Sudden death in early infancy due to delayed cardiac tamponade complicating central venous line insertion and cardiac catheterization.

Cardiac tamponade is an unusual cause of sudden death in the first weeks of life. We present two cases of cardiac tamponade in the neonatal period that caused death 5 to 6 days following the insertion of intracardiac lines, to draw attention to the possibility of a "delay phenomenon" between the time of the initial procedure and the occurrence of sudden and unexpected death. The presence of blood or clear fluid within the pericardial sac should prompt careful examination of the myocardium for small foci of traumatic damage, particularly when the fluid is under pressure or of large volume. Although the development of circulatory impairment or shock in the days following central line insertion or catheterization raises the possibility of tamponade, it should be noted that sudden death may occur in the absence of any significant antemortem symptoms or signs.     

Intravenous digital subtraction angiography: an index of collateral cerebral blood flow in internal carotid artery occlusion

The objective of this investigation was to correlate Xenon-133 inhalation rCBF measurements with the pattern of cortical arterial filling on intravenous DSA in 18 patients with unilateral internal carotid artery occlusion. Of 9 patients showing symmetrical filling of hemispheric cortical arteries, none showed an inter-hemispheric difference in rCBF ( delta Fg) greater than 10ml/100gm/min. Of 9 patients showing delayed cortical opacification ipsilateral to the internal artery occlusion, 3 showed a delta Fg greater than 10ml/100gm/min, 3 showed a delta Fg in the 7-10ml/100gm/min range, and 3 had a delta Fg less than 7ml/100gm/min. All patients with asymmetric abnormalities in the rCBF profile had the delayed pattern of cortical filling on DSA. The presence of symmetrical hemispheric opacification of cortical arteries on DSA indicates adequate interhemispheric redistribution of rCBF and patent inter-hemispheric collateral channels, but not necessarily normal cerebral blood flow. The presence of delayed cortical arterial opacification on the side of internal carotid artery occlusion does not necessarily imply significant inter-hemispheric rCBF differences, nor does it rule out a normal rCBF. The presence of bilateral reduction of rCBF and symmetrical cortical artery filling on DSA may represent an "interhemispheric steal".     

Parental knowledge of school backpack weight and contents.

Parental knowledge of their students' backpack weight and contents was assessed by identifying 188 students who carried backpacks weighing at least 10% of their body weights through a survey of 745 students in three elementary schools. Most parents (96%) had never checked their child's backpack weight; 34% had never checked the backpack contents.     

Peak height velocity as a maturity indicator for males with idiopathic scoliosis

We retrospectively studied 43 adolescent boys treated with orthoses for idiopathic scoliosis to assess the usefulness of the timing of peak height velocity for predicting growth remaining and the likelihood of curve progression when compared with Risser sign, closure of the triradiate cartilage, and chronologic age. We compared the peak height velocity data in boys to our previous work for girls with adolescent idiopathic scoliosis. We found the median height velocity plots showed a similar high peak and sharp decline as is found in girls. All 13 patients with a curve magnitude > 30 degrees at the time of peak height velocity had progression of their scoliosis to > 45 degrees despite bracing. Four of 29 patients (14%) with curves < or = 30 degrees at peak height velocity progressed to 45 degrees. These values generate a sensitivity of 76%, specificity of 100% and accuracy of 91% in predicting progression to 45 degrees. Similar values have been found in female patients. The use of peak height velocity to predict the length of time for remaining growth was superior to Risser sign and chronologic age for boys with idiopathic scoliosis. Closure of the triradiate cartilage approximated the timing of peak height velocity in boys.     

N-acetyltransferase polymorphisms and colorectal cancer: a HuGE review

The two expressed genes coding for N-acetyltransferase (NAT) activity, NAT1 and NAT2, are located on chromosome 8 at 8p21.3-23.1 and are polymorphic. Both enzymes are capable of N-acetylation, O-acetylation, and N,O-acetylation and are implicated in the activation and detoxification of known carcinogens. Single base-pair substitutions in NAT2 tend to occur in combination with other substitutions within the gene. As yet, less work has been done to characterize NAT1 allelic variants. Various methods for the detection of the reported polymorphisms exist. It is important to select a method that is appropriate to the population being studied. The functional significance of many NAT allelic variants has not been determined. Geographic and ethnic variation in the frequency of NAT2 genotypes associated with fast or intermediate acetylation has been observed. Insufficient data for NAT1 genotypes are available to reveal a clear geographic pattern. No consistent association has been found between acetylator phenotype or genotype and colorectal cancer. The lack of consistency can in part be accounted for by methodological factors, including limited statistical power. Possible interactions between the NAT genes and either environmental exposures or other polymorphic genes encoding xenobiotic metabolizing enzymes have been investigated in only a minority of these studies, and these studies have lacked statistical power to detect interactions.     

Hemoglobin and albumin adducts of benzene oxide among workers exposed to high levels of benzene

Benzene oxide (BO) reacts with cysteinyl residues in hemoglobin (Hb) and albumin (Alb) to form protein adducts (BO-Hb and BO-Alb), which are presumed to be specific biomarkers of exposure to benzene. We analyzed BO-Hb in 43 exposed workers and 42 unexposed controls, and BO-Alb in a subsample consisting of 19 workers and 19 controls from Shanghai, China, as part of a larger cross-sectional study of benzene biomarkers. The adducts were analyzed by gas chromatography-mass spectrometry following reaction of the protein with trifluoroacetic anhydride and methanesulfonic acid. When subjects were divided into controls (n = 42) and workers exposed to < or =31 (n = 21) and >31 p.p.m. (n = 22) benzene, median BO-Hb levels were 32.0, 46.7 and 129 pmol/g globin, respectively (correlation with exposure: Spearman r = 0.67, P < 0.0001). To our knowledge, these results represent the first observation in humans that BO-Hb levels are significantly correlated with benzene exposure. Median BO-Alb levels in these 3 groups were 103 (n = 19), 351 (n = 7) and 2010 (n = 12) pmol/g Alb, respectively, also reflecting a significant correlation with exposure (Spearman r = 0.90, P < 0.0001). The blood dose of BO predicted from both Hb and Alb adducts was very similar. These results clearly affirm the use of both Hb and Alb adducts of BO as biomarkers of exposure to high levels of benzene. As part of our investigation of the background levels of BO-Hb and BO-Alb found in unexposed persons, we analyzed recombinant human Hb and Alb for BO adducts. Significant levels of both BO-Hb (19.7 pmol/g) and BO-Alb (41.9 pmol/g) were detected, suggesting that portions of the observed background adducts reflect an artifact of the assay, while other portions are indicative of either unknown exposures or endogenous production of adducts.      

Increased aneusomy and long arm deletion of chromosomes 5 and 7 in the lymphocytes of Chinese workers exposed to benzene

Two of the most common cytogenetic changes in therapy- and chemical- related leukemia are the loss and long (q) arm deletion of chromosomes 5 and 7. The detection of these aberrations in lymphocytes of individuals exposed to potential leukemogens may serve as useful biomarkers of increased leukemia risk. We have used a novel fluorescence in situ hybridization (FISH) procedure to determine if specific aberrations in chromosomes 1, 5 and 7 occur at an elevated rate in the blood cells of workers exposed to benzene. Forty-three healthy workers exposed to a wide range of benzene concentrations (median 31 p.p.m., 8 h time-weighted average) and 44 unexposed controls from Shanghai were studied. Whole blood was cultured and metaphase spreads were harvested at 72 h. Benzene exposure was associated with increases in the rates of monosomy 5 and 7 but not monosomy 1 (P < 0.001, P < 0.0001 and P = 0.94, respectively) and with increases in trisomy and tetrasomy frequencies of all three chromosomes. Long arm deletion of chromosomes 5 and 7 was increased in a dose-dependent fashion (P = 0.014 and P < 0.0001) up to 3.5-fold in the exposed workers. These results demonstrate that leukemia-specific changes in chromosomes 5 and 7 can be detected by FISH in the peripheral blood of otherwise healthy benzene-exposed workers. We suggest that aberrations in chromosomes 5 and 7 may be useful biomarkers of early biological effect for benzene exposure.      

A comparison of the degree of curvature in the cancer incidence dose-response in Japanese atomic bomb survivors with that in chromosome aberrations measured in vitro

PURPOSES: To compare the degree of curvature in the dose-response for chromosome aberrations and for radiation-induced cancer. MATERIALS AND METHODS: Comparison of the ratio of the quadratic and linear coefficients (in dose) in Japanese atomic bomb survivor cancer incidence data, based on follow-up to 1987 and taking account of random errors in DS86 dose estimates with the same ratio in four datasets of chromosome aberrations in peripheral blood lymphocytes measured in vitro and exposed to 60Co gamma radiation. RESULTS: There are no statistically significant differences between the four in vitro datasets in the ratio of the quadratic to the linear coefficients for dicentrics or chromosome translocations, nor are there indications of differences between this ratio for dicentrics and that for complete chromosome translocations (p > 0.1 in all cases). If the 0-4 Gy dose range is used in the Japanese atomic bomb survivor data, the ratio of the quadratic to the linear coefficients for all solid cancers is 0.06 -1 (95% CI -0.22, 0.67) and so is not significantly different from 0; this ratio is statistically highly inconsistent (p<0.0001) with the analogous ratio estimated for the in vitro chromosome aberration data (4.20 Sv-1; 95% CI 3.06, 6.51). By contrast, there are no statistically significant differences (p=0.42) between the ratio of the quadratic to the linear coefficients for leukaemia incidence in the Japanese cohort, 1.81 Sv-1 (95% CI 0.21, > 1,000), with that for chromosome aberrations in vitro. These results are not markedly changed if the 0-2 Gy dose range is used in the Japanese atomic bomb survivor data. CONCLUSIONS: It is unlikely that in vitro chromosome aberrations could be a correlate for the initiating radiogenic lesions leading to radiation-induced solid cancers. However, taken together with certain other biological information, it may not be unreasonable on this basis to use in vitro chromosome aberrations in peripheral blood lymphocytes as a correlate of the radiogenic lesions leading to radiation-induced leukaemia.     

Ethonomics: the ethics of the unaffordable

The most familiar basis for medical ethics since the 1950s has been principle-based ethics. The 4 basic principles are known as the "Georgetown mantra" of beneficence, nonmaleficence, respect for autonomy, and justice. These principles have served us well since their enunciation in the wake of the activities of the Nazi doctors in the concentration and extermination camps of World War II. In the past 15 years, however, they have begun to serve less well. In the era of resource constraints, however, the clinical relationship has become more complex. It now involves many more stakeholders, who control funds, make policy, and effectively ration services. Lawyers are also involved in important ways. All these people take part with varying directness in the processes of consultation and treatment. The consulting room has become a crowded office. For these reasons, the old ethics will no longer serve us. We need a new ethics that recognizes the involvement of the new stakeholders, and recognizes that resource constraints influence clinical practice.