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Retinal hemorrhaging (RH) is indicative and prevalent in abusive head trauma (AHT)—yet the direct cause of the RH from AHT is unknown. Our hypothesis is that RH in AHT is the combination of shaking forces and hypertension. This combination of effects explains why RH is not normally observed in common childhood accidents but is nearly exclusively observed in AHT. An experimental model using porcine eyes was designed to ascertain the required pressure change for sudden RH and, via a computer model, the subsequent stress increase in blood vessels. The porcine eyes were cannulated via the maxillary artery and pressurized until perfusion and RH were observed. Fluid was injected into the head with a computer-controlled continuous flow syringe pump; video of the fundus was recorded during perfusion; and the pressure of the fluid entering the eye was recorded as well. A computer model was created in COMSOL to simulate loading from hypertension, shaking, and the combination of the forces. This model was validated via experimental data collected from the porcine model. It was found that hypertension or shaking alone did not cause an increase in stress required to cause RH. But when the loading of shaking and hypertension was combined, as would occur in AHT, the stress increases were greater than those extrapolated from the porcine model and would cause RH.

Since the late 1980s, elevated atrial natriuretic peptide (ANP) was considered the cause of brisk diuresis in adult patients with paroxysmal supraventricular tachycardia (PSVT). Pro-brain natriuretic peptide (pro-BNP) and related molecules, e.g., N-terminal pro b-type natriuretic peptide (NT-pro-BNP) are known biomarkers of heart failure in adult patients from many causes with probable relevance in children. Perhaps, pro-BNP or related molecules such as NT-pro-BNP are useful in the management of PSVT in infants, thus hastening treatment in children who may otherwise significantly decompensate. Case series of one infant and two neonates presenting with cardiogenic shock and evidence of heart failure are presented. Cardiac monitoring or electrocardiogram (ECG) confirmed the presence of PSVT. Adenosine was administered resulting in successful chemical cardioversion with each case. Significantly elevated NT-pro-BNP levels correlated with heart failure prior to cardioversion. In each case, patients were discharged home with lower NT-pro-BNP levels and maintenance with a β-blocker. Due to documented relationships between elevated pro-BNP level and heart failure in adults, the authors measured the related biomarker NT-pro-BNP in each case, as the relationship could be similar in pediatric PSVT. Based on our experience with children in acute heart failure from other causes, NT-pro-BNP can increase to potentially extreme levels in infants. It appears to correlate with clinical signs of insufficient cardiac output, such as tachycardia, respiratory distress, and moribund appearance. Indeed, in the case series, extremely high NT-pro-BNP values were obtained when the patients appeared moribund from decompensated PSVT. The question arising from these observations is: At what level of elevated NT-pro-BNP, would patients be identified for cardioversion prior to appearance of other signs and symptoms? For each patient within the case series, NT-pro-BNP levels of approximately 20,000 pg/mL were indicative of decompensated heart failure, which was subsequently confirmed by examination of the patient. Further investigation is needed to determine the clinical significance of NT-pro-BNP and related peptides in pediatric patients with PSVT and intermittent PSVT. However, the possibility exists that an increase in NT-pro-BNP and related peptides could be a biomarker for cardiac decompensation after prolonged or intermittent PSVT, thereby shortening the time of diagnosis and intervention, and hence, potentially preventing morbidity, mortality, and extended hospitalization. Additional evidence-based research would help provide biomarker information during PSVT allowing practitioners to more objectively analyze risks.

Background and Purpose Traumatic brain injury conveys significant morbidity and mortality to infants and children. In the newborn pig, opioids contribute to pial artery vasconstriction after fluid percussion injury (FPI). FPI attenuates vasodilation and cGMP production by methionine enkephalin (Met) and leucine enkephalin (Leu) and reverses dynorphin (Dyn) from a dilator to a constrictor. Superoxide anion (O 2 − ) production contributes to altered cerebral hemodynamics after FPI, and O 2 − scavengers partially restore decreased dilator responses after FPI. Endothelin-1 (ET-1), a purported mediator of cerebral vasospasm, has been suggested to alter nitric oxide function and cGMP concentration. The present study was designed to determine the contribution of ET-1 to altered opioid-induced dilation after FPI and the role of O 2 − in such altered responses. Methods Injury of moderate severity (1.9 to 2.3 atm) was produced by the lateral FPI technique in anesthetized newborn pigs equipped with a closed cranial window. Superoxide dismutase (SOD)–inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O 2 − generation. Results FPI increased cerebrospinal fluid ET-1 from 20±2 to 93±6 pg/mL (≈10 −10 mol/L). Topical ET-1 (10 −10 mol/L) increased SOD-inhibitable NBT reduction from 1±1 to 16±3 pmol/mm 2 , similar to previously reported NBT reduction after FPI (14±2 pmol/mm 2 ). BQ123 (10 −6 mol/L), an ET-1 antagonist, blunted the NBT reduction observed after FPI (4±1 pmol/mm 2 ). Met produced pial vasodilation that was attenuated by FPI and partially restored by BQ123 pretreatment (7±1%, 11±1%, and 17±1% versus 3±1%, 6±1%, and 9±2% versus 5±1%, 9±1%, and 14±2% for 10 −10 , 10 −8 , and 10 −6 mol/L Met during control conditions, after FPI, and after FPI pretreated with BQ123, respectively). Met-induced dilation was associated with increased cerebrospinal fluid cGMP, and these biochemical changes were likewise blunted by FPI and partially restored by BQ123 (357±12, 455±15, 500±19, and 632±11 versus 264±4, 267±4, 295±12, and 305±15 versus 309±19, 432±11, 529±10, and 593±4 pg/mL for resting conditions, 10 −10 , 10 −8 , and 10 −6 mol/L Met during control conditions, after FPI, and after FPI pretreated with BQ123, respectively). Similar partial restoration of vascular and biochemical parameters was observed for Leu and Dyn. Conclusions These data show that ET-1, in concentrations similar to that present in cerebrospinal fluid after FPI, increases O 2 − production. These data also indicate the opioid-induced vasodilation and cGMP production are partially restored after FPI by ET-1 receptor blockade. These data suggest that ET-1 contributes to altered cerebral hemodynamics after FPI, at least in part, through elevated O 2 − production.

To the Editor. The studies by Gregoire et al1 and by Banks et al2 in the May 1998 issue serve to extend our understanding somewhat of the entity known as bronchopulmonary dysplasia (BPD). However, both these studies (and the journal) continue the disservice of defining patients as having BPD in terms of the patient's “requirement” of a therapeutic intervention ie, oxygen. Because we do not define, for example, a patient as having group B streptococcal meningitis because the patient is being treated with penicillin (requirement for penicillin?), why do we continue to define BPD so poorly as an oxygen-dependent state (who among us is not oxygen-dependent)? By whose criteria do these patients require oxygen, the physician or the physiology? Dr Gregoire and associates reported that “oxygen was given to maintain a transcutaneous saturation of between 90% and 92%.” Why? Was there a problem with oxygen delivery to the tissues at saturation levels below this? If so, for what age intervals will this continue to be a problem; ie, at what age will the patients continue to “require” …

Cell size homeostasis is a conserved attribute in many eukaryotic species involving a tight regulation between the processes of growth and proliferation. In budding yeast S. cerevisiae, growth to a “critical cell size” must be achieved before a cell can progress past START and commit to cell division. Numerous studies have shown that progression past START is actively regulated by cell size control genes, many of which have implications in cell cycle control and cancer. Two initial screens identified genes that strongly modulate cell size in yeast. Since a second generation yeast gene knockout collection has been generated, we screened an additional 779 yeast knockouts containing 435 new ORFs (~7% of the yeast genome) to supplement previous cell size screens. Upon completion, 10 new strong size mutants were identified: nine in log-phase cells and one in saturation-phase cells, and 97% of the yeast genome has now been screened for cell size mutations. The majority of the logarithmic phase size mutants have functions associated with translation further implicating the central role of growth control in the cell division process. Genetic analyses suggest ECM9 is directly associated with the START transition. Further, the small (whi) mutants mrpl49Δ and cbs1Δ are dependent on CLN3 for cell size effects. In depth analyses of new size mutants may facilitate a better understanding of the processes that govern cell size homeostasis.