Cancer mortality in relation to monitoring for radionuclide exposure in three UK nuclear industry workforces

Cancer mortality in 40,761 employees of three UK nuclear industry facilities who had been monitored for external radiation exposure was examined according to whether they had also been monitored for possible internal exposure to tritium, plutonium or other radionuclides (uranium, polonium, actinium or other unspecified). Death rates from cancer were compared both with national rates and with rates in radiation workers not monitored for exposure to any radionuclides. Among workers monitored for tritium exposure, overall cancer mortality was significantly below national rates [standardized mortality ratio (SMR) = 83, 165 deaths; 2P = 0.02] and none of the cancer-specific death rates was significantly above either the national average or rates in non-monitored workers. Although the overall death rate from cancer in workers monitored for plutonium exposure was also significantly low relative to national rates (SMR = 89, 581 deaths; 2P = 0.005), mortality from pleural cancer was significantly raised (SMR = 357, nine deaths; 2P = 0.002); none of the rates differed significantly from those of non-monitored workers. Workers monitored for radionuclides other than tritium or plutonium also had a death rate from all cancers combined that was below the national average (SMR = 86, 418 deaths; 2P = 0.002) but prostatic cancer mortality was raised both in relation to death rates in the general population (SMR = 153, 37 deaths; 2P = 0.02) and to death rates in radiation workers who had not been monitored for exposure to any radionuclide [rate ratio (RR) = 1.65; 2P = 0.03]. Mortality from cancer of the lung was also significantly increased in workers monitored for other radionuclides compared with those of radiation workers not monitored for exposure to radionuclides (RR = 1.31, 164 deaths; 2P = 0.01). For cancers of the lung, prostate and all cancers combined, death rates in monitored workers were examined according to the timing and duration of monitoring for radionuclide exposure, with rates of radiation workers not monitored for any radionuclide forming the comparison group. In tritium-monitored workers, RRs for prostatic cancer varied significantly according to the number of years in which they were monitored (2P = 0.03). In workers monitored for plutonium exposure, RRs for all cancers combined increased with the number of years in which they were monitored (2P = 0.04) and with the number of years since first monitoring (2P = 0.0003). There was little suggestion of systematic variation in RRs for workers monitored for other radionuclides in relation to the timing or duration of monitoring, nor did it appear that their raised rates of cancer of the lung and prostate were explained by external radiation dose. These analyses of cancer mortality in relation to monitoring for radionuclide exposure reported in a large cohort of nuclear industry workers suggest that certain patterns of monitoring for some radionuclides may be associated with higher death rates from cancers of the lung, pleura, prostate and all cancers combined. Some of these findings may be due to chance. Moreover, because of the paucity of related data and lack of information about other possible exposures, such as whether plutonium workers are more likely to be exposed to asbestos, firm conclusions cannot be drawn at this stage. Further investigations of the relationship between radionuclide exposure and cancer in nuclear industry workers are needed.     

A clinical trial to reduce restraints in nursing homes

Plasma concentrations of isepamicin, a new aminoglycoside antibiotic, were determined by radioimmunoassay (RIA), microbiological assay (MA), and high-performance liquid chromatography (HPLC) in healthy volunteers after administration of 7.5 mg/kg intramuscular dosages once daily for 10 days. Plasma samples were collected on days 1, 7, and 10. The limit of quantitation (LOQ) was 0.1 microg/ml for HPLC and RIA and 0.5 microg/ml for MA. The HPLC and RIA yielded superimposable plasma concentration-time curves, whereas the plasma concentrations obtained with MA appeared to be 20% to 30% lower. Regression analysis indicated good correlations among the three assays, with coefficients of correlation measuring 0.935 to 0.960 for RIA compared with HPLC, 0.925 to 0.945 for MA compared with HPLC, and 0.920 to 0.945 for RIA compared with MA.     

Farnesyltransferase inhibitors versus Ras inhibitors

BACKGROUND: Intra-arterial regional anaesthesia (IARA) may be useful for ambulatory hand surgery in patients with poor veins. This randomized, double-blind study assessed which of the three doses of lignocaine gives the optimal analgesia with a minimum of adverse effects. METHODS: A preservative-free, alkalinized 0.5% lignocaine 1, 2 or 2.89 mg/kg body weight was injected into the radial arteries of 60 adult patients, allocated to three equal groups, to produce anaesthesia for carpal tunnel releases, capsulotomies, tenosynovectomies, palmar fasciectomies, Z-plastics, arthroplastics, arthrodeses etc. RESULTS: Surgical analgesia and motor block were best in group 3 (P < 0.01), whereas injection and tourniquet pain scores were similar in the three groups. Onset of analgesia was similar in all groups, and varied between 2 and 15 min. Cannulation time, surgery start time and tourniquet time were also similar in all groups, as were operating conditions and patient's acceptance of the method. No significant cardiovascular changes were observed after tourniquet release in any of the groups. Plasma lignocaine concentrations were lowest in group 1 (1 mg/kg) (P < 0.001). Five patients in group 1, seven in group 2 and seventeen in group 3 developed small bruises at the cannulation site (P < 0.001). Six patients (two in group 1, three in group 2 and one in group 3) had minor symptoms of lignocaine toxicity after tourniquet release (NS). No other complications were observed. CONCLUSIONS: The highest dose of lignocaine produces best surgical analgesia, without increasing the risk of toxicity. However, many patients receiving this dose will develop bruises at the injection site, and an occasional patient may need supplemental analgesia.     

Pulmonary contusion: a collective review

Pulmonary contusion is the most common injury identified in blunt chest trauma. Despite improvements in diagnostic imaging and critical care, the associated mortality has not appreciably changed over the last three decades. Parenchymal injury ultimately manifests as alveolar collapse and lung consolidation. Early detection and intervention toward minimizing injury progression provides the greatest chance for survival. Avoiding fluid overload, oxygen therapy, and a low threshold for mechanical ventilation are useful therapeutic guidelines. Complications include pneumonia and adult respiratory distress syndrome, which may occur in up to one half of all cases. Pulmonary contusion is a serious injury that may complicate patient management as well as pose a vital threat.     

Central injection in rats of alpha-melanocyte-stimulating hormone analog: effects on food intake and brain Fos

Lateral cerebroventricular (LCVT) administration of the alpha-MSH agonist analog Nle4DPhe7alpha-MSH (NDP-MSH) inhibited food intake in food-deprived rats, but did not inhibit water intake in water-deprived rats. When NDP-MSH was administered into the fourth ventricle (4CVT), comparable suppressions of food intake were observed. LCVT and 4CVT administration of NDP-MSH also reduced spontaneous 24 h food intake. LCVT injection of NDP-MSH greatly attenuated food intake stimulated in sated rats by acute CVT administration of neuropeptide Y (NPY). These and other data suggest that alpha-MSH is an important endogenous regulator of food intake, possibly acting downstream of NPY. In an attempt to assess further the sites of action of NDP-MSH, a qualitative mapping study of Fos-like immunoreactive (Fos-ir) neurons was performed following LCVT administration of NDP-MSH. LCVT injection of NDP-MSH induced Fos-ir in several forebrain regions including cortex, striatum, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and arcuate nucleus. The combination of NPY and NDP-MSH did not produce obvious antagonism or cancellation of effects in any region examined. Thus, the site(s) of action of NDP-MSH on food intake remain to be clarified.     

Arterial and pulmonary arterial concentrations of the enantiomers of bupivacaine after epidural injection in elderly patients

Bupivacaine HCl is a 50:50 racemic mixture of the levo [S(-)] and dex [R(+)] enantiomers. The R(+) enantiomer exhibits greater cardiac tissue binding and toxicity. To determine whether the lung exhibits selective uptake of one of the enantiomers of bupivacaine, we measured pulmonary artery and radial artery blood concentrations of the two enantiomers after a lumbar epidural injection of 20 mL of 0.75% bupivacaine in 10 elderly patients undergoing one-stage bilateral total knee arthroplasty. Significantly lower concentrations of R(+) than S(-) were noted in both pulmonary artery and arterial blood. Both enantiomers were absorbed by the lung to a similar extent within the first 5 min after epidural injection (extraction ratio approximately equal to 0.1 or 10%). Mean time of maximal concentration (Tmax) was 6 min. In 3 of the 10 patients, Tmax occurred in 1-3 min. We conclude that the lung absorbs both the R(+) and S(-) enantiomers of bupivacaine to a similar extent after epidural injection and that this is of doubtful clinical significance. This study also suggests that peak concentrations of bupivacaine may occur earlier after epidural injection in certain elderly patients than previously believed. Implications: In the first 5 min after epidural injection, approximately 10% of the local anesthetic bupivacaine was absorbed by the lung. Absorption of the two enantiomers (mirror images) of bupivacaine were similar. Lung absorption of bupivacaine is unlikely to influence local anesthetic toxicity.     

Backbone NMR assignments and secondary structure of the N-terminal domain of DnaB helicase from E. coli

A case of adult onset myopathy who showed a peculiar sleep-related respiratory disorder (SRRD) is reported. She recovered from respiratory failure after tracheostomy and/or with the aid of the respirator used only during the night. Sleep study without the use of respirator revealed that her sleep was highly fragmented by frequent arousal responses due to inspiratory effort but not by apnea or hypopnea. To our knowledge this type of SRRD has not been described.     

Cancer of the prostate: a nutritional disease?

Biotinidase deficiency is an autosomal recessively inherited disorder that results in the inability to recycle the vitamin biotin. The disorder can cause neurologic and cutaneous abnormalities that can be treated effectively with pharmacologic doses of biotin. We identified 21 mutations that cause profound biotinidase deficiency in 37 symptomatic children (30 different probands and 7 siblings), as well as provide relevant biochemical and clinical information for each child. The two most common mutations (G98:d7i3 and R538C) were found in 31 of 60 alleles (52%), whereas the remainder of the alleles are accounted for by the 19 other unique mutations. Serum samples were available from 18 children, of these 11 had no detectable cross-reacting material (CRM) to antibody prepared against normal human serum biotinidase, three had reduced quantities of CRM and four had normal quantities of CRM in serum. All of these mutations result in complete absence of biotinyl-transferase activity in serum. Two polymorphisms were also identified in normal individuals. It is apparent that a child who inherits any of these mutations, either in the homozygous state or in combination, can develop the clinical features of the disorder if untreated. There are, however, no clear genotype/phenotype correlations that would allow for the prediction of the type, severity, or age of onset of symptoms.     

Association of parvovirus B19 genome in children with myocarditis and cardiac allograft rejection: diagnosis using the polymerase chain reaction

BACKGROUND: Inflammatory diseases of the heart, including myocarditis and cardiac transplant rejection, are important causes of morbidity and mortality in children. Although viral infection may be suspected in either of these clinical conditions, the definitive etiology is often difficult to ascertain. Furthermore, the histology is identical for both disorders. Coxsackievirus has long been considered the most common cause of viral myocarditis; however, we previously demonstrated by polymerase chain reaction (PCR) analysis that many different, and sometimes unexpected, viruses may be responsible for myocarditis and cardiac rejection. In this study, we describe the association of parvovirus genome identified through PCR analysis of cardiac tissue in the clinical setting of myocarditis and cardiac allograft rejection. METHODS AND RESULTS: Myocardial tissue from endomyocardial biopsy, explant, or autopsy was analyzed for parvovirus B19 using primers designed to amplify a 699-base pair PCR product from the VP1 gene region. Samples tested included those obtained from patients with suspected myocarditis (n=360) or transplant rejection (n=200) or control subjects (n=250). Parvoviral genome was identified through PCR in 9 patients (3 myocarditis; 6 transplant) and no control patients. Of the 3 patients with myocarditis, 1 presented with cardiac arrest leading to death, 1 developed dilated cardiomyopathy, and the other gradually improved. Four of the 6 transplant patients had evidence of significant rejection on the basis of endomyocardial biopsy histology. All transplant patients survived the infection. CONCLUSIONS: Parvovirus is associated with myocarditis in a small percentage of children and may be a potential contributor to cardiac transplant rejection. PCR may provide a rapid and sensitive method of diagnosis.