[Malignant multi-secretion insulinoma. A case].
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Female↗
Biomedical subjects
M Heim
Publications and source records attributed to M Heim.
Complement activation during storage of blood under normal blood bank conditions. Effects of proteinase inhibitors and leukocyte depletion.
During storage of CPD-A1 preserved whole blood factors of the complement cascade become activated, as evidenced by a rapid increase in the concentrations of C3a-desArg and C4a-desArg. After 10 to 14 days of whole blood storage, the elevations of C3a and C4a levels were highly significant. This increase was paralleled by an increase in the concentration of the lysosomal proteinase elastase from polymorphonuclear (PMN) granulocytes. By contrast, the concentration of the C3 activator complex C4b2b remained unchanged even after 3 weeks of storage. The supplementation of the anticoagulant CPD-A1 with the polyvalent-proteinase-inhibitor aprotinin and the specific elastase-inhibitor eglin C failed to inhibit complement activation, whereas leukocyte depletion could partially abolish the increase of the concentration of C4a, but had no effect on C3a concentrations. These observations support the notion that cleavage of C4 during storage of whole blood is partially leukocyte dependent, whereas the activation of C3 is possibly caused by the activation of the alternate pathway of the complement system by contact of plasma with plastic surfaces.
Aprotinin↗
[Spinal cord injuries caused by aviation accidents].
During the past 15 years fewer than 1% of those treated in the National Spinal Cord Injury Center were injured as a result of aviation accidents. In addition to 9 such patients treated at the center since 1973, another 6 were found among the many hundreds receiving ambulatory care in our clinics. 3 patients had survived a helicopter crash, 2 were injured while ejecting from combat aircraft, 3 were injured in crashes of light aircraft, 1 fell from a hand glider and 6 were injured in parachute drops. Of the 15 reviewed, 6 use wheelchairs, 3 walk assisted by orthopedic devices, while 6 ambulate freely. Although initial hospitalization was not substantially longer than in other patients with spinal cord injuries, extended ambulatory psychological intervention was necessary.
Accidents, Aviation↗
Reflex sympathetic dystrophy in a child.
We describe a 9 1/2 year old girl who suffered from severe recurrent pain and functional limitation in her right leg with hyperesthesia, hyperalgesia, color change and edema as the presenting symptoms, during the previous two months. All laboratory tests were found to be normal and diagnosis of reflex sympathetic dystrophy was made.
Child↗
Pupil's knowledge about health and illness.
Three hundred twenty high school pupils were evaluated concerning their knowledge about health and disease. The knowledge of 170 students in the first school in which they received lectures and had regular talks about health topics was higher in comparison with the knowledge of 150 students in the second high school who did not receive these lectures. We recommended that health topics be integrated in the school program starting at the first grade and continuing until graduation from high school.
Adolescent↗
Circumcision in hemophilia: the use of fibrin glue for local hemostasis.
Circumcision can be fatal in hemophilia patients unless they are treated with the missing coagulation factor. We describe 10 severe hemophilia patients in whom circumcision was performed with local fibrin glue instead of infusion of factor concentrate. Of the 10 patients 3 had postoperative bleeding and only 2 of them required infusion of factor VIII concentrate. Fibrin glue is a useful treatment modality for circumcision in patients with bleeding diathesis, and it is safer and cheaper than the infusion of factor concentrate.
Adolescent↗
Adjusted dose continuous infusion of factor VIII in patients with haemophilia A.
Surgical interventions in patients suffering from haemophilia A require infusions of large doses of factor VIII (F VIII) concentrates. These are expensive and may pose a burden on the immune system, which is already compromised in many haemophiliacs. F VIII is usually given as bolus injections, although there are reports on fixed dose continuous infusion. We have developed a continuous infusion programme with dosage adjusted according to daily calculation of the clearance of F VIII. Twenty-four haemophiliacs received a total of 205 d of continuous infusion with F VIII (168 d in hospital, 37 d home therapy). Eighteen patients underwent surgeries (11 elective, seven emergency) and six were treated for serious haemorrhages. We observed a significant, progressive decrease of the clearance of F VIII over the first 5 d from 3.2 (2.8-3.5) to 1.7 (1.3-1.9) ml/kg/h (median and interquartile range). The decrease of the clearance together with the fact that a continuous infusion requires less drug than bolus injections to keep the same minimal concentration, contributed to much lower doses of F VIII than reported in the literature or than required by historical controls, matched for the type of operation. Other advantages of our method are improved safety with stable activities of F VIII, lack of hazardous troughs below the haemostatic range, and the convenience, which permits ambulant therapy even when high doses of F VIII are required.
Adolescent↗
Effects of leukocyte depletion on the formation of anaphylatoxins in stored whole blood.
As reported earlier, factors of the complement cascade get activated in CPD-A1-stabilized whole blood. As early as after 10 days of storage under normal blood bank conditions the elevations of the concentrations of C3a-desArg and C4a-des-Arg were highly significant. By contrast, the concentration of the C3 activator complex C4b2b remained unchanged even after 3 weeks of storage. Leukocyte depletion partially inhibited the activation of C4 but had no effect on C3a concentrations. Therefore, cleavage of C4 during storage of whole blood seems to be partially leukocyte-dependent, whereas the activation of C3 is possibly due to the activation of the alternate pathway of the complement system by contact of blood to plastic surfaces. Even through the radioimmunologically measured C3a might be inactive as an anaphylatoxin, these observations are of clinical importance since the inactivated C3a-desArg still possesses biological activities such as activation of platelets which may lead to hypercoagulability and thrombosis.
Blood Preservation↗
Decreased formation of the complement component C4A in leukocyte-depleted stored whole blood.
As reported earlier, factors of the complement cascade get activated in CPD-A1-stabilized whole blood. While leukocyte depletion inhibited partially the activation of C4, it had no effect on C3a concentrations. Therefore cleavage of C4 during storage of whole blood seems to be partially leukocyte-dependent, whereas the activation of C3 is possibly due to the activation of the alternate pathway of the complement system by contact of blood to plastic surfaces. Even though the radioimmunologically measured C3a might be inactive as an anaphylatoxin, these observations are of clinical importance since the inactivated C3a-desArg still possesses biological activities, like activation of platelets which may lead to hypercoagulability and thrombosis.
Blood Preservation↗
[Coronary disease of transplanted heart. Physiopathology, prevention].
Coronary artery disease in cardiac transplant recipients is the main cause of mortality after the first postoperative year. This atheroma has unique anatomical features with widespread infiltration of the intima by inflammatory cells. The different physiopathological hypotheses are analysed. Immunological processes are probably responsible, suggesting chronic rejection. The cytomegalovirus could be an inductive mechanism. The classical vascular risk factors probably play a role but their action is not as clear as that of immunological and viral factors. Hyperlipidaemia is a causative mechanism and the predisposing role of steroid therapy is also recognised. From the practical point of view, correction of the classical risk factors is the only available therapeutic possibility at present.
Animals↗
[Comparative study of LpAI lipoparticles, HDL cholesterol and apolipoprotein AI in a control population, in a group of subjects with coronary diseases, and in a group of subjects with angiographically normal coronary vessels].
A new method for directly measuring LpAI lipoparticles containing apolipoprotein AI, but not apolipoprotein AII, is now disponible for laboratories. Concentrations of LpAI were measured in serum from 158 presumably healthy normolipidemic subjects (72 male, 86 female), for the age group 30-60 years. Concentrations of LpAI were also measured in subjects with angiographically defined coronary artery disease (coro+) and without angiographically defined coronary artery disease (coro-). After comparison of the groups, lipoprotein particle LpAI did not appear to be a better discriminative marker than HDL cholesterol or apolipoprotein AI for atherogen risk.
Adult↗
[Lipid indicators of vascular risk. A cross-sectional study of a group of coronary patients, a group of subjects with normal coronary angiography and a control group].
During a transverse survey, 3 groups of men with the same weight and age were compared. Group I included 42 patients with coronary disease documented by coronarography, group 2 included 19 subjects with normal coronary angiograms, and group 3 included 27 healthy controls who had not undergone coronarography. Subjects presenting diabetes or any factor associated with secondary dyslipidemia or able to modify lipid levels were excluded from study. The following parameters were measured: total cholesterol (Chol), triglycerides (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), apoprotein A1 (apoA1), apoprotein B (apoB), lipoprotein (a) or Lp(a), fibrinogen, insulinemia and plasminogen activator inhibitor activity (PAI). The levels of chol, LDL-C and ApoB were the same in the 3 groups. The levels of TG, HDL-C, apoA1 and the ApoA-1/APoB ratio were significantly different between groups 1 and 2, on the one hand, and groups 1 and 3, on the other hand. The levels of Lp(a) and insulin were similar in the 3 groups. Fibrinogen levels were slightly higher in group 1 than in group 3. There was no significant difference between groups 1 and 2 with regard to any of the parameters. Subjects with angiographically normal coronary arteries and subjects with documented coronary disease exhibited similar lipid abnormalities. In this study, TG, HDL-chol, apoA1 and the apoB ratio were better predictors of cardiovascular risk than Chol, LDL-C or apoB.
Adult↗
Imaging rounds #112. Congenital short Achilles tendon.
Too often a relatively minor surgical procedure can prevent complications at a later stage. The diagnosis in children is often missed because of normal physiologic states that closely resemble the pathology. The early detection and correction of congenital short Achilles tendons can prevent further developmental abnormalities.
Achilles Tendon↗
Molecular mechanism of slow acetylation of drugs and carcinogens in humans.
The acetylation polymorphism is one of the most common genetic variations in the transformation of drugs and chemicals. More than 50% of individuals in Caucasian populations are homozygous for a recessive trait and are of the "slow acetylator" phenotype. They are less efficient than "rapid acetylators" in the metabolism of numerous drugs and environmental and industrial chemicals. The acetylation polymorphism is associated with an increased risk of drug toxicity and with an increased frequency of certain cancers. We report the identification of the primary mutations in two alleles of the gene for the N-acetyltransferase (NAT; acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) isozyme NAT2 associated with slow acetylation. These alleles, M1 and M2, account for more than 90% of slow acetylator alleles in the European population we have studied. M1 and M2 were identified by restriction fragment length polymorphisms with Kpn I and Msp I and subsequently cloned and sequenced. M1 and M2 each are characterized by a combination of two different point mutations, one causing an amino acid substitution (Ile-113----Thr in M1, Arg-197----Gln in M2), the other being silent (C 481----T in M1, C 282----T in M2). Functional expression of M1 and M2 and of chimeric gene constructs between mutant and wild-type NAT2 in COS-1 cells suggests that M1 causes a decrease of NAT2 protein in the liver by defective translation, whereas M2 produces an unstable enzyme. On the basis of the mutations described here and a rare mutant allele (M3) reported recently, we have developed a simple DNA amplification assay that allows the predictive genotyping of more than 95% of slow and rapid acetylator alleles and the identification of individuals at risk.
Acetylation↗
Predicting debrisoquine phenotype.
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Alleles↗
Genetic analysis of the interethnic difference between Chinese and Caucasians in the polymorphic metabolism of debrisoquine and codeine.
The Far Eastern and Caucasian populations are strikingly different with respect to the debrisoquine/sparteine hydroxylation polymorphism. The number of poor metabolizers, as defined for Caucasians, is very low among Chinese and Japanese. We investigated the molecular basis for this difference by analysis of the CYP2D6 gene in 115 Chinese subjects, combined with phenotypic classification of codeine and debrisoquine metabolism. A correlation between the rates of metabolism of these two drugs and genotype, as analyzed by RFLP using XbaI, was observed among the Chinese. A high frequency (37%) of alleles indicative of gene insertions (reflected by XbaI 44kb fragments) was recorded in the Chinese, but was not associated with the poor metabolizer phenotype, as it is in Caucasians. PCR amplification of part of the CYP2D6 gene with mutation specific primers for CYP2D6A (29A) and CYP2D6B (29B) allelic variants revealed that the XbaI 44kb fragment in Chinese apparently contains a functional CYP2D6 gene, in contrast to the situation among Caucasians. The results provide a molecular explanation of the interethnic difference in the metabolism of drugs affected by the debrisoquine hydroxylation polymorphism.
Adolescent↗
Debrisoquine/sparteine hydroxylation genotype and phenotype: analysis of common mutations and alleles of CYP2D6 in a European population.
Four different mutations of the cytochrome P450 CYP2D6 gene associated with the poor metabolizer phenotype (PM) of the debrisoquine/sparteine polymorphism were analyzed by Xba I restriction fragment length polymorphism (RFLP) analysis and a polymerase chain reaction (PCR)-based DNA amplification method in DNA of 394 healthy European subjects; 341 of these were phenotyped by sparteine or debrisoquine administration and urinary metabolic ratios (MR). Our study demonstrates the efficiency of the PCR-test for phenotype prediction; 96.4% of individuals were correctly predicted, i.e., 100% of the extensive metabolizers (EMs) and 86.0% of the poor metabolizers (PMs). In contrast, Xba I RFLP analysis was far less informative, predicting the phenotype in only 26.8% of PMs. By combining both DNA tests, the prediction rate of the PM phenotype increased to 90.6%. A point mutation at a splice-site consensus sequence termed D6-B represented the most common mutant CYP2D6 gene and accounted for more than 75% of mutant alleles. In addition, other known mutations such as D6-D (14%), D6-A (5%), and the rare D6-C mutation bring the identified mutant alleles to greater than 95% of all mutant PM-alleles. Most of Xba I 44-kb alleles were confirmed as mutant alleles carrying the D6-B mutation. However, 9.7% did not have this mutation and may express a functional CYP2D6 gene. Moreover, all Xba I 16 + 9-kb alleles contained the D6-B mutation. Heterozygous EM individuals had a significantly higher MR when compared to homozygous EMs. Genotyping provides an important advantage for investigations of the influence of CYP2D6 activity on drug therapy and its association with certain diseases.
Alleles↗
A pilot study to investigate whether sport influences psychological parameters in the personality of asthmatic children.
Sixteen asthmatic children were interviewed about the influence of sport activity upon their psychological character. Fourteen additional children with asthma of the same severity who did not take part in any sport served as the control group. The results of this study show that asthmatic children practicing sport have a better self image than the control group, are less anxious and cope better with the disease. They also showed better interfamily relationships. The conclusions of this pilot study indicate that asthmatic children should be encouraged to participate in sport activities, which seem to assist in their general well being.
Adolescent↗