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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

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

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

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

Mandibular reconstruction using vascularized bone grafts.

Total oromandibular reconstruction following cancer extirpation remains a significant challenge to the head and neck surgeon. Reconstructive goals must address occlusion, salivary continence, mastication, deglutition, and articulation. In this article, various methods of mandibular reconstruction, with special attention to the most recent advances in vascularized bone and free tissue transfer techniques, are reviewed.

Bone Transplantation

Snake bite in Australia--the problems involved and a protocol for hospital management.

Despite a great deal of original research into Australian snakes and their complex venoms, there is still confusion about the correct first-aid and hospital management of the bitten patient. This review illustrates the difficulties in diagnosis and treatment and presents a well tried protocol for the successful management of snake bite.

Antivenins

Peripheral stimulation and human cyclofusional response.

Cyclofusional responses consisting of both motor and nonmotor components were measured during stimulation in the peripheral visual field. A 5.75 degree torsional disparity presented in 10 degrees, 30 degrees, and 50 degrees diameter visual stimulus fields induced binocular, torsional eye movements averaging 2.8 degrees to 3.4 degrees. When torsional disparity was excluded from regions up to 30 degrees diameter in the center of the visual field, binocular torsional eye movements of 3.5 degrees to 4.4 degrees were observed. A presentation of simultaneous, conflicting torsional disparities in center and annular surround regions of the stimulus field also induced torsional eye movements which reduced the disparity in only one of the two regions while increasing it in the other. The directions of eye movement changed when the surround stimulus area was enlarged at the expense of the area of the conflicting central stimulus. Based on an objective method of monitoring eye position, the findings in this report suggest that peripheral stimulation exercises a strong influence on the cyclofusional motor response component and that under suitable conditions such stimulation may have a greater influence on the cyclofusional motor response than central stimulation.

Eye Movements