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Biomedical subjects

J H Kelly

Publications and source records attributed to J H Kelly.

At least 19 recordsLinked to original sources
PubMed1997

Use of manometry in the evaluation of dysphagia.

Measurement of manometric pressures in the upper gastrointestinal tract has been done for the past 40 years. Although extensive amounts of data have been compiled for the lower esophageal sphincter and the esophageal body, technical problems have limited the usefulness of measurements of the upper esophageal sphincter and the pharynx. Newer equipment and methods may solve these technical problems, but more normative data and more widespread use of these technologies must be obtained before manometry is clinically useful in the diagnosis of pharyngeal dysphagia.

Deglutition Disorders↗
PubMed1997

Extracorporeal liver support: cell-based therapy for the failing liver.

It is perhaps self-evident to state that a liver support device is possible as long as the artificial organ provides liver function. This basic concept has received woefully little attention, mainly because "liver function" escapes precise definition. We have seen a variety of liver-assist devices that have little to do with liver function over the past 30 years. Recent work has focused on the liver as a biochemical reactor, rather than an excretory organ, and the paradigm has shifted away from blood purification and toward metabolic support. This new generation of devices includes viable liver cells, which provide the necessary biochemical function without needing to identify the numerous metabolic pathways necessary to support the patient with a failing liver. This approach is the most effective and least invasive method available with current technology, and it has yielded exciting data. Questions about the mass of cells required to provide adequate support, the timing and length of treatment, and the source of cellular material continue to be debated. Here we address theoretical and practical problems in developing an extracorporeal liver-assist device (ELAD) and suggest the future role of extracorporeal liver support in the management of liver failure.

Animals↗
PubMed1996

Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure.

The objective of this pilot controlled study was to evaluate the extracorporeal liver assist device (ELAD) in patients with acute liver failure who were judged to still have a significant chance of survival (approximately 50%) and in those who had already fulfilled criteria for transplantation. Twenty-four patients were divided into two groups, 17 with a potentially recoverable lesion (group I) and 7 listed for transplantation (group II), and then randomly allocated to ELAD haemoperfusion or control. The median period of ELAD haemoperfusion was 72 hours (range 3-168 h). Biocompatibility of the device was good, with no acceleration in platelet consumption, and haemodynamic stability was maintained. Two patients were withdrawn from the study because of worsening of preexisting disseminated intravascular coagulation in one case and a hypersensitivity reaction in the other. Deterioration with respect to encephalopathy grade was more frequent in the control patients, 7 of 12 (58%), than in the ELAD-treated patients, 3 of 12 (25%). In group I where survival for the ELAD cases was 7 of 9 (78%), there was a higher than expected survival in the controls, 6 of 8 (75%). For group II cases, survival was 1 of 3 (33%) for the ELAD-treated patients, and 1 of 4 (25%) for the controls. Both of the survivors underwent transplantation. Assessment of additive function for the device revealed an improvement in galactose elimination capacity after 6 hours of haemoperfusion. Based on the results of this pilot-controlled trial, better indices of prognosis will be required, in addition to those used to select for transplantation, if patients at an earlier stage of clinical deterioration are to be included in future studies.

Adolescent↗
PubMed1996

Myology of the pharyngoesophageal segment: gross anatomic and histologic characteristics.

Although numerous studies have been performed on the function and dysfunction of the pharyngoesophageal segment, few studies have investigated features of the musculature in this area. Thus, the purpose of this study was to systematically exam. ine the structure (gross anatomy and histology) in this area and to relate these findings to the functions of the pharyngoesophageal segment. Twenty-one autopsy and surgery patients underwent careful measurement and observation of 1. the vertical (cephalad-caudad) height of the cricopharyngeus muscle (CP); 2. the presence or absence of Kilfian's dehiscence; and 3. the separation or blending of the CP with the upper esophageal circular muscles. Of the 21 subjects, muscle specimens were removed from 8 (4 autopsy, 4 surgical) to include a muscle strip from the upper esophageal circular muscles, CP, and inferior pharyngeal constrictor and submitted to a battery of histological and histochemical tests. Gross anatomic measurements of the vertical height of the CP were substantially longer than those reported elsewhere. Killian's dehiscence was shown to be present in fewer than one third of the specimens. Histology of these muscles also showed significant differences from the muscles discussed in other published reports, particularly when fresh and autopsy material were compared. These specialized muscles, therefore, require further detailed study.

Connective Tissue↗
PubMed1996

Primary omental torsion in children.

OBJECTIVE: A retrospective review was conducted to establish the prevalence and clinical features of omental torsion or infarction as a cause of acute abdominal pain in childhood. METHODOLOGY: The case records were analysed for all patients admitted with primary omental pathology to the Department of General Surgery, Royal Children's Hospital, Melbourne, between January 1975 and July 1994. RESULTS: From 1975 to 1994 (20 years) 13 children were admitted to our General Surgical Department with primary omental disease. There were nine males and four females under 16 years of age. The presenting complaint was abdominal pain with vomiting or diarrhoea. Four children had major medical conditions. Pre-operative diagnosis in all cases was acute appendicitis. Appendicectomy and omentectomy were performed without complication in all cases. Histology of the omentum demonstrated torsion, infarction or haemorrhage. CONCLUSIONS: All children presented with features of acute appendicitis, a majority were male, and two out of the 13 patients were obese. The absence of any children under 4 years was consistent with the relative paucity of omental fat in younger children. We found no clear mechanism for primary omental torsion, although rotation around the right epiploic artery was observed.

Adolescent↗
PubMed1996

Artificial liver support.

Without adequate liver function, the body is unable to sustain several vital metabolic functions, such as energy supply, acid-base balance and thermoregulation. Whereas the clinical picture of chronic liver failure is often dominated by portal hypertension, fulminant hepatic failure (FHF) is typically characterized by an acute metabolic deficit. Another important distinction between these two conditions is that the liver can recover from an acute injury such as FHF. Hepatocytes retain the ability to divide in vivo; therefore, recovery from FHF is possible, although rare, if the liver can regenerate before the patient succumbs to the disease. This review examines the theoretical and practical aspects of metabolic liver support, with FHF as the paradigm.

Animals↗
PubMed1996

Laser decompression of the facial nerve.

Laser decompression of the facial nerve is an experimental approach to evaluating the parameters for laser usage at a nerve-bone interface. This article summarizes the anatomic considerations and indications for facial nerve decompression, and the advantages and disadvantages of laser decompression of the facial nerve. Preliminary studies using the Vanderbilt free electron laser are described, and future directions for research are outlined.

Electrons↗
PubMed1996

Nutritional management of the patient with a neurologic disorder.

Maintaining nutrition in patients with neurologic disorders can be a difficult task. The best results can be expected with individual treatment plans based on a thorough knowledge of the disease process and carried out by a multidisciplinary team working in concert.

Brain Ischemia↗
PubMed1995

Differential expression and release of CD54 induced by cytokines.

Intercellular adhesion molecule-1 (ICAM-1, CD54) is upregulated in many cell types stimulated by cytokines. A human hepatoblastoma cell line (C3A, a subclone of HepG2/C3 that is currently being used as a surrogate liver) and human lung adenocarcinoma cells (A549) were stimulated with interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma), or IL-6 to determine any differences in cell type responsiveness to individual cytokines for ICAM-1 upregulation. Time courses were performed with each cytokine evaluating ICAM-1 mRNA, surface expression, and cICAM-1 in the cell culture media. Between 3 and 6 hours, IL-1 beta (30 U/mL) stimulated the greatest increase in hepatocyte ICAM-1 mRNA, followed by IFN gamma (100 U/ mL), and IL-6 (100 U/mL) in order of potency. Except for IL-6, cytokine-induced hepatocyte surface levels of ICAM-1 (immunofluorescence flow cytometry, mAb R6.5) were dose dependent, with inhibition at higher concentration. Highest levels followed stimulation with INF gamma (P < .05). Significantly less was found after both IL-1 beta and TNF alpha; none was detected after IL-6 (P < .05). In contrast, IL-1 beta stimulated significantly more cICAM-1 release from hepatocytes than the other cytokines (P < .001), and IL-6 stimulated modest cICAM-1. Between 3 and 6 hours in the A549 cells, IL-1 beta stimulated the greatest increase in ICAM-1 mRNA, followed by TNF alpha. Both responses were greater than that observed in the hepatocytes. IFN gamma- and IL-6-induced ICAM-1 mRNA synthesis was not different from unstimulated A549 cells. Cytokine-induced A549 surface levels of ICAM-1 (immunofluorescence flow cytometry, mAb R6.5) was highest for IL-1 beta (peak levels similar to hepatocyte response), modest with TNF alpha (peak levels less than hepatocytes), detectable with IFN gamma (much less than hepatocytes), and nondetectable after IL-6. No ICAM-1 release from A549 cells was induced under any condition. In hepatocytes the amount of ICAM-1 mRNA was best accounted for by considering both cell surface levels of ICAM-1 and cICAM-1 levels. In human lung adenocarcinoma cells, the cytokine induction of ICAM-1 mRNA could potentially be accounted for by observing cell surface levels of ICAM-1 because no cICAM-1 was produced. These results suggest that surface ICAM-1 and cICAM-1 may be differentially controlled by each cytokine and by each parenchymal cell type.

Adenocarcinoma↗
PubMed1994

A treatment system for implementing an extracorporeal liver assist device.

Biologically active devices are receiving increasing attention, especially in the management of endocrine pancreatic failure (diabetes) and acute liver failure. In both instances, mechanical devices have been unable to replace the function of the original organ, and consequences range from inconvenient (e.g., regular insulin shots, diabetic vasculopathy) to fatal (e.g., fulminant hepatic failure). In developing a cell-based liver assist device, we concluded that currently available extracorporeal blood treatment systems are not suited to the delivery of high molecular weight substances and that they do not adequately address the metabolic needs of the device. We therefore developed a system that provides safe, continuous perfusion of an extracorporeal organ. We detail the design and first clinical use of the system.

Animals↗
PubMed1994

The Hepatix extracorporeal liver assist device: initial clinical experience.

Eleven patients were treated with the Hepatix extracorporeal liver assist device (ELAD) between June 1991 and August 1993. The first 2 patients were treated according to Food and Drug Administration guidelines ("Emergency Use of Unapproved Medical Devices," October 22, 1985), and the remaining 9 were treated according to an Investigational Device Exemption (IDE). The goal of the study was to establish the short-term safety of ELAD therapy, with a focus on acute medical complications such as hemodynamic instability, complement activation, and deterioration of vital organ function. As secondary goals, the metabolic capacity of ELAD cartridges and their clinical impact were assessed. Treatment was considered successful if the patient recovered sufficient liver function to survive weaning from the ELAD or was stabilized until orthotopic liver transplantation was performed. No short-term safety problems were associated with ELAD use. In addition, metabolic support was documented in 10 of the 11 patients, and 6 patients reached a successful end-point. The Hepatix ELAD is safe, and it provides measurable metabolic support in patients with late-stage liver failure. This pilot study provides the impetus to perform controlled trials of ELAD therapy in the treatment of various types of end-stage liver disease.

Adult↗
PubMed1994

Extended supracricoid partial laryngectomy with tracheocricohyoidoepiglottopexy.

Extended supracricoid partial laryngectomy with tracheocricohyoidoepiglottopexy (TCHEP) was studied as an alternative to total laryngectomy in 16 patients with glottic carcinoma presenting a 10-15 mm of anterior subglottic extent. The technique of the procedure is described. Results were analyzed for tumor free margins, tracheostomy decannulation, oral alimentation, phonation and disease free interval. The 3-year survival and local control rate were 68% and 86.7%, respectively. Our preliminary data suggest that the TCHEP procedure is a viable alternative to total laryngectomy for patients presenting with varying degrees of carcinoma extension below the free edge of the true vocal cords.

Adult↗
PubMed1994

A case of syncytial giant-cell hepatitis treated with an extracorporeal liver assist device.

Syncytial giant cell hepatitis (SGCH) has recently been reported to be a cause of severe hepatitis, with little chance of patient recovery without orthotopic liver transplantation. We have recently seen a patient with multisystem disease and histologic features of SGCH. Upon reaching stage IV coma, she was treated with an extracorporeal liver assist device containing 200 g of cultured liver cells. There was an immediate improvement in her galactose elimination capacity, and her own liver recovered to the point that therapy could be discontinued after 58 h. The patient recovered slowly from her multisystem disease and was discharged with mildly elevated transaminases and biochemical evidence of cholestasis. All laboratory values are normal at 2 yr, and the patient appears to have no sequelae of her disease.

Artificial Organs↗
PubMed1994

Extracorporeal liver support. Application to fulminant hepatic failure.

Artificial liver support is urgently needed. Mechanical devices such as hemodialysis and hemoperfusion do not correct the metabolic abnormalities that exist in endstage liver disease, and biologically active devices have been impracticable because of limitations in the availability and viability of cultured liver cells. This deficit in the medical armamentarium is a major concern best illustrated by current management of fulminant hepatic failure (FHF). Medical treatment for FHF is largely unsuccessful, and orthotopic liver transplantation (OLT) is the intervention against which all future therapeutic interventions must be judged. The OLT procedure, however, is not benign. The cost is high, and survivors face a lifetime of immunosuppression and medical supervision. By comparison, patients who survive without surgery recover full liver function and have a normal life expectancy. A device that provides liver support during the critical stages of FHF would stabilize patients until a suitable donor organ was found and might negate the need for transplant altogether if the liver were able to regenerate. We review theoretical and practical aspects of biologically active devices using FHF as a paradigm of liver disease.

Animals↗