95% CI, 1.23–1.67)], enforcing trends in the Norwegian population.

Conclusions

ANGPT2 and ANGPTL4 were significantly associated with outcome in similar ACS patient cohorts recruited on two continents.

Clinical Trial Registration

ClinicalTrials.gov Identifier: NCT00521976. ClinicalTrials.gov Identifier: NCT01377402.