Faculty Bibliography

A new Global Investment Framework for Women's and Children's Health demonstrates how investment in women's and children's health will secure high health, social, and economic returns. We costed health systems strengthening and six investment packages for: maternal and newborn health, child health, immunisation, family planning, HIV/AIDS, and malaria. Nutrition is a cross-cutting theme. We then used simulation modelling to estimate the health and socioeconomic returns of these investments. Increasing health expenditure by just $5 per person per year up to 2035 in 74 high-burden countries could yield up to nine times that value in economic and social benefits. These returns include greater gross domestic product (GDP) growth through improved productivity, and prevention of the needless deaths of 147 million children, 32 million stillbirths, and 5 million women by 2035. These gains could be achieved by an additional investment of $30 billion per year, equivalent to a 2% increase above current spending.

The clinical manifestations of Fanconi's anemia, an autosomal recessive disorder, include progressive pancyto-penia, a predisposition to neoplasia, and nonhematopoietic developmental anomalies [1-3]. Hypersensitivity to the clastogenic effect of DNA-cross-linking agents such as diepoxybutane acts as a diagnostic indicator of the genotype of Fanconi's anemia, both prenatally and postnatally [3-6]. Prenatal HLA typing has made it possible to ascertain whether a fetus is HLA-identical to an affected sibling [7]. We report here on hematopoietic reconstitution in a boy with severe Fanconi's anemia who received cryo-pre-served umbilical-cord blood from a sister shown by prenatal testing to be unaffected by the disorder, to have a normal karyotype, and to be HLA-identical to the patient. We used a pretransplantation conditioning procedure developed specifcally for the treatment of such patients [8]; this technique makes use of the hypersensitivity of the abnormal cells to alkylating agents that cross-link DNA [9,10] and to irradiation [11] In this case, the availability of cord blood obviated the need for obtaining bone marrow from the infant sibling. This use of cord blood followed the suggestion of one of us that blood retrieved from umbilical cord at delivery, usually discarded, might restore hematopoiesis - a proposal supported by preparatory studies by some of us [12] and consistent with reports on the presence of hematopoietic stem and multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in human umbilical-cord blood (see the references cited by Broxmeyer et al. [12]). 1989 Massachusetts Medical Society. All rights reserved

BACKGROUND: Ventricular aberrant conduction has a confounding effect on the known relationships between the electrocardiogram (ECG) and left ventricular (LV) mass. By relating the ECG of right ventricular pacing to LV mass and to nonpaced recordings, clarification of these effects might emerge. METHODS AND RESULTS: In 30 patients (age, 81 +/- 7 years; 13 women) who had right ventricular paced ECGs and echocardiograms, 24 of who also had nonpaced ECGs, comparative analyses were performed. Although the nonpaced ECGs had strong correlations with various echocardiographic measurements, for paced ECGs, only QRS complex voltage and interventricular septal thickness (IVS) were significantly related. However, paced QRS complex voltage relationships correlated with those of nonpaced QRS complexes, ranging from an r = 0.54, P < 0.006, for the sum of the R in aVL and the S in V-3 to r = 0.78, P < 0.001, for the sum of the R in I and the S in III. Paced ECGs had a QRS complex with a greater spatial amplitude, a longer duration, and a more superior position, and had more deeply inverted T waves than nonpaced ECGs. The differences between the voltages of paced and nonpaced QRS complexes, moreover, diminished as LV mass and/or IVS increased. When compared with nonpaced ECGs, paced ECGs showed the most similarity to nonpaced ECGs having a left bundle branch block (LBBB) pattern. Except for the presence of more superiorly directed QRS complexes, paced impulses were not significantly different (P < 0.008) from nonpaced impulses having a LBBB pattern. Also, the nonpaced ECG pattern had no discernable effect on ECG produced by right ventricular (RV) pacing. CONCLUSIONS: Despite having weak relations with echocardiographic measurements, the QRS complex voltage of the paced ECG correlated with those of nonpaced ECGs, and the voltage differences between them were smaller as LV mass increased

BACKGROUND: Contrary to intuitive expectations and dissimilar from that which occurs in the atria, left ventricular (LV) depolarization and repolarization proceed in opposite directions, creating a concordance of the spatial QRS complex and T-wave angles (QRS-T). By defining the determinants of QRS-T, it might be possible to distinguish a primary (caused by an abnormality of repolarization) from a secondary (caused by a delay in ventricular depolarization) T-wave abnormality. METHODS AND RESULTS: From a near-consecutive series of 154 patients (age, 60 +/- 16 years; 81 females) in sinus rhythm, Doppler echocardiographic and 12-lead electrocardiogram (ECG) findings were related to the total cosine of the angle subtended by the spatial QRS complex and T wave (TCRT). Using the QRS complex and T-wave angles in the frontal and horizontal planes, TCRT was obtained from the table cited in the article of Helm and Fowler (Am Heart J 1953;45:835). TCRT correlated negatively with age, QRS duration (QRS), interventricular septal thickness (IVS) and posterior wall thickness, LV mass, LV cross-sectional area (CSA), LV relative wall thickness (RWT), left atrial dimension, and atrial velocity time integral (all, P < .001), but it was not related to LV diastolic dimension or systolic function. In multivariate analyses of the entire cohort or of patients without a left bundle branch block, QRS, CSA, RWT, and atrial velocity time integral emerged as independent variables (all, P < .001). When patients with right bundle branch block were also excluded, IVS, instead of CSA and RWT, was significant (P < .001). Overall, TCRT distinguished normal patients from those with heart disease, and patients with diabetes mellitus and hypertension from those not having these conditions. However, residuals of regression, TCRT = (-1.6IVS [cm]) + (-0.01QRS [milliseconds]) + 3, distinguished patients with coronary disease, but not other disorders, from normals, and diabetics, but not patients with hypertension or hyperlipidemia, from those not having these conditions (the regression having adjusted for secondary QRS-T discordance). CONCLUSIONS: The determinants of TCRT can be quantified and expressed as a regression that may be used to distinguish primary from secondary T-wave abnormalities

The purpose of this investigation was to determine whether heart rate variability (HRV) in atrial fibrillation (AF) can be related to any echocardiographic-derived measurements of cardiac dimensions or function. AF is characterized by marked HRV. Although HRV in normal sinus rhythm has been studied and shown to have important clinical implications, there have been relatively few published reports dealing with the phenomenon in AF. This study examines HRV in AF taking into account the influence of heart rate. HRV measurements were obtained in 38 patients with persistent AF who had undergone 24-hour ambulatory electrocardiographic monitoring. Taking into account a strong heart rate dependence of the HRV measurements, regressions were calculated. The relations were then re-examined using the differences (diff) in HRV from the expected for the average RR intervals. No significant correlations were found between unadjusted HRV measurements and any clinical features or echocardiographic variables. However, taking into account heart rate relations, with negative HRVdiff signifying less HRV than expected, reduced HRV correlated with increasing left atrial and left ventricular dimensions. On multivariate regression analysis, left atrial dimension emerged as an independent determinant of HRV. Also, HRV was greater in patients with lone AF than in those with cardiac disorders. HRV in AF is highly rate dependent. Unless this influence is taken into account, important relations may be obscured. When HRVdiff are related to echocardiographic measurements, increasing left atrial dimensions correlate with less HRV

PURPOSE: To evaluate prospectively the effects on survival, relapse-free survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions) compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in patients 3 to 21 years of age with low-stage medulloblastoma, minimal postoperative residual disease, and no evidence of neuraxis disease. PATIENTS AND METHODS: The Pediatric Oncology Group and Children's Cancer Group randomized 126 patients to the study. All patients received posterior fossa irradiation to a total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged postoperatively with contrast-enhanced cranial computed tomography, myelography, and CSF cytology. Of the registered patients, 38 were ineligible. RESULTS: The planned interim analysis that resulted in closure of the protocol showed that patients randomized to the reduced neuraxis treatment had increased frequency of relapse. In the final analysis, eligible patients receiving standard-dose neuraxis irradiation had 67% event-free survival (EFS) at 5 years (SE = 7.4%), whereas eligible patients receiving reduced-dose neuraxis irradiation had 52% event-free survival at 5 years (SE = 7.7%) (P =.080). At 8 years, the respective EFS proportions were also 67% (SE = 8.8%) and 52% (SE = 11%) (P =.141). These data confirm the original one-sided conclusions but suggest that differences are less marked with time. CONCLUSION: Reduced-dose neuraxis irradiation (23.4 Gy) is associated with increased risk of early relapse, early isolated neuraxis relapse, and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The 5-year EFS for patients receiving standard-dose irradiation is suboptimal, and improved techniques and/or therapies are needed to improve ultimate outcome. Chemotherapy may contribute to this improvement.