Cerebral Effects in Superior Vena Caval Cannula Obstruction: The Role of Brain Monitoring

A pediatric cardiac case of transient obstruction of the superior vena cava by the venous cannula before cardiopulmonary bypass is presented. With venous obstruction and increase in central venous pressure, reduced cerebral blood flow velocities and absence of diastolic Doppler flow were detected. This was followed by regional cerebral venous oxygen desaturation and global electroencephalographic slowing. Reposition of the venous cannula led to the recovery of these physiologic indicators and a noncomplicated clinical outcome.     

Evaluation of collateral blood flow by myocardial contrast enhanced echocardiography.

Contrast enhanced cross sectional echocardiography is a new method for the real-time evaluation of regional myocardial perfusion. Two patients with a history of anteroseptal myocardial infarction and echocardiographically detected septal dyskinesia were examined by this new method. The first patient had two severe stenoses of the left anterior descending coronary artery and normal echocontrast opacification of the interventricular septum caused by collaterals from the right coronary artery. The second patient had good patency of left anterior descending coronary artery and no septal opacification. Thus contrast enhanced cross sectional echocardiography can be used to assess the importance of collateral blood flow in the myocardium.     

Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside

Genetic defects of the dystrophin-glycoprotein complex (DGC) cause hereditary dilated cardiomyopathy. Enteroviruses can also cause cardiomyopathy and we have previously described a mechanism involved in enterovirus-induced dilated cardiomyopathy: The enteroviral protease 2A directly cleaves dystrophin in the hinge 3 region, leading to functional dystrophin impairment. During infection of mice with coxsackievirus B3, the DGC in the heart is disrupted and the sarcolemmal integrity is lost in virus-infected cardiomyocytes. Additionally, dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy in vivo, suggesting a pathogenetic role of the dystrophin cleavage in enterovirus-induced cardiomyopathy. Here, we extend these experimental findings to a patient with dilated cardiomyopathy due to a coxsackievirus B2 myocarditis. Endomyocardial biopsy specimens showed an inflammatory infiltrate and myocytolysis. Immunostaining for the enteroviral capsid antigen VP1 revealed virus-infected cardiomyocytes. Focal areas of cardiomyocytes displayed a loss of the sarcolemmal staining pattern for dystrophin and -sarcoglycan identical to previous findings in virus-infected mouse hearts. In vitro, coxsackievirus B2 protease 2A cleaved human dystrophin. These findings demonstrate that in human coxsackievirus B myocarditis a focal disruption of the DGC can principally occur and may contribute to the pathogenesis of human enterovirus-induced dilated cardiomyopathy.     

Differences in extent of genetic introgression between sympatric Culex pipiens and Culex quinquefasciatus (Diptera: Culicidae) in California and South Africa

Comparisons of five morphological characters, 12 enzyme electrophoresis profiles, and Wolbachia pipientis infection rates were used to characterize populations of members of the Culex pipiens L. complex in California and South Africa. In South Africa, male phallosome DV/D ratio, male maxillary palp index, branching of siphonal seta 1a, the enzyme locus Mdhp-1, and W. pipientis infection rates proved highly diagnostic for separating Culex quinquefasciatus from Cx. pipiens phenotypes. In Johannesburg, where sympatric members of the Cx. pipiens complex were analyzed as one population, a significant Wahlund Effect was observed in the enzyme loci such as Ao, 6-Pgdh, Mdh-2, and Pgm. In California, all populations of the Cx. pipiens complex were in Hardy Weinberg equilibrium at all polymorphic enzyme loci examined. Additionally, in California, all populations had similar W. pipientis infection rates and appeared morphologically identical (except for DV/D ratio, in extreme north and south). These findings indicate that in South Africa, Cx. pipiens and Cx. quinquefasciatus remain as genetically distinct populations and behave as separate species. Conversely, in California, there is considerable genetic introgression between Cx. pipiens and Cx. quinquefasciatus, and they behave as a single species.     

Comparison of couples referred and not referred for genetic counseling in a genetic clinic after the birth of a child with a congenital anomaly: A study in a population in the northeastern Netherlands

After the birth of a child with a congenital anomaly, parents have many questions about cause, prognosis, and recurrence risk. An important means of transmitting such information is referral to a genetic clinic. We were interested in knowing what determines whether or not parents are referred for genetic counseling. Data from the local registration of congenital anomalies in the northeastern Netherlands (birth years 1981–1986; 1,217 children/fetuses) and data of the local genetic clinic were compared. The parents of 204 cases (16.8%) had been referred for genetic counseling. Of the couples referred, 76% were referred within one year after birth, usually by a pediatrician (48%). Parents of children with a single anomaly, recognized syndrome, or multiple anomalies not recognized as a syndrome were referred in 5%, 43%, and 26% of cases, respectively. Parents of liveborn children who died were referred in 38% of cases, parents of liveborn/still-alive and stillborn children in 13% and 22%, respectively. Previous affected sibs and absence of previous livebirths increased the likelihood of referral.     

Accuracy of family history of cancer: clinical genetic implications

Family medical history is the cornerstone of clinical genetic diagnosis and management in cases of familial cancer. The soundness of medical decisions can be compromised if reports by the family on affected relatives are inaccurate. Although very time consuming, family medical histories are therefore routinely verified. To investigate whether such verification is clinically justified, we retrospectively analysed the accuracy of a consecutive series of 383 tumour reports from counsellees on 120 families in our clinic. We evaluated these families for the impact of verification on clinical genetic diagnosis and management. Accuracy according to cancer type showed marked variation, ranging from 93% and 89% for breast cancer and colorectal cancer, respectively, to 42% and 37% for extra-colorectal alimentary tract cancer and uterine cancer. Accuracy was related to the degree of kinship of the affected relative, but not to age and gender of the counsellee, nor to the reason for referral or personal history of cancer. Age at diagnosis and multiple primary tumours were reported accurately in 97% and 94% of cases, respectively. In six out of 120 families verification data changed clinical genetic management, in five of these the genetic risk was reduced. Although verification of all reported cancer cases in a family remains the 'gold standard' for clinical as well as research purposes, verification of reports on breast cancer can be limited without seriously compromising medical decision making. In cases where verification is impossible because medical records are unavailable, findings from studies such as ours may help in interpreting family histories.     

The family of Caenorhabditis elegans tyrosine kinase receptors: similarities and differences with mammalian receptors

Transmembrane receptors with tyrosine kinase activity (RTK) constitute a superfamily of proteins present in all metazoans that is associated with the control and regulation of cellular processes. They have been the focus of numerous studies and are a good subject for comparative analyses of multigene families in different species aimed at understanding metazoan evolution. The sequence of the genome of the nematode worm Caenorhabditis elegans is available. This offers a good opportunity to study the superfamily of nematode RTKs in its entirety and to compare it with its mammalian counterpart. We show that the C. elegans RTKs constitute various groups with different phylogenetic relationships with mammalian RTKs. A group of four RTKs show structural similarity with the three mammalian receptors for the vascular endothelial growth factors. Another group comprises RTKs with a short extracellular region, a feature not known in mammals; the genes encoding these RTKs are clustered on chromosome II with other gene families, including genes encoding chitinase-like proteins. Most of the C. elegans RTKs have no direct orthologous relationship with any mammalian RTK, providing an illustration of the importance of the separate evolution of the different phyla.