Clinical Follow-up and Parental Attitudes Towards Neonatal Screening

ABSTRACT. Sveger, T. and Thelin, T. (Departments of Paediatrics and Psychiatry, University of Lund, Malmö General Hospital, Malmö, Sweden). Four-year-old children with α₁-antitrypsin deficiency. Acta Paediatr Scand, 70:171, 1980. –Two hundred thousand infants born in Sweden between November 1972 and September 1974 were screened at birth for a,-antitrypsin (a, AT) deficiency. At age 4 years 172 of 183 children with a, AT deficiency were examined and compared with 80 randomly selected control children. The children with a, AT deficiency had the following Pi types: 118 PiZ, 50 PiSZ, 2 PiZ-, 1 PiS-, and 1 PiFZ. Two PiZ children have severe liver cirrhosis and 1 PiZ boy had died of aplastic anemia. Abnormal levels of serum alanine aminotransferase (S-ALAT) were found in one PiSZ and 47 PiZ children. Upper and lower respiratory infections, otitis, eczema, urinary infections or complications of child diseases did not occur more often in children with α₁ AT deficiency than in controls. More parents of α₁ AT deficient children had stopped smoking and their fathers smoked significantly less. Forty parents of children with α₁ AT deficiency PiZ answered a questionnaire concerning their reaction to, knowledge about and attitudes towards neonatal screening for α₁ AT deficiency. Many parents reported having reacted with lack of understanding, shock or depression upon learning that the child had α₁ AT deficiency. About 4 years later 44 % reported still lack of understanding, and 18 % depression or feelings of guilt. About two-thirds had not fully understood why a , AT deficiency had been identified, despite the fact that they had seen their doctor 3–4 times for check-ups and counselling since birth.     

VARIATIONS OF PROTEASE INHIBITORS IN FOETUSES, NEWBORN INFANTS and IN SOME NEONATAL DISORDERS

ABSTRACT: Sveger, T. and Ekelund, H. (Departments of Clinical Chemistry and of Paediatrics, Malmö General Hospital, Malmö, Sweden). Variations of protease inhibitors in foetuses, newborn infants and in some neonatal disorders. Acta Paediatr Scand, 64:763, 1975.–Low levels of protease inhibitors have been found on the 1st day of life in IRDS infants. 19 IRDS infants were studied together with foetuses and control term and preterm infants. α₁-antitrypsin, antichymotrypsin and α₂-macroglobulin were measured with the electroim-muno assay. IRDS infants had significantly reduced concentration of α₁-antitrypsin and antichymotrypsin on the 1st day, the level increasing to normal on the 2nd day. In foetuses α₁-antitrypsin was normal, antichymotrypsin 2% and α₂-macroglobulin 1/3 of the normal adult level. The protease inhibitors are increased in infants born after premature rupture of foetal membranes. The part, if any, played by protease inhibitors is not entirely understood. The inhibitors may, theoretically, be of some importance in the dissolution of the hyaline membranes, protect against pulmonary vasoconstriction, protect pulmonary tissue against leucocyte and macrophage proteolytic enzymes and inhibit the release of or counteract vasoactive substances that might take part in the development of shock in IRDS babies.     

The Natural History of Liver Disease in (α1-Antitrypsin Deficient Children

ABSTRACT. During 1972–1974, 200 000 Swedish infants were screened for α₁-antitrypsin deficiency. Of 127 PiZ (Protease inhibitor) children followed from infancy to 12 years of age, four PiZ children with neonatal liver disease have died; two of liver cirrhosis, one was found to have liver cirrhosis at autopsy, having died of aplastic anemia and the fourth died in an accident. Liver microscopy showed a mild increase of periportal fibrous tissue. Another PiZ child died of anaphylactic shock. At 12 years of age, none of the PiZ children have clinical symptoms of liver disease. No PiZ-, PiSZ, PiS- or PiFZ child has had any clinical symptom of liver disease. One PiSZ child died of sudden infant death syndrome. Laboratory analyses from birth through 12 years of age have shown increased S-Bilirubin levels in 11% of the PiZ infants, which normalized within the first half year of life. S-GT was abnormal in about half of the infants, but had normalized when checked at 8 and 12 years of age in all but 6-3% of the PiZ children. The percentage of abnormal S-ALAT test results have decreased from 73% during the first year of life, to about 15% at the age of 12. The range of the abnormal levels also decreased considerably. Abnormal S-GT or S-ALAT levels were found in about 20% of the PiSZ infants, the proportion decreasing to 2% at the age of 12.     

Recent Preoperative Myocardial Infarction Increases the Risk of Surgery for Unstable Angina

Patients with postinfarction angina undergoing surgery for unstable angina face an increased risk of operative mortality. Between January 1982 and December 1987, clinical, angiographic, and operative data was collected prospectively in 588 unstable patients with a prior myocardial infarction within 30 days of surgery (MI) and 5951 unstable patients without preoperative damage (NONMI). MI patients were characterized as being older (age greater than or equal to 70 years: MI, 19.7%; NONMI, 11.6%; p less than 0.001) and having more left ventricular dysfunction (left ventricular ejection fraction less than 40%: MI, 34.8%; NONMI, 26.4%; p less than 0.001). Semi-elective surgery was performed in 82.0% of NONMI patients while 76.9% of MI patients underwent urgent surgery. Operative mortality was increased in MI patients (MI, 11.1%; NONMI, 4.0%; p less than 0.001) which was related to the extent of preoperative MI (non-Q wave, 8.3%; Q wave, 17.5%; p less than 0.001). Stepwise logistic regression analysis identified preoperative MI as an independent risk variable of operative mortality for unstable angina. Separate multivariate analyses were performed to identify the independent predictors for MI and NONMI patients. The multivariate predictors of operative death for MI patients were left ventricular dysfunction, reoperative coronary surgery, nonuse of the internal mammary, age, transmural MI (relative risk 2.11 vs non-Q wave infarction) and left main stenosis. For NONMI patients, the independent variables were urgent operation, left ventricular dysfunction, reoperation, female gender, left main stenosis, and age. The results of this study indicate that recent preoperative MI adversely influences the surgical results in patients with unstable angina. Alternative treatment strategies are warranted for high risk patients, particularly those with transmural MIs and impaired ventricular function.     

Neuropharmacology: Amitriptyline and Clomipramine Increase the Concentration of Administered L-Tryptophan in the Rat Brain

The tricyclic antidepressant amitriptyline has been shown to reduce concentrations of large neutral amino acids (LNAA) in rat plasma. Compounds with that property might interact with such amino acids used as therapeutic agents with a central site of action by causing a change in the relationship between the administered LNAA and its endogenous LNAA competitors for carrier-mediated transport through the blood–brain barrier into the brain. This study was performed to investigate if the antidepressant agents amitriptyline and clomipramine could, by such a mechanism, increase brain concentrations of administered tryptophan. Intraperitoneal administration of L-tryptophan alone (100 mg kg^?1) resulted in an increase in the concentration of tryptophan in the rat brain from 14 ±0.7 to 100 ± 4.3 nmol g^?1 compared with rats given saline only. When rats were given tryptophan with amitriptyline (25 mg kg^?1, i.p.) or clomipramine (25 mg kg^?1, i.p.) brain concentrations of tryptophan were increased even further, to 150 ±4.5 and 157 ± 10.2 nmol g^?1, respectively. Administration of L-tryptophan alone resulted in an increase in the rat plasma tryptophan ratio [(concentration of tryptophan)/(total concentration of LNAAs)] from 0.14±0.003 to 0.42±0.011 compared with rats given saline only. When rats were given tryptophan with amitriptyline or clomipramine the plasma tryptophan ratios were increased even further to 0.52 ±0.017 and 0.54 ±0.025, respectively. All these effects were statistically significant (P < 0.001). These findings support the hypothesis that tricyclic antidepressants could interact with administered tryptophan by changing the relationship in plasma between tryptophan and its endogenous LNAA competitors for transport into the brain, resulting in higher concentrations of tryptophan in the brain. It is possible that this could be the mechanism of the previously reported finding that clomipramine and tryptophan potentiate each other in the treatment of depression.