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We describe ribavirin administration in hospitalized children over an 11-year period. Most patients were immunocompromised; there was variability in ribavirin use across hospitals. There was a clear shift toward the use of oral ribavirin despite a lack of evidence for its use.

Objective.The goal of this effort was to reduce central venous catheter (CVC)-associated bloodstream infections (BSIs) in pediatric intensive care unit (ICU) patients by means of a multicenter evidence-based intervention.Methods.An observational study was conducted in 26 freestanding children's hospitals with pediatric or cardiac ICUs that joined a Child Health Corporation of America collaborative. CVC-associated BSI protocols were implemented using a collaborative process that included catheter insertion and maintenance bundles, daily review of CVC necessity, and daily goals. The primary goal was either a 50% reduction in the CVC-associated BSI rate or a rate of 1.5 CVC-associated BSIs per 1,000 CVC-days in each ICU at the end of a 9-month improvement period. A 12-month sustain period followed the initial improvement period, with the primary goal of maintaining the improvements achieved.Results.The collaborative median CVC-associated BSI rate decreased from 6.3 CVC-associated BSIs per 1,000 CVC-days at the start of the collaborative to 4.3 CVC-associated BSIs per 1,000 CVC-days at the end of the collaborative. Sixty-five percent of all participants documented a decrease in their CVC-associated BSI rate. Sixty-nine CVC-associated BSIs were prevented across all teams, with an estimated cost avoidance of $2.9 million. Hospitals were able to sustain their improvements during a 12-month sustain period and prevent another 198 infections.Conclusions.We conclude that our collaborative quality improvement project demonstrated that significant reduction in CVC-associated BSI rates and related costs can be realized by means of evidence-based prevention interventions, enhanced communication among caregivers, standardization of CVC insertion and maintenance processes, enhanced measurement, and empowerment of team members to enforce adherence to best practices.

This report describes procedures and results of recent outdoor tests in evaluating a prototype single particle fluorescence analyzer (SPFA), an instrument that is being developed to simultaneously monitor ambient concentrations of both biological and nonbiological aerosols using optical techniques. Recent modifications to the SPFA are also noted and discussed. During recent outdoor tests, aerosols were generated containing four different types of biological material: ova albumin, MS-2 phage, Erwinia herbicola vegetative cells and Bacillus subtilis spores. Analysis of the SPFA results indicates that a probability of detection of at least 87% was achieved for target aerosol concentrations as low as a few (1–5) particles/liter. Moreover, comparison with different reference instruments indicate that the SPFA can achieve absolute quantitative detection efficiencies for individual biological aerosols of at least 70% (assuming appropriate alignment and threshold settings are made). During some of the outdoor tests different nonbiological aerosols were also released that generally did not generate any significant fluorescent signals. Although official test scores have not yet been distributed, we provide here the SPFA results for each of the aerosol releases made during the test. Analysis of the relative fluorescent intensities in the visible and UV spectral bands suggests that these data can be used in the future to provide an indication of the type of biological aerosol being released as well. © 2001 John Wiley & Sons, Inc. Field Analyt Chem Technol 5: 205–212, 2001

This report describes the design and principles of operation of an instrument for separately monitoring ambient aerosol concentrations of biological and nonbiological composition. A method of outdoor testing, and recent results, are also described. The single-particle fluorescence analyzer (SPFA) draws ambient air into an optical chamber through a sampling nozzle. Detection signals from each aerosol particle consist of an elastic scattering response as well as fluorescent emission in two distinct spectral bands. Differentiation of biological aerosols is based on the relative intensity of ultraviolet (UV) fluorescence measured from the particles following excitation with a 266-nm-wavelength laser pulse. During outdoor tests two types of organisms were released as aerosol sprays: Erwinia herbicola vegetative cells and Bacillus subtilis spores. The SPFA participated in 39 of a total set of 40 outdoor tests. Twenty-seven tests released E. herbicola and nine released B. subtilis. Analysis of these results indicates that a reliability of detection of about 90% for E. herbicola, and of about 87% for B. subtilis were achieved under the conditions of the tests, with a sensitivity near 1 particle/l. Some tests involved release of nonbiological aerosols that did not result in a significant change in fluorescent signals in the instrument. © 1999 John Wiley & Sons, Inc.* Field Analyt Chem Technol 3: 249–259, 1999

An adult with angina was found to have anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Review of the literature regarding this anomaly in teen-agers and adults disclosed only 25 cases diagnosed during life. Eighteen additional cases of ALCAPA in this age group have been diagnosed post mortem. In this report, we will review the management of teen-agers and adults in whom ALCAPA was correctly diagnosed during life. We shall also describe the eighth case of successful aorta–left coronary artery grafting with the saphenous vein in this age group. This case brings the total in the literature to 44. Of those patients offered surgical therapy, 13 underwent successful ligation of the anomalous artery. Saphenous vein grafts were employed in 8. Five did not undergo ligation or saphenous vein grafting. There was one death. It would appear that saphenous vein grafting is the definitive means of surgically correcting ALCAPA, because it restores the dual coronary circulation.

A total of 101 patients (mean age 64.9 years) underwent surgical correction of postinfarction ventricular septal defect at this institution over a 15-year period (1973 to 1988). The overall early mortality rate was 20.8%, although the most recent experience with 36 patients (January 1987 to October 1988) has seen this decline to 11.1%. Factors found to influence early death significantly, when analyzed univariately, were as follows: (1) site of infarction (anterior 12.1%, inferior 32.6%, p = 0.02); (2) time interval between infarction and operation (<1 week 34.1%, >1 week 10.5%, p = 0.008); (3) cardiogenic shock (present 38.1%, absent 8.5%, p = 0.001). Nonsignificant variables included preoperative renal function, age, and concomitant coronary artery bypass, although older age (>65 years) became significant when examined in a multivariate fashion. Of the 80 hospital survivors, eight were subsequently found to have a recurrent or residual defect necessitating reoperation, with survival in seven. Late follow-up is 99% complete and reveals an actuarial survival rate for 100 patients of 71.1% at 5 years (95% confidence interval 60.6 to 80.0), and 40.0% at 10 years (95% confidence interval 21.7 to 58.4). A significant recent change in policy of not using coronary angiography in patients with a ventricular septal defect caused by anterior wall infarction has not resulted in any increase in either the early mortality or in the late prevalence of angina. The functional status of 38 surviving patients has been analyzed by a graded treadmill exercise protocol, whereas left ventricular functional assessment was by nuclear scan with additional information on mitral valve function by echocardiogram. Color Doppler flow mapping has been used to determine the presence of a residual defect. Most late survivors have limited exercise tolerance related to both cardiac and noncardiac factors. Left ventricular function is moderately impaired (mean ejection fraction = 0.39). However, many patients are elderly and have adapted to their residual symptoms without significant changes in life-style.

Summary High dose narcotic anesthesia with fentanyl or morphine is not associated with significant direct myocardial depression. Morphine is reported to produce arteriolar dilatation and a decrease in SVR (probably due to histamine release) while fentanyl is not. Studies were undertaken to determine if morphine or fentanyl caused histamine release; if such a release correlated with hemodynamic changes, and if H1 and H2 antagonists could provide protection. In a randomized double blind study of 40 patients in 4 groups, patients who received morphine (1 mg/kg) demonstrated significant increases in plasma histamine (880±163 to 7,437±2,684 pg/ml-p<0.01) accompanied by an increase in CI (2.4±0.2 to 3.0±0.2 l/min/m2-p<0.01) and decreases in (88±4 to 61±4 torr-p<0.01) and SVR (15.5±1 to 9.0±1 torr-l-min-1p<0.01). The prior administration of H1 (dyphenhydramine 1 mg/kg) and H2 (cimetidine 4 mg/kg) antagonists provided significant protection (SVR 17.4±1 to 14.6±1 torr-l-min-1-p<0.05) although histamine increased comparably (1,059±22 to 7,653±4,242 pg/ml-p<0.05). In a separate study, seven patients receiving fentanyl 50 µg/kg showed no histamine changes (935±51 to 685±51 pg/ml) and no significant hemodynamic response. Eight patients receiving morphine 1 mg/kg again showed significant increases in plasma histamine (880±163 to 7,480±2,230 pg/ml-p<0.05) which collelated with the decrease in SVR (r=0.81). These data demonstrate that morphine releases histamine in amounts which correlate with the hemodynamic changes seen. Prior administration of H1 and H2 histamine antagonists provide significant protection — more so than either alone. Fentanyl produced no histamine release which may account for much of the cardiovascular stability reported with this drug.

Thyroid glands from 8-day-old rat pups were incubated in serum-free medium for 6 hr. Both calcitonin (CT) and calcitonin gene-related peptide (CGRP) released into medium were measured by radioimmunoassay. In 6 separate experiments CGRP was easily detected in medium in ng/ml concentrations. In 4 of the 6 experiments, where CT release was stimulated by high medium [Ca], the concentration of CGRP in medium showed a positive, significant correlation with the medium CT concentration (r=0.41-0.69, p < .05-<.01). The results are in concert with reports describing the presence of CGRP in the C-cell, and they further show that CGRP, as Well as CT, Can be Secreted by C-Cell.

Burn patients are at risk for bone disease due to aluminum (AI) exposure from use of antacids and albumin, partial immobilization, and increased production of endogenous glucocorticoids. Moreover, severely burned children are growth impaired up to 3 years after the burn. To determine the extent of bone disease, we studied nine men and three women, ages 18–41 years, with greater than 50% body surface area burn. Seven patients underwent iliac crest bone biopsy following double tetracycline labeling, one additional patient expired after a single label, and three others had postmortem specimens obtained for quantitative AI only. Serial serum and urine samples were obtained weekly until biopsy or death. All biopsied patients had reduced bone formation and osteoid area, surface, and width, with mineral apposition rate, osteoblast surface, and osteoclast number with normal eroded surfaces compared to age‐ and sex‐matched normal ambulatory volunteers. Burn patients also had reduced bone formation, mineral apposition rate, osteoid area, and surface compared to age‐matched volunteers at short‐term bed rest. Serum levels of osteocalcin were low. Most patients had mild hypercalcemia but only a third had hypercalciuria. All patients had elevated AI in blood or urine; urine AI correlated inversely with serum osteocalcin. In 60% significant bone AI was detectable by stain or quantitation. Our data are compatible with burn patients having markedly reduced bone turnover. AI loading, partial immobilization, endogenous corticosteroids, and cytokine production may be among the etiologic factors.

Effects of vagotomy, acetyl-choline and various adrenergic drugs on serum immunoreactive gastrin levels were studied in the rat. In rats fasted 24 hr or longer serum gastrin concentrations generally were <50 pg/ml; 60 min after the onset of feeding, serum gastrin concentrations reached levels >100 pg/ml. In rats fasted overnight, injections of epinephrine, isoproterenol and phenoxybenzamine all raised the serum gastrin level. Pretreatment with propranolol, a β-adrenergic blocking agent, abolished the hypergastrinemic affect of iso-proterenol. Administration of propranolol also lowered basal serum gastrin levels and reduced the increase in serum gastrin produced by feeding. In vagotomized rats, iso-proterenol futher increased the already elevated serum gastrin levels while propranolol alone slightly reduced the elevated basal gastrin levels in four or five vagotomized rats. Bathing the antral mucosa by gavage with isoproterenol (even in 0.01 NHC1) also increased serum gastrin levels, indicating that isoproterenol acted directly on the antrum and not indirectly by elevating intra-gastric pH.Possible interactions between cholinergic and adrenergic agents on serum gastrin responses also were examined. Acetylcholine given by gavage produced its well known large increase in serum gastrin. An anticho-linergic drug, atropine, given orally, greatly restricted the ability of acetylcholine to raise serum gastrin, and propranolol given orally also inhibited the increase in serum gastrin levels produced by oral acetylcholine. The findings support the idea that both cholinergic and adrenergic systems influence gastrin secretion in the rat.The authors wish to thank Drs. Paul L. Munson, Philip F. Hirsch, Tai-Chan Peng, and Fred W. Ellis for advice during the course of this work. The technical assistance of Mr. Johnny F. Obie, Mrs. Deloris B. Alston, and Mr. John R. Hagaman, Jr. is deeply appreciated.

Bombesin was administered to young fasted rats, and blood levels of immunoreactive gastrin and calcitonin (CT) were measured. Doses of bombesin up to 100 μg/rat i.v. did not affect serum calcium or phosphorus. Five minutes after bombesin, 10 or 50 μg/rat, serum gastrin increased 1- to 2-fold and, by 30 min, it was elevated 5- to 10-fold. Time-course and dose-response studies showed that doses of 10–100 μg/rat increased gastrin and that gastrin rose within 5 min after 50 μg/rat and remained elevated for at least 2 hr. Despite bombesin-induced hyper-gastrinemia, CT remained low or undetectable (<50–100 pg/ml) at all times. In one study, somatostatin (50 μg/rat i.v.), given together with bombesin, inhibited the rise in serum gastrin by 50%, but serum CT, which was detectable, was unaffected by either bombesin or somatostatin. We conclude that bombesin stimulates gastrin release in the rat, but the elevated gastrin does not promote CT secretion. The results support our earlier findings which indicate that gastrin is weak or ineffective in the rat as a CT secretagogue.The technical assistance of Ms. Deloris B. Alston and Ms. Lillie T. Williams is gratefully acknowledged.

Transforming growth factor β (TGF‐β) is now recognized as an important growth regulator and modulator in bone, where it apparently acts in an autocrine or paracrine fashion. In an effort to help elucidate how TGF‐β may interact with parathyroid hormone (PTH) to influence bone turnover, we examined the idea that TGF‐β might alter the number or affinity of PTH receptors in osteoblastic bone cells, PTH receptor binding was assessed in cultured ROS 17/2.8 cells using [125I]PTHrP‐(1–34) as labeled ligand. Specific binding to intact cells was measured in the presence of up to 1 μM unlabeled rPTH‐(1–34), and cAMP in cell extracts was determined by RIA. Incubation of ROS cells with 2 ng/ml of TGF‐β for the maximally effective time of 3 days increased the number of PTH binding sites (Bmax) by 47 ± 13%, with no change in the Kp(3 nM). TGF‐β also increased the intracellular cAMP response to 0.3 nM rPTH‐(1–34) (ED50) by 53 ± 22%. Both effects were dose dependent, with 1–4 ng/ml of TGF‐β producing maximal effects, and both effects were blocked by the protein synthesis inhibitor cycloheximide (2–5 μM). Since TGF‐β induced comparable increases in both PTH binding and cAMP formation, the findings suggest that TGF‐β can increase the number of functional PTH receptors in cultured ROS 17/2.8 cells. This effect may reflect an action of TGF‐β to slow replication and promote differentiated functions in these cells.

Hypothermic potassium cardioplegia has become the most popular technique for myocardial preservation during coronary revascularization. However, an older technique continues to yield comparable results with some potential advantages. Myocardial preservation was achieved with systemic hypothermia to 28° C, pericardial cooling, elective ventricular fibrillation, maintenance of systemic perfusion pressure between 80 and 100 mm Hg, routine left ventricular venting, and local vessel isolation during distal anastomoses without aortic occlusion. Proximal anastomoses were performed prior to atrial cannulation and cardiopulmonary bypass. Nonemergency isolated bypass grafting was performed in 500 consecutive patients, of whom 51% had had a prior myocardial infarction, 24% had unstable angina, and 21% had left main coronary stenosis. Primary grafting was performed in 483 patients and reoperations in 17. The mean number of grafts per patient was 3.8. Perioperative myocardial infarction occurred in 1.8%. Hospital mortality was 0.4%. Late follow-up was obtained for all survivors at a mean postoperative interval of 17.8 months. All survivors were asymptomatic or improved over their preoperative status. The 3 year actuarial survival rate was 95.8%, equivalent to that for the matched general population. Of 287 male patients under age 65, 68.4% were working preoperatively and 69.5% postoperatively. This technique provides results comparable to bypass grafting with cardioplegia and may be useful when aortic occlusion or administration of cardioplegic solutions is not desireable.

Two different anti-somatostatin antisera, R-101 and OAL-273, cross-react with rat calcitonin gene-related peptide (1–37) (CGRP). CGRP amounts, in excess of 6.25 × 10-9M, cross-react with R-101 in the somatostatin radioimmunoassay. CGRP amounts, in excess of 1.6 × 10-9M, cross-react with OAL-273. Both CGRP displacement curves are parallel to that of synthetic somatostatin (1–14). Comparison of ID50's shows that the cross-reactivity of CGRP with R-101 and OAL-273 are 0.02 and 0.1% of somatostatin, respectively.

Previously we reported a homologous radioimmunoassay for rat thyrocalcitonin (TCT) which was sensitive enough (2-3 ng/ml serum) to measure TCT in thyroid venous blood or thyroid gland extracts but could not detect TCT in peripheral blood even after provocative challenge with iv calcium. In the present study chicken antisera to rat TCT were developed which were sufficiently sensitive (120-240 pg/ml serum) to permit initial evaluation of changes in TCT in rat peripheral blood. The following results were observed: (1) Basal serum TCT in young male Holtzman rats was undetectable, being < 120-240 pg/ml; (2) induction of marked hypercalcemia by iv calcium increased TCT to ∼1000-3000 pg/ml within 5 min; (3) thyroid cautery increased TCT to ∼1000 pg/ml in 5-15 min; (4) calcium gavage (12.2 mg Ca/100 g) produced modest hypercalcemia in 30-60 min and increased serum TCT to ∼500 pg/ml; (5) injection of isoproterenol raised serum TCT detectably; (6) injection of large doses of gastrin or pentagastrin did not produce detectable increases in TCT 5 or 30 min later.The results show that suitable antisera to rat TCT can be developed in chickens and applied to the measurement, by radioimmunoassay, of elevated circulating levels of TCT in the rat.The authors wish to acknowledge advice from Drs. Paul L. Munson and Tai-Chan Peng, and technical assistance from Mrs. Deloris B. Alston and Mr. John R. Hagaman, Jr.

Daily fluctuations in plasma calcium concentrations in rats trained to a closely regulated feeding pattern have been compared to corresponding plasma gastrin and calcitonin concentrations. The time period studied was that extending from 4 hr prior to the start of the feeding period through the first 2 hr of feeding. Both plasma calcium and phosphate levels fell prior to the start of the feeding period and remained low at least for the first 2 hr of feeding. This pattern was also observed in rats in which food was withheld for 2 hr past the regular feeding time. Plasma 45Ca and 32P concentrations (radionuclide injected at least one week prior to sampling) did not follow the pattern of their stable counterparts. Instead, these values rose or remained constant until after feeding had commenced, after which they fell precipitously. Both plasma calcitonin and gastrin levels rose rapidly after the start of the feeding period. The primary point of emphasis is that calcitonin secretion was produced in these rats by an intestinal related stimulus and not by a rise in plasma calcium concentration.The technical assistance of Dorothy B. Raneri, Blanche P. Holloway and Johnny F. Obie is acknowledged and appreciated. Thanks are expressed to Merlene Moore for clerical assistance.

Patients are at risk for a diminished anticoagulant response to heparin during coronary artery bypass graft operations. To answer the question of whether preoperative heparin therapy and intra-aortic balloon counterpulsation are associated with a diminished response in the period before cardiopulmonary bypass, we observed prospectively the baseline and postheparinization activated clotting times in 76 patients undergoing elective coronary artery bypass graft procedures. They included 42 patients who had received preoperative heparin therapy (26 had intra-aortic balloon pumps and 16 did not). Thirty-four comparison patients (controls) were matched for age, sex, race, and heparin lot. Patients receiving preoperative heparin therapy, either with or without intra-aortic balloon pumps, had significantly lower activated clotting times than patients in the control group after a 300 IU/kg dose of porcine intestinal heparin. Total preoperative heparin dose, days of preoperative heparin therapy, and baseline activated clotting times were not predictive of heparin resistance. In conclusion, patients receiving preoperative heparin therapy (with or without intra-aortic balloon pumps) are at increased risk for inadequate heparinization before cardiopulmonary bypass.