Association between oxygen delivery and consumption in patients undergoing cardiac surgery. Is there supply dependence?

Numerous investigators have suggested that cell glycoconjugates are modified by the development of cancer and the progression of this to a malignant form. Accordingly, in the present work, beta-D-galactosidase, alpha-L-fucosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities were studied in human thyroid and gastric tumours. Samples were obtained from human gastric mucosa and thyroid gland tumours together with a part of the surrounding normal tissue (control). Enzyme activity was determined spectrophotometrically based on the release of p-nitrophenol from suitable p-nitrophenyl-derivative substrates. Results showed that beta-D-galactosidase, alpha-L-fucosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities were detected in tumour and control samples from thyroid and gastric tissues. The gastric mucosa also showed alpha-L-mannosidase activity. The specific activities of these glycosidases were higher (two- or three-fold) in tumour tissues as compared with their controls. beta-D-galactosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities from thyroid and gastric tumours showed a significant increase in V(max) as compared with their respective controls (P < 0.05 or P < 0.001). Thyroid alpha-L-fucosidase activity showed a statistically and significantly increased affinity (lower K(m)) in tumour samples as compared to normal tissue. In conclusion both gastric and thyroid tumours showed enhanced glycosidase activity as compared with enzyme activity observed in normal tissue. These results are in agreement with the notion of a markedly raised degradation within lysosomes of tumour cells.     

Confirmatory factor analysis of the Wechsler Memory Scale-Revised in a sample of clients with alcohol dependency

Previous analyses of the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987) have reported one-, two-, and three-factor solutions and raised questions about the validity of the visual memory subtests. These various findings may stem in part from different methods of analysis, and from the study of different participant samples. To address these issues, we analysed data from the WMS-R and a spatial maze test administered to 154 participants with a history of alcohol dependence. Results from confirmatory factor analysis supported the interpretation of three factors underlying the WMS-R subtests and the spatial maze score in this sample, namely, attention-concentration, immediate memory, and delayed recall. This result held despite the inclusion of the maze score which is a well-validated measure of visuo-spatial memory.     

External and internal electrostatic potentials of cholinesterase models

The electrostatic potentials for the three-dimensional structures of cholinesterases from various species were calculated, using the Delphi algorithm, on the basis of the Poisson–Boltzmann equation. We used structures for Torpedo californica and mouse acetylcholinesterase, and built homology models of the human, Bungarus fasciatus, and Drosophila melanogaster acetylcholinesterases and human butyrylcholinesterase. All these structures reveal a negative external surface potential, in the area around the entrance to the active-site gorge, that becomes more negative as the rim of the gorge is approached. Moreover, in all cases, the potential becomes increasingly more negative along the central axis running down the gorge, and is largest at the base of the gorge, near the active site. Ten key acidic residues conserved in the sequence alignments of AChE from various species, both in the surface area near the entrance of the active-site gorge and at its base, appear to be primarily responsible for these potentials. The potentials are highly correlated among the structures examined, down to sequence identities as low as 35%. This indicates that they are a conserved property of the cholinesterase family, could serve to attract the positively charged substrate into and down the gorge to the active site, and may play other roles important for cholinesterase function.     

Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B

BACKGROUND: About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions. METHODS: We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3-hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment. RESULTS: Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). In contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups. CONCLUSIONS: These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.     

Can radioactive iodine be used in the treatment of diffuse non-toxic goiter?

Traditional treatment modalities of diffuse nontoxic goitre are thyroid hormone suppression or surgery. When treating nodular nontoxic goitre with 131I treatment, a reduction in thyroid volume to about 50% is seen. In the present study we evaluated the effect of 131I treatment in 21 patients treated for a diffuse nontoxic goitre and followed by evaluation of thyroid volume measured by ultrasound. Thyroid volume declined in all patients from median of 66 ml (range 27-160 ml) to 21 ml (9-108 ml) over a year, a reduction of 62%. Three patients developed hypothyroidism in the follow-up period (14%), one of these had a temporary hyperthyroid fase. In conclusion, 131I treatment of diffuse nontoxic goitre reduces thyroid volume by approximately 60% within 12 months. Hypothyroidism developed in 14% during a limited follow-up period.     

Semantic processing of spoken words in Alzheimer's disease: an electrophysiological study

Patients suffering from Alzheimer's disease (AD) have severe difficulties in tasks requiring the use of semantic knowledge. The semantic deficits associated with AD have been extensively studied by using behavioral methods. Many of these studies indicate that AD patients have a general deficit in voluntary access to semantic representations but that the structure of the representations themselves might be preserved. However, several studies also provide evidence that to some extent semantic representations in AD may in fact be degraded. Recently, a few studies have utilized event-related brain potentials (ERPs) that are sensitive to semantic factors in order to investigate the electrophysiological correlates of the semantic impairment in AD. Interest has focused on the N400 component, which is known to reflect the on-line semantic processing of linguistic and pictorial stimuli. The results from studies of N400 changes in AD remain somewhat controversial: Some studies report normal or enlarged N400 components in AD, whereas others report diminished ones. One issue not reported in previous studies is whether word-elicited ERPs other than N400 remain normal in AD. In the present study our aim was to find out whether the ERP waveforms N1, P2, N400, and Late Positive Component (LPC) to semantically congruous and incongruous spoken words are abnormal in AD and whether such abnormalities specifically reflect deficiencies in semantic activation in AD. Auditory ERPs from 20 scalp sites to semantically congruous and incongruous final words in spoken sentences were recorded from 17 healthy elderly adults and 9 AD patients. The early ERP waveforms N1 and P2 were relatively normal for the AD patients, but the N400 and LPC effects (amplitude difference between congruous and incongruous conditions) were significantly reduced. We interpret the present results as showing that semantic-conceptual activation and other high-level integration processes are defective in AD. However, a word congruity effect earlier than N400 (phonological mismatch negativity), reflecting lexical selection processes, is at least to some extent preserved in AD.     

On the theory of Δk radar observations of ocean surface waves

We consider the theory of waves scattered from a moving, rough, and dispersive surface in the small perturbation limit. The first-order scattered field for a time-dependent surface is obtained in the far zone of scattering in terms of the two-dimensional spectral amplitude of the surface and its dispersion relation. We develop a rigorous Δk radar theory and show that the nonzero output of a Δk radar occurs only when the Bragg condition for each signal component is satisfied separately. The frequency correlation function of the scattered field is then proportional to the mean value of the product of the spectral amplitudes of the surface at the corresponding Bragg wavenumbers. The mean value of this product is nonzero only for surfaces that have a locally varying spectrum and is proportional to the Fourier transform (with the argument Δk) of the variation of the local spectrum with respect to the pattern position. Such variations may be caused by either amplitude or phase modulation of the surface structure. In the former case, our results are similar to the results of existing theory. The latter case of phase modulation of the surface (for example, internal waves interacting with capillary waves) cannot be explained by previous theory     

Tumor necrosis factor-alpha production enhancing activity of substituted 3'-methylthalidomide: influence of substituents at the phthaloyl moiety on the activity and stereoselectivity

The synthesis and tumor necrosis factor (TNF)-alpha production enhancing activity of substituted 3'-methylthalidomides on human leukemia cell line HL-60 stimulated with 12-O-tetradecanoyl-phorbol 13-acetate (TPA) are described. Though the introduction of an electron-donating amino group at the phthaloyl moiety of alpha-methylthalidomides enhanced the activity, substituted alpha-methylthalidomides showed decreased stereoselectivity as compared to that of non-substituted alpha-methylthalidomide. The data indicates that the TNF-alpha production enhancing activity of thalidomide derivatives depends on both the electronic-state of substituents at the fused benzene ring and the stereochemistry of the glutarimide moiety.