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Biomedical subjects

T M Egan

Publications and source records attributed to T M Egan.

At least 19 recordsLinked to original sources
PubMed1992

Clozapine protocol: a collective approach to use of an unregistered medicine.

We describe a protocol for the use of an unregistered antipsychotic medicine, clozapine, in a mental health service. Traditionally, prescribing of unregistered medicines has been a matter between prescriber and patient alone. However, clozapine carries a high risk of agranulocytosis and its use requires strict adherence to monitoring procedures. Persons most likely to benefit from it include many who, because of their psychosis, may be unable to give truly informed consent or to react appropriately to adverse reactions. We have designed a protocol which seeks to ensure that this medicine is given only to those whose severity of illness and lack of response to all other reasonable treatment outweighs the risk of agranulocytosis, that it is used with maximum safety and that only persons who have been shown to benefit from the medicine continue to receive it after an initial trial. Although this protocol has been accepted by the medical staff, questions of clinical autonomy and liability in the event of medical misadventure remain.

Adult↗
PubMed1992

Na(+)-activated K+ channels are widely distributed in rat CNS and in Xenopus oocytes.

We recorded the activity of K+ channels activated by sodium (KNa channels) in two widely used preparations, primary cell cultures prepared from neocortex, cerebellum, midbrain, brainstem and spinal cord, and Xenopus oocytes. KNa channels from all regions shared an absolute dependence on [Na+], had conductances of 140-170 pS in symmetrical 150 mM K+ and exhibited characteristic substates. The role of this channel must now be considered in terms of its widespread distribution.

Animals↗
PubMed1992

Isolated lung transplantation for end-stage lung disease: a viable therapy.

Since January 1990, we have performed 29 isolated lung transplantations in 28 patients with end-stage lung disease (12 single, 16 bilateral). Recipient diagnoses were: cystic fibrosis (11), chronic obstructive pulmonary disease (6), pulmonary fibrosis (6), eosinophilic granulomatosis (1), postinfectious lung disease (1), adult respiratory distress syndrome (1), and primary pulmonary hypertension (2). There have been four deaths, two in patients with pulmonary fibrosis and two in patients with primary pulmonary hypertension. Four patients have undergone transplantation while on ventilatory support for respiratory failure (2 with cystic fibrosis, 1 having redo lung transplantation with cystic fibrosis, and 1 with adult respiratory distress syndrome); all of these have survived. Six patients required cardiopulmonary bypass, which was associated with increased transfusion requirement. All patients 2 months after discharge have returned to an active life-style, except for 2 patients who currently await retransplantation. Preoperative pulmonary rehabilitation has resulted in significant improvement in exercise performance in all patients. Immunosuppression consists of cyclosporine, azathioprine, and antilymphoblast globulin (University of Minnesota), withholding systemic steroids in the early postoperative period. We have employed bronchial omentopexy in all but four transplants; there has been one partial bronchial dehiscence, two instances of bronchomalacia requiring internal stenting, and one airway stenosis. Cytomegalovirus disease has been seen frequently (15 cases), but has responded well to treatment with ganciclovir. Other complication shave included one drug-related prolonged postoperative ventilation, thrombosis of a left lung after bilateral lung transplantation requiring retransplantation, five episodes of unilateral phrenic nerve palsy after bilateral lung transplantation (4 resolved), and the requirement of massive transfusion (greater than 10 units) in 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Single lung transplantation for eosinophilic granulomatosis.

A 26-year-old woman with end-stage lung disease due to eosinophilic granulomatosis had single right lung transplantation with an excellent function result that persists beyond 9 months of follow-up. Single lung transplantation offers excellent palliation to selected patients with end-stage lung disease.

Adult↗
PubMed1992

Whence the lungs? A study to assess suitability of donor lungs for transplantation.

Efforts at clinical lung transplantation have been hampered by an insufficient donor pool. To estimate the number of potential suitable lung donors, we conducted a UNOS-sponsored survey of organ procurement organizations and collected data with respect to possible lung donation from human cardiac donors. Contact with OPOs was made by telephone after cardiac donors were identified by UNOS. Of 150 cardiac donors, 7 were utilized for lung or heart-lung transplantation. By our criteria, however, 47 additional donors had lungs that may have been suitable for transplantation but were not utilized, and frequently were not offered for transplantation for a variety of reasons. This survey implies that approximately 25% of cardiac donors likely have lungs that may be suitable for transplantation.

Adult↗
PubMed1992

Optimal timing of administration of a free radical scavenger in lung preservation.

The optimal timing of administration of free radical scavengers in lung preservation has yet to be determined. In previous studies, the oxygen free radical scavenger dimethylthiourea (DMTU) has improved pulmonary function when added to Eurocollins flush solution at the time of lung harvest and infused at the time of lung reimplantation. To determine when DMTU must be administered in order to preserve lung function most effectively, 16 dogs underwent lung allotransplantation. Donor lungs were flushed with modified Eurocollins solution (50 ml/kg) and stored for 12 hr at 4 degrees C. DMTU was either added to the flush solution (5 g) or infused (20 g over 2 hr) at the time of reimplantation. Investigators were blinded to the time of DMTU administration. The contralateral pulmonary artery was ligated after a 1-hr stabilization period. Measurements were recorded for 8 hr while keeping FiO2 constant at 40%. The flush group demonstrated significantly improved survival and oxygenation compared with the infusion group. The mortality rate was 50% in the infusion treatment group, while no deaths occurred in the flush animals. Lung function is adequately preserved after 12-hr storage when DMTU is administered in the flush solution at the time of harvest. It would appear that oxygen free radical scavengers must be present in lung tissue during storage in order to be effective.

Animals↗
PubMed1992

Lung transplantation in cystic fibrosis.

Lung transplantation has emerged in the last decade as a valid therapeutic endeavor for patients with end-stage lung disease. Although the presence of highly resistant organisms in the airway and sinuses of patients with cystic fibrosis (CF) increases the perioperative risk of infection following lung transplantation, transplant procedures can be undertaken in properly selected CF patients with acceptable morbidity and mortality at experienced centers. The introduction of a modification in the technique of double-lung transplantation has resulted in improved operative survival of CF patients undergoing lung transplantation. Whereas problems with posttransplant obliterative bronchiolitis, infection, and lymphoproliferative disorders contribute to morbidity, it is clear that lung transplantation can offer CF patients with end-stage lung disease improvement in both the quality and quantity of life. The most serious impediment to more widespread application of this therapy in CF is the inadequate number of donor organs.

Cystic Fibrosis↗
PubMed1992

Properties and rundown of sodium-activated potassium channels in rat olfactory bulb neurons.

We have used single-channel recording techniques to investigate the properties of sodium-activated potassium channels (KNa channels) in cultured rat olfactory bulb neurons, and in large neurons in the mitral cell layer of thin slices of olfactory bulb. Ion channels highly selective for potassium over sodium and chloride, and requiring 10-180 mM internal sodium (Nai) for their activation, were present in approximately 75% of inside-out membrane patches detached from cultured olfactory bulb neurons. Most of these patches contained several KNa channels. KNa channels were seen in cell-attached patches only when Nai was raised by including veratridine in the extracellular medium. Preincubation of the cell in TTX or removal of extracellular sodium prevented this effect of veratridine, confirming that the channels observed under these conditions were indeed KNa channels. Lithium did not substitute for Nai in activating these channels. With 150 mM potassium on both sides of the membrane, KNa channels had a single-channel conductance of 172 pS, and at least two subconducting states were observed in addition to this fully open state. Under these ionic conditions, the channels exhibited linear fully open channel current-voltage curves over the potential range of -100 to 0 mV. At voltages more positive than the potassium equilibrium potential, the single-channel currents exhibited inward rectification as a result of sodium block of outward potassium current. The channels opened in bursts, during which they fluctuated between the fully open and closed states, and the substates. Between bursts they sometimes entered a long-lived inactive state that could last for up to several minutes. In addition, KNa channels in the detached patches exhibited rundown, a progressive irreversible loss in activity, over a time course that varied from less than 1 min to longer than 1 hr. Rundown of KNa channel activity in cell-attached patches (in the presence of veratridine) did not occur, suggesting that some intracellular factor necessary for KNa channel activity is lost when the membrane patch is detached from the cell.

Animals↗
PubMed1992

Lung preservation.

Pulmonary transplantation is now a clinical reality that offers hope to large numbers of patients with end-stage lung disease. Current methods of preserving pulmonary function allow for transplantation, but operation must be expeditious, and transportation time and operating time become critical factors in determining outcome. The ability to preserve lungs for longer time intervals could potentially allow for more widespread distribution of donor organs of unusual size or blood type, and could set the stage for more appropriate HLA matching between donor and recipient. Furthermore, a more thorough understanding of the pathophysiology of preservation injury will likely lead to a better understanding of the pathophysiology of other types of lung injury. In turn, this could increase the size of the pulmonary donor pool by allowing transplantation of lungs with suboptimal gas exchange function at the time of donor brain death. Finally, a more thorough understanding of lung metabolism and determinants of cellular viability in the lung would be useful for the potential application of the use of lungs from circulation-arrested cadavers for transplantation.

Animals↗
PubMed1991

Enhanced pulmonary function using dimethylthiourea for twelve-hour lung preservation.

Current preservation techniques for lung transplantation limit ischemic time to 6 hours. The purpose of this study was to evaluate the ability of dimethylthiourea, a low molecular weight free radical scavenger, to prolong this interval. An in vivo canine transplantation model was used to assess lung function. At harvest and after circulatory arrest, the donor lung was flushed with modified Euro-Collins solution (50 mL/kg). In a blinded fashion, dimethylthiourea (5 g) or saline solution was added to the flush solution at harvest and also infused (20 g over 2 hours) at reimplantation. Harvested lungs were stored for 12 hours at 4 degrees C. Allotransplantation was performed in recipient dogs ventilated with 40% O2. After 1 hour, the contralateral pulmonary artery was ligated, forcing the dog to be dependent on the transplanted lung. Twelve dogs were studied, with 6 randomly assigned to each treatment group in a blinded fashion. Measurements were recorded for 8 hours, keeping the inspired oxygen fraction constant at 0.40. All dimethylthiourea-treated dogs survived the observation period, whereas one third of the dogs that received saline solution died. Dimethylthiourea-treated dogs had significantly greater arterial oxygen tension and significantly less pulmonary vascular resistance compared with control animals. These results suggest that treatment of the lung with a free radical scavenger (dimethylthiourea) improves pulmonary function after reimplantation in a canine model after 12-hour hypothermic storage.

Animals↗
PubMed1991

A strategy to increase the donor pool: use of cadaver lungs for transplantation.

A shortage of suitable donors is a serious obstacle to the widespread application of isolated lung transplantation for end-stage lung disease. We hypothesized that lung tissue likely remains viable for a sufficient period of time to allow for safe postmortem retrieval of lungs for transplantation. Studies were conducted in a nonsurvival model of canine lung allotransplantation. Donor animals were sacrificed, and subsequent lung harvest was delayed for 1 hour, 2 hours, or 4 hours. Pulmonary retrieval was then performed in a standard fashion, flushing the lung block with modified Euro-Collins solution. Lungs were then stored for 4 hours before single allotransplantation. Recipient animals were maintained anesthetized, and followed up for 8 hours. By occlusion of the pulmonary artery and bronchus to the native lung, recipient animals were forced to survive solely on the transplanted lung, with a constant inspired oxygen fraction of 0.40. All 5 recipient animals of 1-hour cadaver lungs survived the 8-hour observation period with excellent hemodynamics and gas exchange. Two of 5 recipients of 2-hour cadaver lungs survived the observation period, whereas a third animal survived for 5 hours with excellent gas exchange. One of 4 animals transplanted with a 4-hour cadaver lung survived the observation period. Retrieval of lungs from cadavers whose hearts are not beating may prove to be a safe and effective method to increase the pulmonary donor pool.

Animals↗
PubMed1991

Analysis of referrals for lung transplantation. The Washington University Lung Transplantation Group.

In the first year of our lung transplantation program, 211 patients with end-stage pulmonary disease were referred for consideration. Over 50 percent of the patients had chronic obstructive pulmonary disease, and almost 20 percent had idiopathic pulmonary fibrosis. The referrals were screened according to predefined criteria of eligibility for single and double lung transplantation. After screening, 46 of the referred patients were admitted for an extensive inpatient evaluation, and 18 of these were accepted as candidates for transplantation. Although interest in lung transplantation is growing in both the medical and lay communities, a significant number of patients with endstage pulmonary disease were ineligible by our current criteria. As experience with these procedures is gained, criteria for selection may become less restrictive, and more patients may be candidates for transplantation.

Adult↗
PubMed1990

Myocardial abscess in a patient with AIDS-related complex: pericardial patch repair.

A hemophiliac with acquired immunodeficiency syndrome-related complex was seen with sepsis related to a ventricular septal abscess. The abscess was debrided and the septum was patched with a single layer of autologous pericardium. The patient recovered and survived 6 months before dying of acquired immunodeficiency syndrome. At autopsy, the septal patch was well healed with no evidence of recurrent endocarditis.

AIDS-Related Complex↗
PubMed1990

Direct revascularization of bronchial arteries for lung transplantation: an anatomical study.

Direct revascularization of the bronchial arteries for both single-lung and double-lung transplantation would improve airway healing and reduce airway complications after transplantation. We studied the anatomical pattern of bronchial arteries in 30 autopsy cases. In 28 of 30 cases (93.3%), at least one left bronchial artery arose directly from the anterior wall of the descending thoracic aorta. In 25 of the 30 cases (83.3%), at least one right bronchial artery was related to the first right intercostal artery. Injection studies showed that this right intercostobronchial artery supplies the proximal left main bronchus and carina as well as the right bronchus. We developed a technique for extracting the lungs along with the right intercostobronchial artery and a patch of aorta at its origin and applied it to 19 of the dissections. In 17 of the 19 cases studied (89.4%), the right intercostobronchial artery pedicle obtained had a length varying from 6.5 to 8.5 cm, sufficient for attachment of its origin to the ascending aorta of the recipient after double-lung transplantation. The right intercostobronchial artery pedicle provides the possibility for direct bronchial revascularization in right single-lung, double-lung, and lung-heart transplantation. A similar technique, utilizing the left bronchial artery, can be used to revascularize a left lung transplant.

Aorta, Thoracic↗
PubMed1990

Injection site reactions after intramuscular administration of haloperidol decanoate 100 mg/mL.

The authors report four cases of injection site reaction after intramuscular administration of haloperidol decanoate 100 mg/mL. In each case, the injection site became edematous, red, pruritic, and tender, and a palpable mass remained for up to 3 months. No systemic symptoms were reported. All four patients had previously received the 50 mg/mL haloperidol decanoate injection without incident. Two of these events followed the initial injection of haloperidol decanoate 100 mg/mL. Rechallenge with the 100 mg/mL product in one case and the 50 mg/mL product in two resulted in similar reactions. The incidence of this reaction at the authors' facility is estimated to be 7.7%. The authors speculate that the reaction is most likely to be related to the concentration of haloperidol decanoate in the injection.

Adult↗
PubMed1990

Surgical aspects of single lung transplantation.

Single lung transplantation is a viable therapeutic option for selected patients with end-stage lung disease. The techniques described, in conjunction with rigorous preoperative physiotherapy, diligent postoperative care, immunosuppression with early avoidance of steroids, and postoperative rehabilitation, have resulted in a gratifying rate of success. Transplantation of the lung involves not a mere technical transfer of the organ from one body to another. It is a complex logistic undertaking requiring a large team of professionals who attend to the many essential components including patient selection, preoperative rehabilitation, donor selection, postoperative care, immunosuppression, rehabilitation, and long-term follow-up. The operation itself represents an integral, but small, component.

Adult↗