Classification of sudden infant death (SID) cases in a multidisciplinary setting. Ten years experience in Styria (Austria)

OBJECTIVE: Sudden infant death syndrome (SIDS) remains a challenge for health professionals despite decreasing rates in recent years. The figures for different areas and time periods are hardly comparable, because of differences in postmortem investigations and classification criteria. In 1992, the European Society for the Study and Prevention of Infant Deaths (ESPID) proposed a classification for any sudden and unexpected death in infancy. This proposal has been used in our study since 1993 to better classify sudden infant death (SID) cases. METHOD: 56 consecutive SID cases observed between 1993 and 2002 in Styria, the south-eastern province of Austria, were analysed by a multidisciplinary team of health professionals. The study group consisted of pediatricians, forensic pathologists, pathologists, psychologists, nurses, members of the parents' association and health authorities. SID cases were analysed with regard to potential risk factors during pregnancy and early life, the circumstances of death (death scene) and post-mortem findings. From the latter, every SID was classified as either 1) classic SIDS, 2) borderline SIDS, 3) non-autopsied SID or 4) explained death. RESULTS: Of the 56 SID cases, 22 were assigned to category 1, 19 to category 2, four to category 3, and in 11 cases death could be explained by major post-mortem findings. For 17/22 cases in category 1 and 11/19 cases in category 2, the death scene investigation showed the typical risk profile of manner of bedding and/or environmental conditions. In three cases, child abuse or infanticide was considered possible but could not be proven despite careful autopsy. In recent years, SIDS incidence in Styria has decreased to approximately 0.18/1,000 live-born infants, and the few deaths still occurring mainly present with the typical risk profile. CONCLUSION: An extensive analysis of SID events is a prerequisite for reliable and comparable SIDS statistics. Our data show that in several SID cases careful post-mortem examinations led to an explanation of death. In other cases, minor alterations may have contributed to the lethal event. These findings should therefore be considered in the classification of SIDs. The ESPID classification of 1992 appears to be very useful for this purpose and its use may therefore be recommended.     

Persistent hypercapnia in children after treatment of obstructive sleep apnea syndrome by adenotonsillectomy

Obstructive sleep apnea syndrome (OSAS) in childhood is frequently in part a consequence of enlarged adenoids and/or tonsils and may lead to hypoxemia and hypercapnia during sleep. Whereas long-term blood gas alterations are well documented in adults, only few polygraphic data are available for children. It was the aim of this study to document blood gas alterations before and after treatment in this population. 9 children with OSAS (6 male, 3 female, median age 5.9 years, range 1.1-13.5 years) were investigated by polysomnography before and after adenotonsillectomy. Prior to intervention most children presented with moderate hypercapnia (ETCO2 mean 44.3 +/- 3.8 mm Hg, ETCO2 maximum 53.2 +/- 5.2) and hypoxemic episodes (oxygen saturation mean 93.2 +/- 3.2%, minimum 74.4 +/- 16.5%). Following adenotonsillectomy subsequent polygraphic investigations displayed normalisation of oxygen saturation (saturation mean 96.1 +/- 0.8%, minimum 90.1 +/- 3.1%). In contrast, moderate hypercapnia in several patients persisted up to five months after treatment (ETCO2 mean 44.9 +/- 2.8 mm Hg, ETCO2 maximum 51.2 +/- 3.6). Persistent hypercapnia most likely reflects an adaptation process of chemosensitivity and respiratory control due to preceding long-term hypercapnia.     

The influence of venous thromboembolism on quality of life and severity of chronic venous disease.

BACKGROUND: It is not known whether burden-of-illness differs in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. OBJECTIVE: To compare severity of disease and quality of life in chronic venous disease patients with and without prior venous thromboembolism. PATIENTS and METHODS: The VEINES Study population is an international cohort of 1531 outpatients with chronic venous disease in Belgium, France, Italy and Canada. Clinical severity of chronic venous disease graded using the seven-category 'CEAP' scale, and quality of life using standardized generic (SF-36) and venous disease-specific (VEINES-QOL/Sym) questionnaires were compared in patients with and without venous thromboembolism. Multivariable analyses with adjustment for known confounders were used to examine associations between venous thromboembolism and quality of life. RESULTS: One hundred and fifty-one (10%) patients had prior venous thromboembolism. These patients had more severe chronic venous disease than those without venous thromboembolism (P <0.0001), including a higher frequency of healed or active ulcers (29% vs. 7%, respectively). Multivariable analyses controlling for age, sex, country, education, body mass index, years of chronic venous disease and comorbid conditions demonstrated that prior venous thromboembolism was an independent predictor of poorer generic quality of life (SF-36 Mental Component Summary score, P=0.047; SF-36 Physical Component Summary score, P=0.012) and venous disease-specific quality of life (VEINES-QOL, P = 0.0002; VEINES-Sym, P=0.009). CONCLUSIONS: Disease severity is worse and quality of life poorer in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. Our findings support the need for further research of interventions to prevent and treat the long-term complications of venous thromboembolism.     

IgG titer, subclass, and light-chain phenotype of pregnancy-induced HPA-5b antibodies that cause or do not cause neonatal alloimmune thrombocytopenia

BACKGROUND: The most common pregnancy-induced platelet-specific antibody is HPA-5b. Neonatal alloimmune thrombocytopenia that results from anti-HPA-5b may cause severe hemorrhage in only a few infants, but the sequelae for the affected children can be severe. It is therefore essential that infants at risk for neonatal alloimmune thrombocytopenia are identified. STUDY DESIGN AND METHODS: The IgG titer, subclass, and light-chain composition of pregnancy-induced anti-HPA-5b were determined by the monoclonal antibody-specific immobilization of platelet antigens assay. Sera were from 12 mothers, who among them had 16 pregnancies that resulted in an HPA-5-mismatched fetus (positive for HPA-5b). Eight mothers gave birth to an infant with a normal platelet count. Three maternal sera were obtained after delivery of a severely thrombocytopenic infant. Three alloimmunized women were followed repeatedly during the course of a subsequent pregnancy, again with an HPA-5-mismatched infant. RESULTS: There was no difference in the antibody titer or its subclass in mothers who had a thrombocytopenic child and the titer or subclass in mothers compared with those who had a child with a normal platelet count. All pregnancy-induced HPA-5b antibodies were of a predominant, lambda, light-chain type. The IgG subclass did not change during pregnancy. CONCLUSION: Neither the antibody titer nor the subclass composition predict the occurrence of thrombocytopenia in a newborn whose mother is alloimmunized against HPA-5b.     

Effect of stress-induced reversible ischemia on serum concentrations of ischemia-modified albumin,natriuretic peptides and placental growth factor

Summary Objective There is controversy whether new biomarkers are able to identify myocardial ischemia in the absence of myonecrosis. Method We measured NT-pro BNP, NT-pro ANP, ischemia-modified albumin (IMA) and placental growth factor (PlGF) in patients undergoing nuclear stress testing for suspected ischemic heart disease. A thallium scan was used for detection of reversible myocardial ischemia and cardiac troponin T (cTnT) for exclusion of stress-induced myonecrosis. Of 195 patients, 24 with reversible and 62 with no perfusion defect were included in the analysis. Plasma levels were measured before, 18 min and 4 h after stress testing. Results Of the 86 patients, 52 received an exercise stress and 34 dipyridamol. New myonecrosis indicated by cTnT could be excluded in all patients. Plasma levels of NT-pro BNP and NT-pro ANP before testing were significantly higher in patients who later developed reversible perfusion defects (NT-pro BNP 139.00 (58.25/367.01) pg/mL vs 327.45 (120.50/972.85) pg/mL, p < 0.05; NT-pro ANP 732.5 (470.0/ 1220.0) pg/mL vs 1470.0 (694.0/ 1910.0) pg/mL, p < 0.05). Plasma levels of NT-pro BNP, NT-pro ANP and PIGF did not change significantly after stress testing, IMA levels rose significantly after 4 h in patients with and without reversible perfusion defects. Conclusion The elevation of NTpro BNP and NT-pro ANP at baseline may represent the cumulative effect of repeated bouts of myocardial ischemia. A single brief episode of provoced ischemia does not cause a significant increase of the measured biomarkers beside from IMA after exercise stress test potentially indicating skeletal muscle ischemia.     

Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase. A new action for an old drug.

Hydralazine has been shown to reduce mortality in patients with congestive heart failure when given concomitantly with isosorbide dinitrate. Recently, we demonstrated that nitrate tolerance is in part due to enhanced vascular superoxide .O2- production. We sought to determine mechanisms whereby hydralazine may prevent tolerance. Rabbits either received no treatment, nitroglycerin patches (1.5 micrograms/kg/min x 3 d), hydralazine alone (10 mg/kg/d in drinking water), or hydralazine and nitroglycerin. Aortic segments were studied in organ chambers and relative rates of vascular .O2- production were determined using lucigenin-enhanced chemiluminescence. Nitroglycerin treatment markedly inhibited relaxations to nitroglycerin (maximum relaxations in untreated: 92 +/- 1 vs. 64 +/- 3% in nitroglycerin-treated patients and increased vascular .O2- production by over two-fold (P < 0.05). Treatment with hydralazine in rabbits not receiving nitroglycerin significantly decreased .O2- production in intact rabbit aorta and increased sensitivity to nitroglycerin. When given concomitantly with nitroglycerin, hydralazine completely prevented the development of nitrate tolerance and normalized endogenous rates of vascular .O2- production. Studies of vessel homogenates demonstrated that the major source of .O2- was an NADH-dependent membrane-associated oxidase displaying activities of 67 +/- 12 vs. 28 +/- 2 nmol .O2-.min-1.mg protein-1 in nitroglycerin-treated vs. untreated aortic homogenates. In additional studies, we found that acute addition of hydralazine (10 microM) to nitroglycerin-tolerant vessels immediately inhibited .O2- production and NADH oxidase activity in vascular homogenates. The chemiluminescence signal was inhibited by a recombinant heparin-binding superoxide dismutase (HBSOD) demonstrating the specificity of this assay for .O2-. These observations suggest that a specific membrane-associated oxidase is activated by chronic nitroglycerin treatment, and the activity of this oxidase is inhibited by hydralazine, providing a mechanism whereby hydralazine may prevent tolerance. The ability of hydralazine to inhibit vascular .O2- anion production represents a novel mechanism of action for this drug.     

Prophylactic use of hyperimmunoglobulin for cytomegalovirus infection in heart transplantation

Cytomegalovirus (CMV) infection in solid organ recipients can endanger the immunosuppressed patient and increase vulnerability to secondary infections and the high risk of rejection triggered by the viral disease. The effect of passive immunization against CMV was examined in 69 heart transplant patients. The patients received weekly administrations of 1 ml/kg of CMV hyperimmunoglobulin from the day of transplantation until the 30th postoperative day. Forty-four of the patients were monitored clinically and serologically up to the 120th postoperative day. Nine patients showed clinical and serologic signs of CMV infection; in 15 the only evidence of CMV infection was a rise in antibody titers. The remaining 20 patients showed no clinical or serologic signs of CMV infection. Three patients who were seronegative preoperatively remained seronegative until the end of the observation period. The results indicate a potential therapeutic benefit of hyperimmunoglobulin prophylaxis to prevent infectious complications due to CMV in heart transplant patients.