Radiosynthesis of [18F]PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

PBR111 (2‐(6‐chloro‐2‐(4‐(3‐fluoropropoxy)phenyl)imidazo[1,2‐a]pyridin‐3‐yl)‐N,N‐diethylacetamide) is a novel, reported, high‐affinity and selective ligand for the translocator protein (18 kDa). PBR111 has been labelled with fluorine‐18 (half‐life: 109.8 min) using our Zymate‐XP robotic system. The process involves (A) a simple one‐step tosyloxy‐for‐fluorine nucleophilic aliphatic substitution (performed at 165°C for 5 min in DMSO using K[¹⁸F]F‐Kryptofix^®222 and 6.8–7.6 µmol of the corresponding tosylate as precursor for labelling) followed by (B) C‐18 PrepSep cartridge pre‐purification and (C) semi‐preparative HPLC purification on a Waters Symmetry^® C‐18. Up to 4.8 GBq (130 mCi) of [¹⁸F]PBR111 could be obtained with specific radioactivities ranging from 74 to 148 GBq/µmol (2–4 Ci/µmol) in 75–80 min (HPLC purification and SepPak^®‐based formulation included), starting from a 37.0 GBq (1.0 Ci) [¹⁸F]fluoride batch. Overall non‐decay‐corrected isolated yields were 8–13% (13–21% decay‐corrected). Copyright © 2008 John Wiley & Sons, Ltd.     

Mortality in a cohort of women given X-ray therapy for metropathia haemorrhagica

Mortality to January 1, 1991, has been studied in 2,067 women in Scotland given X-ray therapy for metropathia haemorrhagica during the period 1940–1960. Average follow-up was 28 years. Overall, 1,313 deaths were observed compared with 1,297.01 expected from Scottish rates [standardized mortality ratio (SMR): 1.01]. Mortality was increased for cancers of heavily irradiated pelvic sites (SMR 5+ years after irradiation: 1.46) following mean doses to organs in the vicinity of the pelvis in the range 2.6–5.3 Gy. For these cancers the SMR was higher 30+ years after irradiation than at 5–29 years, indicating that the effects of exposure last for over 30 years, and in this period bladder cancer mortality was exceptionally high (SMR = 4.91). Mortality was also raised for leukaemia (SMR 2+ years after irradiation: 2.05), following a mean bone-marrow dose of 1.3 Gy, and for multiple myeloma (SMR 5+ years after irradiation: 2.59). For leukaemia the SMR was lower 30+ years after irradiation than at earlier periods, but remained greater than unity. For other cancers mortality was similar to Scottish rates, except for breast cancer for which mortality was low (SMR 5+ years after irradiation: 0.53), even in women aged over 50 at irradiation (SMR 5+ years after irradiation: 0.14). The deficit was principally due to a large deficit of breast cancer in women with ovarian doses of at least 5 Gy.     

The health of students in institutes of higher education: an important and neglected public health problem?

BACKGROUND: A survey of students in three UK higher education establishments was undertaken to obtain information about students' physical and emotional well-being, their attitudes to, and beliefs about health, and the prevalence of risk factors for future ill health. METHODS: Health was measured by the prevalence of longstanding illness and by the SF-36 health status measurement tool. Survey results were compared with equivalent data for 18- to 34-year-olds in the local population. The prevalence of long-standing illness was also compared with two national surveys. RESULTS: The survey achieved a 49 per cent response rate. More than one-third of respondents reported a long-standing illness, a higher prevalence than in all comparison surveys. Students scored significantly worse than their peers in the local population on all eight SF-36 dimensions. The greatest difference was for role limitations as a result of emotional problems. The main sources of emotional distress were study or work problems and money. CONCLUSION: The poor response rate in this survey dictates the need for caution in interpretation of the results. However, they suggest that the health of students is poor relative to that of their peers, and that their emotional health is more of a problem than their physical health. Public health practitioners might want to pay more attention to the health of this important and relatively neglected group. Worries about studies and money appear to be affecting students' academic work, and this should be of concern to higher education establishments.     

Establishing special needs car seat loan program

Car seat loan and rental programs have provided many families with low-cost access to child restraints. When an infant or child is unable to be accommodated in a standard car seat or seat belt owing to physical or medical problems, parents of these children have few, if any available resources. The establishment and operation of a loan program at the Indiana University School of Medicine for children who are medically fragile is reviewed in this article. This program was developed by the Automotive Safety for Children Program at the James Whitcomb Riley Hospital for Children, Indiana University Medical Center, to meet the special transportation needs of children with respiratory, orthopaedic, and other medical and physical difficulties. A summary table is included to highlight restraints that have performed satisfactorily during dynamic crash tests and are used to meet patient transportation needs at Riley Hospital. Guidelines for establishing and maintaining a child restraint loan program for children with special needs are outlined to encourage replication of this effort.     

Experimental evaluation and early clinical results of a new low-profile bileaflet aortic valve

We performed an experimental and clinical evaluation of a new low-profile bileaflet aortic valve (Regent, St. Jude Medical Inc., St. Paul, MN, U.S.A.). Common valve sizes were experimentally tested for leakage volume, pressure drop, and transvalvular hemodynamics using a pulse duplicator. Thirty patients (mean age 60 +/- 7 years, predominant valve stenosis n = 25) received the Regent prosthesis for initial clinical evaluation. In vitro evaluation revealed equivalent leakage volumes, larger performance indices (0.552 versus 0.513), and lower pressure drops in comparison to SJM hemodynamic plus valve controls. Clinically, 21 mm (n = 9), 23 mm (n = 12), and 25 mm (n = 9) valves were implanted with no significant perioperative complications. Echocardiography revealed low transvalvular flow velocities (2.2 +/- 0.4 m/s) and low pressure gradients (20 +/- 6 mm Hg) postoperatively and at 6 months follow-up. In vitro testing and early clinical results are promising; however, long-term performance has to be proven.     

Acetylator phenotype and genotype in HIV-infected patients with and without sulfonamide hypersensitivity

Adverse reactions to sulfonamides occur at a higher frequency in patients infected with the human immunodeficiency virus (HIV) than noninfected patients. Some studies have suggested that patients with the slow acetylator phenotype are predisposed to these reactions, whereas other studies suggest that the slow acetylator genotype is not a predisposing factor. To rationalize these seemingly contradictory observations, the authors determined the N-acetyltransferase 2 (NAT2) genotype and phenotype in patients with and without a history of hypersensitivity reactions to sulfonamides. HIV-infected patients with a history of a delayed-type hypersensitivity reaction to trimethoprim-sulfamethoxazole were enrolled, along with a group of AIDS patients with no history of hypersensitivity (delayed or immediate). NAT2 phenotype was determined in both groups using dapsone, while the genotype was determined using a polymerase chain reaction-restriction fragment length polymorphism assay. Ten of 14 patients (71%) with a history of hypersensitivity exhibited the slow acetylator phenotype, while 8 of 14 patients (57%) without such a history exhibited this same phenotype (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 0.4-9.0; p = 0.69, Fisher's Exact Test). While 9 of 14 patients (64%) with a history of hypersensitivity exhibited a slow acetylator genotype, only 4 of 14 patients (29%) without such a history exhibited this genotype (ns). There were more instances of discordance between deduced and actual phenotype in the nonhypersensitive patients (n = 4) than in the hypersensitive patients (n = 1). The reported higher frequency of the slow acetylator phenotype among patients with a history of hypersensitivity to sulfonamides does not appear to be explained by metabolic changes that would cause discordance between acetylator genotype and phenotype.     

Minimal access aortic valve replacement: effects on morbidity and resource utilization

BACKGROUND: The aim of this study was to compare outcomes in patients undergoing minimal access versus conventional aortic valve replacement (AVR). METHODS: We reviewed prospectively gathered data on all patients who were undergoing first-time AVR, with or without replacement of the ascending aorta, over a 1-year period at our institution. RESULTS: A total of 176 patients underwent minimal access and 258 underwent conventional AVR. The conventional group was older, had more incidence of diabetes, and more aortic stenosis (all p < 0.05). Eight minimal access AVR patients (2%) required conversion to a complete sternotomy. Minimal access AVR patients had longer aortic crossclamp times than conventional AVR patients (60 +/- 22 vs 55 +/- 23 minutes, p = 0.03) but similar CPB times (93 +/- 38 vs 88 +/- 42 minutes, p = 0.20). Postoperative creatine kinase-MB levels were similar for the two groups. Total postoperative blood loss was significantly lower in the minimal access group, and these patients received less red blood cell and fresh frozen plasma transfusions. Minimal access AVR patients were less likely to have postoperative respiratory failure (3% vs 10%); they had shorter intensive care unit stays (3.7 +/- 5.4 vs 4.5 +/- 5.6 days) and shorter hospital stays (10 +/- 6 vs 12 +/- 7 days, all p < 0.05). Mortality was lower in patients undergoing minimal access surgery (3% vs 9%, p = 0.008) by univariate analysis. Multivariate predictors of mortality were age, hypertension, and CPB time. CONCLUSIONS: Although patient selection may have influenced some of the observed differences between our patient groups, minimal access surgery appears to be associated with decreased morbidity and resource use when compared to conventional AVR.     

The level of haemoglobin in anaemic cancer patients correlates positively with quality of life

The aim of this study was to assess the relationship between haemoglobin level and quality-of-life in anaemic cancer patients. Patients, diagnosed with one of four cancers, were recruited if their haemoglobin level was <12 g dl(-1) (female) or <13 g dl(-1) (male). The condition-specific Functional Assessment of Cancer Therapy-Anaemia and the generic SF-36 were used to assess quality-of-life. Thirty-six per cent of the 179 recruited patients had breast cancer, 28% ovarian cancer, 25% lung cancer, and 11% multiple myeloma. Their mean (s.d.) haemoglobin level was 10.66 (1.04) g dl(-1). Partial correlations controlling for the potentially confounding effects of age, gender, and time since diagnosis found significant positive relationships between haemoglobin and all domains of the Functional Assessment of Cancer Therapy-Anaemia, and with all but two of the SF-36 domains. On linear regression controlling for the same factors, each unit haemoglobin rise equalled an average 8.19 Functional Assessment of Cancer Therapy-Anaemia, and an average 6.88 Functional Assessment of Cancer Therapy-Fatigue, increase. Haemoglobin accounted for a similar amount of variability (8%) in SF-36 scores. In conclusion, quality-of-life has been found to be significantly positively related to haemoglobin level in anaemic cancer patients. This suggests that normalisation of haemoglobin in cancer patients is likely to increase their quality-of-life. The greater sensitivity of the condition-specific Functional Assessment of Cancer Therapy-Anaemia compared with the generic SF-36 suggests that the Functional Assessment of Cancer Therapy-Anaemia can be used alone to assess quality-of life in this patient group.