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Biomedical subjects

M J Sullivan

Publications and source records attributed to M J Sullivan.

At least 19 recordsLinked to original sources

Ondansetron antiemetic therapy for chemotherapy and radiotherapy induced vomiting in children.

AIM: To evaluate ondansetron as the sole antiemetic in children treated with emetogenic chemotherapy and irradiation. METHODS: Fifteen children aged 3-11 years were studied. Seven had acute lymphoblastic leukaemia, two acute myeloid leukaemia, two lymphoma and four had other tumours. Ondansetron 5 mg/m2 IV or 4 mg by mouth was given immediately before chemotherapy or radiation treatment and continued eight hourly for 24 hours. Nausea and vomiting was assessed during treatment and for the next 48 hours, and graded using WHO criteria. RESULTS: Thirty-eight courses of chemotherapy were assessed, 27 severely emetogenic and 11 moderately emetogenic. Two included total body irradiation. The most severe nausea and vomiting was grade 2 (transient vomiting) reported in six children. Nausea and vomiting was abolished on subsequent courses in four of these children by increasing the ondansetron dose frequency to six hourly. The remaining children experienced no nausea or vomiting (n = 7) or only nausea (n = 2). Nausea and vomiting were each completely controlled in 27 courses. CONCLUSIONS: Ondansetron is a cost effective and safe antiemetic in children receiving chemotherapy and total body irradiation, minimises weight loss on treatment and enables outpatient chemotherapy in some cases.

Child

Amastatin potentiates drinking elicited by osmotic stimuli: evidence for peptidergic mediation of intracellular dehydration-induced thirst.

Aminopeptidase inhibitors have been demonstrated to enhance the behavioral effects of both exogenously applied and endogenously released neuropeptides. In this study peptidase inhibitors were used as probes for involvement of central neuropeptides in osmotically-induced drinking behavior. Intracerebroventricular (i.c.v.) injections of amastatin, an aminopeptidase A inhibitor, potentiated water intake induced by subcutaneous injections of hypertonic saline. Drinking responses to i.c.v. infusions of hypertonic saline were also enhanced when amastatin was added to the infusions. The effect was not attenuated by the angiotensin receptor antagonist, [Sar1, Thr8]angiotensin II, which suggests that angiotensins do not play a role in the over-drinking. Drinking responses to centrally infused hypertonic saline were not enhanced by i.c.v. thiorphan, an endopeptidase inhibitor; this provides evidence that the effects of amastatin are specific for a particular class of peptidases. These results suggest that there is a role for an endogenous, non-angiotensinergic brain peptide in the mediation of osmotic thirst.

Aminopeptidases

Lateral arm free flap in head and neck reconstruction.

The lateral arm fasciocutaneous free flap is a versatile donor site of sensate soft tissue for reconstruction and augmentation of the head and neck. The lateral arm flap can be quickly harvested without interference to the head and neck team and with minimal morbidity to the patient. For these reasons, this flap has become our soft-tissue flap of choice.

Arm

Central hemodynamic response to exercise in patients with chronic heart failure.

Although the pathophysiology of exercise intolerance in patients with chronic heart failure (CHF) is not fully understood, it appears that the cardiac output response plays an important role in limiting exercise in this disorder. Although previous studies have demonstrated that peak VO2 is not related to left ventricular (LV) ejection fraction, studies have consistently identified peak exercise cardiac output as an important predictor of peak VO2. It is likely that a reduced cardiac output to work rate relationship in CHF causes hypoperfusion of both working skeletal muscle and visceral organs, which leads to early anaerobic metabolism and fatigue. Several factors may influence the cardiac output response in patients with severe systolic LV dysfunction, including heart rate, diastolic LV function, and the mitral regurgitation fraction. Although stroke volume increases through use of the Frank-Starling mechanism in many patients with severe systolic LV dysfunction, some patients with this disorder may not increase stroke volume during exercise due to diastolic LV dysfunction or pericardial constraint. The finding that this latter group has more severe exercise intolerance suggests that diastolic dysfunction may further decrease peak VO2 in this disorder. Variations in the mitral regurgitation fraction also have been found to have an important effect on exercise stroke volume in some patients with CHF. Therefore, the finding that LV ejection fraction at rest or during exercise is not related to peak VO2 in patients with systolic LV dysfunction does not necessarily indicate that central hemodynamics do not play a role in exercise intolerance. Rather, it is likely that variability in the LV ejection fraction with exercise, which does not take variable increases in LV end-diastolic volume or mitral regurgitation into account, plays only a modest role in determining the stroke volume and cardiac output response to exercise in patients with severe systolic dysfunction.

Chronic Disease

Dissociation of experimentally induced drinking behavior by ibotenate injection into the median preoptic nucleus.

Adult male Sprague-Dawley rats were injected with either ibotenic acid (5 micrograms/1 microliter) or vehicle in the ventral median preoptic nucleus. The injections were given during either methoxyflurane or ketamine anesthesia. None of the rats injected with ibotenic acid were adipsic after surgery. After at least one week of recovery, all rats were tested for drinking responses to angiotensin II (1.5 and 3 mg/kg s.c.) and hypertonic saline (3% and 12% 1 ml/100 g b.wt.). Rats injected with ibotenic acid during methoxyflurane anesthesia drank significantly less than the vehicle injected control group in tests with both doses of angiotensin II and both concentrations of hypertonic saline. The rats that were injected with ibotenic acid during ketamine anesthesia drank significantly less than the control group when tested with 3% hypertonic saline but not when tested with angiotensin II. Histological examination of the injection sites indicated significant reductions in the volume of the median preoptic nucleus only in rats that had been injected with ibotenic acid during methoxyflurane anesthesia. The results are consistent with the interpretation that the drinking response to angiotensin II is dependent upon the integrity of neurons with postsynaptic N-methyl-D-aspartate receptors within the median preoptic nucleus.

Analysis of Variance

Stroke volume increases by similar mechanisms during upright exercise in normal men and women.

To define the effects of gender on stroke volume control during upright exercise in normal subjects, we examined central hemodynamics in 34 men and 27 women during staged bicycle ergometry. Central hemodynamics were assessed by right-sided cardiac catheterization and simultaneous radionuclide angiography. Left ventricular end-diastolic and end-systolic volumes were calculated from the stroke volume (by direct Fick) and the corresponding left ventricular ejection fraction. Men were larger than women (1.85 +/- 0.11 vs 1.65 +/- 0.13 m2, p less than 0.001) but groups were matched for age (39 +/- 12 vs 36 +/- 9 years, p = 0.27). Oxygen consumption at peak exercise was higher in men than in women (2.51 +/- 0.50 vs 1.74 +/- 0.30 liters/min, p less than 0.001) but was not different when adjusted for body weight (31.5 +/- 8.1 vs 28.4 +/- 6.4 ml/kg/min, p = 0.14), indicating similar levels of overall fitness in the 2 groups. At rest and during submaximal and maximal exercise, stroke volume and left ventricular end-diastolic and end-systolic volumes were higher in men than in women, but there were no intergroup differences in stroke volume index, left ventricular ejection fraction, and left ventricular end-diastolic or end-systolic volume indexes. Comparison of derived regression equations of cardiac index, stroke volume index and left ventricular end-diastolic and end-systolic volume indexes revealed no differences in the time course or magnitude of changes with respect to oxygen consumption, expressed as percentage of peak oxygen consumption, in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of exercise training on cardiorespiratory function in men and women older than 60 years of age.

This study reports the physiologic effects of up to 14 months of aerobic exercise in 101 older (greater than 60 years) men and women. After an extensive baseline physiologic assessment (Time 1), in which aerobic capacity and blood lipids were measured, subjects were randomized to an aerobic exercise condition (cycle ergometry, 3 times per week for 1 hour), nonaerobic yoga (2 times per week for 1 hour), or a waiting list nonexercise control group for 4 months, and then underwent a second (Time 2) assessment. At the completion of the second assessment, all remaining subjects completed 4 months of aerobic exercise and were reevaluated (Time 3). Subjects were given the option of participating in 6 additional months of supervised aerobic exercise, and all available subjects completed a fourth assessment (Time 4) 14 months after their initial baseline evaluation. Results indicated that subjects generally exhibited a 10 to 15% improvement in peak oxygen consumption after 4 months of aerobic exercise training, and a 1 to 6% improvement in aerobic power with additional aerobic exercise training. On the other hand, subjects, especially men, continued to have improvements in submaximal exercise performance (i.e., anaerobic threshold). In addition, aerobic exercise was associated with an improved lipid profile; subjects participating in aerobic exercise for up to 14 months exhibited increased levels of high-density lipoprotein cholesterol. Maintenance of regular aerobic exercise for an extended time interval is associated with greater cardiovascular benefits among older adults than has been reported previously.

Aged

Mandible reconstruction with vascularized bone grafts. A histologic evaluation.

To our knowledge, a histologic evaluation of bone healing after mandible reconstruction with vascularized human bone grafts has not been previously reported. Serial sections through both the decalcified graft and the junction between mandible and graft were evaluated in four patients who required surgical removal of their reconstructed mandibles. A failed scapular bone graft that had been wrapped within a pectoralis major myocutaneous flap for salvage following pedicle thrombosis showed markedly resorbed but viable bone with a fibrous union to the native mandible. Viable vascularized grafts without evidence of ongoing resorption characterized an iliac osteocutaneous bone graft and two scapula osteocutaneous grafts that healed with continuity of healthy bone between graft and mandible. Observations from the evaluation of these specimens are made regarding bone circulation, bone union, and bone graft survival as they occur clinically. Implications regarding the techniques of bone plating and indications for use of vascularized bone in mandible reconstruction are discussed.

Bone Transplantation

Protracted Lhermitte's sign following head and neck irradiation.

Lhermitte's sign is a rare complication of head and neck irradiation involving the delivery of dose to the cervical spinal cord. Although uncommon, symptoms of lightning-like electric sensations spreading into both arms, down the dorsal spine, and into both legs on neck flexion following head and neck irradiation, causes great concern in both the patient and the physician. This spontaneously reversible phenomenon is important for the otolaryngologist and radiation oncologist to recognize and discuss. A particularly severe and protracted case of Lhermitte's sign involving a patient recently completing a radical course of radiation for nasopharyngeal carcinoma is described in detail, including a review of the literature surrounding the cause and management of this condition.

Carcinoma, Squamous Cell

Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism.

Invasive cardiopulmonary exercise testing was performed in 7 patients who presented with congestive heart failure, normal left ventricular ejection fraction and no significant coronary or valvular heart disease and in 10 age-matched normal subjects. Compared with the normal subjects, patients demonstrates severe exercise intolerance with a 48% reduction in peak oxygen consumption (11.6 +/- 4.0 versus 22.7 +/- 6.1 ml/kg per min; p less than 0.001), primarily due to a 41% reduction in peak cardiac index (4.2 +/- 1.4 versus 7.1 +/- 1.1 liters/min per m2; p less than 0.001). In patients compared with normal subjects, peak left ventricular stroke volume index (34 +/- 9 versus 46 +/- 7 ml/min per m2; p less than 0.01) and end-diastolic volume index (56 +/- 14 versus 68 +/- 12 ml/min per m2; p less than 0.08) were reduced, whereas peak ejection fraction and end-systolic volume index were not different. In patients, the change in end-diastolic volume index during exercise correlated strongly with the change in stroke volume index (r = 0.97; p less than 0.0001) and cardiac index (r = 0.80; p less than 0.03). Pulmonary wedge pressure was markedly increased at peak exercise in patients compared with normal subjects (25.7 +/- 9.1 versus 7.1 +/- 4.4 mm Hg; p less than 0.0001). Patients demonstrated a shift of the left ventricular end-diastolic pressure-volume relation upward and to the left at rest. Increases in left ventricular filling pressure during exercise were not accompanied by increases in end-diastolic volume, indicating a limitation to left ventricular filling.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Muscle activity localization with 31P spectroscopy and calculated T2-weighted 1H images.

Using 31P spectroscopy and magnetic resonance imaging (MRI), the authors studied changes in muscle phosphorous metabolites and T2 with isometric knee extension to evaluate the potential role of T2 images in coil placement for exercise spectroscopy studies. Increased signal intensity was visible in active muscles on T2 images after exercise. Calculated T2-weighted values were elevated immediately after exercise in the quadriceps (P less than .01). T2 increases for individual quadricep muscles varied, with the largest changes in the rectus femoris and the least in the vastus lateralis. 31P spectroscopy studies demonstrated similar findings: percent change in T2 correlated positively with inorganic phosphorus to phosphocreatine ratio (Pi/PCr) (r = 0.89, P less than .01) and negatively with pH (r = -0.88, P less than .01). The correlations between imaging and spectroscopy suggest that T2 images may allow more precise placement of phosphorous coils in exercise studies. The heterogeneity of T2 changes within the quadriceps with exercise suggests that assumptions about muscle activity may be misleading. T2 images may provide muscle activity verification for exercise studies.

Adult

Warm blood cardioplegia as an adjunct to myocardial preservation during coronary artery bypass grafting.

A review of the first 52 consecutive coronary artery bypass surgery patients to receive oxygenated blood cardioplegia, with warm reperfusion cardioplegia ('hot shot'), was undertaken to evaluate its effectiveness in myocardial protection. The chosen parameters of ischaemia were: (i) the occurrence of ventricular fibrillation (VF) on release of the aortic cross-clamp (ACC); (ii) the occurrence of bradycardia due to cardiac conduction defects; (iii) the use of inotropes with or without the use of the intra-aortic balloon pump (IABP); (iv) evidence of myocardial infarction (MI) on the postoperative electrocardiograph (ECG); and (v) peri-operative cardiogenic mortality. Warm induction cardioplegia was cooled after cardiac standstill. Repeat cold cardioplegia was given as required at intervals and warm reperfusion cardioplegia was given prior to release of the ACC. Of the 52 patients studied none developed VF after release of the ACC; one patient with pre-operative complete heart block required temporary cardiac pacing; no patient required inotropes or IABP and there was no postoperative MI or mortality. The warm blood cardioplegia technique has not resulted in any detectable evidence of inadequate myocardial protection. A beneficial effect has been demonstrated by the absence of VF, cardiac conduction defects, myocardial failure, MI and mortality.

Adult

Dynamic regulation of leg vasomotor tone in patients with chronic heart failure.

We examined the central hemodynamic (n = 5) and leg blood flow (n = 9) responses to one- and two-leg bicycle exercise in nine ambulatory patients with chronic heart failure due to left ventricular systolic dysfunction (ejection fraction 17 +/- 9%). During peak one- vs. two-leg exercise, leg blood flow (thermodilution) tended to be higher (1.99 +/- 0.91 vs. 1.67 +/- 0.91 l/min, P = 0.07), whereas femoral arteriovenous oxygen difference was lower (13.6 +/- 3.1 vs. 15.0 +/- 2.9 ml/dl, P less than 0.01). Comparison of data from exercise stages matched for single-leg work rate during one- vs. two-leg exercise demonstrated that cardiac output was similar while both oxygen consumption and central arteriovenous oxygen differences were lower, indicating relative improvement in the cardiac output response at a given single-leg work rate during one-leg exercise. This was accompanied by higher leg blood flow (1.56 +/- 0.76 vs. 1.83 +/- 0.72 l/min, P = 0.02) and a tendency for leg vascular resistance to be lower (92 +/- 54 vs. 80 +/- 48 Torr.l-1.min, P = 0.08) without any change in blood lactate. These data indicate that, in patients with chronic heart failure, leg vasomotor tone is dynamically regulated, independent of skeletal muscle metabolism, and is not determined solely by intrinsic abnormalities in skeletal muscle vasodilator capacity. Our results suggest that relative improvements in central cardiac function may lead to a reflex release of skeletal muscle vasoconstrictor tone in this disorder.

Aged

Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity.

BACKGROUND: Exertional fatigue, which frequently limits exercise in patients with chronic heart failure, is associated with early anaerobic metabolism in skeletal muscle. The present study was designed to examine the skeletal muscle metabolic response to exercise in this disorder and determine the relation of reduced muscle blood flow and skeletal muscle biochemistry and histology to the early onset of anaerobic metabolism in patients. METHODS AND RESULTS: We evaluated leg blood flow, blood lactate, and skeletal muscle metabolic responses (by vastus lateralis biopsies) during upright bicycle exercise in 11 patients with chronic heart failure (ejection fraction 21 +/- 8%) and nine normal subjects. In patients compared to normal subjects, peak exercise oxygen consumption was decreased (13.0 +/- 3.3 ml/kg/min versus 30.2 +/- 8.6 ml/kg/min, p less than 0.01), whereas peak respiratory exchange ratio and femoral venous oxygen content were not different (both p greater than 0.25), indicating comparable exercise end points. At rest in patients versus normals, there was a reduction in the activity of hexokinase (p = 0.08), citrate synthetase (p less than 0.02), succinate dehydrogenase (p = 0.0007), and 3-hydroxyacyl CoA dehydrogenase (p = 0.04). In patients, leg blood flow was decreased at rest, submaximal, and maximal exercise when compared to normal subjects (all p less than 0.05), and blood lactate accumulation was accelerated. In patients, during submaximal exercise blood lactate levels were not closely related to leg blood flow but were inversely related to rest citrate synthetase activity in skeletal muscle (r = -0.74, p less than 0.05). At peak exercise there were no intergroup differences in skeletal muscle glycolytic intermediates, adenosine nucleotides, or glycogen, whereas in patients compared to normal subjects less lactate accumulation and phosphocreatine depletion were noted (both p less than 0.05), suggesting that factors other than the magnitude of phosphocreatine depletion or lactate accumulation may influence skeletal muscle fatigue in this disorder. CONCLUSIONS: The results of the present study suggest that in patients with chronic heart failure reduced aerobic activity in skeletal muscle plays an important role in mediating the early onset of anaerobic metabolism during exercise. Our findings are consistent with the concept that reduced aerobic enzyme activity in skeletal muscle is, in part, responsible for determining exercise tolerance and possibly the response to chronic intervention in patients with chronic heart failure.

3-Hydroxyacyl CoA Dehydrogenases

Arytenoid subluxation: diagnosis and treatment.

Both arytenoid subluxation and recurrent laryngeal nerve paralysis (RLNP) may result from injury to the larynx, and they may be difficult to distinguish clinically. A patient with arytenoid subluxation who was initially believed to have RLNP was treated with medialization laryngoplasty 1 year after the injury. Preoperative magnetic resonance imaging and computed tomography effectively demonstrated the cricoarytenoid subluxation, which was confirmed by intraoperative electromyography (EMG) showing normal electrical activity in the thyroarytenoid muscle. Photographs from preoperative fiberoptic laryngoscopy are presented to identify the appearance of arytenoid subluxation. Computed tomographic findings and photographs from laryngoscopy of two patients with RLNP documented by intraoperative EMG evaluation are presented to help distinguish the clinical appearance of this disorder from arytenoid subluxation. An integrated approach to the diagnosis and treatment of arytenoid subluxation is presented.

Adult

Evaluation, treatment, and follow-up results of post polio patients with dysphagia.

Twenty consecutive patients were evaluated for reports of dysphagia from post-polio clinics. Only half the patients reported a history of swallowing problems at the time of their acute poliomyelitis. Each patient received a videofluorographic evaluation of the oral and pharyngeal phases of swallowing, and then was provided with recommendations to improve swallowing skills. A follow-up questionnaire was sent to all patients. The respondents had an average interval of 12 months since the initial evaluation. Of the 18 patients responding to the questionnaire, 14 (77%) reported regular use of the swallowing suggestions. Comparison of pre-evaluation results to followup of the 18 respondents yielded a statistically significant decline in the frequency of choking (p = 0.0156) and food sticking in the throat (p = 0.0195). We conclude that a dysphagia program can result in significant improvement of the swallowing symptoms reported with the post-polio population.

Adult