Controlled study of respiratory viruses and wheezing.
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Biomedical subjects
Publications and source records attributed to M Goldbach.
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BACKGROUND AND AIM OF THE STUDY: The St. Jude Medical (SJM) Regent heart valve is a new bileaflet prosthetic valve modified from the currently marketed SJM mechanical valve, with a modified external profile that results in a larger geometric orifice area without changing the existing design of the pivot mechanism or blood contact surface areas. The aim of the present study was to report the early hemodynamic and clinical results of an on-going multicenter trial investigating the clinical performance of the Regent mechanical aortic valve prosthesis. METHODS: The early results from 204 patients at 11 centers in North America and Europe who underwent implantation of a Regent mechanical aortic valve prosthesis are described. Clinical status was prospectively recorded, and echocardiography with Doppler performed at hospital discharge, and at two and six months and one year postoperatively. RESULTS: Follow up to date is 109.3 patient-years (average follow up 0.5+/-0.4 years per patient; range: 0 to 1.7 years). NYHA class improved for the group, and there were low rates of clinical adverse effects. Echocardiographic mean pressure gradient at six months was 13.8+/-10.3, 7.4+/-4.1, 5.4+/-3.2, 5.2+/-2.8, 3.4+/-2.3 and 3.6 mmHg, respectively, for 19, 21, 23, 25, 27 and 29 mm valves; effective orifice area was 1.5+/-0.6, 2.0+/-0.7, 2.4+/-1.0, 2.5+/-0.7, 3.6+/-1.4 and 4.8 cm2, respectively. There was a statistically significant decrease in left ventricular mass index between early postoperative (169.1+/-57.7 g/m2) and six months follow up (137.2+/-42.7 g/m2, delta = -30.1+/-42.5 g/m2, p <0.0001). CONCLUSION: The SJM Regent aortic valve has excellent associated hemodynamics with rapid and significant left ventricular mass regression. In all cases of adverse events, rates fell within Objective Performance Criteria guidelines. Long-term clinical assessment is on-going.
Vagal afferent signals, have been implicated in cytokine mediated interactions between the periphery and the central nervous system. Studies in experimental animals have shown that cytokine induced activation of brain mediated responses to infection such as fever, sickness behaviour and pituitary-adrenal activation, are inhibited by subdiaphragmatic vagotomy. We have previously proposed that the peripheral signal to the brain in fever is of a humoral nature while others have suggested that either neural afferents or a mixture of both humoral and neural signals may be involved. The objective of the present study was to examine further the role of vagal transmission, in mediating the febrile response to a systemic injection of IL-1beta in rats and to compare this with changes in social exploration behaviour. Intraperitoneal injection of IL-1beta (1.0-30.0 microg/kg) inhibited social exploration in rats and this was attenuated in vagotomized animals. Injection of increasing concentrations of IL-1beta (0.1-1.0 microg/rat) induced significant (P<0.001) increases in core body temperature. However, in contrast to effects on social exploration, the increase in temperature was not inhibited by vagotomy at any of the doses used. These observations demonstrate a dissociation between the two brain mediated events, one of which is dependent on the integrity of the vagus nerve (social exploration) while the other (fever) is apparently generated by different mechanisms which may include circulating pyrogens.
A simulation to model traffic on a multilane freeway is introduced starting from microscopic driving rules. The model takes each individual car into account with its individual features and actual situations, so that a distribution of parameters as well as different behaviors can easily be analyzed. Therefore, a detailed study of certain situations, driving tactics, vehicle properties, and their influence on the global traffic flow can be performed. The model is discussed, as are first results such as the influence of driver behavior on the fundamental diagram and, in addition, the dynamics of microscopic, individual quantities like separation and difference in speed between successive cars. It turns out that a hysteresis in the reaction of the driver for speeding up and slowing down plays an important role, and effects macroscopic quantities like the shape of the fundamental diagram, e.g., the metastable behavior around the maximum flow and on the speed of observed jams running backward. Furthermore, microscopic time resolved characteristics are strongly influenced, e.g., oscillations in the distance and relative speed between successive cars.
Using data from one of our randomised trials, we investigated post-hoc whether male neonatal circumcision is associated with a greater pain response to routine vaccination at 4 or 6 months. Pain response during routine vaccination with diphtheria-pertussis-tetanus (DPT) alone or DPT followed by Haemophilus influenzae type b conjugate (HIB) was scored blind. 42 boys received DPT and 18 also received HIB. After DPT, median visual analogue scores by an observer were higher in the circumcised group (40 vs 26 mm, p = 0.03). After HIB, circumcised infants had higher behavioural pain scores (8 vs 6, p = 0.01) and cried longer (53 vs 19 s, p = 0.02). Thus neonatal circumcision may affect pain response several months after the event.
Therapy to eradicate pharyngeally carried group A streptococci (GAS) has increasingly been used in the management of institutional outbreaks and is now recommended for household contacts of patients with streptococcal toxic shock syndrome. In this randomized, controlled trial, contacts of patients with GAS infections were screened for pharyngeal GAS colonization. Those whose cultures were positive were randomized to receive either cefixime (8 mg/[kg.d]; maximum 400 mg) or rifampin (20 mg/kg; maximum, 600 mg) once a day for 4 days. Two to five days following completion of therapy, repeated cultures were negative for 13 (38%) of 34 rifampin recipients and 71 (77%; 95% CI, 69%-85%) of 97 cefixime recipients. At 10-14 days after treatment, only 53% of cefixime recipients remained culture-negative. Rates of successful clearance improved with increasing age (P < .01); among 17 adults who received cefixime, the success rate was 94%. Four days of therapy with rifampin is not effective for eradication of pharyngeally carried GAS. Four days of therapy with cefixime may be effective for adults, but further studies are needed.
PURPOSE: To determine whether use of lidocaine-prilocaine 5% cream (EMLA) decreases pain associated with diphtheria-pertussis-tetanus (DPT) vaccination in infants. METHODS: Randomize, double-blind, controlled trial in outpatient pediatric practice, Toronto, Ontario, Canada. Before vaccination, parents applied 2.5 gm of EMLA or placebo to the infant's leg and covered it with an occlusive dressing for at least 60 minutes. The infant received a 0.5 ml intramuscular injection of DPT at 2 degree to 8 degree C with a 1.6 cm 25-gauge needle; the infant was videotaped. The Modified Behavioral Pain Scale (MBPS) was used to assess baseline and postvaccination pain scores. Latency and duration of infant cry were also measured. RESULTS: A total of 49 evaluable infants received EMLA, and 47 infants received placebo. There were no significant differences in demographic data; mean age was 5 months; and 50% of the subjects were male. The median difference in pre-vaccination and postvaccination MBPS scores was lower for EMLA than for placebo (p = 0.001). The latency to the first cry was longer for subjects who were treated with EMLA (p = 0.0004)), but the total crying time was shorter (10.3 seconds vs 25.2 seconds; p = 0.027). Of the study group, 90% (45/50) of subjects treated with EMLA and 12% (6/49) of subjects treated with placebo had local skin reactions (p < 0.0001), mainly skin blanching. CONCLUSIONS: Pretreatment with EMLA decreases infant pain from DPT vaccinations. Application of these data is limited to healthy infants receiving DPT vaccinations.
The number of heart transplantations performed over the past 3 years has plateaued. However, the number of pediatric transplantations continues to slowly increase. Unlike adult heart transplantation, for which cardiomyopathy remains the most frequent indication, structural congenital heart disease is the primary indication in children. This report reviews our experience with orthotopic heart transplantation in the presence of structural congenital heart disease with and without prior palliative repair. The diagnoses included transposition of the great arteries, common atrium, left superior vena cava with and without a bridging innominate vein, dextrocardia, and univentricular configurations. The palliative repairs included Blalock-Taussig shunt, bilateral Glenn shunt, Fontan repair, and Mustard and Rastelli procedure. There were no early deaths. Two rejection-related late deaths have occurred at 8 months and at 3 years postoperatively. Extended use of donor tissue and modifications to surgical technique allowed for successful orthotopic heart transplantation in these patients who had structural congenital heart disease with and without prior surgical palliation.
Although use of the internal thoracic artery (ITA) for coronary artery bypass grafting results in superior graft patency and improved patient survival, our initial clinical observations suggested an increased incidence of pleuropulmonary morbidity with its use. One hundred consecutive patients with left ITA grafts were studied prospectively and compared with a consecutive retrospective group of 100 patients undergoing coronary artery bypass grafting with saphenous vein grafts only. Preoperative, postoperative day (POD) 2, POD 6, and postoperative week 8 chest roentgenograms were analyzed for atelectasis and effusion. Postoperative left lower lobe atelectasis was common in both groups on both POD 2 (saphenous vein, 43%, versus ITA, 53%; not significant) and POD 6 (saphenous vein, 40%, versus ITA, 41%; not significant). There was a significantly higher incidence of pleural effusion on POD 6 in the ITA group (84% versus 47%; p less than 0.05) but most of these were small. There was more chest tube drainage (1,413 versus 1,028 mL; p less than 0.01) and a greater need for secondary thoracostomy or thoracentesis (4% versus 0%) in the ITA group. The left pleural space was opened in 67 of the 100 ITA patients but pleurotomy did not appear to influence postoperative morbidity. We conclude that use of the internal thoracic artery for coronary artery bypass grafting results in a small but significant increase in pleuropulmonary morbidity.
Severe hepatotoxicity from phenobarbital occurred in an infant boy who had a complicated illness with chronic bilateral subdural hematomas and sepsis. Skin rash began after 2 weeks of treatment, and signs of hepatocellular failure developed 3 weeks after phenobarbital had been started. Signs of severe liver disease included elevated aminotransferases, conjugated hyperbilirubinemia, significant coagulopathy, hepatosplenomegaly and ascites. Other features of this adverse drug reaction were unremitting fever, leukocytosis with eosinophilia and atypical lymphocytosis, and proteinuria. Sepsis, viral hepatitis, and metabolic liver disease were excluded. The child was on no other medication and had been previously well. In-vitro rechallenge of the patient's lymphocytes with cytochrome P-450 generated metabolites of phenobarbital showed extensive cytotoxicity compared to control. These data support the hypothesis that a defect in drug detoxification was responsible for the child's susceptibility to this drug hepatotoxicity.
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Adverse reactions after diphtheria, pertussis, tetanus, polio vaccination at 18 months of age were investigated in three groups: 74 children injected in the deltoid muscle with a 16-mm (5/8-in) needle, 64 in the anterolateral thigh with a 16-mm needle, and 67 in the anterolateral thigh with a 25-mm (1-in) needle. No significant differences in systemic reactions were observed. Severe pain occurred in 30.5% of the groups injected in the thigh compared with only 8.1% of the group injected in the arm (P less than .001). Children vaccinated in the thigh had decreased movement of the extremity significantly more often than those injected in the arm (49.9% v 25.6%, P less than .0005), and two thirds of the former limped for 24 to 48 hours. Redness and swelling were observed more often after injection in the arm than in the thigh (58.1% v 26.7%, P less than .0005). The only effect of changing needle length in the groups injected in the thigh was the occurrence of more redness and swelling in children vaccinated with the 16-mm needle compared with the 25-mm needle. Overall, parents rated more reactions as moderate to severe among children injected in the thigh than among children injected in the arm (64.2% v 37.9%, P less than .001). The deltoid muscle appears to be the preferred site for administration of diphtheria, pertussis, tetanus, polio vaccine at 18 months of age.
The effect of acetaminophen on reducing the frequency and severity of adverse reactions following diphtheria-pertussis-tetanus toxoids-polio vaccine was studied in a randomized clinical trial involving 519 vaccinations in 383 infants 2 to 6 months of age and 70 infants 18 months of age. Significantly fewer local and systemic reactions were reported in acetaminophen-treated infants at 2 to 6 months of age. Acetaminophen also reduced the incidence of fever greater than 38.0 degrees C from 44% to 27%. Only 0.9% of acetaminophen-treated infants had overall behavioral changes rated as severe by parents compared to 13% of the placebo group. Infants vaccinated at 18 months of age had higher rates of systemic and local reactions than younger infants. Acetaminophen did not result in significant reductions in reaction rates after the booster at 18 months. We conclude that acetaminophen administered at the time of primary vaccination with diphtheria-pertussis-tetanus toxoids-polio can significantly reduce the frequency and severity of common adverse reactions.
Twenty-two patients developed one or more aortoenteric fistulae following aortic reconstruction with a dacron graft. Endoscopy was performed on 11 of these patients on 17 occasions and a preoperative diagnosis was made in eight patients. Fistulous communication was most common between the aorta and duodenum (60%), and a further 30% penetrated into the jejunum and ileum. The mean period from operation to time of diagnosis was 36 months and the mean length of bleeding was 25 days, allowing ample time for preoperative evaluation. Surgery was performed on 21 of the 22 patients with an overall mortality of 77%. The best surgical results were obtained with graft resection, closure of the aorta, and maintenance of circulation by an axillofemoral graft.
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In a prospective study of cephalothin prophylaxis for patients who underwent aortocoronary bypass an unacceptably high rate (44%) of Staphylococcus aureus sternotomy infections occurred in a placebo-treated group. In two other groups of patients, one group given cephalothin intraoperatively and the other given the antibiotic both intra- and postoperatively, such infections occurred with similar frequency (2.6% and 2.1% respectively). This study demonstrates the need for antistaphylococcal agents during aortocoronary bypass operation. No advantage is derived by extending this therapy beyond the operative period.
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