Risk Factors for Interstage Mortality Following the Norwood Procedure: Impact of Sociodemographic Factors

Interstage mortality remains significant for patients undergoing staged palliation for hypoplastic left heart syndrome and other related single right ventricle malformations (HLV). The purpose of this study was to identify factors related to demographics, socioeconomic position, and perioperative course associated with post-Norwood hospital discharge, pre-stage 2, interstage mortality (ISM). Medical record review was conducted for patients with HLV, born from 1/2000 to 7/2009 and discharged alive following the Norwood procedure. Sociodemographic and perioperative factors were reviewed. Patients were determined to have ISM if they died between Norwood procedure hospital discharge and stage 2 palliation. Univariable and multivariable logistic regressions were performed to identify risk factors associated with ISM. A total of 273 patients were included in the analysis; ISM occurred in 32 patients (12 %). Multivariable analysis demonstrated that independent risk factors for interstage mortality included teen mothers [adjusted odds ratio (AOR) 6.6, 95 % confidence interval (CI) 1.9–22.5], single adult caregivers (AOR 4.1, 95 % CI 1.2–14.4), postoperative dysrhythmia (AOR 2.7, 95 % CI 1.1–6.4), and longer ICU stay (AOR 2.7, 95 % CI 1.2–6.1). Anatomic and surgical course variables were not associated with ISM in multivariable analysis. Patients with HLV are at increased risk of ISM if born to a teen mother, if they lived in a home with only one adult caregiver, suffered a postoperative dysrhythmia, or experienced a prolonged ICU stay. These risk factors are identifiable, and thus these infants may be targeted for interventions to reduce ISM.     

Neuronal Nitric Oxide Synthase (NOS1) Polymorphisms Interact with Financial Hardship to Affect Depression Risk

There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual''s susceptibility to depression.     

Platelet-melanoma cell interaction is mediated by the glycoprotein IIb- IIIa complex

A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa- like GPs. When the melanoma cells were preincubated with LYP 18, tumor- platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions.     

Metabolic activity of phagocytosing granulocytes in chronic granulocytic leukemia: ultrastructural observation of a degranulation defect

The functional capacities of granulocytes in patients with chronic granulocytic leukemia are still a subject of controversy, probably due to the heterogeneity of the abnormalities observed from patient to patient. For a better definition of these abnormalities, 14 patients with untreated chronic granulocytic leukemia were studied. The patients were divided into three groups on the basis of the functional activities of their phagocytosing granulocytes. In four patients (group I), the granulocytes were normal in respect to particle ingestion, nitroblue tetrazolium (NBT)-stimulated reduction, cyanide-insensitive oxygen (O2) consumption, superoxide anion (O2-)-stimulated production, hydrogen peroxide (H2O2) production, and iodination. They also had a normal myeloperoxidase (MPO) content. In four patients (group III), the granulocytes were significantly defective in all of these activities. In the six remaining patients (group II), all the initial metabolic steps of the phagocytosing granulocytes (ingestion, NBT reduction, O2 consumption, O2-production, H2O2 production) were normal, as were the MPO content of the granulocytes, while iodination was strikingly decreased. These metabolic features suggested a degranulation defect which was observed ultrastructurally in the only patient studied among these six. The phagocytosing granulocytes of this patient did not degranulate and no deposits of MPO activity were seen in the phagosomes.