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Biomedical subjects

H J Norton

Publications and source records attributed to H J Norton.

At least 37 records · Page 2Linked to original sources

Pilot study of controlled-release pilocarpine in normal subjects.

OBJECTIVES: Current systemic treatments with sialogogues for patients with xerostomia are limited because of minimal efficacy, short duration of activity, or problems with side effects. The purpose of this pilot study was an initial assessment of safety, efficacy, duration of action, multiple dose tolerance, and side effects of a controlled-release formulation of pilocarpine hydrochloride. STUDY DESIGN: Eight healthy hospitalized subjects were given 15 mg of a controlled-release pilocarpine formulation every 12 hours for three doses. Saliva and blood samples were collected at assigned intervals. Repeated measures analysis and paired t tests were used for statistical analyses. RESULTS: A significant (p < 0.05) increase in both parotid and whole saliva output followed all three doses beginning within 1 hour of dosing and lasting over 10 hours. Mean plasma pilocarpine concentration reached a maximum of 8.2 ng/ml at approximately 1 hour after the first dose, 11.5 ng/ml after the third dose, and declined to near baseline (0.06 ng/ml) 24 hours after the final dose. None of the participants showed evidence of adverse effects including complaints of sweating or gastrointestinal discomfort. CONCLUSIONS: A controlled-release formulation of pilocarpine may overcome the therapeutic weaknesses of current pilocarpine preparations by prolonging salivary secretion and reducing undesirable side effects.

Adult↗

Nosocomial pneumonia in ventilated trauma patients during stress ulcer prophylaxis with sucralfate, antacid, and ranitidine.

OBJECTIVE: To compare the incidence of nosocomial pneumonia in critically injured patients randomized to one of three stress ulcer prophylaxis regimens. DESIGN: Prospective, randomized clinical trial. METHODS: Mechanically ventilated patients admitted to the trauma intensive care unit of a Level I trauma center received sucralfate, antacid, or ranitidine. MEASUREMENTS AND MAIN RESULTS: Two hundred forty-two patients were randomized: sucralfate, n = 80; antacid, n = 82; and ranitidine, n = 80. There was no statistically significant difference in pneumonia rates among the treatment groups (p = 0.875). Pneumonia occurred more frequently in patients with gram-negative retrograde colonization from stomach to trachea (p = 0.02), but this accounted for only 13% of all pneumonias in the study population. The death rate in patients with pneumonia was not statistically different among the three groups. Although 20% developed overt gastrointestinal bleeding, no episode was clinically significant. Mean gastric pH was > 4 in 95% of the study population, including 88% of patients receiving sucralfate. The death rate in the antacid group was significantly higher (p = 0.046) but not because of increased gastrointestinal bleeding or pneumonia. CONCLUSIONS: Our results show no difference in the incidence of nosocomial pneumonia in mechanically ventilated trauma patients during the first 4 days of stress ulcer prophylaxis with sucralfate, antacid, or ranitidine. There is a trend toward decreased pneumonia in the sucralfate group after study day 4. Even after controlling for injury severity, the mortality rate in the antacid group was significantly higher; the reasons for this are unknown.

Adult↗

Aminophylline fails to improve the outcome of cardiopulmonary resuscitation from prolonged ventricular fibrillation: a placebo-controlled, randomized, blinded experimental study.

OBJECTIVES: The purpose of this study was to evaluate systematically the effects of the adenosine antagonist aminophylline on resuscitation outcome in a canine model of postcardioversion nonperfusing rhythm. BACKGROUND: Theoretic considerations and experimental studies indicate that myocardial adenosine accumulation during prolonged ventricular fibrillation might play a significant role in postcardioversion asystole and electromechanical dissociation. A recent uncontrolled clinical trial has suggested that the adenosine antagonist aminophylline might improve the outcome of cardiopulmonary resuscitation from refractory bradyasystolic cardiac arrest. METHODS: Two placebo-controlled, randomized, blinded experimental studies were performed. In protocol 1 (20 dogs), ventricular fibrillation was induced and maintained for 7.5 min. Sixty seconds before cardioversion, dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In protocol 2 (20 dogs), dogs were cardioverted to electromechanical dissociation after 5 min of unsupported ventricular fibrillation. Sixty seconds later, all dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In both experiments, resuscitation efforts were continued until return of spontaneous circulation, or up to 30 min. The primary end point was survival to 1 h. RESULTS: In protocol 1, 4 of 10 dogs survived in the aminophylline group, whereas 7 of 10 dogs survived in the placebo group, a nonsignificant trend toward unfavorable outcome from aminophylline. Pretreatment with aminophylline increased the number of cardioversion applications required to terminate ventricular fibrillation. In protocol 2, 5 of 10 and 6 of 10 dogs survived in the aminophylline and placebo groups, respectively. CONCLUSIONS: The results of this study suggest that aminophylline fails to improve the outcome of resuscitation from prolonged ventricular fibrillation. It does not reverse established electromechanical dissociation and may in fact increase the number of cardioversion applications required to terminate ventricular fibrillation. The rationale for conducting clinical trials with aminophylline during cardiopulmonary resuscitation is questionable.

Aminophylline↗

Neodymium:YAG contact laser photocoagulation of the in vivo canine epicardium: dosimetry, effects of various lasing modes, and histology.

UNLABELLED: Neodymium:YAG laser photocoagulation (LPC) is an investigational technique for the treatment of drug-resistant postinfarction ventricular tachycardia that requires cardiopulmonary bypass and open heart surgery. The purpose of this experimental study was to evaluate the feasibility of contact epicardial LPC to reach subepicardial, deep myocardial, and subendocardial regions without ventriculotomy and to analyze the dose-response relationships of this new technology. In 24 open-chest, closed heart dogs, a total of 219 epicardial laser lesions were generated under sterile conditions. Laser source was a continuous wave 1064 nm Nd:YAG; the delivery system consisted of a 400 mu bare quartz fiber fed into an 8F electrode catheter in direct contact with the epicardial surface. Laser variables were power at 10-15-20 W; lasing time, 6-12-18-24 s; lasing mode, continuous and pulse-pause; fiber mode, optical fiber tip inside and extending out from the electrode catheter. Hearts were harvested at 1 week. Histologic measurements included lesion surface diameter, internal diameter, and depth. RESULTS: Significant linear correlation was found between the total delivered energy and all measured lesion parameters. Transmural lesions were found at energy levels of 270-480 J. Maximum depth measured up to 1.68 cm; at high energies, it was limited by myocardial thickness only. At constant energy levels, power and lasing time did not independently affect lesion dimensions; lasing mode and fiber mode had statistically significant but minor effects. Laser lesions were homogeneous and sharply demarcated without epicardial crater or endocardial thrombus formation. Endocardial surface cooling by circulating blood and the presence of epicardial vessels resulted in modifications in lesion morphology. In 29 out of 74 grossly transmural lesions, there was a 0.082 +/- 0.127 cm thin surviving subendocardium. Forty-five coagulation lesions were truly transmural with no surviving myocardial strands. In conclusion, contact epicardial LPC can result in deep, transmural myocardial coagulation lesions. Lesion dimensions can be adequately controlled by total delivered energy. Closed heart epicardial Nd:YAG laser photocoagulation could become a new, less invasive surgical technique for the treatment of drug-resistant ventricular tachycardia.

Aluminum Silicates↗

Description of an adenovirus type 8 outbreak in hospitalized neonates born prematurely.

An adenovirus (Ad) type 8 outbreak was prospectively studied in a neonatal intensive care unit. Nasopharyngeal secretions were cultured weekly for viruses and clinical information was obtained daily in each infant. Eleven of 112 neonates were infected with Ad; 8 of 9 available isolates represented one variant of Ad 8. The median age at infection was 54 days and the median duration of virus shedding was 2 days. Seven of 11 infants had onset of new symptoms and/or required acute respiratory support; only 2 infants had eye disease. Maternal characteristics, race, gender, age at entry into study and respiratory distress syndrome at birth were similar for both groups. Ad-infected infants tended to have earlier gestations and lower birth weights. Ad-infected neonates stayed longer in the neonatal intensive care unit, required more days of respiratory support and were more likely to develop bronchopulmonary dysplasia. Thus an association was established between lung disease in premature neonates and Ad infection.

Adenovirus Infections, Human↗

Comparison of knitted and woven aortoiliac and aortofemoral Dacron prostheses in the same patient: a 10-year prospective study.

This study represents the final and concise evaluation of all data obtained in a ten-year follow-up period and is a continuation of our previously published investigations. A specially manufactured bifurcated aortic graft with one limb woven and the other knitted was implanted in the aortoiliac or aortofemoral position in 158 patients. During an observation period ranging up to 10 years, no statistically significant difference was found either in platelet adherence or in clinical patency. According to the results of this and previous studies, the pore size of Dacron grafts in these positions does not seem to play any significant role either in platelet adherence or in patency rate. A high mortality rate from cardiovascular disease in the same patient population was also noted.

Aged↗

A comparison of the gastrointestinal side effects of two forms of erythromycin.

BACKGROUND: The gastrointestinal (GI) side effects of erythromycin frequently limit therapy and compliance. PCE Dispertab, a more expensive brand of erythromycin, has been promoted as a well-tolerated new dosage form; however, no studies compare its GI side effects with those of other forms of erythromycin. We compared erythromycin PCE (particles-in-tablet) with E.E.S. (erythromycin ethylsuccinate) to determine whether there is a difference in the incidence and severity of GI side effects. METHODS: This was a multicenter, prospective, single-blind, randomized trial. Observers, but not participants, were blinded to the brand of erythromycin taken until after data analysis. We enrolled ambulatory patients who were at least 18 years old and weighed at least 90 lb for whom erythromycin had been prescribed at a dosage of 1.0 g/d. Subjects were given either the particles-in-tablet form, 333 mg three times daily, or the ethylsuccinate form, 400 mg four times daily, for 10 days and asked to report efficacy, compliance, and the frequency and severity of four GI symptoms (abdominal pain, nausea, vomiting, and diarrhea) in a daily diary. RESULTS: There were no significant differences between the particles-in-tablet and ethylsuccinate forms in incidence of GI side effects (63% and 61%, respectively), average daily GI symptom severity score (0.62 and 0.68, respectively), and GI-related discontinuations (8.5% and 8.2%, respectively). The incidence of moderate or severe nausea was 5% for the particles-in-tablet form and 25% for the ethylsuccinate form (P < .001). CONCLUSIONS: Although ethylsuccinate caused a higher incidence of moderate to severe nausea, there were no differences in the three main outcome measures: incidence of GI side effects, average daily GI-symptom severity score, and GI-related discontinuations. Therefore, we support prescribing erythromycin ethylsuccinate as a first line of treatment because it costs less.

Adult↗

Periprosthetic knee sepsis. The role of irrigation and debridement.

Thirty-three infected total knee arthroplasties were treated by irrigation, debridement, and intravenous antibiotics. These cases were retrospectively reviewed with an average follow-up period of 4.5 years. There were 12 revisions and 21 primary arthroplasties in the series. Thirty-two knees were openly irrigated and debrided, and one was arthroscopically treated. In 20 of 33 knees, infection recurred--a reinfection rate of 61%. The authors attempted to identify factors influencing success and failure of infection eradication. There was a statistically significant improvement in the success rate of knees irrigated and debrided within four weeks of index surgery (p less than .05). No statistically significant correlation was found between success and failure with regard to gender, age, preoperative diagnosis, previous surgery, length of intravenous antibiotics, or time from clinical symptoms to debridement. The authors believe that irrigation and debridement have a role in the immediate postoperative period. Caution should be used in periprosthetic knee infection appearing greater than four weeks from index surgery.

Adult↗

Evaluation of an intravenous immunoglobulin preparation for the prevention of viral infection among hospitalized low birth weight infants.

An intravenous immunoglobulin (IVIG) preparation was evaluated prospectively in hospitalized low birth weight infants for the prevention of respiratory virus infection. Premature neonates were evaluated from October 19, 1987, through July 31, 1988. Nasopharyngeal secretions were cultured weekly for viruses and clinical information was obtained daily on each infant. Ninety-one infants with birth weights between 500 and 1750 g were randomized to receive either IVIG, 500 mg/kg (46 infants), or 5% albumin-normal saline (placebo), 10 ml/kg (45 infants), between Days 3 and 7 of life, 7 days later and every 14 days thereafter for a maximum of 5 doses. Demographic and life event data during pregnancy were similar for IVIG and placebo groups. Birth weight, gestational age, gender, age at entry into the study and incidence of respiratory distress syndrome at birth were also similar in both groups of premature infants. Twenty-six viruses were isolated from 25 infants. There were 13 and 12 infections in the IVIG and placebo groups, respectively. Severity of disease, as measured by clinical factors and outcomes of virus-infected infants were no different in IVIG-treated and placebo groups. Adenoviruses and cytomegalovirus accounted for 57.7 and 23.1%, respectively, of the viral isolates. In this study the use of IVIG did not prevent or modify adenovirus and cytomegalovirus infections in premature infants.

Adenoviridae Infections↗

Prevalence of cytomegalovirus antibody in subjects between the ages of 6 and 22 years.

We determined the prevalence of antibody to cytomegalovirus (CMV) in three groups between 1985 and 1987. Group I consisted of 511 subjects 6-22 y old, group II consisted of 920 subjects 18-21 y old, and group III of 113 subjects 18-22 y old. The overall prevalence of antibody in these three groups was 34%, 24%, and 28%, respectively. Prevalence of antibody in white subjects (24%, 21%, and 24%, respectively) was significantly lower than that in nonwhite subjects. In group I, there was no increase in prevalence with age in white subjects, but the percentage of individuals with antibody increased with age among nonwhite subjects. It is of obvious concern that a large proportion of white women entering childbearing years lack CMV antibody.

Adolescent↗

Symptomatic hyponatremia in rats: effect of treatment on mortality and brain lesions.

Hyponatremia was induced in rats over 3 days with dextrose in water and vasopressin. Eighty-five percent of the rats survived for 5 mo after spontaneous correction of mild hyponatremia. However, spontaneous correction of symptomatic hyponatremia (serum sodium less than 120 meq/l) resulted in 32% survival. Rapid correction of symptomatic hyponatremia by hypertonic saline with an absolute change in serum sodium of greater than 14 and less than 25 meq/l in the first 24 h allowed 100% of the rats to survive for 5 mo without brain lesions. On the other hand, correction of symptomatic hyponatremia with an absolute change in serum sodium of greater than 25 meq/l in the first 24 h resulted in 12% survival and development of brain lesions. We conclude that rapid correction of symptomatic hyponatremia improves survival and is safe if the absolute change in serum sodium is between 14 and 25 meq/l in the first 24 h. Increased mortality and brain lesions are associated with an absolute change in serum sodium of greater than 25 meq/l in the first 24 h.

Animals↗

The older cardiac transplant donor. Relation to graft function and recipient survival longer than 6 years.

A donor age of less than 35 years has long been considered crucial for heart transplantation. Because of limited donor heart supply and increasing demand for cardiac transplants, we attempted to expand the donor pool by using hearts from older individuals. This study was designed to determine if older donor hearts adversely affected cardiac transplant patient prognosis by predisposing them to graft failure from coronary artery disease, ventricular dysfunction, or death. Since 1982, 314 heart transplants have been performed at our institutions. Potential donors were deemed fit if there was no history of heart disease, the chest x-ray film was normal, the electrocardiogram showed nonspecific changes only, and blood pressure was maintained without major pharmacological support. In 47 (15%), donor age was 35 years or greater (group 1: mean age, 39 years; range, 35-49 years). In 267 (85%), donor age was less than 35 years (group 2: mean age, 23 years; range, 2-34 years). Mean group 1 recipient age was 55 years (range, 39-68 years) compared with 46 years (range, 0.7-66 years) in group 2 (p less than 0.01). Pretransplant inotropic support, mechanical support, or both were required in 15 (33%) group 1 patients and in 41 (16%) group 2 patients (p less than 0.01). Group 1 and 2 follow-up intervals were 1.1 +/- 1.0 and 1.8 +/- 1.4 years (mean +/- SD), respectively (p less than 0.0001). Overall survival was 64% versus 65%, group 1 versus group 2, and life table analysis showed no significant difference between the groups. There were three of 17 (18%) deaths due to coronary artery disease in group 1 and 20 of 87 (23%) in group 2 (p = NS). Seven patients in group 2 and none in group 1 required retransplant because of coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Acquisition of cytomegalovirus infection from birth to 10 years: a longitudinal serologic study.

We performed serial serologic tests for cytomegalovirus (CMV) antibody in 177 children born to low- and middle-income families in Houston from 1975 to 1983. Mean duration of participation in the study was 4.8 years (range 1 to 9.6 years). Most rapid acquisition of antibody occurred during the first and second years of life, 13.6% and 12%, respectively; thereafter, annual acquisition varied from 1.5% to 4.6%, up to 10 years. Overall, 59 (33%) of the group were known to seroconvert by age 10 years. This was a minimal figure because of loss to follow-up. Analysis by the Kaplan-Meier method indicated that the probability of remaining seronegative was 65% at age 6 years, and 58% at age 8 years. Variables positively related to seroconversion by multivariate analysis were order of birth, seroconversion in a family member, and breast-feeding. During the first year of life, acquisition of CMV antibody was related to the seroimmune status of the mother. The variables of socioeconomic status, race, age of the mother, and attendance in a day care center did not appear to be related to seroconversion in these children.

Analysis of Variance↗

Thoracoabdominal aortic aneurysms: preoperative and intraoperative factors determining immediate and long-term results of operations in 605 patients.

Graft inclusion and vessel reattachment to openings made in the graft were employed in the treatment of 605 patients with thoracoabdominal aortic aneurysms. These patients were divided into four groups on the basis of the extent of aneurysm. Group I consisted of those patients with involvement of most of the descending thoracic and upper abdominal aorta; group II involved most of the descending thoracic aorta and most or all of the abdominal aorta; group III involved the distal descending thoracic aorta and varying segments of abdominal aorta; and group IV involved most or all of the abdominal aorta including the segment from which the visceral vessels arose. The cause of aneurysm formation was medial degenerative disease in 80%, and dissection in 17%; other causes were responsible in the remaining 3%. The median age was 65 years and associated diseases including aneurysms involving other segments, atherosclerotic occlusive disease, heart disease, chronic obstructive pulmonary disease (COPD), hypertension, and renal insufficiency were frequent. The aneurysm was symptomatic in 70% of cases and rupture had occurred in 4% of cases. There were 54 (8.9%) early (30-day) deaths and 151 late deaths; 400 (66%) patients were still alive 3 months to 20 years after operation, including 60% at 5 years. Statistically significant pre- and intraoperative variables by univariate analysis that were predictive of increased risk of early death were advancing age, associated diseases that included COPD, renal artery occlusive disease, atherosclerotic heart disease, renal insufficiency, and long aortic clamp time. Three of these (age, clamp time, and the presence of COPD) retained significance by multivariate analysis. Variables predictive of risk of late death were age, dissection, extent of aneurysm, rupture, heart disease, cerebrovascular disease, COPD, hypertension, and poor renal function. Age, rupture, renal dysfunction, extent of aneurysm, and dissection retained their significance by multivariate analysis. Variables predictive of neurologic disturbances of the lower extremities included rupture, reattachment of intercostal and lumbar arteries, clamp time, dissection, extent and age. Rupture, reattachment of vessels, dissection, and extent of aneurysm retained significance by multivariate analysis. Thus, the risk of this complication was greatest in patients with extensive lesions (group II) with aortic dissection. The greatest risk of renal failure after operation that required dialysis was in patients who had impaired renal function before operation. Methods employed did not prevent these complications.

Adolescent↗

Long-term assessment of unipolar and bipolar stimulation and sensing thresholds using a lead configuration programmable pacemaker.

Acute and long-term pacing thresholds were measured prospectively in 74 patients with a unipolar/bipolar multiprogrammable pacemaker. At implantation, mean current threshold was 0.48 +/- 0.16 mA with unipolar mode and 0.55 +/- 0.16 mA bipolar mode (p less than 0.01). R wave amplitude at implantation was 7.78 +/- 2.4 mV with unipolar and 7.67 +/- 2.1 mV in bipolar mode (p = NS). During long-term follow-up (mean 9.3 months; range 3 to 24), no clinically significant differences in pacing or sensing thresholds were observed between bipolar and unipolar configurations. Lead configuration was changed 23 times in 11 patients. Symptomatic myopotential inhibition was corrected in two patients by reprogramming to the bipolar pacing mode. High thresholds and loss of capture were corrected in two patients by reprogramming to the unipolar pacing mode. The remaining configurational changes were made for improved sensing or pacing thresholds. This study documents, in a large group of patients, the equivalence of long-term unipolar and bipolar pacing and sensing thresholds and, in addition, demonstrates that lead configuration programmability offered some advantage in a subgroup of patients and may have prevented reoperation in five patients.

Cardiac Pacing, Artificial↗

Comparative effect of disopyramide and ethmozine in suppressing complex ventricular arrhythmias by use of a double-blind, placebo-controlled, longitudinal crossover design.

This placebo-controlled, double-blind, longitudinal crossover study compares the efficacy of disopyramide and ethmozine, a new investigational drug, in suppressing frequent (40 or more per hour) ventricular premature depolarizations (VPDs) in 27 patients completing a 37 day protocol. Although both drugs significantly reduced VPDs relative to placebo, ethmozine was a superior antiarrhythmic drug in ach9eving near-total abolition of VPDs (30% of patients), which was never observed during disopyramide dosing (p less than .05). At the 80% VPD reduction level, ethmozine was effective in 56% of all patients compared with an effectiveness in only 22% of patients during disopyramide therapy (p less than .05). The mean peak plasma level of ethmozine was 0.66 +/- 0.8 micrograms/ml, which significantly fell to a trough level of 0.1 +/- 0.08 micrograms/ml (p less than .001). Mean peak and trough plasma levels of disopyramide exhibited less fluctuation (2.6 +/- 0.9 micrograms/ml vs 2.2 +/- 0.9 micrograms/ml). Ethmozine had no effect on the QT interval, whereas disopyramide prolonged it significantly. Importantly, while disopyramide produced serious side effects in 30% of patients, ethmozine was well tolerated with no statistically significant side effects compared with placebo.

Adult↗