A randomised, controlled trial of a 4% cutaneous emulsion of sodium cromoglicate in treatment of atopic dermatitis in children.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Sodium cromoglicate (SCG) is a chromone with anti-inflammatory, anti-itch and anti-allergic activity. This trial is a 12-week comparison (RCT) of a 4% SCG cutaneous emulsion with its vehicle in AD. MATERIALS AND METHODS: 208 children aged 2-12 years participated, 104 in each group. The primary endpoint was change in SCORAD score. Secondary endpoints included SASSAD score, topical steroid usage and global assessments. RESULTS: SCORAD was reduced by 28% (SCG group) and by 19% (vehicle): difference was statistically significant (p = 0.03) after 8 weeks and nearly significant (p = 0.09) after 12. A similar result occurred in SASSAD (p = 0.001 at 8 weeks). In subjects without major protocol deviations (SCG-64, vehicle-63), difference in SCORAD remained significant at 12 weeks (p = 0.04). Weight of topical steroids reduced in both groups: -0.60 ± 1.3 g/day (35%), SCG and -0.05 ± 1.1 g/day vehicle (p = 0.04). Treatment success, defined as investigator global opinion graded very or moderately effective, was significantly more frequent in SCG group (p = 0.025). Application site discomfort reported by 12.5% of subjects in SCG group and 16.5% in vehicle group. CONCLUSIONS: SCG 4% cutaneous emulsion provides an effective, well-tolerated, steroid-sparing treatment for AD in children.

Neonatal outcome in a randomized, controlled trial of low-dose aspirin in high-risk pregnancies.

OBJECTIVE: To determine the value of low-dose aspirin in high-risk pregnancies, and assess its impact on fetal growth, as well as on perinatal mortality and morbidity. METHODOLOGY: One hundred and eight women with singleton pregnancies were enrolled in a randomized, double-blind, placebo-controlled trial of 100 mg/day aspirin from 17 to 19 week gestation. Enrolment criteria included pre-existing chronic essential hypertension or renal disease, or a history of previous early, severe pre-eclampsia. RESULTS: There were four stillbirths (all aspirin) and two neonatal deaths (both placebo), to yield respective perinatal mortality rates of 69/1000 and 40/1000 (P = 0.499). Liveborn infants in the aspirin group were significantly more mature (P = 0.017) and of heavier birthweight (P = 0.034) but had similar length (P = 0.091) and head circumference (P = 0.257). Fewer infants in the aspirin group were liveborn prematurely (5/54 vs 14/50; P = 0.016) or were of low birthweight (3/54 vs 9/50; P = 0.052). There were no significant between-group differences for standard deviation (Z) scores for weight, length or head circumference, or for skinfold thickness measurements. There was no significant difference in occurrence of low Apgar scores or in neonatal intensive care unit use between the groups. CONCLUSIONS: Low-dose aspirin does not appear to have a significant effect on perinatal morbidity. The increase in weight at birth associated with low-dose aspirin therapy is due to prolongation of pregnancy rather than prevention of intra-uterine growth retardation.

MR imaging of head and neck tumors: comparison of T1-weighted contrast-enhanced fat-suppressed images with conventional T2-weighted and fast spin-echo T2-weighted images.

OBJECTIVE: The purpose of this study was to determine the value of three MR pulse sequences for the detection of tumors and abnormal lymph nodes in the head and neck. This was accomplished by quantifying differences in contrast between tumor, lymph node, and respective adjacent tissue on contrast-enhanced fat-suppressed T1-weighted MR images, conventional spin-echo T2-weighted images, and fast spin-echo fat-suppressed T2-weighted images in a group of patients with head and neck tumors. SUBJECTS AND METHODS: Two groups of patients with head and neck tumors were studied. In the first group (16 patients), contrast-enhanced fat-suppressed T1-weighted images were compared with conventional spin-echo T2-weighted images. In the second group (21 patients), contrast-enhanced fat-suppressed T1-weighted images were compared with fast spin-echo fat-suppressed T2-weighted images. The detectability of tumor and abnormal lymph nodes was measured by calculating the contrast-to-noise ratio. RESULTS: The fat-suppressed T1-weighted images had significantly higher (p < or = .02) contrast-to-noise ratios for both the primary tumor and lymph nodes than either conventional or fast spin-echo T2-weighted images did. However, subjective evaluation of the contrast-to-noise ratios proved satisfactory for tumor detection with all three imaging sequences (contrast-enhanced fat-suppressed T1-weighted, fast spin-echo fat-suppressed T2-weighted, and conventional T2-weighted). CONCLUSION: Our results show that fat-suppressed contrast-enhanced T1-weighted images provide the highest contrast-to-noise ratio for head and neck tumors and abnormal lymph nodes. However, head and neck tumors encompass a broad range of neoplasms that are distributed in a complicated anatomic area. Therefore, in some patients, a combination of contrast-enhanced fat-suppressed T1- and T2-weighted images, preferably fast spin-echo fat-suppressed images, is useful for detection of these tumors and nodal metastases.

The anatomy of the posterior communicating artery as a risk factor for ischemic cerebral infarction.

BACKGROUND: After the occlusion of an internal carotid artery the principal source of collateral flow is through the arteries of the circle of Willis, but the size and patency of these arteries are quite variable. Study of the anatomy of the collateral pathways in patients with internal-carotid-artery occlusion with or without infarction in the watershed area of the deep white matter may identify patterns that afford protection from ischemic infarction. METHODS: Using conventional magnetic resonance imaging and three-dimensional phase-contrast magnetic resonance angiography, we evaluated 29 consecutive patients (32 hemispheres at risk) with angiographically proved occlusion of the internal carotid artery. Four collateral pathways to the occluded vessel were evaluated: the proximal segment of the anterior cerebral artery, the posterior communicating artery, the ophthalmic artery, and leptomeningeal collateral vessels from the posterior cerebral artery. RESULTS: Only features of the ipsilateral posterior communicating artery were related to the risk of watershed infarction. The presence of posterior communicating arteries measuring at least 1 mm in diameter was associated with the absence of watershed infarction (13 hemispheres, no infarcts; P < 0.001). Conversely, there were 4 watershed infarcts in the 6 hemispheres with posterior communicating arteries measuring less than 1 mm in diameter and 10 infarcts in the 13 hemispheres with no detectable flow in the ipsilateral posterior communicating artery. CONCLUSIONS: A small (< 1 mm in diameter) or absent ipsilateral posterior communicating artery is a risk factor for ischemic cerebral infarction in patients with internal-carotid-artery occlusion.

Blood flow in major cerebral arteries measured by phase-contrast cine MR.

PURPOSE: To measure mean blood flow in individual cerebral arteries (carotid, basilar, anterior cerebral, middle cerebral, and posterior cerebral) using a cine phase contrast MR pulse sequence. METHODS: Ten healthy volunteers (22 to 38 years of age) were studied. The cine phase-contrast section was positioned perpendicular to the vessel of interest using oblique scanning planes. This pulse sequence used a velocity encoding range of 60 to 250 cm/sec. From the velocity and area measurements on the cine images, mean blood flow was calculated in milliliters per minute and milliliters per cardiac cycle. In the same subjects, transcranial Doppler measurements of blood velocity in these same vessels were also obtained. RESULTS: There was no difference in blood flow in the paired cerebral arteries. Carotid arteries had mean blood flow in the range of 4.8 +/- 0.4 ml/cycle, the basilar artery 2.4 +/- 0.2 ml/cycle, the middle cerebral artery 1.8 +/- 0.2 ml/cycle, the distal anterior cerebral artery 0.6 +/- 0.1 ml/cycle, and the posterior cerebral artery 0.8 +/- 0.1 ml/cycle. Overall, there was poor correlation between MR-measured and transcranial Doppler-measured peak velocity. CONCLUSION: Although careful attention to technical detail is required, mean blood flow measurements in individual cerebral vessels is feasible using a cine phase-contrast MR pulse sequence.

Qualitative phase contrast MRA in the normal and abnormal circle of Willis.

PURPOSE: To determine the direction of blood flow in the circle of Willis using a 3-D phase contrast MR angiographic (MRA) technique with high spatial resolution. SUBJECTS: Fifty healthy subjects and 15 patients with occlusive disease were studied using 3-D phase contrast MRA. RESULTS: In the 50 normal subjects, 39 (78%) had detectable flow in one or both posterior communicating arteries. In 24 (48%) of these subjects, flow was detected in both posterior communicating arteries, whereas unilateral flow was detected in 15 (30%). In 36 (92%) of the 39 normal subjects, flow in the posterior communicating artery was from anterior to posterior with only 3 (8%) showing reverse flow from posterior to anterior. The A1 segment of both anterior cerebral arteries was identified in 100% of normal subjects with flow in the expected direction from carotid to the A2 segment. In patients with carotid occlusion, the pattern of flow in the circle of Willis was altered with reversed flow in the ipsilateral posterior communicating artery and sometimes in the ipsilateral A1 segment. An ipsilateral posterior communicating artery was present in 10 of 17 occluded carotid arteries, all showing reversed flow. CONCLUSION: 3-D phase contrast MRA provides useful information about the hemodynamics of normal and abnormal blood flow in the circle of Willis.

Determination of cerebral blood flow with a phase-contrast cine MR imaging technique: evaluation of normal subjects and patients with arteriovenous malformations.

This study evaluated a phase-contrast cine magnetic resonance (MR) imaging technique capable of simultaneously allowing determination of velocity and volume flow rate (VFR) in both carotid arteries and the basilar artery. Forty patients were studied; 24 were neurologically normal, and 16 had intracerebral arteriovenous malformations (AVMs). In the normal group, mean basilar flow was significantly less than mean carotid flow. Mean velocity and VFR showed a significant decline with age in the basilar artery. Carotid artery flow and total cerebral blood flow did not decline with age. In the AVM patients, flow and velocity measurements were significantly elevated in all three arteries. Flow in the carotid artery ipsilateral to the AVM was significantly greater than flow in the contralateral carotid artery. VFR increased in all three arteries with increasing AVM volume. Four patients underwent partial embolization, and a corresponding decrease in flow was observed. Phase-contrast cine MR imaging provides rapid, simultaneous, noninvasive velocity and VFR measurement in the major intracranial arteries.

Sodium excretion in normal and hypertensive pregnancy: a prospective study.

One hundred fifty-eight intravenous saline solution infusions (3 mmol Na per kilogram body weight) were performed in (1) normal primigravid women during the second and third trimesters and post partum, after 1 week of either a high, low, or ad libitum salt intake; (2) normotensive primigravid women during midpregnancy who later developed pregnancy-induced hypertension, and (3) seven proteinuric and seven nonproteinuric primigravid women with ad libitum salt intake who had established pregnancy-induced hypertension. Sodium excretion did not differ significantly between pregnancy and after pregnancy despite marked differences in plasma renin activity, aldosterone concentration, volume, and glomerular filtration rate. Sodium excretion after saline solution loading varied according to prestudy sodium intake and was reduced between the second and third trimesters, independent of dietary salt intake. Those destined to develop pregnancy-induced hypertension had sodium excretion similar to that of continuously normotensive subjects during the second trimester, but those with established proteinuric pregnancy-induced hypertension had the lowest plasma volume, plasma aldosterone concentration, and plasma renin activity and retained sodium to the same degree as salt-deplete women with normotension. These results demonstrate that the balance of sodium regulatory factors is similar between pregnancy and post partum, that prestudy salt intake and stage of gestation can alter the natriuretic response to saline solution loading, and that normal pregnant women retain more administered sodium in late pregnancy than in midpregnancy despite further increases in plasma volume and no alterations to blood pressure or glomerular filtration rate. Those with established proteinuric pregnancy-induced hypertension retain sodium avidly without stimulation of plasma renin activity or plasma aldosterone concentration, findings not apparent during midpregnancy in those who later developed this disorder.

Spirometric findings in capacitor workers occupationally exposed to polychlorinated biphenyls (PCBs).

Spirometric findings (forced vital capacity [FVC], forced expiratory volume at one second [FEV1], FEV1/FVC) in a population of capacitor workers with occupational exposure to polychlorinated biphenyls (PCBs) are described during active PCB use (1976) and following the PCB ban (1979 and 1983). The initial finding of restrictive impairment (16%) in 1976 was not supported by chest roentgenogram findings, nor confirmed in 1979 and 1983, and was interpreted as artifactual due to test operator inexperience and inadequate expiratory efforts. Obstructive impairment was consistently found in 15% of the total population in 1976 and 1979. A history of respiratory illness and/or symptomatology and reduced FEV1/FVC was correlated with PCB exposure and serum PCB levels (lower homologs) in females in 1976, but not in males. Smoking was correlated with reduced FEV1 values. No correlation of spirometric variables with past exposure or serum PCB levels was found for either sex in 1979.

Relationship between 201Tl uptake and oxidative metabolism in cultured myocardial cells.

The uptake of thallium-201 (201Tl) by myocardial cells in cultures was assessed in the presence of 10(-3) M potassium cyanide (KCN), an inhibitor of mitochondrial respiration, and 10(-4) M dinitrophenol (DNP), an uncoupler of oxidative phosphorylation. The cultures were incubated with 14C-glucose or 14C-octanoate, allowing the measurement of the oxidative metabolism and beta-oxidation from the production of 14CO2. The results demonstrated a moderate decrease in the ratio between the intra/extracellular concentration of 201Tl (Tl i/e) in the presence of KCN (28.9 +/- 8.1 versus 35.6 +/- 9.7 in the controls, n.s.) and no change with DNP (37.6 +/- 9.7). Glycolysis and fatty acid oxidation were lowered with KCN (-28 +/- 15 and -45 +/- 22% respectively, p less than 0.05 in both cases) and were non significantly increased with DNP (+37 +/- 23 and +10 +/- 52% respectively). These results show that 201Tl intracellular uptake is not related directly, but is not totally independent of glycolysis and fatty acid oxidation.

Antihypertensive treatment in pregnancy: analysis of different responses to oxprenolol and methyldopa.

One hundred and eighty three hypertensive pregnant women were randomly assigned to antihypertensive treatment with oxprenolol (96 women) or methyldopa (87 women). Control of hypertension was equivalent in both treatment groups, and in 64 (35%) cases hydralazine had to be added to the treatment to achieve the therapeutic goal (diastolic blood pressure below 85 mm Hg). Five perinatal deaths occurred, one in the oxprenolol group and four in the methyldopa group. Detailed analysis confirmed a previous report of greater fetal growth in the group treated with oxprenolol; this trend was present regardless of severity of hypertension and parity. With increasing duration of treatment the differences between the two groups diminished, and there was no difference after 10 weeks of treatment, a finding that may explain some of the reported discrepancies among therapeutic studies. As hypertension in pregnancy may pursue an accelerated course, necessitating urgent delivery, and there is no satisfactory method of predicting the duration of treatment in individual patients fetal benefit is most likely to be achieved by treatment with oxprenolol, provided that there is no maternal contraindication to treatment with beta blockers.

Effects of grisorixin on the distribution of thallium-201 and on the oxidative metabolism in cultured myocardial cells.

Previous experiments in the dog and guinea-pig have shown that grisorixin, a monocarboxylic ionophore, can significantly increase the coronary blood flow and the myocardial uptake of 201Tl, as well as have a stimulant effect on the heart. In this study, cultures of myocardial cells were used in order to isolate the cells from the vascular and extracardiac influences so that any ionophorous effect on 201Tl could be evidenced. The effects of grisorixin on the oxidative metabolism were simultaneously studied. The technique described by Harary was used to prepare the cultures. The activity of the 14CCO2 produced by oxidation of [14C]glucose and [14C]octanoate added to the medium of culture and the intra/extracellular ratio of 201Tl concentrations (Tl i/e) were measured. In the controls (n = 8), the Tl i/e was 40 +/- 10 while it was 17 +/- 6 (p less than 0.05) in the cells that received 201Tl and grisorixin at the same time (n = 4), and 19 +/- 5 (p less than 0.05) in the flasks where 201Tl was injected after grisorixin (n = 7). A significant decrease of the [14C]octanoate oxidation was found in the flasks treated with grisorixin (n = 4, -50 +/- 16%, p less than 0.01) while the [14C]glucose oxidation was not significantly lowered (n = 3; -11 +/- 12%). The conclusion is that grisorixin decreases both the intracellular concentration of 201Tl and the fatty-acids oxidation in cultured myocardial cells. The beneficial effects previously observed in vivo were probably the consequence of the strong coronary dilatation and of an indirect stimulation.

Effects of PCB exposure on biochemical and hematological findings in capacitor workers.

Certain former operations in capacitor manufacturing resulted in extensive direct contact of the workers with electrical grade polychlorinated biphenyls (PCBs). A study group of 194 such individuals, all exposed to Aroclor 1016 and many previously exposed to Aroclors 1242 and/or 1254, was examined before (1976) and after (1979) discontinuance of PCB use in the operations (1977). At the two examinations, the approximate geometric mean serum levels (in ppb) and 5 to 95% ranges were for lower PCBs (LPCB), 363 (57-2270) and 68 (12-392); and for higher PCBs (HPCB), 30 (6-142) and 19 (4-108), respectively. The statistical associations among 42 measured clinical chemical and hematological parameters, five different measures of PCB exposure, and seven confounding variables observed in the two examinations were determined by three regression procedures. Similar regressions were performed with DDE, which was present at background levels. The principal statistical findings were a depression in serum bilirubin and elevations in serum GGTP and lymphocyte levels at the time of the first examination, and only an elevation in monocytes at the second. Appraisal of the results suggested an induction of microsomal enzymes which appeared to be subsiding after the cessation of direct exposure to PCBs. The statistical association between serum levels of PCBs and lipids reported by others was confirmed, but shown to be explained by the partitioning behavior of PCB in the body, rather than to changes in liver function. No evidence for health impairment related to PCBs was found, despite the high serum levels of PCBs in the study population.

Comparability and precision of serum PCB measurements.

The 95% prediction interval for single measurements of serum "Aroclor" reported by a reputable commercial analyst was found to be approximately +/- 42%. The geometric mean serum PCB levels in a population of capacitor workers who had formerly had direct exposure to the commercial PCBs--Aroclors 1016, 1242, and 1254-were found to be alternatively reportable as 1905 ppb minimum initial PCBs (as calculated from most persistent peaks present); 1093 ppb non-overlapping analytical "Aroclor" levels (as calculated by the conventional sum-of-the-peak-heights method); 303 ppb total PCBs actually present; or 19 ppb "human PCB" (as calculated by the NHMP procedure). The broad spread in reportable values was relatable to the PCB isomer distribution and clearance patterns in the occupationally exposed population.

Laboratory-based surveillance of influenza virus in the United States during the winter of 1977-1978. I. Periods of prevalence of H1N1 and H3N2 influenza A strains, their relative rates of isolation in different age groups, and detection of antigenic variants.

Influenza A (H3N2) viruses were isolated from outbreaks and epidemics of disease during the period December 1977 to March 1978. For the last two months of this period, H1N1 strains of influenza A were also responsible for epidemics. In some regions (e.g., Hawaii) co-circulation of H1N1 AND H3N2 strains occurred, whereas in other regions (e.g., Wisconsin) isolation of H3N2 strains had almost ceased prior to isolation of H1N1 strains. Few influenza B isolates were reported. Analysis of the ages of patients from whom specimens were submitted for influenza virus isolation confirmed that, whereas H3N2 strains were isolated from persons of all ages, greater than 97 per cent of H1N1 isolates in six states analyzed were recovered from patients less than 26 years old, although specimens were tested from older persons who were ill during the period of prevalence of H1N1 influenza. The majority of H3N2 isolates tested by hemagglutinin-inhibition reaction were similar to A/Texas/1/77, and the majority of H1N1 isolates were similar to A/USSR/90/77. Antigenic analysis of isolates, however, identified a small number of variants of H3N2 and H1N1 strains.

Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities.

An epidemic form of arthritis has been occurring in eastern Connecticut at least since 1972, with the peak incidence of new cases in the summer and early fall. Its identification has been possible because of tight geographic clustering in some areas, and because of a characteristic preceding skin lesion in some patients. The authors studied 51 residents of three contiguous Connecticut communities -- 39 children and 12 adults -- who developed an illness characterized by recurrent attacks of asymmetric swelling and pain in a few large joints, especially the knee. Attacks were usually short (median: 1 week) with much longer intervening periods of complete remission (median: 2.5 months), but some attacks lasted for months. To date the typical patient has had three recurrences, but 16 patients have had none. A median of 4 weeks (range: 1-24) before the onset of arthritis, 13 patients (25%) noted an erythematous papule that developed into an expanding, red, annular lesion, as much as 50 cm in diameter. Only 2 of 159 family members of patients had such a lesion and did not develop arthritis (P less than 0.000001). The overalll prevalence of the arthritis was 4.3 cases per 1,000 residents, but the prevalence among children living on four roads was 1 in 10. Six families had more than 1 affected member. Nine of 20 symptomatic patients had low serum C3 levels, compared to none of 31 asymptomatic patients (P less than 0.005); no patient had iridocyclitis or a positive test for antinuclear antibodies. Neither cultures of synovium and synovial fluid nor serologic tests were positive for agents known to cause arthritis. "Lynne arthritis" is thought to be a previously unrecognized clinical entity, the epidemiology of which suggests transmission by an arthropod vector.

Measles immunization status in 1972 among first- and second-grade school children in Danbury, Connecticut.

An increased incidence of rubeola among first-grade Danbury school children in 1973 led to a study of seroimmunity to rubeola in a random sample of 60% of the first- and second-grade school children (299) from whom blood samples had been obtained in October 1972 during a voluntary meningococcal vaccination program. Immunization histories derived from physicians' statements on school entry were obtained from school health department records and included date of immunization. Seventy-five percent of the study group had received measles vaccine. Of those immunized prior to 11 months of age only half had an hemagglutinating inhibiting titer (HAI) of greater than or equal to 5 five to seven years later. This antibody level correlates with immunity. Eighty-five to ninety percent of those immunized during or after the 11th month had an antibody titer of greater than or equal to 5. Seventy-one percent of those never immunized also had an HAI titer of greater than or equal to 5 indicating natural infection had occurred. As a result of this investigation, a community-wide program was initiated to vaccinate those who were more than 1 year old as well as reimmunize those who had been vaccinated before the 11th month in accord with current U.S. Public Health Service recommendations for measles immunization.