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Biomedical subjects

M J Sullivan

Publications and source records attributed to M J Sullivan.

At least 127 records · Page 7Linked to original sources

In vitro photosensitization of human head and neck squamous cancer cells by dihematoporphyrin-ether.

In vitro experiments were performed to evaluate the direct cytotoxic and photosensitizing effects of dihematoporphyrin-ether (DHE) on the head and neck squamous cancer cell line, UM-SCC-38. Normal fibroblasts, normal cultured keratinocytes, and the UM-MEL-1 pigmented malignant melanoma cell line were used as controls. The parameters of duration of light exposure, drug concentration, and incubation periods were studied. Uptake of DHE by squamous cancer cells, as assessed microscopically by intensity of fluorescence, was rapid and reached a dose-dependent maximum intensity within 10 minutes. Cells were irradiated with polychromatic light with an energy of one milliwatt/cm2 at a distance of 1.5 ft. Cells growing in plastic dishes were incubated in the dark for 1 to 4 hours with DHE in concentrations that ranged from 1.25 to 50 micrograms/ml. The cell monolayers were washed and irradiated for periods of time ranging from 15 to 120 min. Dose-dependent loss of cell viability could be detected by trypan blue dye uptake as early as 1 hour after radiation and continued to increase until 4 hours after light exposure. No further loss of cell viability was observed over the next 10 hours. There was no phototoxicity in the absence of DHE. UM-SCC-38 cells were more sensitive to the photosensitizing effects of DHE than were either normal fibroblasts or malignant melanoma cells. Recovery from the photosensitizing effects of DHE was observed if the DHE-containing medium was removed and the cells were incubated in the dark for periods that ranged from 1 to 14 hours before light exposure. UM-SCC-38 cells recovered more rapidly than normal fibroblasts, normal keratinocytes, or UM-MEL-1 cells.

Adult↗

Diltiazem and exercise performance in patients with chronic atrial fibrillation.

To evaluate the influence of calcium entry blockade (diltiazem 60 mg qid) on exercise capacity in patients with chronic atrial fibrillation, nine men (mean age 65 years) with atrial fibrillation underwent maximal treadmill exercise on and off diltiazem therapy. Heart rate, blood pressure, and measured ventilatory parameters were assessed at a standard submaximal workload (3.0 mph/0% grade), the gas exchange anaerobic threshold (ATge), and maximal exercise. Significant reductions in heart rate at all stages of exercise were demonstrated: maximum heart rate decreased from 171 +/- 30 beats/min to 142 +/- 27 beats/min (17 percent, p less than .01) and submaximal exercise heart rate decreased from 123 +/- 22 beats/min to 96 +/- 16 beats/min (22 percent, p less than .01). However, there were no significant changes in blood pressure or gas exchange data, ie, oxygen uptake, minute ventilation, or respiratory exchange ratio at any of the exercise workloads. These data demonstrate that in patients with chronic atrial fibrillation, diltiazem controls the ventricular rate response throughout exercise without attenuating blood pressure or exercise capacity.

Aged↗

Heightened blood pressure and drinking responsiveness to intracerebroventricularly applied angiotensins in the spontaneously hypertensive rat.

The effects of bolus intracerebroventricular (i.c.v.) injections of angiotensin II (AII) and angiotensin III (AIII) on blood pressure and water consumption were investigated in Okamoto-Aoki spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive controls. Heightened sensitivity to i.c.v. administered AII and AIII was observed in the SHR as compared with WKY and SD strains for both pressor and drinking responses. The results are consistent with the notion that the SHR has a genetic defect that directly perturbs central angiotensinergic transmission. Two types of defects appear plausible, an alteration in the central angiotensin receptor and its associated transduction system and/or a decrease in the efficiency of signal termination. The present results are interpreted to primarily support the second possibility that a dysfunction in central aminopeptidase activity results in an extended life expectancy of angiotensin, and perhaps other peptides, that contribute to the hypersensitivity seen in the SHR.

Angiotensin II↗

An unusual complication of tracheostomy.

Synthetic pediatric tracheostomy tubes have been a major advance for both short- and long-term airway support. We present a late complication from the use of a Shiley silicone pediatric tracheostomy tube (Silastic), and its radiologic manifestations. To our knowledge, this complication has not been previously reported.

Child, Preschool↗

Airway growth following cricotracheal resection in puppies.

A canine animal model was developed to study the effects of cricoid resection on cricoid cartilage growth and subglottic lumen size. Twenty-four healthy, postweanling mongrel puppies, aged 5 to 7 weeks, were randomly divided into two groups. The first group, consisting of 13 puppies, underwent cricotracheal resection with primary anastomosis. A second group, consisting of 11 puppies, served as controls and did not have surgery. Animals from both groups were killed at age 13 weeks. Most of the animals, however, were allowed to mature to adulthood and were killed between age 26 to 28 weeks. Comparative histologic examinations of the laryngotracheal complexes of operated-on and control dogs showed uninterrupted cartilage growth at the anastomosis site after cricotracheal resection. There was no significant difference in the mean area of the cricoid lumen between the two groups when luminal area was adjusted for body weight. The results demonstrate that cricotracheal resection in this animal model does not interrupt cricoid luminal area or cricoid cartilage growth, and provides rationale for further investigation of cricoid resection with primary anastomosis in humans. Cricotracheal resection in growing puppies appears to be an excellent model for further studies in the surgical treatment of acquired subglottic stenosis in infants and children.

Airway Obstruction↗

Position as a variable for cardiovascular responses during exercise.

Twenty-one normal young male subjects underwent resting and exercise (bicycle) radionuclide angiography in the full supine and 70 degrees upright tilt positions in order to examine the effects of position on left ventricular size and performance, hemodynamics, and exercise duration. All subjects also underwent full (90 degrees) upright bicycle ergometry with respiratory gas analysis to establish the level of maximal exercise capacity for each. Body position significantly (p less than 0.05) affected resting and exercise cardiovascular parameters. End-diastolic and endsystolic left ventricular volumes and stroke volume were larger in the supine position, both at rest and during exercise. The cardiac output at rest and during exercise were comparable for the two positions; an increase in resting and exercise heart rate in the 70 degrees tilt position compensated for the reduced stroke volume of this posture. At maximal exercise, the 70 degrees upright position was associated with a greater response in left ventricular ejection fraction, otherwise this parameter was not position related. Exercise capacity, in terms of duration and workload, was significantly higher in the supine (1870 +/- 390 s) and full upright (1830 +/- 250 s) positions than in the 70 degrees tilt position (1730 +/- 260 s). Changes in body position significantly alter parameters of ventricular, cardiovascular, and exercise performance.

Adult↗

The anterior cricoid split in puppies.

The acute and long-term effects of the anterior cricoid split on the subglottis of puppies intubated from 7 to 14 days are documented. The anterior cricoid split acutely increased the intralumenal cricoid surface area in puppies with intubation-induced airway injury. An intense inflammatory response with mucosal ulceration and granulation tissue is elicited by 14 days of intubation by using the canine model of induced subglottic stenosis developed by Supance et al. [19]. When animals intubated for 14 days underwent an anterior cricoid split on day 7, the airway appears essentially normal by day 14. The split cricoid cartilage maintained a 'U' configuration following the procedure. The region of deficient cartilage anteriorly is bridged by fibrous tissue with normal epithelium lining the lumenal surface. Splitting the cricoid cartilage anteriorly increased the intralumenal area and no long term complications resulted from the procedure. The mechanisms by which the anterior cricoid split expands the airway intralumenal area while maintaining airway support have been reviewed.

Animals↗

Comparative ototoxicity of gentamicin in the guinea pig and two strains of rats.

Gentamicin ototoxicity and nephrotoxicity were compared in two strains of rats, Sprague-Dawley and Fisher-344, and in the Hartley albino guinea pig. Treatment groups consisting of 8 male rats of each strain and four male guinea pigs were dosed subcutaneously for 14 days with either 80 or 100 mg/kg of gentamicin sulfate in saline. Brainstem auditory evoked response (BAER) thresholds were recorded from each animal in each group on day 11 post-administration. Blood urea-nitrogen and serum creatinine were measured in blood obtained on day 11 post-administration as measures of nephrotoxicity. Kidney weight/body weight ratios were also determined. Loss of sensory hair cells was observed in the basal region of the organ of Corti from all animals treated with 100 mg/kg of gentamicin. The hair cell loss and BAER threshold elevations were greatest in the guinea pigs. Fisher-344 rats showed more extensive hair loss and greater BAER threshold elevations than Sprague-Dawley rats. The Fisher-344 rats exhibited increased blood urea-nitrogen and kidney weight/body weight ratios. Sprague-Dawleys did not suffer any nephrotoxic effects. These data indicate that the Fisher-344 rat is useful animal in which to study aminoglycoside ototoxicity as it exhibits both functional and morphological changes after gentamicin administration.

Animals↗

Delayed cerebroventricular metabolism of [125I]angiotensins in the spontaneously hypertensive rat.

This study was designed to evaluate the hypothesis that impaired brain angiotensin signal termination contributes to the sustained blood pressure elevations noted in the genetically hypertensive rat model of human essential hypertension. A technique that combined the intracerebroventricular injection of [125I]angiotensins, followed by focused microwave fixation to stop all peptidase activity and subsequent HPLC analyses, was used for determining half-lives of [125I]angiotensin II and [125I]angiotensin III in the ventricular space. The results indicate that the spontaneously hypertensive rat evidenced significantly longer half-lives for intracerebroventricularly injected [125I]angiotensin II over those measured for the Wistar-Kyoto and Sprague-Dawley normotensive rat strains: 45.0, 27.2, and 25.0 s, respectively. This was also true for intracerebroventricularly administered [125I]angiotensin III: 19.5, 11.4, and 9.0 s, respectively. These results support the notion that a dysfunction in central aminopeptidase activity in the spontaneously hypertensive rat may result in prolonged half-lives of endogenously synthesized angiotensins II and III, which are known to serve as ligands at central angiotensin receptors responsible for the control of cardiovascular function. The extended half-lives of these ligands may contribute to the sustained elevations in blood pressure observed in this animal model.

Angiotensins↗

Malignant parotid gland tumors: a retrospective study.

This is a comprehensive retrospective study (1965-1984) of 130 patients with malignant parotid gland tumors. Patients were studied by comparison of presenting symptoms, histopathologies, treatments, disease-free intervals, and ultimate intervals. Facial paralysis was noted on presentation in 23% of the cases and regional neck node metastases were noted in 13%. Both findings correlated with prognosis. Seventy patients underwent surgery alone and 30 patients received combined therapy. The remaining patients were excluded from the study. The overall 5-year survival rate was 50%, with a 44% risk of recurrence. Fifty-six percent of the patients whose conditions subsequently recurred had their facial nerves sacrificed at time of surgery. Selected patients who received combined therapy experienced better local regional control and a prolonged disease-free interval as compared with those who underwent surgery alone. Combined therapy, however, provided no survival benefit for this group of patients. Adjuvant radiation therapy is recommended in the treatment planning of selected malignant tumors of the parotid gland.

Adenocarcinoma↗

Intraparotid facial nerve neurofibroma.

Neurogenic neoplasms of the intraparotid facial nerve are uncommon and are usually diagnosed intraoperatively by tissue biopsy. Fifty-six cases of primary neurogenic neoplasms involving the facial nerve have been reported. The majority of these have been schwannomas. A case of a solitary neurofibroma involving the main trunk of the facial nerve is presented. Schwannomas and neurofibromas have distinct histological features which must be considered prior to the management of these tumors. The management of neurogenic tumors associated with normal facial function is a particularly difficult problem. A new approach for the diagnosis and management of neurogenic neoplasms is described utilizing electroneurography.

Adult↗

Surgery of the bony and cartilaginous dorsum.

Successful management of the bony and cartilaginous dorsum requires accurate preoperative assessment and surgical planning. Careful management of the dorsum avoids most of the common pitfalls in rhinoplasty and contributes to patient satisfaction.

Cartilage↗

Hemodynamic and metabolic responses of the exercising lower limb of humans.

This study was performed to determine the hemodynamic and metabolic responses of the human lower limb during exercise. Blood flow to the lower extremity was measured and sampled for lactate, catecholamines, and oxygen content in 12 normal men at rest, at all stages of bicycle ergometry, and during the postexercise recovery period. Whole body oxygen consumption and cardiac output were recorded throughout the experiment. Limb blood flow increased in a near-linear manner with both whole body and limb oxygen consumption. Although cardiac output rose with increasing whole body oxygen consumption, the increment in cardiac output diminished between submaximal and maximal levels of exercise resulting in a curvilinear relationship between blood flow to the exercising limb and cardiac output; this indicates that a major redistribution of cardiac output to the exercising lower extremity occurs, particularly at maximal levels of exercise. Covariance analysis suggested that limb oxygen consumption was the primary determinant of limb blood flow and limb vascular resistance during exercise. Arterial and venous lactate and catecholamine concentrations, obtained from the exercising lower extremity, could not be implicated as factors having a major influence on blood flow to that limb. The rate of lactate efflux from the limb during and after exercise, however, was directly related to limb blood flow.

Adult↗

Binding, degradation and pressor activity of angiotensins II and III after aminopeptidase inhibition with amastatin and bestatin.

In the metabolism of angiotensin peptides by tissue angiotensinases, aminopeptidases A, B, M and leucine aminopeptidase have been identified as being particularly effective. Because the inhibitory actions of amastatin (AM) and bestatin (BE) are relatively specific for these aminopeptidases, we have examined the effects of these inhibitors on the binding, degradation and pressor activity of angiotensin II (AII) and angiotensin III (AIII). Within 30 min at 37 degrees C, significant metabolism of 125I-AII and 125I-AIII by homogenates of a block of tissue containing hypothalamus, thalamus, septum and anteroventral third ventricle regions of the brain was observed. A majority of 125I-AIII metabolism was due to soluble peptidases, whereas that of 125I-AII primarily resulted from membrane-bound peptidases. AM, BE and reduced incubation temperatures significantly decreased the metabolism of 125I-AII and 125I-AIII. After appropriate adjustments to reflect the proportion of intact radioligand bound, temperature- or inhibitor-induced decreases in metabolism were matched by corresponding increases in specific binding. Heat-treated bovine serum albumin, as a nonspecific peptidase inhibitor, had no effect on either the metabolism or binding of the ligands used. In accordance with their actions in vitro, i.c.v. administration of AM and BE prolonged the pressor activity of subsequently applied AII and AIII. Unexpectedly, the amplitude of the pressor response to AIII was increased by BE, whereas that to AII was decreased by AM. The results of this study indicate that the metabolism of AII and AIII by aminopeptidases is relatively specific and acts to modulate the actions of these peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopeptidases↗

Simulated cardiac arrests for monitoring quality of in-hospital resuscitation.

To improve monitoring of the quality of resuscitation after cardiac arrest staff performance in 47 simulated cardiac arrests was assessed. The exercise revealed many unsuspected deficiencies. Nurses did not apply mouth-to-mouth resuscitation, use the hand-held defibrillator, or give supplementary oxygen while awaiting the arrival of the arrest team; the availability of different models of defibrillators led to confusion and delay in defibrillation; suction equipment did not suck hard enough; lack of special protocols for areas such as paediatrics led to medication errors. Remedial measures included in-service education for nurses, purchase of new defibrillators and portable suction machines, and preparation of detailed protocols for paediatric, haemodialysis, and obstetric units. The use of mock arrests helps in the immediate and definitive identification of deficiencies in the quality of cardiac resuscitation. Furthermore information obtained by the use of mock arrests spurs physicians and hospital administrators to correct the deficiencies promptly.

Child↗

Usefulness of low dose guanfacine, once a day, for 24-hour control of essential hypertension.

The 24-hour duration of the antihypertensive effect of guanfacine, a centrally acting alpha 2-adrenoceptor agonist administered once a day, was demonstrated in a 12-week, multicenter, double-blind, placebo-controlled study. Two hundred and forty-nine patients who remained mildly to moderately hypertensive following a 5-week period, during which they had been weaned from previous antihypertensive medications and stabilized on 25-mg chlorthalidone taken once a day, were involved. Of the 249 patients, 126 received guanfacine as a step-2 agent and 123 received placebo. Both groups were further subdivided so that blood pressure (BP) measurements were determined either 12 or 24 hours after dosing. The initial dose of guanfacine was 1 mg/day, which could be raised 1 mg at 2-week intervals to a maximum daily dose of 3 mg/day at the discretion of each investigator. The daily dose could also be lowered by 1 mg at 2-week intervals, depending on patient response. The mean 24-hour reductions with guanfacine in sitting diastolic BP (-11 mm Hg), systolic BP (-14 mm Hg) and mean arterial pressure (-12 mm Hg) were statistically significant (p less than 0.01) compared with the reductions in BP with placebo. Heart rate also decreased with guanfacine, but no clinically relevant bradycardia (less than 60 beats/min) was observed. Dry mouth (47%), constipation (16%), fatigue (12%) and drowsiness (4%) were the most frequently reported side effects. The highly acceptable side-effects profile of guanfacine was also indicated by the small percentage of patients (7%) who prematurely left the study because of adverse reactions.

Administration, Oral↗