ST Variability during the First 4 Hours of Acute Myocardial Infarction Predicts 1‐Year Mortality

Background: Early and complete myocardial reperfusion is the goal when treating a patient with acute myocardial infarction. To achieve this in each individual, an on‐line, accurate, easily handled and preferably noninvasive technique to monitor flow alterations is needed. Recurrent ST‐segment elevation has been shown to reflect cyclic disturbances in perfusion. Methods: We have retrospectively analyzed ST variability in 102 patients with acute myocardial infarction randomized to 100 mg of rt‐Pa or placebo. Patients were monitored for 24 hours using vectorcardiography. Results: Patients alive at one year (86%) had significantly less ST variability during the first four hours: 4.3 versus 7.1 episodes, P = 0.007. Patients having six or more ST episodes showed a 31.3% one‐year mortality as compared to no mortality in patients having no ST variability. Furthermore ST variability was reduced by fibrinolysis. Conclusion: Early ST variability detectable in real time is associated with worse outcome. A.N.E. 2001; 6(3):198–202     

Influence of CD4 or CD8 deficiency on collagen-induced arthritis

The role of T cells in the mouse collagen-induced arthritis (CIA) model for rheumatoid arthritis is not clarified, and different results have been reported concerning the role of CD4 and CD8 T cells. To address this issue, we have investigated B10.Q mice deficient for CD4 or CD8. The mice lacking CD4 were found to be less susceptible to disease, but not completely resistant, whereas the CD8 deficiency had no significant impact on the disease. No difference in the development of late occurring relapses was noted. Interestingly, the CD4-deficient mice had a severely reduced response to the glycosylated form of the immunodominant type II collagen (CII) 256-270 peptide whereas the response to the non-glycosylated peptide was not significantly different. Furthermore, CD4-deficient mice had lower antibody responses to CII, explaining the lower disease susceptibility. In comparison with previously reported results, it is apparent that the lack of CD4 molecules has a different impact on CIA if present on different genetic backgrounds, findings that could possibly be related to the occurrence of different disease pathways of CIA in different mouse strains.     

Back pain and degenerative abnormalities in the spine of young elite divers

Several studies have been published on disc degeneration among young athletes in sports with great demands on the back, but few on competitive divers; however, there are no long-term follow-up studies. Twenty elite divers between 10 and 21 years of age, with the highest possible national ranking, were selected at random without knowledge of previous or present back injuries or symptoms for an MRI study of the thoraco-lumbar spine in a 5-year longitudinal study. The occurrence of MRI abnormalities and their correlation with back pain were evaluated. Eighty-nine percent of the divers had a history of back pain and the median age at the first episode of back pain was 15 years. Sixty-five percent of the divers had MRI abnormalities in the thoraco-lumbar spine already at baseline. Only one diver without abnormalities at baseline had developed abnormalities at follow-up. Deterioration of any type of abnormality was found in 9 of 17 (53%) divers. Including all disc levels in all divers, the total number of abnormalities increased by 29% at follow-up, as compared to baseline. The most common abnormalities were reduced disc signal, Schmorl's nodes, and disc height reduction. Since almost all divers had previous or present back pain, a differentiated analysis of the relationship between pain and MRI findings was not possible. However, the high frequency of both back pain and MRI changes suggests a causal relationship. In conclusion, elite divers had high frequency of back pain at young ages and they run a high risk of developing degenerative abnormalities of the thoraco-lumbar spine, probably due to injuries to the spine during the growth spurt.     

Dietary insulin as an immunogen and tolerogen

We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin-specific immune response in infants. Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3-7 days and/or 3 months after delivery. After exclusive breast-feeding, the children received either CM formula or casein hydrolysate during the first 6-8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta-cell autoimmunity when compared with autoantibody-negative children (p = 0.030); this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast-fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI. However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance.     

Synthesis of analogs of L-valacyclovir and determination of their substrate activity for the oligopeptide transporter in Caco-2 cells.

L-Valacyclovir, a prodrug of acyclovir, is a substrate for the peptide transporter (PepT1) in the intestinal mucosa, which accounts for its higher than expected oral bioavailability. The substrate activity of L-valacyclovir for PepT1 is surprising, particularly when one considers that the molecule has the structural features of a nucleoside rather than a peptide. In an attempt to better understand the structure-transport relationships (STR) for the interactions of L-valacyclovir with PepT1, analogs of this molecule with structural changes in the guanine moiety were synthesized and their substrate activity for PepT1 in Caco-2 cell monolayers was determined. The analogs synthesized include those that had the guanine moiety of L-valacyclovir substituted with purine, benzimidazole, and 7-azaindole. All three analogs (purine, benzimidazole, and 7-azaindole) exhibited affinity for PepT1 in binding studies, but only the purine analog (as the L-valine ester) showed PepT1-associated transcellular transport across Caco-2 cell monolayers. The benzimidazole and 7-azaindole analogs (as their L-valine esters) were rapidly metabolized by esterase when applied to the apical surface of Caco-2 cells, which probably explains their low penetration as the intact prodrugs via PepT1.     

Quartz-dust-induced production of reactive oxygen metabolites by human granulocytes

We studied the effect of quartz on the production of reactive oxygen species by human polymorphonuclear leukocytes (PMN) in vitro by a chemiluminescence (CL) assay. Quartz caused a rapid dose-dependent CL response in the cells. Diamond dust used as an inert control did not stimulate the production of reactive oxygen metabolites by PMN. The quartz-induced activation of oxygen metabolism was also demonstrated by measuring oxygen consumption, nitroblue tetrazolium reduction, and superoxide and hydrogen peroxide production by PMN. Poly-vinyl-pyridine N-oxide (a quartz surface modifying agent) completely abolished the quartz-induced response, but had no effect on opsonized zymosan-induced CL response of PMN. The effect of N-acetylcysteine (a known antioxidant) was inhibitory to the CL formation induced by both quartz and opsonized zymosan. Our results are in agreement with the hypothesis that quartz-induced production of reactive oxygen metabolites is a possible mechanism by which quartz dust produces chronic inflammation and tissue injury of the lung. Agents interfering with the generation of reactive oxygen metabolites may provide a rationale for treatment of mineral-dust-induced pulmonary disease.     

Neonatal resuscitation after severe asphyxia - a critical evaluation of 177 Swedish cases.

AIM: To evaluate neonatal resuscitation of infants born with severe asphyxia. METHOD: All case records of the 472 claims for financial compensation due to suspected medical malpractice in conjunction with childbirth in Sweden between 1990 and 2005 were scrutinized. Inclusion criteria were: gestational age > or =33 completed weeks, planned vaginal onset of delivery, a reactive CTG at onset of labour, neonatal asphyxia (defined as metabolic acidosis [pH of < 7.05 and/or a base excess of < -12]), or an Apgar score <7 at 5 min. It was assessed that 177 infants suffered from cerebral palsy or early death due to severe asphyxia presumably caused by malpractice around labour. RESULTS: Median Apgar score at 5 min was 3, indicating that all infants needed immediate and extensive resuscitation. There was insufficient adherence to guidelines concerning neonatal resuscitation, including delayed initiation of excessive resuscitation in 19 infants, lack of satisfactory ventilation in 79 infants, and untimely interruption of resuscitation in 38 infants. CONCLUSIONS: Compliance with guidelines for resuscitation of severely asphyctic newborn may be improved, especially concerning ventilation and prompt paging for skilled personnel in cases of imminent asphyxia. Documentation of neonatal resuscitation must be improved to enable reliable evaluation.