Use of extracorporeal life support for adult patients with respiratory failure and sepsis

Na+,K+-ATPase activity is abundant on the basolateral infoldings of the strial marginal cells and contributes to the maintenance of the characteristic electrolyte composition of the endolymph. However, the stria vascularis of the cochlea is known not to be innervated. In order to clarify its humoral regulation by serotonin, the K+-p-nitrophenylphosphatase activity of strial marginal cells was investigated with a cerium-based method in normal guinea pigs and in guinea pigs treated with reserpine, 5-hydroxytryptamine or reserpine plus 5-hydroxytryptamine. K+-p-nitrophenylphosphatase activity was almost completely depressed 3-20 days after reserpine administration. Ten days after reserpinization, followed by repeated 5-hydroxytryptamine treatment, the enzyme activity was detectable. These results suggest that 5-hydroxytryptamine increases the phosphatase activity. Thus, the function of the stria vascularis in producing cochlear endolymph may be regulated by 5-hydroxytryptamine.     

Initiation and bidirectional propagation of chromatin assembly from a target site for nucleotide excision repair

To restore full genomic integrity in a eukaryotic cell, DNA repair processes have to be coordinated with the resetting of nucleosomal organization. We have established a cell-free system using Drosophila embryo extracts to investigate the mechanism linking de novo nucleosome formation to nucleotide excision repair (NER). Closed-circular DNA containing a uniquely placed cisplatin-DNA adduct was used to follow chromatin assembly specifically from a site of NER. Nucleosome formation was initiated from a target site for NER. The assembly of nucleosomes propagated bidirectionally, creating a regular nucleosomal array extending beyond the initiation site. Furthermore, this chromatin assembly was still effective when the repair synthesis step in the NER process was inhibited.     

Objectification of functional improvement after nonoperative care

STUDY DESIGN: In this article, the authors review the three broad categories of measures that have been used to objectify functional improvement after nonoperative care of painful spinal disorder patients-physical, psychological, and socioeconomic. For each of the three categories, the major measures used are discussed, as well as research relating to the efficacy of the measures. OBJECTIVE: To point out the many differences that still exist among research studies regarding which functional outcome measures to use and when to use them. SUMMARY OF BACKGROUND DATA: During the past few decades, it has been made abundantly clear that painful spinal disorders, particularly when associated with work disability and/or financial benefits, result from a complex interaction of medical, psychological, and social factors. This has resulted in frequent confusion regarding what constitutes the primary roots of the disabling process. Currently, a more comprehensive biopsychosocial perspective of chronic pain and disability has emerged that has significant implications for diagnostic and treatment philosophies of practitioners. METHODS: Identifying the measures frequently used to address the important biopsychosocial factors, and evaluating their relative benefits and drawbacks. RESULTS AND CONCLUSIONS: It is demonstrated that there has been an overall trend in recent years toward using more objective, quantifiable instruments, encompassing the physical, psychological, and socioeconomic parameters of outcomes research in painful spinal disorders. These changes will certainly improve the ability of researchers to tease out which factors tap more directly into such tissue as physical impairment, as well as create greater uniformity of measures that will permit direct comparisons between studies.     

Risk factors for myocardial infarct: a case-control study in Oporto, Portugal

A case-control study of coronary heart disease (CHD) was conducted in Oporto, Portugal. The cases series consisted of 100 consecutive patients with first time acute myocardial infarction who were admitted to the Coronary and Intermediate Care Units of a major teaching hospital. The community controls were 198 individuals without evidence of CHD by the Rose questionnaire and electrocardiography, selected by random digit dialing, with a participation rate of 70%. Data was collected by trained interviewers using a structured questionnaire and blood samples were obtained for selected laboratory data. The main analysis was made through unconditional logistic regression with calculations of odds ratios (OR). Age, OR: 1.5 (95% CI: 0.8-2.9), male gender, OR: 6.7 (3.6-12.3), family history of premature CHD, OR: 2.4 (1.4-4.3), diabetes, OR: 3.4 (1.6-7.4), antecedents of hypertension, OR:1.9 (1.1-3.1), history of high cholesterol levels, OR: 2.3 (1.4-3.9), high levels of physical activity, OR: 2.0 (0.9-4.1) and tobacco smoking, OR: 8.3 (3.8-18.5) were significant risk factors of acute myocardial infarction. After controlling for demographic variables and for the mutual confounding effects of the risk factors, the investigated factors that remained significantly associated with the risk of developing acute myocardial infarction were male gender, OR: 17.3 (4.8-62.3), family history of CHD, OR: 3.6 (1.4-9.6), diabetes, OR: 4.2 (1.0-18.1), high cholesterol levels OR: 2.7 (1.2-6.1) and smoking habits, OR: 7.7 (1.8-32.4). A negative association with high education levels was significant after controlling for all the variables, OR: 0.01 (0.01-0.5).     

Succinate and malate improve development of hamster eight-cell embryos in vitro: confirmation of viability by embryo transfer

The in vitro development of hamster preimplantation embryos is supported by non-glucose energy substrates. To investigate the importance of embryonic metabolism, influence of succinate and malate on the development of hamster 8-cell embryos to blastocysts was examined using a chemically defined protein-free modified hamster embryo culture medium-2 (HECM-2m). There was a dose-dependent influence of succinate on blastocyst development; 0.5 mM succinate was optimal (85.1% +/- 3.9 vs. 54.5% +/- 3.5). In succinate-supplemented HECM-2m, blastocyst development was reduced by omission of lactate (68.5% +/- 7.2), but not pyruvate (85.8% +/- 6.2) or glutamine (84.1% +/- 2.1). Succinate along with either glutamine or lactate or pyruvate poorly supported blastocyst development (28%-58%). Malate also stimulated blastocyst development; 0.01 mM malate was optimal (86.3% +/- 2.8). Supplementation of both succinate and malate to HECM-2m supported maximal (100%) blastocyst development, which was inhibited 4-fold by the addition of glucose/phosphate. The mean cell numbers (MCN) of blastocysts cultured in succinate-supplemented HECM-2m was higher (28.3 +/- 1.1) than it was for those cultured in the absence of glutamine or pyruvate (range 20-24). The MCN was the highest (33.4 +/- 1.6) for blastocysts cultured in succinate-malate-supplemented HECM-2m followed by those in succinate (28.3 +/- 1.1) or malate (24.7 +/- 0.5) supplemented HECM-2m. Embryo transfer experiments showed that 29.8% (+/- 4.5) of transferred blastocysts cultured in succinate-malate-supplemented HECM-2m produced live births, similar (P > 0.1) to the control transfers of freshly recovered 8-cells (33.5% +/- 2.0) or blastocysts (28.9% +/- 3.0). These data show that supplementation of succinate and malate to HECM-2m supports 100% development of hamster 8-cell embryos to high quality viable blastocysts and that non-glucose oxidizable energy substrates are the most preferred components in hamster embryo culture medium.     

Accommodation without feedback suggests directional signals specify ocular focus

Accommodation was monitored continuously under open-loop conditions while subjects viewed a sinusoidally oscillating sine-wave grating (0.2 Hz; +/- 1 D; 2.7 c/d; 0.56 contrast) in a Badal optometer. The target was illuminated by monochromatic light (590 nm) or white light (3000 K) with longitudinal chromatic aberration (LCA) normal, doubled, neutralized and reversed. Subjects (12) accommodated well in white light with LCA normal and doubled (mean gains = 0.85 and 0.94), gain was reduced in the neutralized condition (0.54), in monochromatic light (0.43), and especially when LCA was reversed (0.30). The results suggest that accommodation responds to changes in the relative contrast of spectral components of the retinal image and perhaps to the vergence of light.     

Ex vivo cytotoxic drug evaluation by DiSC assay to expedite identification of clinical targets: results with 8-chloro-cAMP

There is a pressing need to reduce the time and cost of developing new cytotoxic agents and to accurately identify clinically active agents at an early stage. In this study, the differential staining cytotoxicity (DiSC) assay was used to assess the efficacy of the novel antitumour cAMP analogue, 8-chloro-cAMP (8-Cl-cAMP) (and its metabolite 8-Cl-adenosine) against 107 fresh specimens of human neoplastic and normal cells. Diagnoses included chronic and acute leukaemias, myeloma, non-Hodgkin's lymphoma (NHL) and miscellaneous solid tumours. The aim was to identify targets for subsequent phase I, II and III trials. 8-Cl-cAMP was tested at 4-985 microM, along with standard chemotherapeutic drugs. 8-Cl-cAMP and its metabolite caused no morphologically observable cell differentiation but induced dose-dependent cytotoxicity. Compared with untreated patients, previously treated chronic lymphocytic leukaemia (CLL) patients showed no increase in ex vivo resistance to 8-Cl-cAMP (P = 0.878); minimal cross-resistance with other cytotoxic drugs was detected. Compared with normal cells (mean LC90 = 1803 microM), 8-Cl-cAMP showed significant ex vivo activity against CLL (117.0 microM; P < 0.0001) and NHL (140.0 microM; P < 0.0001), of which eight were mantle cell NHL (84.7 microM), and greatest activity against cells from patients with acute myeloid leukaemia (AML; mean LC90 = 24.3 microM; in vitro therapeutic index 74-fold, P < 0.0001). Solid tumour specimens were comparatively resistant to 8-Cl-cAMP. The results highlight the clinical potential of 8-Cl-cAMP, point to several new phase I, II and III trial possibilities and provide a rationale for the inclusion of ex vivo cytotoxic drug evaluation in the drug development process.