Curaçao patients with coronary artery disease have a higher prevalence of the HFE C282Y mutation

Epidemiological studies indicate a positive relation between iron status and coronary artery disease (CAD) risk The HFE C282Y allele is associated with increased iron status and higher CAD risk. We investigated whether HFE C282Ymight be a CAD risk factor in Cura?ao in a case-control study design. The patient group comprised 42 men and 10 women. Fifty-four men and 30 women without history of CAD served as age and gender matched controls. HFE C282Y genotypes were established using sequence-specific priming polymerase chain reaction. None of the investigated subjects were homozygous for HFE C282Y, whereas 5/52 (9.6%) CAD patients and 1/84 controls (1.2%) were heterozygous for HFE C282Y (p = 0.03). The HFE C282Y mutation was 8.8 fold (95% CI 1.001, 77.8; p = 0.049) more prevalent in CAD patients than in controls. The HFE C282Y allele frequency in Cura?ao is higher than that of African populations, but comparable with that of Jamaica. We conclude that Cura?ao CAD patients have somewhat higher frequency of HFE C282Y heterozygosity than controls, and that the HFE C282Y allele frequency in the Cura?ao population is higher than might be expected in persons of African descent. The consequences of HFE C282Y heterozygosity as CAD risk factor are as yet uncertain, since there is no proof that iron lowering reduces CAD risk.     

Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration

Studies in vitro and in animal models of colorectal and hepatocellular cancers suggest that curcumin is an effective chemopreventive agent. In this pilot trial, we investigated whether oral administration of curcumin results in concentrations of the agent in normal and malignant human liver tissue, which are sufficient to elicit pharmacological activity. In total, 12 patients with hepatic metastases from colorectal cancer received 450-3600 mg of curcumin daily, for 1 week prior to surgery. Levels of curcumin and its metabolites were measured by HPLC in portal and peripheral blood, bile and liver tissue. Curcumin was poorly available, following oral administration, with low nanomolar levels of the parent compound and its glucuronide and sulphate conjugates found in the peripheral or portal circulation. While curcumin was not found in liver tissue, trace levels of products of its metabolic reduction were detected. In patients who had received curcumin, levels of malondialdehyde-DNA (M(1)G) adduct, which reflect oxidative DNA changes, were not decreased in post-treatment normal and malignant liver tissue when compared to pretreatment samples. The results suggest that doses of curcumin required to furnish hepatic levels sufficient to exert pharmacological activity are probably not feasible in humans.     

Inhaler technique in older people in the community

BACKGROUND: Good inhaler technique and medication concordance is important for symptom and disease control in chronic airways disease. OBJECTIVES: Establish the prevalence of inhaler use; the main inhaler devices used by older people at home; their ability to use the inhalers they have been prescribed; and the relationship between perceived ease of use and actual performance. DESIGN: Cross-sectional population based study. SUBJECTS: Subjects aged 70 years and over living at home. METHODS: 500 subjects were randomly selected from 5002 subjects aged 70 years and over living at home. Inhalers used over the previous 24 hours were identified by a nurse on home visit. Those with cognitive impairment were excluded. Inhaler system was assessed and graded by a doctor as acceptable (perfect or minor errors) or unacceptable (major errors), using previously published criteria. Perceived ease of use of the device was rated as easy, moderate or difficult. RESULTS: 423 subjects participated in the study. The population prevalence of inhaler use was 15.8% (12.0, 19.7). Of the 91 inhaler devices used, 39 (42.8%) were metered dose inhalers, 34 (37.4%) were metered dose inhalers with large volume spacers, and 18 (19.8%) were breath-actuated devices. Thirty-two subjects (82.1%) using metered dose inhalers had an acceptable technique compared with 33 (97.1%) of those using metered dose inhalers with large volume spacers and 13 (72.2%) of those using breath-actuated devices (P < 0.05). Up to three quarters of inhalers were considered easy to use but 12% of subjects who rated their inhaler device as being easy to use made major errors. CONCLUSION: Metered dose inhaler was the most frequently prescribed inhaler and was used correctly by most subjects especially in combination with large volume spacers. Major errors were more common with breath-actuated devices. Inhaler technique should be checked as patients' perception of their inhaler skills correlates poorly with actual performance.     

Extended ex vivo myocardial preservation in the beating state using a novel polyethylene glycolated bovine hemoglobin perfusate based solution

Cardiac preservation for transplantation is generally limited by ischemic hypothermic storage of 4-6 hours. Earlier studies in the authors' laboratory have demonstrated that hypothermic perfusion preservation using a novel oxygen carrying hemoglobin solution may extend preservation times to 8 hours and decrease ischemic injury. The purpose of this study was to compare extended cardiac function after 12 and 24 hours of continuous hypothermic perfusion with a polyethylene glycolated bovine hemoglobin perfusate (PEG-Hb) solution to the clinical standard of hypothermic ischemic preservation. The hearts of 54 anesthetized and intubated New Zealand White rabbits were harvested after cold cardioplegic arrest. Group I (n = 12) hearts were perfused with a PEG-Hb solution at 20 degrees C and 30 mm Hg for 24 hours. Group II (n = 10) hearts were preserved similarly with PEG-Hb for 12 hours. Group III (n = 12) hearts were preserved for 8 hours with PEG-Hb; Group IV (n = 10) were preserved by cold ischemic storage for 4 hours at 4 degrees C; and Group V (n = 10) were tested after fresh extirpation. Left ventricular (LV) function was measured in the nonworking state at 15 minute, 1 hour, and 2 hour intervals after transfer to a standard crystalloid Langendorff circuit. Developed LV pressure at 0.5 ml LV volume was superior in Group II at early time points, yet it was similar in all preserved groups at 2 hours. +dP/dt(max) at 0.5 ml LV volume was consistent at all time points and greater in PEG-Hb preserved groups compared with Group V. -dP/dt(max) at 0.5 ml LV volume was significantly greater in Groups II and III compared with Group V initially (p < 0.05), but all were similar at the end of testing. Continuous perfusion preservation of rabbit hearts for time increments up to 24 hours with this novel PEG-Hb solution at 30 mm Hg and 20 degrees C yields LV function that is similar to 4 hours of ischemic hypothermic storage. Extended cardiac perfusion preservation with this PEG-Hb solution deserves further investigation in large animal transplant models.     

The molecular basis of the antigenic cross-reactivity between measles and cowpea mosaic viruses

Two nonrelated viruses, cowpea mosaic virus (wtCPMV) and measles virus (MV), were found to induce cross-reactive antibodies. The nature of this cross-reactivity was studied and results are presented here demonstrating that antiserum raised against wtCPMV reacted with peptide from the fusion (F) protein of MV. Furthermore, the F protein of MV was shown to share an identical conformational B cell epitope with the small subunit of CPMV coat protein. Passive transfer of anti-wtCPMV antibodies into BALB/c mice conferred partial protection against measles virus induced encephalitis. The results are discussed in the context of cross-protection.     

Nasal delivery of chitosan-DNA plasmid expressing epitopes of respiratory syncytial virus (RSV) induces protective CTL responses in BALB/c mice

Respiratory syncytial virus (RSV), an important pathogen of the lower respiratory tract, is responsible for severe illness both in new born and young children and in elderly people. Due to complications associated with the use of the early developed vaccines, there is still a need for an effective vaccine against RSV. Most pathogens enter the body via mucosal surfaces and therefore vaccine delivery via routes such as the nasal, may well prove to be superior in inducing protective immune responses against respiratory viruses, since both local and systemic immunity can be induced by nasal immunisation. Previously we have shown that intradermal immunisation of a plasmid DNA encoding the CTL epitope from the M2 protein of RSV induced protective CTL responses. In the present study, the mucosal delivery of plasmid DNA formulated with chitosan has been investigated. Chitosan is a polysachharide consisting of copolymers of N-acetylglucosamine and glucosamine that is derived from chitin, a material found in the shells of crustacea. Intranasal immunisation with plasmid DNA formulated with chitosan induced peptide- and virus-specific CTL responses in BALB/c mice that were comparable to those induced via intradermal immunisation. Following RSV challenge of chitosan/DNA immunised mice, a significant reduction (P<0.001) in the virus load was observed in the lungs of immunised mice compared to that in the control group. These results indicate the potential of immunisation with chitosan-formulated epitope-based vaccines via the intranasal route.     

Cement, cancers and clusters: an investigation of a claim of a local excess cancer risk related to a cement works

BACKGROUND: We investigated claims by a campaigning group of a cancer cluster associated with a local cement works. METHODS: To investigate cancer rates in the town we defined the study area as the Census wards matching the geographical area code supplied to the campaigning group. Standard methods were applied to registered cases of cancer for the area for the years 1974-1989 to derive observed and expected numbers. The significance of the relative risk was assessed using the Poisson distribution. By selecting a different denominator population we attempted to reproduce the results of the campaign group. Cancer rates around the cement works were investigated for four cancer types plausibly associated with emissions, using cancer registrations for the years 1985-1994. Cases were mapped to 1981 Census ward boundaries, and the same statistical methods were used, but expected counts were also adjusted for deprivation. Rates were calculated for an inner 2 km zone and outer zone 2-5 km from the works. Relative risk was calculated and the ratio of risks was examined for evidence of increased risk closer to the works. RESULTS: Relative risks were not significantly elevated either in the town or around the cement works itself. We were able to reproduce the likely errors that resulted in the elevated relative risks for five cancer groups claimed by the campaigning group. CONCLUSIONS: We found no evidence of increased incidence of cancer around the cement works. Incorrect handling of cancer registration data can result in spurious cancer clusters and unnecessary public alarm.     

Latest trends in cancer incidence among UK South Asians in Leicester

Using cancer registry data, we show that although South Asians have lower rates of cancer than the rest of the population, this is changing with age and time. Younger South Asians, particularly children, are at increased risk. While generally cancer rates have fallen over the last decade, they are increasing among South Asians.     

Topoisomerase II alpha and II beta expression in childhood acute lymphoblastic leukaemia: relation to prognostic factors and clinical outcome

BACKGROUND/AIMS: Many regimens used in the treatment of childhood acute lymphoblastic leukaemia (ALL) include Daunorubicin or Etoposide, which act as topoisomerase poisons. It has been suggested that there may be a relation between topoisomerase expression and response to topoisomerase poisons, based mainly on results from in vitro studies. Therefore, the aim of this study was to investigate this relation in a clinical setting and determine whether topoisomerase II alpha and II beta might be of predictive value in ALL. METHODS: Cellular expression of topoisomerases II alpha and II beta was assessed in 177 cases of ALL by immunohistochemistry using monoclonal antibodies to the two enzymes. The percentages of cell nuclei showing positive staining for topoisomerase II alpha and II beta expression were assessed. RESULTS: Taking the series as a whole, a clear separation of survival curves was seen with the established prognostic markers white blood cell (WBC) count, CD10 status, and sex. However, topoisomerase II alpha and II beta expression showed no relation to survival. No association was found between the topoisomerases and the prognostic markers CD10 and WBC count; however, topoisomerase II alpha expression was found to be related to sex, with expression being lower in girls (p = 0.002). CONCLUSIONS: These results suggest that the response to topoisomerase poisons cannot be predicted by the assessment of topoisomerase II alpha and II beta expression as defined by immunohistochemistry.     

Stability of respiratory quotient and growth outcomes of very low birth weight infants

Nutritional management of very low birth weight (VLBW) infants involves promoting growth at rates that mimic intrauterine rates. Nutritional intake at the recommended energy level to promote growth results in fat accretion at levels that exceed intrauterine rates for fat accretion. The respiratory quotient (RQ), the ratio of carbon dioxide produced to oxygen consumed during oxidation, provides a measure of the percentage of substrates used for energy. An RQ of greater than 0.9 indicates carbohydrate is used to meet energy needs, allowing the majority of fat intake to be stored as new tissue. The purpose of this study was to examine the stability of the RQ across time in relation to nutritional intake and growth in VLBW infants. Subjects were 9 enterally fed VLBW infants. Measurements to determine the RQ were obtained weekly for 3 weeks by indirect calorimetry. Nutritional intake and growth velocity were examined. There was no significant difference in the RQ across 3 weeks. The mean (+/- SD) RQs for each of the 3 weeks were 1.08 (+/- 0.04), 1.06 (+/- 0.05), and 1.06 (+/- 0.07), respectively. No significant differences were found across the 3 weeks for any of the macronutrient variables. Growth velocity for the period was 15.7 g/kg/day. By discharge from the NICU, 66% of the infants had weights less than the 10th percentile on an intrauterine growth reference. An RQ greater than 1.0 indicates VLBW infants are depositing excess fat. However, increased accretion rates of fat did not improve the growth outcomes of these VLBW infants.