Myocardial structure as a determinant of pre- and postoperative ventricular function and long-term prognosis after valve replacement for aortic stenosis

BACKGROUND: Long-term results after aortic value replacement for aortic stenosis can be correlated to a cardiac-related pre-operative risk profile. This predictability indicates that there is a common basis in subtle or overt structural abnormalities of left ventricular myocardium. METHODS AND RESULTS: Forty-nine patients aged 24-82 (mean 61) years, with aortic stenosis had a full wall thickness transmural biopsy of the left ventricular antero-lateral free wall during aortic valve replacement. Echocardiography and radionuclide ventriculography were performed prior to, and 18 months (n = 41) after, the operation. Postoperative follow-up to a maximum of 7.7 years was 100% complete. Pre-operatively, all patients had an increase in both the left ventricular mass index (202 +/- 67 g.m-2) and the muscle cell diameter (41 +/- 8 microns); other morphological data included a muscle cell nucleus volume of 752 +/- 192 microns3, a muscle cell mass index of 163 +/- 54.m-2, and a fibrous tissue mass index of 39 +/- 16 g.m-2. Patients with a pre-operative episode of clinical left ventricular failure (n = 19) had significantly greater morphological variables than those without. Pre-operative ejection fraction and other measures of systolic function correlated inversely with the morphological data, except for the fibrous tissue mass index; diastolic function indices correlated inversely with all the morphological variables. At the 18-month re-study, the same general picture was noted, but with an underlying strengthening, especially of the muscle cell mass index. Overall, the mass index dropped to 152 +/- 51 g.m-2 (P < 0.0001), but in 17% of the patients it became normal; the mass index at 18 months was directly correlated to morphological variables. A high muscle cell nucleus volume was identified as an independent predictor of early and late mortality. CONCLUSIONS: Abnormalities of the hypertrophied left ventricular muscle cell and the degree of muscle hypertrophy are, to some degree, underlying determinants of pre-operative symptomatology, pre- and postoperative ventricular function, and early and late mortality after valve replacement for aortic stenosis. Incomplete hypertrophy impaired results, was related to pre-operative myocardial structural abnormalities.     

Olfactory stimuli provoke diffuse esophageal spasm: reversal by ipratropium bromide

Diffuse esophageal spasm (DES) is a motor disorder of the esophageal smooth muscle characterized by multiple spontaneous contractions and by swallow-induced contractions that are of simultaneous onset, large amplitude, long duration, and repetitive occurrence. Although the pathogenesis of DES is unknown, provocative studies with cholinergic stimulation, esophageal balloon distention, or acid instillation have suggested involvement of both sensory and motor mechanisms. This report describes a patient with DES who would predictably become symptomatic with dysphagia and chest pain upon inhalation of perfume or other strong odors. Using esophageal scintigraphy to quantitate and analyze esophageal transit in this patient, we report for the first time that olfactory stimulation triggers episodes of DES and that such phenomena are mediated through the vagus nerve, because they can be ameliorated by the administration of ipratropium bromide. These observations suggest a new (sensory) pathway for the induction of DES and raise the intriguing possibility that inhaled anticholinergics may have a therapeutic role in the management of spastic esophageal motility disorders.     

Mercury in human hair and relation to fish consumption in Bangladesh

Human scalp hair mercury concentrations were determined in 219 hair samples from male individuals from different regions of Bangladesh. Total hair mercury concentrations were very low with a mean value of 0.44 +/- 0.19 micrograms Hg/g (range 0.02-0.95) for a moderately elevated fish consumption averaging 2.1 kg/month (range 1.4-2.6). A highly significant positive correlation (r = 0.88, P < 0.001) was found between fish consumption and hair mercury concentration. Neither age, region nor occupation had any influence on the hair mercury content. Our results in agreement with literature values, are described by equation (X = 183Y + 0.16) linking calculated daily methylmercury intake (X, mg) and hair total mercury level (Y, micrograms/g). Low concentrations in hair were linked to extremely low levels of daily mercury intake, the determining factor being remarkably low mercury levels in Bangladesh fish.     

CYFRA 21-1 enzyme-linked immunosorbent assay. Evaluation as a tumor marker in non-small cell lung cancer

BACKGROUND: The CYFRA 21-1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21-1 is a sensitive and specific tumor marker for non-small cell lung cancer. METHODS: CYFRA 21-1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21-1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer. RESULTS: The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21-1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21-1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21-1 assay has the highest sensitivity. The median level of CYFRA 21-1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p<0.001). The serum level and sensitivity of CYFRA 21-1 were well correlated with staging and tumor size in squamous cell carcinoma. The CYFRA 21-1 values were measured for monitoring progression of disease in 20 patients with squamous cell carcinoma. There is significant difference in paired observation of CYFRA 21-1 level in patients with progressive disease (Wilcoxon signed-rank test, p<0.05), but no difference was observed in patients with stabilized disease (p>0.1). CONCLUSION: For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.     

Long-term survival and nutritional data in patients with cystic fibrosis treated in a Danish centre

BACKGROUND: Adequate nutrition and optimal treatment of bronchopulmonary infections are both of critical importance in maintaining the health of patients with cystic fibrosis. The cystic fibrosis centre in Copenhagen has followed a regimen of very early and aggressive antimicrobial treatment, especially against Pseudomonas aeruginosa infection. An unrestricted diet of low fat and high protein without hyperalimentation was recommended before 1985 which was then changed to a high fat, high calorie intake. METHODS: The overall impact of the treatment regimen was evaluated by a cross sectional analysis of all 223 patients who attended the centre in 1989. Growth and nutritional parameters were combined with lung function parameters and with a retrospective analysis of chronic P aeruginosa infection and its duration. Survival curves for all 313 patients treated at the centre since 1949 were calculated. RESULTS: All the patients with cystic fibrosis had normal height, although the final height was achieved a little later than in healthy controls. Body weight was lower than normal in males above 15 and in females above 10 years of age. The body mass index (BMI), which was approximately 98% of normal in the younger patients, declined to 90% in adult men and to 83% in adult women with cystic fibrosis, and was strongly correlated with lung function parameters. In 1989 the median age of survival of all patients treated in the centre since 1949 was 30 years (32 years in males and 29 years in females). CONCLUSIONS: The overall treatment regimen in the cystic fibrosis centre in Copenhagen is associated with growth and survival rates that are at least equal to those in other cystic fibrosis centres in other countries.     

Dynamic internal testing of CMOS circuits using hot luminescence

Subnanosecond pulses of hot electron luminescence are shown to be generated coincident with logic state switching of individual devices in CMOS circuits. These pulses are used to directly observe 90 ps gate delays in a ring oscillator as well as the logic switching and gate delays of a counter. By use of a detector with both space- and time-resolution, the dynamics of all the gates of the circuit are simultaneously measured. This noninvasive technique can be extended to smaller device size, as well as probing from the backside of the wafer. The optical emission may provide an alternative to electron beam testing for measuring the dynamics of high-speed CMOS circuits     

Benign recurrent intrahepatic cholestasis (BRIC): evidence of genetic heterogeneity and delimitation of the BRIC locus to a 7-cM interval between D18S69 and D18S64

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disease characterized by multiple episodes of cholestasis without progression to chronic liver disease. The gene was previously assigned to chromosome 18q21, using a shared segment analysis in three families from the Netherlands. In the present study we report the linkage analysis of an expanded sample of 14 BRIC families, using 15 microsatellite markers from the 18q21 region. Obligate recombinants in two families place the gene in a 7-cM interval, between markers D18S69 and D18S64. All intervening markers had significant LOD scores in two-point linkage analysis. Moreover, we identified one family in which the BRIC gene seems to be unlinked to the 18q21 region, or that represents incomplete penetrance of the BRIC genotype.     

Epstein-Barr virus and CD21 expression in gastrointestinal tumors

OBJECTIVES: Animal inhalation studies and theoretical models suggest that the pattern of formation of benzene metabolites changes as exposure to benzene increases. To determine if this occurs in humans, benzene metabolites in urine samples collected as part of a cross sectional study of occupationally exposed workers in Shanghai, China were measured. METHODS: With organic vapour monitoring badges, 38 subjects were monitored during their full workshift for inhalation exposure to benzene. The benzene urinary metabolites phenol, catechol, hydroquinone, and muconic acid were measured with an isotope dilution gas chromatography mass spectroscopy assay and strongly correlated with concentrations of benzene air. For the subgroup of workers (n = 27) with urinary phenol > 50 ng/g creatinine (above which phenol is considered to be a specific indicator of exposure to benzene), concentrations of each of the four metabolites were calculated as a ratio of the sum of the concentrations of all four metabolites (total metabolites) and were compared in workers exposed to > 25 ppm v < or = 25 ppm. RESULTS: The median, 8 hour time weighted average exposure to benzene was 25 ppm. Relative to the lower exposed workers, the ratio of phenol and catechol to total metabolites increased by 6.0% (p = 0.04) and 22.2% (p = 0.007), respectively, in the more highly exposed workers. By contrast, the ratio of hydroquinone and muconic acid to total metabolites decreased by 18.8% (p = 0.04) and 26.7% (p = 0.006), respectively. Similar patterns were found when metabolite ratios were analysed as a function of internal benzene dose (defined as total urinary benzene metabolites), although catechol showed a more complex, quadratic relation with increasing dose. CONCLUSIONS: These results, which are consistent with previous animal studies, show that the relative production of benzene metabolites is a function of exposure level. If the toxic benzene metabolites are assumed to be derived from hydroquinone, ring opened products, or both, these results suggests that the risk for adverse health outcomes due to exposure to benzene may have a supralinear relation with external dose, and that linear extrapolation of the toxic effects of benzene in highly exposed workers to lower levels of exposure may underestimate risk.     

Neurovascular supply of the gracilis muscle: a study in the monkey and human

A comparison of the gross anatomy, extramuscular nerve branches, and intramuscular blood supply of the gracilis muscle showed similar patterns in both monkey and human. The number and pattern of distribution of the extramuscular terminal branches to the muscle were similar. The intramuscular neural pattern demonstrated with the Sihler's staining technique was also similar in both species. In vivo electrical stimulation studies in the monkey revealed that stimulating each extramuscular terminal nerve branch produced a distinct segmental contraction of the muscle. Independent contraction with force generation was observed when the monkey muscle was split into anterior and posterior segments and stimulated through each of the two subdivisions of the main nerve trunk to the muscle. Angiograms verified that circulation was preserved in these two segments.