General illness and psychological factors in patients with chronic nasal symptoms.

OBJECTIVES: Only a minority of patients referred to specialists with sinonasal symptoms have clear evidence of chronic rhinosinusitis (CRS). This study aims to estimate the prevalence of and associations between (i) general illness factors (fatigue, autonomic dysfunction) and (ii) psychological factors (anxiety, depression, somatisation, personality traits) in patients presenting with sinonasal symptoms. DESIGN: The following validated questionnaires were administered to patients: the Sino-Nasal Outcome Test-22 (SNOT-22) identifying symptom burden, Composite Autonomic Symptom Score-31 (COMPASS-31) measuring autonomic function, Chalder Fatigue Questionnaire, Patient Health Questionnaire-15 (PHQ-15) addressing somatisation symptoms, Hospital Anxiety and Depression Scale (HADS), and the International Personality Item Pool-50 (IPIP-50). Comparisons were made with normative and general population data, and relationships were analysed using nonparametric correlation. SETTING: Secondary care ENT outpatients. PARTICIPANTS: Adults referred with chronic sinonasal symptoms. MAIN OUTCOME MEASURES: SNOT-22, COMPASS-31, Chalder, PHQ-15, HADS, and IPIP-50 questionnaire scores. RESULTS: Sixty-one patients were included. There was a high prevalence of all general and psychological factors assessed compared with controls. Total SNOT-22 scores showed significant correlation with Chalder fatigue scores, total autonomic dysfunction score, anxiety, depression, somatisation tendencies and the emotionally unstable personality trait. Emotional instability and psychological dysfunction correlated significantly with sleep and psychological subscales of SNOT-22 but not the rhinological or ear/facial subscales. CONCLUSION: Patients with sinonasal symptoms demonstrate high prevalence and complex associations of general illness factors, psychological distress and certain personality traits. The SNOT-22 is a valuable tool, but its utility is limited by correlations with these confounding factors (eg psychological factors) that may exaggerate the total score. The use of the SNOT-22 component subscales is likely to provide more clinically meaningful and discriminant information.

The reporting quality of parallel randomised controlled trials in ophthalmic surgery in 2011: a systematic review.

PURPOSE: Randomised controlled trials (RCTs) represent a gold standard for evaluating therapeutic interventions. However, poor reporting clarity can prevent readers from assessing potential bias that can arise from a lack of methodological rigour. The Consolidated Standards of Reporting Trials statement for non-pharmacological interventions 2008 (CONSORT NPT) was developed to aid reporting. RCTs in ophthalmic surgery pose particular challenges in study design and implementation. We aim to provide the first assessment of the compliance of RCTs in ophthalmic surgery to the CONSORT NPT statement. METHOD: In August 2012, the Medline database was searched for RCTs in ophthalmic surgery reported between 1 January 2011 and 31 December 2011. Results were searched by two authors and relevant papers selected. Papers were scored against the 23-item CONSORT NPT checklist and compared against surrogate markers of paper quality. The CONSORT score was also compared between different RCT designs. RESULTS: In all, 186 papers were retrieved. Sixty-five RCTs, involving 5803 patients, met the inclusion criteria. The mean CONSORT score was 8.9 out of 23 (39%, range 3.0-14.7, SD 2.49). The least reported items related to the title and abstract (1.6%), reporting intervention adherence (3.1%), and interpretation of results (4.7%). No significant correlation was found between CONSORT score and journal impact factor (R=0.14, P=0.29), number of authors (R=0.01, P=0.93), or whether the RCT used paired-eye, one-eye, or two-eye designs in their randomisation (P=0.97). CONCLUSIONS: The reporting of RCTs in ophthalmic surgery is suboptimal. Further work is needed by trial groups, funding agencies, authors, and journals to improve reporting clarity.

OxLDL-targeted iron oxide nanoparticles for in vivo MRI detection of perivascular carotid collar induced atherosclerotic lesions in ApoE-deficient mice.

Atherosclerotic disease is a leading cause of morbidity and mortality in developed countries, and oxidized LDL (OxLDL) plays a key role in the formation, rupture, and subsequent thrombus formation in atherosclerotic plaques. In the current study, anti-mouse OxLDL polyclonal antibody and nonspecific IgG antibody were conjugated to polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, and a carotid perivascular collar model in apolipoprotein E-deficient mice was imaged at 7.0 Tesla MRI before contrast administration and at 8 h and 24 h after injection of 30 mg Fe/kg. The results showed MRI signal loss in the carotid atherosclerotic lesions after administration of targeted anti-OxLDL-USPIO at 8 h and 24 h, which is consistent with the presence of the nanoparticles in the lesions. Immunohistochemistry confirmed the colocalization of the OxLDL/macrophages and iron oxide nanoparticles. The nonspecific IgG-USPIO, unconjugated USPIO nanoparticles, and competitive inhibition groups had limited signal changes (p < 0.05). This report shows that anti-OxLDL-USPIO nanoparticles can be used to directly detect OxLDL and image atherosclerotic lesions within 24 h of nanoparticle administration and suggests a strategy for the therapeutic evaluation of atherosclerotic plaques in vivo.

Postnatal hemodynamic changes in very-low-birthweight infants.

The purpose of this study was to characterize postnatal changes in regional Doppler blood flow velocity (BFV) and cardiac function of very-low-birthweight infants and to examine factors that might influence these hemodynamic changes. Mean and end-diastolic BFV of the middle cerebral and superior mesenteric arteries, cardiac output, stroke volume, and fractional shortening were measured in 20 infants birthweight 1,002 +/- 173 g, gestational age 28 +/- 2 wk) at 6, 30, and 54 h after birth and before and after feedings on days 7 and 14. Postnatal increases in cerebral BFV, mesenteric BFV, and cardiac output were observed that were not associated with changes in blood pressure, hematocrit, pH, arterial PCO(2), or oxygen saturation. The postnatal pattern of relative vascular resistance (RVR) differed between the cerebral and mesenteric vasculatures. RVR decreased in the middle cerebral but not the superior mesenteric artery. Physiological patency of the ductus arteriosus did not alter postnatal hemodynamic changes. In response to feeding, mesenteric BFV and stroke volume increased, and mesenteric RVR and heart rate decreased. Postprandial responses were not affected by postnatal age or the age at which feeding was initiated. However, the initiation of enteral nutrition before 3 days of life was associated with higher preprandial mesenteric BFV and lower mesenteric RVR than was later initiation of feeding. We conclude that in very-low-birthweight infants over the first week of life 1) systemic, cerebral, and mesenteric hemodynamics exhibit region-specific changes; 2) asymptomatic ductus arteriosus patency and early feedings do not significantly influence these postnatal hemodynamic changes; and 3) cardiac function adapts to increase local mesenteric BFV in response to feedings.

Effects of prophylactic low-dose indomethacin on hemodynamics in very low birth weight infants.

Indomethacin decreases cerebral and mesenteric blood flow velocities in premature infants with symptomatic patent ductus arteriosus. Low-dose indomethacin is recommended for the prevention of intraventricular hemorrhage in very low birth weight infants. The hemodynamic effects of prophylactic indomethacin have not been previously examined. We hypothesized that prophylactic indomethacin does not change cerebral and mesenteric blood flow velocities and cardiac function in very low birth weight infants. Twenty-one infants (775 to 1245 gm, 24 to 31 weeks' gestation) were studied before and after indomethacin (0.1 mg/kg) administration at 6, 30, and 54 hours of life. Mean and end-diastolic cerebral and mesenteric blood flow velocities decreased (ANOVA, p < 0.05) after prophylactic indomethacin. The 38% increase in cerebral relative vascular resistance was significantly greater than the 18% increase in mesenteric relative vascular resistance (ANOVA, p < 0.05). In five infants who were fed 1 hour after the third indomethacin dose, the postprandial mesenteric blood flow velocity was significantly greater than the mesenteric blood flow velocity before both indomethacin and feeding (ANOVA, p < 0.05). Cardiac output, stroke volume, fractional shortening, and blood pressure did not change after prophylactic indomethacin administration. We conclude that prophylactic indomethacin (1) reduces cerebral and mesenteric blood flow velocity without affecting cardiac function, (2) increases cerebral more than mesenteric relative vascular resistance, and (3) does not prevent postprandial increases in mesenteric blood flow velocity. We speculate that the increase in cerebral relative vascular resistance is a beneficial effect that contributes to protection against intraventricular hemorrhage.

Pancreatic calcification in an 18-yr-old patient following gallstone pancreatitis and recurrent pseudocysts.

Most authors believe that biliary pancreatitis rarely progresses to chronic pancreatitis. Here, we present a case of an 18-yr-old white male with a history of gallstone pancreatitis and pancreatic pseudocyst resulting in radiographic and pathologic evidence of pancreatic calcification over a 16-mo period.

Relationship between intrauterine growth retardation and early postnatal superior mesenteric artery blood flow velocity.

During the first week of life, we examined the changes in the systemic, intestinal and cerebral circulation, and the circulatory responses to feeding in 10 small for gestational age (SGA) infants using the ultrasound Doppler technique. From day 1 to day 3, preprandial cardiac output decreased (p < 0.01), whereas mean blood pressure (p < 0.01), superior mesenteric artery mean flow velocity (Vmean; p < 0.01) and middle cerebral artery Vmean (p < 0.01) increased. On day 1, cardiac output was higher in the SGA than in those of term and preterm appropriate for gestational age infants reported from our laboratory. Preprandial superior mesenteric artery Vmean was inversely related to the degree of growth retardation (r = 0.63, p < 0.05). However, growth retardation did not influence the postprandial increase in superior mesenteric artery Vmean and end-diastolic flow velocity, or the cerebral circulation.

Mesenteric blood flow velocity and its relation to transitional circulatory adaptation in appropriate for gestational age preterm infants.

We investigated the early postnatal changes of the mesenteric circulation and its relation to the systemic circulation in 15 preterm infants. The infants were studied before the first feeding on d 1 and pre- and postprandially on d 3, 4, 5, and 7. Blood flow velocity was measured by ultrasound Doppler in the superior mesenteric artery, middle cerebral artery, and the aortic orifice for cardiac output calculations. Blood pressure and heart rate were monitored. From d 1 to d 3, the preprandial stroke volume decreased [1.5 +/- 0.3 to 1.3 +/- 0.2 mL/kg (mean +/- SD), p < 0.05], whereas blood pressure (36 +/- 3 to 50 +/- 7 mm Hg, p < 0.001), superior mesenteric artery mean velocity (Vmean) (0.17 +/- 0.08 to 0.30 +/- 0.11 m/s, p < 0.05), and middle cerebral artery Vmean increased (0.15 +/- 0.05 to 0.22 +/- 0.03 m/s, p < 0.001). From d 3 through d 7, the preterm infants demonstrated higher preprandial end diastolic flow velocity in the superior mesenteric artery than we previously reported in term infants (0.15 +/- 0.05 versus 0.12 +/- 0.04, p < 0.05). Like the term infants, preterm infants increased their superior mesenteric artery Vmean by 83% postprandially and maintained a stable cerebral circulation with feeding. Unlike the term infants, feeding in the preterm infants induced a blood pressure decrease (51 +/- 6 to 48 +/- 6 mm Hg, p < 0.01) and a cardiac output increase (176 +/- 30 to 188 +/- 32 mL/kg/min, p < 0.001). These findings suggest that, in contrast to term infants, healthy preterm infants require compensatory systemic hemodynamic changes in response to feeding.

Mesenteric blood flow velocity and its relation to circulatory adaptation during the first week of life in healthy term infants.

We investigated early postnatal changes of the mesenteric circulation and its relationship to the systemic circulation in two groups of newborn infants. Group I (n = 10) was studied before the first feeding at 1 h and preprandially at 6 and 24 h. Group II (n = 10) was studied before the first feeding at 2 h of age and preprandially and postprandially at d 3, 4, and 5. Blood flow velocity was measured with ultrasound Doppler in the superior mesenteric artery (SMA), middle cerebral artery, subclavian artery, and aortic orifice for cardiac output (CO) calculations. Blood pressure and heart rate were monitored. SMA mean velocity (Vmean) decreased from 1 [0.33 +/- 0.07 m/s (mean +/- SD)] to 6 h (0.23 +/- 0.08 m/s, p < 0.005) in group I, probably due to ductal steal, returning to the 1-h value at 24 h. In contrast, middle cerebral artery Vmean remained unchanged in the first 24 h. From d 3, SMA Vmean increased 92% postprandially, with no relation to increasing amounts of food. The postprandial increase in SMA Vmean was not associated with changes in CO and blood pressure; however, a fall in relative mesenteric vascular resistance suggested regional redistribution of CO. Middle cerebral artery Vmean increased from h 2 to d 3 with a further increase on d 4 (p < 0.01). This increase was associated with an increase in blood pressure. The relative fraction of CO to middle cerebral artery increased during the first days of life, suggesting a redistribution of blood flow to the metabolically active organs in the neonatal period.

Phototherapy-associated changes in mesenteric blood flow response to feeding in term neonates.

Doppler blood flow velocity of the superior mesenteric artery was measured preprandially and postprandially in 12 term neonates during phototherapy and 4 hours after discontinuation of this therapy. The postprandial increase in blood flow velocity was significantly less during than after phototherapy. We suggest that the phototherapy-induced peripheral vasodilation may be responsible for diverting blood from the intestines and limiting the normal neonatal postprandial response.

Age-related superior mesenteric arterial flow changes in piglets: effects of feeding and hemorrhage.

Cardiovascular (CV) responses to feeding before and after 15% blood volume hemorrhage (H) were studied in lightly anesthetized piglets less than or equal to 2-days and greater than 2-wk-old. Superior mesenteric (Mes) and renal (Ren) arterial flows (F) were registered by electromagnetic probes before and continuously for 2 h after milk feeding (26 ml/kg) by gavage. Postprandially, in piglets less than or equal to 2-days-old MesF tended to increase (maximum change, mean +/- SE, 16.0 +/- 4.7%) at 30 min, whereas Mes vascular resistance (R) significantly decreased at 30, 90, and 120 min (17.3 +/- 6.2%). In piglets greater than 2-wk-old, MesF significantly increased by 30 min, which lasted 120 min (37.7 +/- 11.7%); MesR decreased by 20.0 +/- 5.8% at 90-120 min. Compared with the less than or equal to 2 days olds, the older piglets demonstrated greater and more sustained postprandial MesF increase. After H, regional F and pulse pressure (PP) decreased, heart rate and R increased in both groups. After stabilization, feeding induced insignificant CV changes in less than or equal to 2-day-old piglets. In contrast, increased MesF (44 +/- 14.4%) and PP (24 +/- 8.5%) and decreased MesR (31 +/- 8.9%) were observed in the greater than 2-wk-olds. MesF changes differed significantly between the age groups. The Ren vascular bed showed no consistent response in both age groups. Thus Mes vascular responses to feeding with or without preceding H in developing piglets were age related.

Beta-adrenoceptor function in white blood cells from newborn infants: no relation to plasma catecholamine levels.

The maturity of beta-adrenoceptors in newborn infants was studied in relation to the catecholamine surge during labor. Umbilical blood was collected at birth from 12 infants delivered vaginally and 13 infants delivered by elective cesarean section. Granulocytes and lymphocytes were isolated. Receptor numbers and binding affinity were determined in the granulocytes by incubation with 125I-iodohydroxybenzylpindolol. Receptor responsiveness was tested by assessing isoproterenol-induced cyclic AMP accumulation in lymphocytes. Significantly higher plasma noradrenaline, adrenaline, and dopamine concentrations were found in infants born vaginally (108; 8.9; 0.9 nmol/liter, liter, respectively, median values) as compared with those delivered by cesarean section (11.0; 2.4; 0.2 nmol/liter). No significant differences in beta-adrenoceptor binding sites (receptor number: 39.2 +/- 2.6 versus 44.7 +/- 5.9 fmol/mg protein and binding affinity: 66.6 +/- 7.8 versus 65.0 +/- 6.2 pM) or responsiveness (maximal isoprenaline induced cAMP formation 52.4 +/- 10.3 versus 40.6 +/- 8.9 pmol/10(6) cells) were found between the two groups of infants. Lymphocyte beta-adrenoceptor sensitivity was similar to that found in adults. The beta-adrenoceptors on whole blood cells seem to be mature at birth and have the same responsiveness as in adults. The higher catecholamine surge during vaginal delivery as compared to elective cesarean section does not seem to affect beta-adrenoceptor function. Our results do not support the idea that reduced beta-adrenoceptor function is the cause of the previously observed inappropriately small cardiovascular and metabolic responses to the exceptionally high plasma catecholamine concentrations at birth.

Age-related responses to stimulation of cardiopulmonary receptors in swine.

Cardiovascular responses to stimulation of cardiopulmonary receptors were evaluated in standard breed developing swine (1-2 days, 1-2 wk, and 2 mo of age) and sexually mature miniswine anesthetized with 0.25-0.50% halothane in O2. Cryptenamine, a mixture of veratrum viride alkaloids (VVA), was administered as right atrial or left ventricular bolus injections in doses of 5-20 micrograms/kg. In developing swine, mean aortic pressure (AoP) decreased after 10-20 micrograms/kg VVA in 1- to 2-wk olds and after 5-20 micrograms/kg VVA in 2-mo olds. Bradycardia was always elicited. Renal (Ren) and femoral (Fem) vasodilation occurred in the 1- to 2-wk-old and 2-mo-old groups after 5-20 micrograms/kg VVA. Mesenteric (Mes) vasodilation was elicited with 10-20 micrograms/kg VVA in the 1- to 2-wk-old group and with 5-20 micrograms/kg VVA in 2-mo olds. In the 1- to 2-day-old group, VVA did not significantly alter Ren, Fem, and Mes vascular resistance. In mature miniswine, 20 micrograms/kg VVA elicited decreases in AoP and heart rate that were similar in magnitude to responses obtained with only 5 micrograms/kg VVA in dogs. Cardiovascular responses to VVA were abolished after bilateral vagotomy but were not altered after denervation of the carotid sinuses. The results indicate postnatal maturation of the Bezold-Jarisch reflex in swine.

The effect of blood volume expansion on gastrointestinal oxygenation in piglets.

Regional and total gastrointestinal (GI) blood flow, O2 delivery, O2 extraction, and O2 consumption were measured before and after acute blood volume expansion in 2-day-old piglets. Blood flow was measured with radionuclide-labeled microspheres. Sixty minutes after a rapid transfusion of age- and hematocrit-matched piglet donor blood, 51Cr-measured blood volume increased 19% while an increase in hematocrit suggested plasma transudation to the extravascular space had occurred in response to blood volume loading. Following transfusion, total GI blood flow and O2 delivery did not change, although O2 extraction decreased by 31 +/- 4%. O2 consumption by the GI tract decreased from 2.0 +/- 0.19 ml O2 X min-1 X 100 g-1 to 1.46 +/- 0.24 ml O2 X min-1 X 100 g-1 1 h after transfusion. Feeding was then accomplished via orogastric tube to determine if animals stressed by blood volume loading would increase GI O2 consumption in response to feeding. The postprandial increase in GI O2 consumption was similar to that previously reported in newborn piglets. Therefore, in the fasting state, acute blood volume loading disrupts GI O2 transport at the capillary level and decreases GI O2 consumption. However, animals subjected to blood volume loading appear capable of increasing GI O2 consumption after feeding.

Atropine prevents increases in brain blood flow during hypertension in newborn piglets.

Cerebral hyperperfusion associated with hypertension, may play an important role in the pathogenesis of intraventricular hemorrhage in preterm infants. To examine the effect of hypertension on changes in total and regional brain blood flow (BBF), we increased the mean arterial blood pressure (MABP) in nine awake newborn piglets by an infusion of 0.7 mg/kg of metaraminol bitartrate (Aramine) (group I) and studied cerebral circulatory changes. In order to prevent the Aramine-associated bradycardia, we pretreated nine other piglets with atropine, which produced a higher level of hypertension (group II). MABP and BBF were measured and cerebral vascular resistance (CVR) was calculated during baseline, the Aramine infusion, and twice at decreasing MABP following the discontinuation of the Aramine infusion. In group I, the significant increase in MABP from 68 +/- 3 to 100 +/- 3 mm Hg (mean +/- SEM) during the Aramine infusion resulted in a significant increase in BBF (98 +/- 9 to 118 +/- 11 ml X min-1 X 100 g-1). MABP decreased significantly (although remained significantly above baseline levels), when Aramine was discontinued; however, total BBF remained elevated. CVR increased during the Aramine infusion, but decreased significant (versus the Aramine-infused state) in the post-Aramine period. Regional BBF increased significantly to the cerebrum and cerebellar cortex, but remained unchanged to the other regions including the brain stem. In group II, the Aramine infusion resulted in a significantly greater increase in MABP, a sustained increase in vascular resistance, and no increase in total BBF. Thus, atropine prevents increased BBF during hypertension in the newborn piglet.

Peripheral circulatory response to feeding in newborn low-birth-weight infants.

The effect of feeding on calf blood flow (CBF) was investigated in 27 preterm and 10 term small-for-gestational-age (SGA) neonates using the venous occlusion plethysmographic method pre- and postprandially. Blood pressure and heart rate were simultaneously monitored. Feeding consisted of commercially prepared formula with average amounts of 20 ml/kg for preterm and 30 ml/kg for term SGA infants. As a group, the preterm neonates showed no significant CBF changes 1/2 h postprandially from the control value of 8.4 +/- 2.6 ml/min/100 ml (mean +/- SD). Although the difference was not statistically significant, 10 of the 27 preterm infants showed a mean CBF decrease of 9% and 17 showed no change to a slight increase immediately postprandially. These changes were followed by a 35% mean increment in CBF of all preterm infants at 2-2 1/2 h postprandially. CBF decreased in term SGA infants by 40% at 1/2 h postprandially from a control flow of 8.6 +/- 2.9 ml/min/100 ml (p less than 0.01). CBF returned to the control level 1-1 1/2 h postprandially and superseded the control value by 16% at 2-2 1/2 h. Peripheral vascular resistance varied inversely with CBF. Blood pressure and heart rate showed no significant changes. These observations indicated that unlike term infants, most preterm infants manifest no significant immediate peripheral vascular response to feeding before the onset of a hyperdynamic circulatory state. This difference was related to gestational age rather than to birth weight as term SGA infants responded like term appropriate-for-gestational-age infants. The possible mechanisms involved in these CBF changes with feeding are discussed.

Gastrointestinal blood flow and oxygen consumption in awake newborn piglets: effect of feeding.

Regional and total gastrointestinal (GI) blood flow, O2 delivery, and whole-gut O2 extraction and O2 consumption were measured before and 30, 60, and 120 min after feeding in nonanesthetized, awake 2-day-old piglets. Cardiac output and blood flow to kidneys, heart, brain, and liver were also determined. Blood flow was measured using the radiolabeled microsphere technique. In the preprandial condition, total GI blood flow was 106 +/- 9 ml X min-1 X 100 g-1, while O2 extraction was 17.2 +/- 0.9% and O2 consumption was 1.99 +/- 0.19 ml O2 X min-1 X 100 g-1. Thirty minutes after slow gavage feeding with 30 ml/kg artificial pig milk, O2 delivery to the GI tract and O2 extraction rose significantly (P less than 0.05) by 35 +/- 2 and 33 +/- 2%, respectively. The increase in O2 delivery was effected by a significant increase in GI blood flow, which was localized to the mucosal-submucosal layer of the small intestine. O2 uptake by the GI tract increased 72 +/- 4% 30 min after feeding. Cardiac output and blood flow to non-GI organs did not change significantly with feeding, whereas arterial hepatic blood flow decreased significantly 60 and 120 min after feeding. The piglet GI tract thus meets the oxidative demands of digestion and absorption by increasing local blood flow and tissue O2 extraction.

Early arterial lesions in infancy and childhood and ways of prevention.

Arterial lesions appear in the human vascular system early in life. In some predisposed arterial segments calcifications of the internal elastic sheets have regularly been demonstrated macroscopically in infancy and early childhood. Atherosclerotic lesions also begin in childhood, and the seeds of their later clinical manifestations are probably sown in infancy. Hyperlipemia, hypertension, and cigarette smoking represent the major risk factors of atherosclerosis and its premature development. Accordingly, the main task of pediatricians is early identification of the risk groups and their appropriate treatment, particularly of children with hyperlipoproteinemia type II and those with family history indicating a premature atherosclerotic event, hypertension, and diabetes mellitus. In most populations, however, elevated serum cholesterol levels are probably not caused by genetically determined metabolic disorders but mainly promoted by environmental factors, such as nutrition. Therefore, establishment of beneficial nutritional habits early in life may prevent the development or at least limit the extent of fatty streaks and their further transformation into fibrous plaques or more advanced atherosclerotic lesions. The education of the community, especially of parents, to the hazards of the cardiovascular risk factors must become an essential part of preventive programs directed to sound cardiovascular health. The wide individual variation of the extent of early lesions, e.g., of fatty streaking in childhood even in most homogeneous population subgroups, points to the existence of still undiscovered risk factors. Cooperative efforts between pediatric pathologists and pediatricians appear, therefore, a necessity for further progress in the evaluation of these factors and for establishing successful preventive programs.

Autonomic regulation of cardiovascular function in neonates.

The degree of participation of the vascular bed supplied by the superior mesenteric artery in autonomic regulation of cardiovascular function during postnatal maturation was evaluated in piglets, ranging in age from birth to two months. Animals were anaesthetized with 0.25-0.5% halothane in a 50% mixture of N2O and O2, paralysed with decamethonium bromide and artificially ventilated to maintain normal arterial blood gases and pH. Mesenteric arterial flow was recorded continuously with an electromagnetic flow transducer; simultaneously aortic pressure, heart rate, and femoral, renal and carotid flows were monitored. Resistance was calculated as the ratio of mean aortic pressure to mean flow. The central neural regulation of the cardiovascular system was altered: (1) by electrical stimulation of medullary vasoactive sites, (2) by changing the input from visceral or somatic afferents and (3) by subjecting the animals to stress, such as haemorrhage or hypoxia. Postnatal development of adrenergic mechanisms was studied with the aid of adrenergic agonist both in vivo and in vitro (helical strips cut from superior mesenteric artery were placed in an organ bath for isometric tension recordings). Recordings of spontaneous efferent splanchnic discharge permitted a more direct examination of autonomic regulation of the mesenteric vascular bed. The results indicate that the vascular bed supplied by the superior mesenteric artery and innervated by the efferent splanchnic nerve is actively involved in the cardiovascular responses to alterations in the cardiovascular regulatory system. Furthermore, this vascular bed may have an inappropriate response to both feeding and stress such that pathological changes in the gastrointestinal tract may result.

Structure and closure mechanism of the human umbilical artery.

The structure of the fully-patent umbical artery and rearrangement of its structural elements with postnatal closure were examined 10 centimeter long umbilical cord segments which were double-clamped at different time intervals after delivery. The fully-patent umbilical artery consists of two main layers: an outer layer of circularly arrange smooth muscle cells and an inner layer which shows rather irregularly and loosely arranged cells embedded in abundant metachromatic ground substance. No predominantly longitudinal arrangements of cells and fibers reported by earlier investigators could be identified in the inner layer. Closure of the umbilical arteries is initiated by numerous localized contractions which are mainly formed by muscle cells of the outer circular layer. Ultimate closure of larger segments of the umbilical arteries is also mainly produced by contractions of the outer layer. In contrast, the inner layer (which is rich in ground substance) seems to serve mainly as a plastic tissue which can easily be shifted in an axial direction and then folded into the narrowing lumen to complete closure. Electron microscopy reveals that the cells of this layer represent rather poorly differentiated smooth muscle cells which contain only a few tiny myofilaments and can therefore hardly contribute actively to the process of closure.