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Biomedical subjects

J H Kelly

Publications and source records attributed to J H Kelly.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

Improved liver function following treatment with an extracorporeal liver assist device.

A 68-year-old woman with fulminant hepatic failure of unknown etiology was treated with a bioartificial liver assist device. Prior to treatment, she had a number of clinical and laboratory features that suggested a hopeless outcome. Treatment was associated with a dramatic change in her mental status, and her clinical picture improved progressively during 6 days of continuous therapy. Evidence of recovery of native liver function allowed the discontinuation of treatment, and she continued to improve for a further 3 1/2 days before her demise from septic shock. We propose that a metabolically active liver assist device is a logical and practical method for treating the critical phase of fulminant hepatic failure.

Aged↗

Extracorporeal liver assist in the treatment of fulminant hepatic failure.

Our goal in developing a liver assist device is to provide liver support and improve the metabolic state of the patient so that the native liver has the opportunity to regenerate. Failing this, the patient should at least remain in satisfactory health so that liver transplantation can be performed safely. We have no idea how much metabolic support will be required to sustain life, but we have a set a goal of 20% of the normal hepatocyte mass. Our initial results suggest that this is an appropriate number, and a clinical trial to determine safety and efficacy is under way at the Texas Medical Center.

Animals↗

An improved model of acetaminophen-induced fulminant hepatic failure in dogs.

We have established an improved model of fulminant hepatic failure in dogs. Buthionine sulfoximine is used to inactivate glutathione synthesis, and small increments of acetaminophen are given intravenously to maintain the plasma level at approximately 200 micrograms/ml for 20 hr. This regimen produces severe liver injury along with many of the features seen in humans with acetaminophen poisoning. The first sign of impending liver failure is hypoglycemia. This occurs about 15 hr into the experiment and requires treatment with a continuous infusion of glucose. Between 15 and 20 hr, serum ALT activity begins to rise, indicating the onset of liver necrosis. Over the following 15 to 20 hr ALT activity continues to rise and is accompanied by an increase in bilirubin, a prolongation of the prothrombin time and the development of fetor hepaticus. Thirty to 48 hr after the initial acetaminophen dose, the animals begin to exhibit symptoms of encephalopathy and progress from lethargy to the inability to maintain posture and then coma, seizures and death. Liver biopsy specimens obtained at several stages throughout the study showed progressive necrosis, ultimately resulting in the complete destruction of zones 2 and 3.

Acetaminophen↗

Reversal of fulminant hepatic failure using an extracorporeal liver assist device.

Liver transplantation is currently the only effective therapy for patients with fulminant hepatic failure. The availability of an artificial liver could bridge these patients through the relatively brief crisis period and allow their own livers to regenerate, providing a more favorable outcome and sparing the trauma and expense of transplant. We have developed a device consisting of a highly differentiated human liver cell line cultured in a hollow fiber cartridge. This device is capable of supporting dogs with acetaminophen-induced fulminant hepatic failure for a period long enough for their own livers to resume function. Even though liver function tests such as albumin and prothrombin time became extremely abnormal during the course of the experiment, the dogs did not become encephalopathic. Two of the three treated animals recovered sufficient liver function after 42 to 48 hr of treatment that they could be disconnected from the device, and they survived the experiment. Histological results and serum ALT levels suggest that the device affected the course of the disease in two animals, allowing recovery of hepatocytes that would otherwise have lysed. In the third animal, regenerative nodules demonstrated that, even in the presence of severe liver injury, the device was capable of supporting total liver function.

Animals↗

Assessment of an extracorporeal liver assist device in anhepatic dogs.

We have used an anhepatic dog model to demonstrate the efficacy of a bioartificial liver assist device. Six dogs underwent total hepatectomy. Three received only medical care (controls) while the remainder were connected to an extracorporeal liver assist device (ELAD). The control dogs failed to regain consciousness after anesthesia although all lived 4-5 h postoperatively. Plasma ammonia concentration increased by an average of 250 mumol/L between the end of surgery and the demise of the animals. The treated dogs lived 3-12.5 h, and 2 of them required repeated doses of thiamylal sodium to maintain sedation. Plasma ammonia concentration was unchanged after connection to the ELAD except in the longest survivor, whose ammonia began to rise after 8 h on the ELAD. The short survival in the other 2 treated dogs was the result of uncontrolled intraabdominal bleeding. This device is capable of replacing the metabolic function of the liver, and might provide hepatic support in patients awaiting transplantation or in fulminant hepatic failure.

Ammonia↗

Disturbance in respiratory mechanics with extreme truncal flexion during anaesthesia in children.

Respiratory mechanics were studied in five anaesthetised children, aged 3 to 33 months undergoing urological surgery, in both the supine position and with extreme truncal flexion. Extreme truncal flexion was associated with a reduced respiratory system compliance. Dynamic compliance decreased significantly, by 30% (range 12-55%) and static compliance decreased significantly, by 40% (range 18-65%). There were no changes in respiratory system resistance. Tidal volume was also significantly reduced (mean 20%) despite a significant increase (mean 22%) in peak ventilator pressure. These changes in mechanics must be recognised to avoid alveolar hypoventilation, with a consequent decrease in gas exchange during surgery.

Anesthesia, General↗

Modulation of the liver specific phenotype in the human hepatoblastoma line Hep G2.

The human hepatoblastoma line Hep G2 modulates gene expression in vitro in response to increasing culture density. Two stages of growth can be defined. At low density (less than 200,000 cells/cm2) the cultures have a doubling time of 24 h and exhibit several characteristics of fetal liver cells, including increased synthesis of alphafetoprotein, reduced synthesis of albumin, a predominance of the fetal isoenzymes of both aldolase and pyruvate kinase and a reduced level of the cell surface receptor for asialoglycoproteins. Confluent, high density cultures of Hep G2 (greater than 1 X 10(6) cells/cm2) have a doubling time of 193 h, a four fold higher level of albumin production, increased levels of the adult isoenzymes of aldolase and pyruvate kinase and increased asialoglycoprotein receptor. The alteration in albumin and alphafetoprotein synthesis was reflected by changes in the messenger RNA levels and the relative transcription of these two genes. Hep G2 provides a cell culture model for the modulation of the liver phenotype which occurs during fetal/adult development or during liver regeneration.

Asialoglycoproteins↗

Lumbar ureteral shunt--an unusual cause of ureteral obstruction.

In a neurosurgical patient with a lumbar ureteral shunt in place for many years ureteral obstruction and hydronephrosis developed. The shunt tubing was removed surgically from the ureter leaving a portion of the shunt in the subarachnoid space without sequelae. Historically, most patients undergoing this type procedure had an ipsilateral nephrectomy performed at the time of shunt placement; however, this patient did not. It is important to be aware of this "antique" procedure as it may cause urologic complications.

Adult↗