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Biomedical subjects

H E Evans

Publications and source records attributed to H E Evans.

At least 19 recordsLinked to original sources

The effect of 60% oxygen on air-space enlargement and cross-linked elastin synthesis in hamsters with elastase-induced emphysema.

Hyperoxia is routinely administered to patients with severe emphysema. To gain insight into the possibly adverse effects of such treatment, hamsters were exposed to 60% oxygen for 5 days, beginning 48 h after induction of pulmonary emphysema by intratracheal instillment of pancreatic elastase. Control groups consisted of (1) animals instilled with elastase and exposed to room air, (2) animals instilled with saline and exposed to 60% oxygen, and (3) animals instilled with saline and exposed to room air. Cross-linked elastin content and synthesis in the lung were measured immediately following termination of hyperoxia, and the mean linear intercept was determined 4 wk later. Cytologic examination of bronchoalveolar lavage fluids was also performed. Statistical significance was determined by a two-way analysis of variance. Results indicate that exposure to 60% oxygen significantly affected (p less than 0.05) air-space size, causing a 51% increase among elastase-treated hamsters (124 versus 82 microns) but only a 4% increment among saline-treated animals (52 versus 50 microns). When compared to other groups, animals treated with both elastase and hyperoxia had a significantly greater (p less than 0.01) percentage of neutrophils (28%) in their lung lavage fluids immediately following exposure to 60% oxygen. Although total lung elastin content was not altered by hyperoxia at this time, labelling of elastin cross-links was significantly increased (p less than 0.05). These studies demonstrate that exposure to 60% oxygen enhances elastase-induced lung injury. They also raise the possibility that oxygen therapy may, under certain circumstances, accelerate the progression of human emphysema.

Animals

Improvement of neutrophil migration by systemic vitamin C in neonates.

The effect of oral vitamin C on chemotactic and random migration of neutrophils in 20 neonates (10 normal and 10 with suspected sepsis) was evaluated. Chemotaxis and random migration were studied between 24 and 48 hours of life, before and 24 hours after the administration of 400 mg (divided in four doses) of vitamin C. Chemotactic migration improved by 65% and random migration by 57% following vitamin C administration. The significant improvement in chemotaxis (P less than .01) and random migration may justify the inclusion of vitamin C as an adjunct to the therapy of neonatal sepsis.

Ascorbic Acid

Morphology and embryological interpretation of a congenital occipito-atlanto-axial malformation in a dog.

A clinical, radiological, and morphological study of a congenital occipito-atlanto-axial malformation in a 13-week-old male Saint Bernard dog that became suddenly tetraplegic at 8 weeks is described. The dog was recumbent, had generalized muscle atrophy, but was alert and responsive. Pain was elicited when the head-neck junction and the cervical vertebrae were palpated, and a bony abnormality was palpated at the occiput and atlas. Clinical signs of upper motor neuron and general proprioceptive deficits in all four limbs were compatible with a focal lesion in the cervical spinal cord. Plain radiographs of the head and neck revealed malformation of the occipital bones, atlas, and axis, unilateral atlanto-occipital fusion, and atlanto-axial subluxation. At necropsy the right half of the atlantal neural arch was fused to the right exoccipital bone. On the axis, the dens was small, malformed, and deviated to the left; the transverse processes were enlarged; and the spinous process was small with a cleft caudally. The spinal cord was severely compressed at the level of the atlanto-axial articulation, and histological examination revealed extensive loss of neuronal cell bodies, axons, myelin, and the central canal. Reactive astrogliosis was also extensive. After a discussion of normal and abnormal development of the vertebral column and its joints, it was concluded that a failure of normal joint development at about 30 days of gestation in the dog could lead to congenital occipito-atlanto-axial malformation.

Animals

Aerosol inhalation teaching device.

To facilitate teaching of inhalation technique to children, we have developed an aerosol inhalation teaching device by modifying the jacket of a canister nebulizer so that inhalation is accompanied by a horn sound and a flashlight is turned on when the canister is actuated. The device was evaluated in 33 children with asthma who had either never used a canister nebulizer (13 patients) or used incorrect technique (20 patients). The inhalation technique was first taught with conventionally, that is, verbal directions and demonstration with a canister nebulizer for 10 minutes. Only 10 (30%) of 33 children learned the technique. The remaining 23 were then taught with the special device. Twenty of 23 learned the technique within 10 minutes, but three others took longer. In a second study, 22 children, 11 of whom were beginners and 11 incorrect users, were instructed with the teaching device from the beginning. Seventeen (77%) learned the technique within 10 minutes; five others took longer. Most children can be taught the aerosol inhalation technique with this easily constructed device.

Adolescent

Single-dose gentamicin therapy of recurrent urinary tract infection in patients with normal urinary tracts.

Results of single-dose therapy of urinary tract infections in pediatric patients have been contradictory mainly because of selection criteria. We evaluated the efficacy of a single dose of gentamicin in patients with normal urinary tracts and in whom urinary tract infections were recurrent. Twenty-one patients were included in the study, and a similar number in a conventional group given treatment for 10 days. Cure rate was 100% in both groups. The recurrence rates of 67% in the study and 52% in the conventional group were comparable. Single-dose therapy seems to have a role in the treatment of urinary tract infection in the absence of urinary tract malformation.

Adolescent

Role of neutrophil chemotaxis in the pathogenesis of urinary tract infection.

Status of neutrophil chemotaxis was evaluated in seventeen infants and children with acute urinary tract infection. Four different chemotactic factors including those generated by patient's own invading pathogens were studied against patient cells. Chemotactic migration was found to be depressed during active infection and gradually returned to normal after successful eradication of the organisms. During a second episode of UTI chemotaxis again became defective. Inhibition of neutrophil chemotaxis seems to be at least one mechanism in the pathogenesis of UTI. Counteracting the suppression may play a role in modifying the inflammatory process and/or enhancing recovery during therapy.

Adolescent

Evaluation of inhalation aids of metered dose inhalers in asthmatic children.

Many patients have incorrect aerosol inhalation technique with metered dose inhalers (MDI). Several inhalation aids have been developed and marketed for these patients. Even those who have correct inhalation technique may benefit from these devices. We compared bronchodilator efficacy of two puffs of albuterol aerosol administered either directly from a MDI mouthpiece, or from an inhalation aid (InspirEase, Aerochamber, Aerosol Bag) in 20 children who had previously demonstrated proper inhalation technique. The children received two puffs of aerosol from a MDI in each of two modalities tested each day on four different days (double blind). One modality contained albuterol aerosol and the other placebo. Pulmonary function was tested before and at 15, 30, 60, 120, and 180 minutes after treatment. Forced expiratory volume in 1 second (FEV1) increased similarly after all four modes of administration. Six patients who had incorrect inhalation technique benefited from the three inhalation aids. The aerosol bag and InspirEase produced slightly greater bronchodilator response than the Aerochamber. The inhalation aids are useful devices for those who have incorrect inhalation technique, but those who have correct technique do not derive any benefit from these devices.

Adolescent

Prenatal development of the composite occipito-atlanto-axial synovial joint cavity in the dog.

In the dog, the synovial cavities of the atlanto-occipital and atlanto-axial joints communicated to form a single large composite joint cavity. The prenatal development of this composite occipito-atlanto-axial joint cavity was studied by examining 26 serially sectioned dog embryos and fetuses that ranged in size from 19 to 68 mm crown-rump length, and were between 30 and 42 days of gestational age. In the composite occipito-atlanto-axial joint, trilaminar interzones developed at 19-22 mm (30-31 days), joint cavities opened at 27-32 mm (33-34 days), and the atlanto-occipital and atlanto-axial cavities first communicated at 48 mm (37 days).

Animals

Defective neutrophil chemotaxis in patients with alpha-1-antitrypsin deficiency.

The PMNs of five infants and children with homozygous alpha-1-antitrypsin deficiency (PiZZ phenotype) revealed defective chemotactic migration, and their PiZZ sera generated a higher quantity of chemotactic factor(s). This defect(s) might have been responsible for the increased incidence of infections found in our deficient PiZZ patients. Further studies are needed to clarify the role of defective chemotaxis in the pathogenesis of chronic lung disease associated with the PiZZ state.

Chemotaxis, Leukocyte

Oxidant-mediated lung disease in newborn infants.

High concentrations of oxygen are administered with increased airway pressure to most preterm neonates with respiratory distress syndrome (RDS). Among 20% to 30% of survivors a form of chronic lung disease, bronchopulmonary dysplasia (BPD), develops. Its pathogenesis may include tissue damage caused by the superoxide anion (O2-) and other free oxygen radicals. Animal experiments and other data suggested a rationale for superoxide dismutase (SOD) administration in an effort to prevent or ameliorate BPD. Our preliminary studies in 19 prematures with RDS demonstrated its safety in human newborns and permitted measurement of its plasma levels. No adverse clinical findings occurred, and laboratory parameters were unchanged. Subcutaneous administration (0.25 mg/kg) of bovine SOD led to detectable levels at 1 1/2 h (mean 0.22 microgram/ml), with a slight rise to a higher peak at 2 1/2-4 h and a plateau over the remainder of the 12-h interval. Following doses 2-5, peak levels of 0.64 microgram/ml occurred at 4-8 h. With this background, a prospective double-blind controlled study of 45 neonates (mean gestational age, 29 weeks; birth weight, 1,100 g) showed a statistically significant reduction in prevalence of clinical and X-ray signs of BPD with fewer days of continuous positive airway pressure required. The safety and pharmacokinetics of bovine SOD were confirmed.

Antioxidants

Lack of cardiac effect from repeated doses of albuterol aerosol. A margin of safety.

To simulate the pattern of use by some patients at home, we studied the effect of frequently repeated inhalation of albuterol aerosol on cardiac rhythm. Fifteen stable outpatient asthmatic children, ages 9-14 years were treated with two puffs of albuterol aerosol (180 mcg) followed either by hourly placebo or hourly albuterol aerosol for 5 hours (10 puffs = 900 mcg) in a randomized, double-blind crossover study. Cardiac rhythm was Holter monitored and pulmonary function was tested hourly for 5 hours. Heart rate (HR) was analyzed at hourly intervals. Pretreatment heart rate of 95.4 bpm +/- 1.9 SEM declined by 0.4-3 (bpm) after single dose and declined by 2.2-5.6 (bpm) from 99.2 (bpm) +/- 2.3 SEM during multiple doses. No one developed arrhythmia, and side effects were infrequent on either day. Forced expiratory volume in 1 second (FEV1) increased similarly on both regimens. It remained stably elevated on the multiple doses, but it started to decline at 120 minutes after the single dose. Our study shows a substantial margin of safety in administration of albuterol aerosol to asthmatic children.

Adolescent

Inherited homeotic midfacial malformations in Burmese cats.

During the past three decades, Burmese cats have been selected for a shorter muzzle and a more rounded face. Recently there arose a line of these animals that consistently exhibit such a brachycephalic appearance; unfortunately, approximately 25% of these kittens are born with a neonatal lethal midfacial malformation. The abnormality is characterized by agenesis of all derivatives of the medial nasal prominence; lateral duplication of most derivatives of the maxillary process; including the canine teeth and whiskers fields; telencephalic meningoencephalocele; and secondary ocular degeneration. The anatomy, embryology, and pattern of inheritance of this unique midfacial malformation are described.

Abnormalities, Multiple

Phototherapy effect on the incidence of patent ductus arteriosus in premature infants: prevention with chest shielding.

Patent ductus arteriosus is common among premature neonates, especially those with birth weights less than 1,500 g. In vitro, room light inhibits the contraction of immature piglet's ductal rings. Because phototherapy is used frequently from the first days of life to treat jaundice in preterm neonates, we compared the occurrence of patent ductus arteriosus among premature infants exposed to this intense light source with those whose chests were shielded. Seventy-four babies with respiratory distress syndrome were randomly assigned to either a treatment group (chest shielded with aluminum foil while on phototherapy, 36 babies) or control group (no shield, 38 babies). All were on radiant warmers, received mechanical ventilation for respiratory distress syndrome, and phototherapy (Air Shields model PTU 78-1) from day 1 of life. Irradiance was maintained at greater than 4.0 microW/cm2/nm in all cases. Although both groups had similar birth weights, gestational ages, severity of respiratory distress syndrome, intravenous fluid intake, and duration of phototherapy, the incidence of patent ductus arteriosus was significantly less in the shield group (shield 11/36 v No shield 23/38; P = .009). Patent ductus arteriosus murmurs developed in shielded patients at a later date, they required less vigorous treatment (ie, indomethacin), and they had shorter hospitalizations (74 v 85 days; P less than .05). The significant reduction of patent ductus arteriosus with shielding suggests that phototherapy may play a role in the occurrence of patent ductus arteriosus in premature infants. Shielding may be a practical method to decrease this common complication should this initial observation be confirmed.

Ductus Arteriosus, Patent

Pharmacokinetic evaluation of cefoperazone in infants.

The pharmacokinetics of cefoperazone were evaluated in 25 infants (mean age, 26 days) after intramuscular and intravenous routes of administration. The levels in blood that were achieved were severalfold higher than those required to inhibit common pathogens. The mean half-life of 240 min was one-half of that observed in 1- to 2-day-old infants but about twice that seen in adults. Further evaluation is needed to study the efficacy of the drug in infants and children.

Cefoperazone