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Biomedical subjects

M J Murray

Publications and source records attributed to M J Murray.

234 records · Page 13Linked to original sources

Strategies in the treatment of diffuse pontine gliomas: the therapeutic role of hyperfractionated radiotherapy and chemotherapy.

This article will review the current treatment of pediatric patients with diffuse pontine gliomas (DPG) and discuss three potential avenues of therapeutic research including (i) radiotherapy (RT) in combination with radiation sensitizers, (ii) dose-intensive, induction chemotherapy with hematopoietic support followed in sequence with RT applied as a "consolidation' therapy, and (iii) the interleafed application of phase-specific chemotherapeutic agents and hyperfractionated external beam radiotherapy (HFEBRT) referred to as "chemoradiotherapy'.

Antineoplastic Agents↗

The effects of convective cooling and rewarming on systemic and central nervous system physiology in isoflurane-anesthetized dogs.

Recent studies have demonstrated that small (i.e., 2-5 degrees C) reductions in temperature may protect the brain and spinal cord from ischemic injury. The present study evaluated the physiologic response of anesthetized animals to convective-based cooling and warming. Six shaved, isoflurane-anesthetized (1.50% end-expired; 1 MAC), pancuronium-paralyzed dogs were subjected to temperature manipulation. The flow of cool (13-14 degrees C) or warm (39-41 degrees C) air was uniformly applied to the the dorsal and lateral surfaces of the dog using an inflatable blanket with perforations in the interior surface. Convective cooling reduced pulmonary artery temperature (Tpa) from 37.0 +/- 0.2 degrees C (Mean +/- S.D.) to 33.0 +/- 0.0 degrees C over a 93 +/- 18 min period. Thereafter, the active cooling was discontinued and passive cooling resulted in a further reduction in Tpa to 32.4 +/- 0.3 degrees C over the next 60 min. Institution of convective warming resulted in an increase in Tpa from 32.4 +/- 0.3 to 33.0 +/- 0.0 degrees C in 23 +/- 14 min and from 33.0 to 37.0 +/- 0.0 in an additional 137 +/- 26 min. During the periods of active cooling, passive cooling and active warming, there were strong correlations between Tpa and temperature within the brain, cisterna magna, parietal epidural space, lumbar subarachnoid space and other commonly used temperature measurement sites non-invasively monitored (e.g. tympanic membrane, esophagus, rectum) r greater than or equal to 0.97; P less than 0.0001). The combination of isoflurane anesthesia (a potent EEG-suppressor) plus mild hypothermia (less than 34 degrees C) resulted in an EEG attenuation in five dogs, two of which progressed to burst suppression. The magnitude of EEG changes correlated with the degree of temperature reduction. Upon rewarming to 37 degrees C, all dogs had normal EEG activity and normal brain concentrations of high energy phosphates, glucose and lactate. Blood pressure and cardiac output did not change during the study and no dog exhibited acid-based anomalies or blood lactate accumulation. Whole body oxygen consumption and heart rate decreased in a temperature-dependent fashion. Cardiac rhythm disturbances were rare. The authors conclude that convection-based corporeal cooling and rewarming are efficacious methods for non-invasively and uniformly altering CNS temperatures without adversely affecting cerebral or systemic physiology.

Anesthesia↗

Intravascular leukostasis and systemic aspergillosis in a horse with subleukemic acute myelomonocytic leukemia.

Leukemia is a neoplastic disease of one or more of the cell types of the hemopoietic system and is rarely diagnosed in the horse. This report describes a case of subleukemic acute myelomonocytic leukemia in an 11-year-old gelding. Preliminary cytological diagnosis was supported by two types of laboratory investigations. Cytochemical characterization of blood and bone marrow neoplastic cells was consistent with a myelomonocytic origin. Neoplastic blast cells in peripheral blood were labeled by monoclonal antibodies specific for cell surface molecules of horse granulocytes, but they were not labeled by antibodies to T- or B-lymphocytes or macrophages. Treatment was attempted but was unsuccessful. At necropsy, intravascular leukostasis was present in all tissues examined. Fungal hyphae were also found in lung interstitium and colonic submucosa, suggesting the presence of a systemic mycosis. Nucleated cells were isolated from peripheral blood and cultured in vitro; they survived for up to 2 weeks and had evidence of cell division that was not sustained. Frozen-thawed cells stored in liquid nitrogen were also successfully cultured in vitro, but no permanent cell lines could be established.

Animals↗

Signs of sympathetic denervation associated with a thoracic melanoma in a horse.

Sympathetic denervation in a 20-year-old, gray, Thoroughbred-Percheron gelding was manifested by cutaneous hyperthermia and sweating over the right side of the body, demarcated by a line from the withers to the elbow and extending cranially. There was cutaneous hyperthermia over the right side of the head, but other signs of Horner's syndrome (sweating, ptosis, miosis, enophthalmos) were not present. The pattern of cutaneous hyperthermia and sweating was consistent with sympathetic denervation localized to the cervicothoracic ganglion, and thoracic radiographs revealed increased density in the craniodorsal thorax. Cytologic evaluation of a sample of pleural effusion revealed mesothelial cells containing melanin and cells suggestive of melanocytes or melanoblasts. Treatment with oral cimetidine and intrapleural cisplatin was not successful. A necropsy was not performed, but the clinical findings supported a diagnosis of thoracic melanoma involving the cervicothoracic ganglion.

Animals↗

Neonatal equine herpesvirus type 1 infection on a thoroughbred breeding farm.

Of 17 foals born on a Thoroughbred breeding farm between March and April 1995, infection with equine herpesvirus type 1 (EHV-1) was associated with neonatal morbidity in 5 foals, 3 of which died or were euthanized. Morbidity and mortality were associated with pulmonary inflammation, and EHV-1 was identified in the lungs of the 3 foals that died. All neonatal EHV-1 infections occurred in foals of mares housed in the same pasture and barn. No other clinical manifestations of EHV-1 infection (e.g., abortion, neurologic disease, or respiratory disease) occurred during this outbreak. Three foals were treated with acyclovir (1 died, 2 survived), which may have influenced the clinical outcome in the surviving foals.

Animals↗

Effects of a fish oil diet on pigs' cardiopulmonary response to bacteremia.

Since an omega 3 fatty acid (FA) diet may have beneficial effects in inflammatory processes, we tested the hypothesis that the physiologic response to sepsis could be modified by altering the eicosanoid precursor pool via an omega 3 FA diet. Two groups (n = 8) of pigs were prefed for 8 days either an omega 3 FA or an omega 6 FA diet (Weaner Pig Feed with either menhaden or corn oil to produce a eucaloric feed with 15% fat) and then injected with live Escherichia coli. The omega 3 FA diet increased the concentration of eicosapentainoic acid (EPA, 20:5 omega 3) in plasma lipids, and increased the ratio of EPA to arachidonic acid (AA, 20:4 omega 6) in platelets from 1:20 to 1:1 over the 8 days. Following the injection of bacteria, there was a fall in PaO2 and blood pressure that was attenuated (p less than 0.05) by the omega 3 FA diet. The omega 3 FA diet, compared to the omega 6 FA diet, also attenuated the rise in thromboxane B2 (3.0 +/- 1.1 vs 12.9 +/- 5.7 ng/mL) and 6 keto-PGF1 alpha (0.8 +/- 0.5 vs 1.7 +/- 1.1 ng/mL) associated with bacteremia. We conclude that dietary omega 3 FA attenuated the physiologic response to sepsis, possibly by modifying arachidonic acid metabolism.

6-Ketoprostaglandin F1 alpha↗

Sepsis: clinical dilemmas.

Sepsis, manifested by systemic inflammatory response syndrome (SIRS), septic shock and multiple organ dysfunction syndrome (MODS), remains the leading cause of morbidity and mortality in critically ill patients. Despite advances and our knowledge of sepsis, there remain clinical dilemmas that impact how we treat patients. These clinical dilemmas include hypotension, cardiac dysfunction and altered oxygen consumption. There is increasing recognition that treatment of these problems does not necessarily improve outcome. As we improve our understanding of sepsis, there is increased recognition that improvement in morbidity and survival will come not only from treating the manifestations of sepsis but also the endogenous mediators responsible for the development of these clinically important conditions. This manuscript discusses the clinical dilemmas associated with sepsis, current therapy and future directions for managing sepsis.

Cardiac Output↗

Endoscopic findings of the gastric antrum and pylorus in horses: 162 cases (1996-2000).

Medical records and endoscopy images were examined for 209 horses that had gastroscopic examinations performed with a 2.5- or 3-m-long endoscope by one of the authors (MJM) during a 4-year period (1996-2000). The antrum and pylorus were viewed in 162 horses, and the duodenum was viewed in 94 horses. Of these 162 horses, the gastric squamous mucosa was seen in 157 horses and 50% or more of the glandular mucosa of the body of the stomach was seen in 156 horses. Erosions or ulcers were seen in the gastric squamous mucosa in 91 (58%) horses. Erosions or ulcers were seen in the glandular mucosa of the body of the stomach in only 8% of the horses. Lesions consisting of erosion or ulceration were seen in the antrum or pylorus in 94 (58%) horses. Lesions consisting of hyperemia and a rough or "bumpy" appearance were seen in the mucosa of the duodenum of 16 horses. An association between the presence of lesions in the squamous mucosa and the presence of lesions in the mucosa of the antrum/pylorus was examined by Fisher's exact test, and the linear association of lesion severity scores between the squamous mucosa and the mucosa of the antrum/pylorus was tested using a Monte Carlo estimate for linear-by-linear association. There was no association (P = .88) between these sites for presence of lesions or lesion severity scores. Similarly, there was no association between scores for the glandular mucosa in the gastric body and those in the antrum/pylorus. Because of the high prevalence of lesions in the antrum and pylorus of the stomachs of adult horses examined in a hospital setting, the entire stomach should be viewed during a gastroscopic examination.

Animals↗

The ecological interdependence of diet and disease in tribal societies.

Observations among nomads suggest there is a strong ecological interdependence of diet and disease in tribal societies which favors survival of man. This relationship may be disrupted by changes in diet to conform to the highly productive technology of the West. Such changes may result in intensification of indigenous disease and in the transfer of disease characteristics of Western societies. To prevent these consequences, relief feeding and long-term attempts to upgrade nutrition should be carried out with traditional foods wherever possible.

Africa↗

Multiple organ dysfunction syndrome.

The multiple organ dysfunction syndrome (MODS), though newly described, has manifested itself in intensive care unit (ICU) patients for several decades. As the name implies, it is a syndrome in which more than one organ system fails. Failure of these multiple organ systems may or may not be related to the initial injury or disease process for which the patient was admitted to the ICU. MODS is the leading cause of morbidity and mortality in current ICU practice. While the pathophysiology of MODS is not completely known, much evidence indicates that, during the initial injury which precipitates ICU admission, a chain of events is initiated which results in activation of several endogenous metabolic pathways. These pathways release compounds which, in and of themselves, are usually cytoprotective. However, an over exuberant activation of these endogenous systems results in an inflammatory response which can lead to development of failure in distant organs. As these organs fail, they activate and propagate the systemic inflammatory response. No therapy has proven entirely efficacious at modulating this inflammatory response and the incidence and severity of MODS. In current ICU practice, treatment is focused on prevention and treating individual organ dysfunction as it develops. With increased understanding of the pathophysiology of MODS therapy will come newer modalities which inhibit or interfere with the propagation of the endogenous systemic inflammatory response. These newer therapies hold great promise and already some are undergoing clinical investigation.

Humans↗