Radial artery flow-mediated dilatation in heart failure patients: effects of pharmacological and nonpharmacological treatment.

Congestive heart failure (CHF) is associated with an impaired flow-mediated vasodilation that reflects an impaired endothelial function. Limited information is available, however, on whether and to what extent this impairment is improved by pharmacological or nonpharmacological treatment. We measured radial artery diameter and blood flow by an echo-tracking Doppler device both at baseline and after 4 minutes of hand ischemia, which increases diameter through NO secretion mediated by an increase in flow and shear stress. Data were collected from 44 CHF patients (New York Heart Association class I to III) under standard treatment (diuretic, digitalis, and enalapril, 20 mg/d), in whom CHF severity was assessed by a cardiopulmonary stress test, and from 16 age- and sex-matched controls. CHF patients were then randomized to maintain for (A) 2 months of standard treatment (n=11), (B) treatment with double the ACE inhibitor dose (n=11), (C) standard treatment with an angiotensin II antagonist (losartan, 50 mg/d; n=11), or (D) standard treatment with bicycle training for 30 minutes, 3 times a week (n=11). At baseline, radial artery diameter and flow were similar in CHF patients and controls; CHF patients had a modest although significant impairment in flow increase (-36%) and a striking impairment (-78%) in diameter increase following the 4 minutes of ischemia. After 2 months, baseline diameter and flow remained unaltered in the 4 groups. After the 4 minutes of ischemia, radial artery flow and diameter increased as before in the group under standard treatment (A), whereas in the other 3 groups, the increase was significantly (P<0.05) and, for diameter, markedly (B, 83%; C, 92%; and D, 95%) greater. The vasodilatation induced by trinitroglycerin was similar in CHF and control subjects and not affected by treatments. In CHF, radial artery shows a marked reduction in flow-mediated vasodilation, reflecting impairment of endothelial function. This impairment can be markedly improved by treatments that effectively block the renin-angiotensin system either at ACE or at ACE plus angiotensin receptor level. This is the case also with nonpharmacological treatment of CHF.

Laboratory investigations of the effects of predator sex and size on prey selection by the Asian crab, Hemigrapsus sanguineus.

Laboratory studies have shown that the nonindigenous Asian shore crab, Hemigrapsus sanguineus, readily consumes three species of commercial bivalves: blue mussels, Mytilus edulis, soft-shell clams, Mya arenaria, and oysters, Crassostrea virginica. Although crabs can eat bivalves of a wide size range, they preferred the smaller prey (

Field and laboratory comparisons of mortality in normal and neoplastic Mya arenaria.

The results of a 6-month mark and recapture experiment involving approximately 900 adult Mya arenaria demonstrated that under natural conditions, significantly higher (P much less than .001, chi 2 test) mortality occurred among animals with neoplasia than those diagnosed as normal. Using a blood screening technique, the clams were diagnosed and placed in one of three diagnostic groups based on the severity of the disease (the percentage neoplastic cells per total number of blood cells): Nonneoplastic (NN), 0%; low severity neoplastic (LSN), less than 50%; and high severity neoplastic (HSN), greater than 50%. Fifty-one percent of those clams initially diagnosed as HSN died by the end of the test period as compared to 8% of the LSN clams and only 3% of the normals. Both progression and remission of the disease were also evident. Approximately 10% of the clams in the NN and LSN groups progressed to a LSN or HSN condition, whereas 16% of those clams initially identified as LSN, and that were recovered alive, underwent complete remission during the test period. Comparison of the field results with those of an 18-week laboratory study suggests that studies of mortality done under laboratory conditions may not provide useful data for the interpretation of the quantitative effects of a disease process, such as molluscan neoplasia, on the natural population of the animal studied.

Arterial blood gas derangements associated with death and intracranial hemorrhage in premature babies.

We evaluated to what extent acidosis and alkalosis and their respiratory and metabolic components during the first 12 hours of life occurred prior to early neonatal death and postnatal intracranial hemorrhage among 206 low birth weight, intubated premature babies participating in a clinical trial of phenobarbital prophylaxis for intracranial hemorrhage. Time-weighted indices included the time each baby spent with abnormal values of pH, PaCO2 and HCO3-. Babies whose birth weight was less than 1 kg suffered adversities associated with prolonged pH less than 7.35. Heavier birth weight babies were at increased risk of adversity if their pH fell below 7.2. Babies who were not severely acidotic initially, but became so within hours, were at prominently increased risk of death and hemorrhage. Babies who had a mild increase of PaCO2 between 45 and 60 mmHg were less likely to develop germinal matrix hemorrhage than their peers who had more severe hypercapnia. A time-weighted measure of metabolic deficit correlated with death, but not with hemorrhage. Prolonged exposure to pH greater than 7.55 was associated with reduced risk of subependymal/intraventricular hemorrhage and death, especially in babies below 1 kg birth weight. We conclude that acidosis is an antecedent of intracranial hemorrhage in low birth weight premature babies, that duration of exposure might convey important risk information, and that birth weight is a correlate of vulnerability to some pH disturbances.

Respiratory complications in low-birth-weight infants who received phenobarbital.

We compared the ventilatory requirements of 127 infants who received phenobarbital for five days with those of 111 infants who received placebo. All infants were intubated, weighted less than 1750 g at birth, and survived the first ten days of life. Those infants who received phenobarbital did not require ventilatory assistance for more days than did placebo receivers. However, a pneumothorax or pulmonary interstitial emphysema was more likely to develop in infants who received phenobarbital than in infants who received placebo, even when adjustment was made for the presence of subependymal-intraventricular hemorrhage. We believe this is the first report of this relationship and recommend additional studies to test the hypothesis that phenobarbital contributes to the occurrence/recognition of pneumothorax or pulmonary interstitial emphysema in very-low-birth-weight infants if phenobarbital continues to be used routinely as prophylaxis or treatment.

The prophylactic clinical trial as a epidemiologic resource.

We encourage investigators to use data collected in a clinical trial of a prophylactic agent or procedure to study the epidemiology of the disease or event the prophylactic was meant to prevent. Making additional use of previously collected data is economically attractive. Problems can arise, however, if the sample is not representative of the universe of all people at risk of the disorder, the data set is not adequate to the task, or the prophylactic and/or its correlates influence the risk of the disorder. Investigators should consider modifying data collection procedures in future prophylactic trials so that they are suitable for an epidemiologic study. They and readers of their reports, however, are advised to be cautious in drawing inferences from epidemiologic studies extracted from prophylactic trials.

Neonatal intracranial hemorrhage and phenobarbital.

We enrolled 280 intubated babies with birth weights of less than 1,751 g in a double-blind randomized prospective clinical trial to evaluate whether phenobarbital influences the likelihood of developing subependymal-intraventricular-intraparenchymal hemorrhage. Phenobarbital was associated with an increased risk of developing any subependymal-intraventricular-intraparenchymal hemorrhage and was not associated with a diminished risk of either severe hemorrhage or germinal matrix hemorrhage. This increased risk was apparent even after we considered the influence of phenobarbital levels, timing of phenobarbital administrations, institutional differences, quality of ultrasound scans, gestational age- and birth weight-specific effects, ascertainment bias, and other possible confounders of phenobarbital administration.

Headache in cerebrovascular disease.

Two hundred fifteen consecutive patients with cerebrovascular events were evaluated prospectively for the incidence and characteristics of headache. Of 163 patients able to communicate, headache occurred in 29% with bland infarcts, 57% with parenchymal hemorrhage, 36% with transient ischemic attacks and 17% with lacunar infarcts. Patients with a history of recurrent throbbing headache were significantly more likely to have headache, usually throbbing in quality, during the present illness. Women developed headache significantly more often than men. Headache began prior to the vascular event in 60% of patients and at its onset in 25%. The quality, onset and duration of the headache varied widely among patients. Headache in cerebrovascular disease is common, though neither its occurrence nor characteristics predict lesion type or location. Though the pathogenesis of the headache is unknown, its association with prior throbbing headache suggests that similar factors may operate in both.

Prognostic significance of vacuoles in L1 lymphoblasts in childhood acute lymphoblastic leukaemia: a report from Children's Cancer Study Group.

From February 1975 to February 1977, 880 patients with acute lymphoblastic leukaemia were enrolled on Children's Cancer Study Group protocol 141 designed to evaluate prognostic factors and more intensive therapy for patients with poor prognosis. 765 diagnostic bone marrow aspirates from 23 institutions were available for classification using the French-American-British system. 60 of 615 patients with L1 morphology had vacuolated lymphoblasts. Patients with vacuolated lymphoblasts had a better disease-free survival (P = 0.14) and a significantly better survival (P = 0.03) but the presence of vacuoles was associated with a low initial WBC and an age range associated with improved prognosis for disease-free and over-all survival.

Quantitative CT assessment of furosemide- and mannitol-induced changes in brain water content.

We studied the effects of two commonly employed antiedema agents, mannitol and furosemide, on CT brain density in eight patients with primary and metastatic brain tumors. Noncontrast CTs were performed before and after IV furosemide or IV mannitol, and serial blood samples were analyzed for osmolality. Computer-generated frequency histograms of CT numbers from "before-and-after" brain slices were using quantile-quantile (QQ) plots and the Kruskal-Wallis statistic. After IV mannitol, there was a progressive increase in CT brain density, which corresponded to an upward shift in the QQ plot over the range 0 to 70 Hounsfield units. The differences between baseline and posttreatment histograms for mannitol patients were significantly different from controls, and maximum differences coincided with peak serum osmolality. No statistically significant effects were observed in the furosemide group despite maximal diuresis. The relative magnitude of the quantitative changes observed after mannitol and furosemide administration are consistent with anticipated changes in brain water content.

Repeated least squares analysis of simulated xenon computed tomographic measurements of regional cerebral blood flow.

Computer simulations were done as a feasibility study of xenon computed tomographic measurements of regional cerebral blood flow. Accuracy of initial least squares estimates of gray matter and white matter rate constants from a two-compartment model depended very little on the number and timing of scans, but did depend significantly on the enhancement-to-noise ratio as well as on the true values of the rate constants and gray/white ratio. Nonlinear least squares gives an optimal fit of the predicted wash-in--wash-out curve to the data rather than optimal estimates of the rate constants. A polynomial correction factor was obtained by regressing initial estimates on the true values used to generate the simulations. The correction factor substantially reduced error in the estimates and, in particular, eliminated large outliers.