Absorption of the n-3 eicosapentaenoic and docosahexaenoic acids as ethyl esters and triglycerides by humans.

Five normolipemic subjects received three test meals containing 28 g n-3 (omega-3) fatty acids provided as 1) triglycerides, 2) ethyl esters, and 3) ethyl esters + 12 g olive oil. The control meal contained olive oil. When equivalent amounts of fat were given, the increase in chylomicron and plasma triglycerides was similar; n-3 fatty acid contents were also similar after n-3 fatty acid intake as ethyl esters or triglycerides. Ethyl esters alone were well absorbed and produced similar n-3 fatty acid responses in plasma triglycerides and chylomicrons. At 24 h after the n-3 fatty acid-containing meals, the fatty acid plasma concentration of these acids was similar. This study showed that n-3 fatty acids in fish oil given as ethyl esters or triglycerides were equally well absorbed. Eicosapentaenoic and docosahexaenoic acids were also equally absorbed.     

Immunoglobulins with hapten-binding activity: structure-function correlations and genetic implications

The N-terminal amino acid sequences of light and heavy chains from mouse myeloma immunoglobulins binding a variety of simple haptens are compared through the first hypervariable region with available sequences from the literature. These comparisons suggest that (a) the heavy chain sequences correlate closely with their respective hapten-binding specificity, and (b) light chain sequences correlate closely in the case of some specificities (e.g., carbohydrate moieties) but fall into several distinct sets with others (e.g., phosphorylcholine and 2,4-dinitrophenyl), We suggest that carbohydrate moieties may bind to the antibody combining site by multiple weak noncovalent interactions that require precise complementarity over an extended portion of the combining site. Accordingly, both the light and heavy chains are highly conserved. In contrast, the phosphorylcholine and 2,4-dinitrophenyl moieties are small and have many possibilities for ionic or charge transfer interactions, but presumably occupy only a small portion of the active site crevice. Hence, a variety of light chain sequences are compatible with active sites that bind these haptens. Even in the case of a small hapten such as phosphorylcholine, however, the light chain sequences place important constraints on the interactions between hapten and immunoglobulin. Heavy/light chain recombination studies reported in this paper reveal the importance of specific heavy/light chain pairing for generation of the antibody specificity to phosphorylcholine. These chain recombination and sequence data also impose important constraints on certain theories of antibody diversity which are discussed.     

Effect of teaching and checklist implementation on accuracy of medication history recording at hospital admission

Background Medication discrepancies at hospital admission is an extensive problem and knowledge is limited regarding improvement strategies. Objective To investigate the effect of teaching and checklist implementation on accuracy of medication history recording during hospitalization. Method Patients admitted to an internal medicine ward were prospectively included in two consecutive periods. Between the periods, non-mandatory teaching lessons were provided and a checklist assisting medication history recording implemented. Discrepancies between the recorded medications at admission and the patient’s actual drug use, as revealed by pharmacist-conducted medication reconciliation, were compared between the periods. The primary endpoint was difference between the periods in proportion of patients with minimum one discrepancy. Difference in median number of discrepancies was included as a secondary endpoint. Results 56 and 119 patients were included in period 1 (P1) and period 2 (P2), respectively. There was no significant difference in proportion of patients with minimum one discrepancy in P2 (68.9 %) versus P1 (76.8 %, p = 0.36), but a tendency of lower median number of discrepancies was observed in P2 than P1, i.e. 1 and 2, respectively (p = 0.087). Conclusion More powerful strategies than non-mandatory teaching activities and checklist implementation are required to achieve sufficient improvements in medication history recording during hospitalization.     

Intraoperative Angiography in Minimally Invasive Direct Coronary Artery Bypass Grafting

Intraoperative angiography in minimally invasive direct coronary artery bypass grafting without cardiopulmonary bypass and in hybrid procedures is reported. Twelve procedures were performed in a specially designed surgical-radiologic suite with a cross-disciplinary organization. In 2 patients the anastomosis was successfully revised on the basis of angiographic findings. In 4 of the 12 patients anastomosis of the left internal mammary artery to the left anterior descending coronary artery performed as a minimally invasive direct coronary artery bypass grafting procedure was combined with percutaneous transluminal coronary angioplasty of lesions in other coronary vessels in the same session. Intraoperative angiography allows a reliable diagnosis of an anastomosis or graft failure and prompt and reliable correction, and it allows the combination of minimally invasive direct coronary artery bypass grafting and angioplasty in one session.     

Basal forebrain projections to somatosensory cortex in the cat

1. This investigation was designed to identify the source of cholinergic basal forebrain projections to somatosensory cortex in the cat. 2. Injections of horseradish peroxidase (HRP) into cortical areas 3a, 3b, and 1 after a 36 to 48-h survival period, labeled neurons in the basal forebrain. The distribution of retrogradely labeled neurons was compared with the distribution of cells labeled by choline acetyltransferase immunocytochemistry. Most retrogradely labeled neurons in the basal telencephalon were found on the border between the globus pallidus and adjacent structures. Sometimes labeled neurons were also found in both limbs of the diagonal band of Broca. 3. Excitotoxin lesions of these regions of the basal telencephalon led to a profound depletion of acetylcholinesterase-containing axons in primary somatosensory cortex. 4. These data lay necessary groundwork for tests of the hypothesis that the cholinergic projection modulates experience-dependent modifications in adult cat somatosensory cortex.     

Screening of first degree relatives of patients operated for colorectal cancer: evaluation of fecal calprotectin vs. hemoccult II.

Fecal calprotectin (CPT) is elevated in the majority of patients with known colorectal cancer (CRC), but the specificity is not clarified. AIM: To evaluate if a CPT test (PhiCal ELISA) was more sensitive than Hemoccult II test in detecting colorectal neoplasia, and to obtain reference values in subjects with normal colonoscopy. To evaluate a possible relation between number and extent of dysplasia of adenomas in first degree relatives of patients with CRC and the stage of the carcinoma in the index casus. Further to study the prevalence of CRC and adenomas in the first degree relatives of patients operated for CRC. METHOD: In a multicenter study, 253 first degree relatives of patients with CRC, aged 50-75 years (mean age 60 years) underwent colonoscopy after having delivered stool samples and three Hemoccult II slides. RESULTS: In 237 first degree relatives from 148 patients with CRC, polyps were found in 118 (50%). Seventy three (31%) had adenomas and 17 had adenomas > or =10 mm. Five had asymptomatic cancers. The specificity of fecal CPT for adenomas at cut off levels 15 mg/l. The sensitivity of Hemoccult II for adenomas was 8%, and 4/5 of patients with carcinoma had negative Hemoccult II. The specificity for adenomas was 95%. CONCLUSION: Fecal CPT test was more sensitive than Hemoccult II in detecting colorectal neoplasia but the specificity was lower. In a high risk group like first degree relatives of patients with CRC, there are good reasons to consider fecal CPT as a first test in selecting patients for endoscopy.     

Enhanced levels of CCL19 in patients with advanced acquired immune deficiency syndrome (AIDS)

Based on the ability to recruit lymphocytes and dendritic cells to lymphoid tissue and to promote inflammation, we hypothesized a role for dysregulated CCL19 and CCL21 levels in human immunodeficiency virus (HIV)-infected patients with advanced immunodeficiency, and in particular in those with accompanying Mycobacterium avium complex (MAC) infection. The hypothesis was explored by studies in HIV-infected patients with and without MAC infection, as well as in vitro, examining the ability of proteins from MAC to promote CCL19 and CCL21 responses in peripheral blood mononuclear cells (PBMC) during highly active anti-retroviral therapy (HAART). Our main findings were: (i) raised serum levels of CCL19 in HIV-infected patients with CD4(+) T cell count <50 cells/μl compared with HIV-infected patients with CD4(+) T cell count >500 cells/μl and healthy controls, with particularly high levels in those with MAC infection; (ii) elevated plasma levels of CCL19 predicted a higher mortality in acquired immune deficiency syndrome (AIDS)-patients, independent of ongoing MAC infection; and (iii) marked production of CCL19 in MAC-stimulated peripheral blood mononuclear cells (PBMC) and pronounced disturbances in MAC-induced CCL19 production in PBMC from HIV patients that was partly reversed during HAART. Our findings suggest the involvement of CCL19 in AIDS patients with advanced immunodeficiency, potentially mediating both adaptive and maladaptive responses.     

Epidemiology of ulcerative colitis in western Norway

The incidence of ulcerative colitis (UC) in the three counties that compose Western Norway was registered in a prospective study during the years 1984 and 1985. Both inpatients and outpatients were included. Five hundred and fifty general practitioners and 12 hospitals participated in the study. A total of 239 patients were diagnosed in this area with 807,000 inhabitants, giving a mean annual incidence of 14.8 per 100,000. For patients between 30 and 35 years of age the age-specific incidence rate was 31.2. The M/F sex ratio was 1.10. Familial occurrence of inflammatory bowel disease was found in 11% of the patients. Patients with rectal involvement only constituted 35% of the patients.     

Reduced thrombus formation in native blood of homozygous factor VII- deficient patients at high arterial wall shear rate

Inhibition of thrombin formation in flowing native blood reduces thrombus formation on subendothelium, dacron, or collagen fibrils at arterial wall shear rates of 450 to 650 s-1. In the present study, we have investigated the role of low levels of factor VII (FVII) in thrombus formation on collagen fibrils at arterial wall shear rates of 650 s-1 (coronary arteries), 2,600 s-1 (mildly stenosed arteries), and 10,510 s-1 (severely stenosed arteries) in parallel-plate perfusion chambers. In the perfusion chamber with the highest wall shear rate, thrombus formation took place at the apex of an eccentric stenosis, which reduced the cross-sectional area of the blood flow channel by 80%, thus simulating thrombus formation at an atherosclerotic plaque rupture. Native blood from 21 healthy volunteers and 12 homozygous FVII- deficient patients was drawn by a pump directly from an antecubital vein over a surface of fibrillar collagen positioned in the respective perfusion chambers. The patients had FVII coagulant activities ranging from 1.3% to 4.5% and FVII antigen levels of 16% to 23% of normal. Immunoaffinity purification of the patients' FVII followed by electrophoresis (sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]) and immunoblotting showed a protein with similar molecular mass as normal FVII. In the perfusion studies, a reduction in thrombus volume of 54% of normal (P < .007) at 10,510 s-1 was observed. The deposition of fibrin on the thrombogenic surface and the plasma level of fibrinopeptide A (FPA) in blood samples collected distal to the perfusion chamber were concomitantly reduced (P < .002 and P < .04, respectively). The plasma FPA level was also reduced at 2,600 s-1 (P < .04), but not at 650 s-1. However, at the lower shear conditions, the thrombus volume and the fibrin deposition were within the ranges observed in normal blood. The platelet-collagen adhesion was not affected at any of the three shear conditions. Thus, low plasma levels of FVII result in significantly less formation of thrombin and fibrin in and around growing platelet masses at high shear condition. This may weaken the thrombus stability and reduce platelet recruitment, thereby lowering thrombus volume. In support of this theory, one patient with afibrinogenemia had an 83% reduction in thrombus volume at this high shear condition.     

Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys

Linolenic acid (18:3 omega 3) is a dietary precursor of docosahexaenoic acid (22:6 omega 3), the major fatty acid in the photoreceptor membranes of the retina. We hypothesized that rhesus monkeys deprived of dietary omega-3 fatty acids during prenatal and postnatal development would show plasma depletion of these fatty acids and visual impairment. Semipurified diets low in omega-3 fatty acids were fed to one group of adult female rhesus monkeys throughout pregnancy and to their infants from birth. A control group of mothers and infants received similar diets but supplying ample linolenic acid. In the plasma phospholipids of deficient infants, linolenic acid was generally undetectable and 22:6 omega 3 levels became progressively depleted, falling from 42% of control values at birth to 21% at 4 wk, 9% at 8 wk, and 6% at 12 wk of age. In the other plasma lipid classes, 22:6 omega 3 was undetectable by 12 wk. The visual acuity of the deprived infants, as measured by the preferential looking method, was reduced by one-fourth at 4 wk (P less than 0.05) and by one-half at 8 and 12 wk (P less than 0.0005) compared with control infants. These results suggest that omega-3 fatty acids may be an essential nutrient, and that 22:6 omega 3 may have a specific function in the photoreceptor membranes of the retina.