Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S)

BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides < or =2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, P<.00001). Simvastatin produced substantial changes in several lipoprotein components, which we have attempted to relate to the beneficial effects observed. METHODS AND RESULTS: The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with triglycerides. We estimate that each additional 1% reduction in LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P<.00001). CONCLUSIONS: These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol, and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients.     

Congenital cystic diseases of liver and extrahepatic bile ducts

The paper presents 30-year experience in treating 158 patients with congenital cystic diseases of the liver and bile ducts. Depending on the pattern of hepatobiliary lesions, the diagnostic value of techniques, such as ultrasound, computerized tomography, scintigraphy of the liver duodenoscopy with THCG was defined. Analyzing the late outcomes provided recommendations for the most optimal surgical management: cystic fenestration and tunneling in hepatic polycystosis, pericystectomy in solitary cysts of the liver, different varieties of bile draining operations in choledochal cysts and Caroli's disease.     

Thyroid hormone induces protein secretion and morphological changes in astroglial cells with an increase in expression of glial fibrillary acidic protein

Degradation and utilization of protein by Prevotella ruminicola B1(4), a proteolytic bacterium that is prominent in the rumen, was examined. In preliminary experiments, proteinaceous N sources produced faster growth rates than did NH4Cl, based on changes in optical density over time. However, ammonium chloride produced a greater maximum cell density than did proteinaceous N sources. Of the proteinaceous N sources, an enzymatic hydrolysate of soybean protein with a relative peptide size of 3 AA residues produced a greater growth rate and maximum cell density compared with the other proteinaceous N sources. Further experiments revealed that P. ruminicola B1(4) grew faster and to a greater final dry weight with soybean protein than with casein. Degradation of both proteins was low as was indicated by the slow disappearance of soluble protein, low concentrations of free AA and peptides, and the decrease in ammonia concentrations over time. Patterns of degradation did differ between the two proteins, however. Accumulation of peptides and free AA from soybean protein peaked 2 h earlier than those from casein, and concentrations of free AA and peptides from soybean protein were lower on average than those from casein. Prevotella ruminicola B1(4) preferentially utilized Asp, Ile, Leu, Lys, and Arg from soybean protein compared with casein. The relative size of peptides that accumulated from both proteins, as determined by the ratio of ninhydrin reaction after HCl hydrolysis to ninhydrin reaction before HCl hydrolysis, suggested that part of the proteolytic activity of P. ruminicola B1(4) is a dipeptidase. Our findings suggest that P. ruminicola may have a greater impact on peptide degradation than on protein degradation in the rumen.     

Reduction of triceps muscle force after shortening of the distal humerus: a computational model

A retrospective case reference study examining the use of alcohol and tobacco in 303 women aged 40 or over suffering from oral or oropharyngeal cancer was conducted in the south-west Netherlands. Both alcohol and tobacco consumption are important in the development of oral and oropharyngeal cancer with increased consumption of both markedly increasing the risks of cancer, but alcohol having the greater effect.     

Perturbations Involving nu1 of NCCN

From high-resolution infrared spectra of 14N12C12C14N, 14N13C13C14N, and 15N12C12C15N, we find that the levels 1000(0)0(0), 1000(0)1(1), 1000(0)2(0,2), and 1000(0)3(1,3) have very pronounced perturbations. Our analysis shows that these perturbations are due to a vibrational resonance among the levels 1000(0)0(0), 0102(0)2(0), and 0102(0)2(2) in the one case, and equivalent levels with one or more additional quanta of nu5 in the other three cases. The resonance constant for the perturbation involving nu1 is 0.25 cm-1. It has the dependence on v5 and l5 that is expected for the sextic potential constant, K124455, although it seems too large for such a high-order constant. The Deltal (or Deltak) = 2 interaction between, for instance, 1000(0)0(0) and 0102(0)2(2e) is shown to be primarily due to the l-type resonance mixing of the 0102(0)2(0) and 0102(0)2(2e) states. The resonance is nearly "turned off" for the 1000(0)2(0,2) and 1000(0)3(1,3) states of 14N13C13C14N because there are no level crossings between the interacting states and the band centers are too far away to have an obvious effect, although careful analysis shows that the perturbation can be seen in their effective centrifugal distortion constants. The spectrum of 15N12C12C15N shows level crossings only in the case of the 1000(0)1(1), 1000(0)2(0,2), and 1000(0)3(1,3) states. Copyright 1999 Academic Press.     

Anterior rhinomanometry in nasal allergen challenges

Even simple and relatively safe provocation procedures like nasal allergen challenges, should aim to allow detection of positivity with the less possible discomfort to the patient. The objective of this work was to evaluate if the use of rhinomanometric measurements during nasal provocation procedures could allow a decrease in the total administered allergen dose, causing less symptoms to the patients but without increasing the number of false-negatives, comparatively to clinical scores or nasal peak-flow measurements. Our results showed that performing rhinomanometric measurements during nasal HDM challenge procedures can lead in many patients to a reduction in the total dose of allergen administered during the challenge, without loss of sensitivity or specificity. This allergen dose reduction translates in less time consumed during the provocation and less patients' discomfort.     

Design of constructions for the expression of proteolytic antibody light chain

A new system for the expression of a catalytic light chain antibody to the vasoactive intestinal peptide is described. The system made possible the isolation the large amounts of a homogeneous protein without any additional peptide domains. The preparation obtained can be used in further experiments on light chain crystallization and in X-ray-structural analysis of its catalytic center.     

Comparison of the pharmacological profile of S-nitrosothiols, nitric oxide and the nitrergic neurotransmitter in the canine ileocolonic junction

1. In organ bath experiments, hydroquinone (30-100 microM) and hydroxocobalamin (30-100 microM) concentration-dependently inhibited the relaxations induced by NO (0.3-30 microM) but not those by nitroglycerin (GTN, 1 microM) in the canine ileocolonic junction (ICJ). Hydroxocobalamin reduced the relaxation to low frequency (2 Hz) stimulation of the non-adrenergic, non-cholinergic (NANC) nerves, whereas hydroquinone only reduced the NANC nerve-mediated relaxations to electrical stimulation at 16 Hz, 0.5 ms. 2. Relaxations to S-nitroso-L-cysteine (CysNO, 1-30 microM), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1-30 microM) were not inhibited by hydroquinone (30-100 microM), hydroxocobalamin (30-100 microM), pyrogallol (30-100 microM) or L-cysteine (1-3 microM). Hydroquinone (100 microM) only reduced the relaxation to 10 microM CysNO. Hydroxocobalamin, but not hydroquinone, pyrogallol or L-cysteine, potentiated the relaxations to the lowest concentration (1 microM) of S-nitrosoglutathione (GSNO, 1-30 microM). 3. In the superfusion bioassay, hydroquinone (100 microM) and hydroxocobalamin (1 microM) concentration-dependently inhibited the biological activity of authentic NO (1-4 pmol) to the same extent as that of the transferable nitrergic factor, released from the canine ICJ in response to NANC nerve stimulation (8-16 Hz, 2 ms). Responses to GTN (10 pmol) or adenosine 5'-triphosphate (10 nmol) were not affected. 4. In conclusion, the nitrosothiols CysNO, SNAP and GSNO relax the canine ileocolonic junction, but these relaxations, pharmacologically, behave differently from the NANC nerve-mediated relaxations. From the bioassay experiments, we conclude that the nitrergic factor, released in response to NANCnerve stimulation of the canine ICJ, behaves pharmacologically like NO but not like a nitrosothiol.Therefore, we suggest NO, and not CysNO, SNAP or GSNO as the inhibitory NANC neurotransmitter in the canine ICJ.     

Genetic basis for diabetes resistance in NOD/Wehi mice

The basis for diabetes resistance in low diabetes incidence NOD/Wehi mice was examined in a breeding study. NOD/Wehi mice were crossed with high diabetes incidence NOD/Lt mice producing F1 hybrid mice which expressed a low incidence of diabetes. To distinguish between genetic and environmental causes for diabetes resistance, these F1 mice were backcrossed to NOD/Lt mice resulting in BC1 hybrid mice which expressed an intermediate incidence of diabetes. Similar results were obtained by examining the severity of insulitis in the hybrid mice. As both the incidence of diabetes and severity of insulitis in the hybrid mice were consistent with a single dominant gene mediating diabetes resistance, an attempt to localize this gene was made. Although over 140 loci which display polymorphism amongst inbred strains were typed in both parental lines, only a single locus, D8Mit9, was found to differ. As heterozygotes at D8Mit9 were not over represented amongst 45 diabetic BC1 hybrid mice examined, it was concluded that a resistance gene was not linked to this locus.     

Cancer genetics, cytogenetics--defining the enemy within

BACKGROUND/AIMS: International comparisons of clinical practice may help in assessing the magnitude and possible causes of variation in cross national healthcare utilisation. With this aim, the indications for cataract surgery in the United States, Denmark, the province of Manitoba (Canada), and the city of Barcelona (Spain) were compared. METHODS: In a prospective multicentre study, patients scheduled for first eye cataract surgery and aged 50 years or older were enrolled consecutively. From the United States 766 patients were enrolled; from Denmark 291; from Manitoba 152; and from Barcelona 200. Indication for surgery was measured as preoperative visual status of patients enlisted for cataract surgery. Main variables were preoperative visual acuity in operative eye, the VF-14 score (an index of functional impairment in patients with cataract) and ocular comorbidity. RESULTS: Mean visual acuity were 0.23 (USA), 0.17 (Denmark), 0.15 (Manitoba), and 0.07 (Barcelona) (p < 0.001). When restricting the sample to eyes with normal retina and macula, no significant difference between United States and Denmark was observed (p > 0.05). Mean VF-14 scores were 76 (USA), 76 (Denmark), 71 (Manitoba), and 64 (Barcelona) (p < 0.001). CONCLUSION: Similar indications for cataract surgery were found in the United States and Denmark. Significantly more restricted indications were observed in Manitoba and Barcelona. Possible explanations for the results are discussed, including differences in sociodemographic characteristics, access to care, surgeons' willingness to operate, and patient demand.