Biomedical subjects

J B Mullen

Publications and source records attributed to J B Mullen.

At least 55 records · Page 3Linked to original sources

PubMed1989

Evidence that cold preservation-induced microcirculatory injury in liver allografts is not mediated by oxygen-free radicals or cell swelling in the rat.

The critical injury of cold preservation is to the hepatic microcirculation. Oxygen free radical injury and cell swelling have been proposed to be causes of allograft failure, and new solutions such as Marshall's isotonic citrate and University of Wisconsin (UW) solutions were designed to prevent cell swelling and free radical injury. Experiments were done to determine whether Marshall's solution and UW solution protect the microcirculation, and whether they do so by preventing cell swelling or free radical-induced injury. To determine if the new solutions reduce sinusoidal lining cell injury, rat livers were examined after preservation at 4 degrees C in NaCl 0.9% and CaCl2 2 mM for 4 hr and 8 hr, in Collins' solution for 8 hr, and in both UW and isotonic citrate solutions for 8 hr and 16 hr. Next, the role of cell swelling in preservation injury was studied by storing livers in hypotonic solutions that accelerate liver weight gain, and in a choline chloride-based preservation solution. Finally, to evaluate the role of active oxygen species, SOD, catalase, and allopurinol were added to preservation solutions. The effect of allopurinol alone was also studied. In a related study, sucrose was substituted for the free radical scavenger, mannitol, in isotonic citrate solution. All livers were studied by light microscopy after perfusion-fixation. Storage in UW and isotonic citrate solutions resulted in clear improvement in the morphology of the sinusoidal lining. Increasing the rate of liver weight gain by the use of hypotonic solutions did not accelerate the endothelial injury. Choline chloride-based solution prevented weight gain during preservation, but unlike UW or isocitrate solutions it did not retard the microcirculatory injury. After preservation in the presence of SOD and catalase, or allopurinol, no improvement in the defined morphological features of the endothelial injury was noted when compared with respective controls; nor was the benefit of isotonic citrate solution lessened by the removal of the free radical scavenger mannitol. We conclude that microvascular injury produced by cold injury is due neither to free radical-mediated injury nor to cell swelling. As both UW and isotonic citrate solutions provide significant protection to the microcirculation, they must do so by a yet-undetermined mechanism.

Allopurinol↗

PubMed1989

Capnography is not as sensitive as pulmonary artery pressure monitoring in detecting marrow microembolism. Studies in a canine model.

We studied several methods for detecting pulmonary embolic events in a model of fat and marrow microembolism during canine cemented arthroplasty procedures. The cardiopulmonary effects of bilateral cemented arthroplasty in this model include increased pulmonary artery pressure and pulmonary vascular resistance accompanying a decrease in arterial oxygen tension. We documented significant fat and marrow microembolism by postmortem quantitative morphometry of lung sections. Vessels occluded ranged in diameter from 0.5 to 190 microns. The acute increases in pulmonary artery pressure (PAP) (to 26.8 +/- 4.4 mm Hg from 15.3 +/- 3.3 mm Hg) after cemented arthroplasty were not detected by changes in continuously monitored end-tidal CO2 or in right atrial or arterial blood pressures. Although capnography is a useful intra-operative monitor, in this model it is less sensitive than PAP monitoring in detection of fat and marrow microemboli.

Animals↗

PubMed1989

High-volume, high-pressure pulsatile lavage during cemented arthroplasty.

To determine the efficacy of high-volume, high-pressure pulsatile lavage in the prevention of cardiopulmonary dysfunction and fat embolism during cemented arthroplasty, we studied twenty-eight mongrel dogs that had had a bilateral cemented arthroplasty. Significant increases in pulmonary-artery pressure and pulmonary vascular resistance, accompanied by decreases in arterial oxygen tension and increases in intrapulmonary shunt fraction (Qs/Qt), characterized cardiopulmonary dysfunction after bilateral cemented arthroplasty when no lavage was used. Low-volume, low-pressure manual lavage did not significantly alter these physiological changes, but there was a significant reduction in the number of fat emboli that were demonstrated in the lungs as compared with the no-lavage group. High-volume, high-pressure pulsatile lavage of the intramedullary cavity after reaming significantly reduced the changes in pulmonary-artery pressure, pulmonary vascular resistance, arterial oxygen tension, and intrapulmonary shunt fraction (Qs/Qt). In the pulsatile-lavage group, the number of fat microemboli that were found in the lungs was reduced to 25.7 per cent of those found in the no-lavage group. We concluded that meticulous high-volume, high-pressure pulsatile lavage reduces both pulmonary physiological derangements and fat emboli during bilateral cemented arthroplasty in dogs.

Animals↗

PubMed1989

Cardiopulmonary responses to Pseudomonas septicemia in swine: an improved model of the adult respiratory distress syndrome.

Bacteremia with resultant damage to multiple organ systems remains a serious problem in intensive care of human patients. We have developed a clinically relevant swine model of sepsis-induced adult respiratory distress syndrome (ARDS). Twenty-three animals were given various doses of Pseudomonas aeruginosa intravenously. Low cardiac output septic shock was prevented with massive fluid infusion. It was found that a dose of 1.0 X 10(7) colony forming units per 20 kg/min for 2 hours reliably produced respiratory failure in a setting of hyperdynamic sepsis which meets the diagnostic criteria of human ARDS.

Animals↗

PubMed1988

Anaphylatoxin C3a peptide contracts human pulmonary vasculature.

Complement anaphylatoxin C3a C-terminus octapeptide Ala-Ala-Ala-Leu-Gly-Leu-Ala-Arg (C3apep) contracted both pulmonary artery (PA) and pulmonary vein (PV) in a dose-dependent manner over the concentration range of 0.1 micrograms/ml to 100 micrograms/ml with the latter having maximal contractile activity. Removal of the terminal arginine caused complete loss of activity of C3apep. Contractions consisted of an early and a sustained component with the latter component being much greater in PV than PA. The early component was inhibited by pretreatment of tissues with the cyclooxygenase inhibitor indomethacin, or the thromboxane synthase inhibitors dazoxiben or U63,557A. The sustained contractile component was inhibited by the leukotriene antagonist FPL55712 or the 5-lipoxygenase inhibitors U60,257 (Piriprost) or nordihydroguaiiararetic (NDGA). C3apep challenge of both PA and PV resulted in the generation of leukotriene C4. These results suggest that C3apep causes contraction of human pulmonary arteries and veins by the production of thromboxane A2 and leukotrienes.

Amino Acid Sequence↗

PubMed1988

Morphologic diagnosis of idiopathic pulmonary alveolar lipoproteinosis-revisited.

The usefulness of transbronchial biopsy in diagnosing idiopathic pulmonary alveolar lipoproteinosis (PAL) is not emphasized in the literature. Therefore, we decided to reassess our approach to the morphologic diagnosis of this disorder in 14 patients diagnosed over the past 13 years in two major teaching hospitals in Toronto. The morphologic diagnosis of idiopathic PAL was established by means of open lung biopsy in 11 patients; the use of transbronchial biopsy was not considered in eight of them. Transbronchial biopsy was performed in six patients, and the diagnosis of idiopathic PAL was reliably established in five cases. We conclude that transbronchial biopsy may be a worthwhile preliminary procedure to open lung biopsy in patients with suspected idiopathic PAL, and it can reliably establish the diagnosis in such cases.

Adolescent↗

PubMed1987

Pulmonary marrow embolism: a dog model simulating dual component cemented arthroplasty.

The cardiopulmonary changes resulting from cemented arthroplasty procedures were monitored in 11 dogs with a single prosthesis implanted and nine dogs with a dual arthroplasty procedure. These changes were characterized by decreased BP, elevated PPA, and elevated PVR, associated with decreases in PaO2, cardiac output and mixed venous oxygen tension. All changes were more pronounced and prolonged in the dual component arthroplasty group. Histologic lung examination and morphometry demonstrated significant degrees of marrow (fat) microembolism in the dual arthroplasty model. Cardiopulmonary collapse has been associated with Guepar dual component arthroplasties clinically and these patients are at increased risk and should be monitored continuously. Prophylactic measures include meticulous lavage of the intramedullary cavity, increased FIO2, and maintenance of intravascular volume and cardiac output. The bilateral arthroplasty model is useful in investigating therapeutic interventions which may detect and prevent the marrow microembolism syndrome intraoperatively.

Animals↗

PubMed1987

Structure of central airways in current smokers and ex-smokers with and without mucus hypersecretion: relationship to lung function.

Forty-five patients who underwent thoracotomy and lung resection for tumour were studied to compare the structure of the central airways in current smokers and ex-smokers. The patients were divided into four groups: current smokers with mucus hypersecretion (n = 15), current smokers without mucus hypersecretion (n = 14), ex-smokers with mucus hypersecretion (n = 5), and ex-smokers without mucus hypersecretion (n = 11). Quantitative histological studies of the airway wall showed no difference in gland size, smooth muscle, connective tissue, or Reid index between the groups. The central airways of patients with mucus hypersecretion showed increased mucosal inflammation. The five ex-smokers in whom mucus hypersecretion persisted after they had stopped smoking had both central and peripheral airways affected by the inflammatory response, and these patients also had an abnormal result in the nitrogen washout test.

Humans↗

PubMed1987

Cardiopulmonary function and pulmonary microemboli during arthroplasty using cemented or non-cemented components. The role of intramedullary pressure.

An experimental model was designed to investigate the role of intramedullary pressure on cardiopulmonary function and pulmonary pathology during arthroplasty using cemented and non-cemented components. Twenty-four dogs were divided randomly into three groups: a group that received a non-cemented implant in which low intramedullary pressure was generated, a group that received a cemented implant, and one that received bone wax and an implant; high intramedullary pressures were generated in the latter two groups. Bone wax was used to generate high intramedullary pressures without the use of bone cement. In the group with the non-cemented implant, few pulmonary microemboli and no significant cardiorespiratory changes were found. In the groups that received bone wax and an implant or the cemented implant, there were many pulmonary microemboli and significant cardiorespiratory changes, including decreased arterial oxygen tension, increased pulmonary arterial pressure, and increased intrapulmonary shunt fraction. There was no evidence that methylmethacrylate monomer was responsible for the cardiorespiratory changes in the group with the cemented implant.

Animals↗

PubMed1986

Nonspecific airway reactivity in cigarette smokers. Relationship to airway pathology and baseline lung function.

To examine the relationship of cigarette smoking, starting airway caliber, and airway pathology to nonspecific airway reactivity, we performed inhalation dose-response curves in 40 patients prior to lung surgery. Airway reactivity was assessed by the provocative concentration of methacholine (n = 30) or histamine (n = 10) resulting in a 20% fall in FEV1 (PC20). All patients had measurements of maximal expiratory flow, diffusing capacity, and lung volumes preoperatively. After resection, the specimens were graded for small and large airways pathology and emphysema. The patients were divided into 4 groups: PC20 less than or equal to 1 mg/ml (n = 6), PC20 1 mg/ml to less than or equal to 4 mg/ml (n = 11), PC20 4 mg/ml to less than or equal to 16 mg/ml (n = 14), and PC20 greater than 16 mg/ml (n = 9). Subjects with PC20 less than or equal to 1 mg/ml had reduced measurements of maximal expiratory flow (FEV1, FEV1/FVC, Vmax50, and Vmax25). There were no differences in measurements of cartilaginous airway disease among the 4 reactivity groups. We found significant independent correlations of cigarette consumption, membranous bronchiole inflammation, and maximal expiratory flow rates (FEV1 and Vmax50) to PC20. The data suggest that cigarette smoking, starting airway caliber, and airway inflammation are associated with nonspecific airway reactivity and that each exerts an effect on airway reactivity that is not dependent on the contribution of the other 2 factors.

Aged↗

PubMed1986

Sarcoidosis simulating pulmonary veno-occlusive disease.

We describe a young woman who presented with a 6-month history of progressive pulmonary hypertension. At autopsy she was found to have noncaseating granulomas obliterating pulmonary veins, without granulomatous involvement of pulmonary arteries. Noncaseating granulomas were also present in the liver and hilar lymph nodes, confirming the diagnosis of sarcoidosis. To our knowledge this is the first reported case of pulmonary hypertension caused by sarcoidosis simulating pulmonary veno-occlusive disease.

Adult↗

PubMed1986

Alveolar epithelial damage. A critical difference between high pressure and oleic acid-induced low pressure pulmonary edema.

The present study was designed to compare high pressure pulmonary edema (HPPE) and oleic acid-induced low pressure pulmonary edema (OAPE) in dogs when similar amounts of extra vascular water were present in the lung. The high pressure edema was produced by intravenous fluid overload and by inflating an aortic balloon catheter (n = 6). The low pressure edema was produced by the injecting 0.08 mg/kg oleic acid suspended in 5 ml saline (n = 6). Comparison of the difference between initial control measurements and final measurements in the edematous states showed that the animals with OAPE had a greater fall in percent oxygen saturation and a greater increase in shunt fractions. The light microscopic studies showed that OAPE was associated with greater amounts of alveolar flooding than HPPE where the edema fluid was located to a greater extent in the peribronchial interstitial space. The electron microscopy studies showed that the alveolar flooding in OAPE was associated with epithelial disruption, and tracer studies carried out in rabbits showed that dextran (150,000 mol wt) could pass from blood to airspace and that dextran (40,000 mol wt) could pass from air-space to blood in OAPE. We conclude that epithelial disruption is responsible for the excessive alveolar flooding in OAPE and that this results in a greater impairment in gas exchange.

Animals↗

PubMed1985

Reassessment of inflammation of airways in chronic bronchitis.

The term chronic bronchitis has been criticised because it is associated with hypersecretion of mucus rather than bronchial inflammation. This study was designed to establish the presence or absence of clinical chronic bronchitis and measure pulmonary function in 45 patients about to undergo resection of the lung. The condition in the cartilaginous and small airways and the severity of the emphysema were then measured in the resected specimen. The results from 20 patients who had clinical chronic bronchitis were compared with those in 25 patients who did not. The data show that patients with chronic bronchitis had greater inflammation (a) on mucosal surfaces (p less than 0.05) of all bronchi larger than 2 mm luminal diameter and (b) around glands (p less than 0.005) and gland ducts (p less than 0.05) in bronchi larger than 4 mm diameter. A variable degree of inflammation was present in the submucosa of smaller bronchi. The groups had equivalent proportions of mucous glands and Reid's indices in central airways, and no differences were noted in measurements of pulmonary function, condition of small airways, or emphysema. These data show that the term chronic bronchitis is justified by inflammation of cartilaginous airways and suggest that this abnormality may be the cause of the chronic productive cough.

Bronchi↗

PubMed1985

Pulmonary function and peripheral airway disease in patients with mineral dust or fume exposure.

Cigarette smoking and mineral dust exposure combined result in small airways function abnormalities difficult to distinguish from smoking effects alone. To determine if mineral dust or fume exposure in smokers results in additional changes in small airways structure and function, we studied small airways disease and pulmonary function in 25 persons (62.4 +/- 8.8 yr) with exposure to mineral dust or fume for 10 yr or more and compared them individually with control subjects without dust exposure (61.8 +/- 8.5 yr) matched for age, smoking history, and lobe resected. All subjects were patients undergoing surgical resection for isolated coin lesions. Occupational histories and measurements of lung volumes, flow rates, small airways function, diffusing capacity, and pressure-volume relationships were obtained preoperatively. Membranous bronchioles were graded for the presence and degree of mural inflammation, fibrosis, muscle, pigment, and squamous and goblet cell metaplasia. Respiratory bronchioles were similarly graded for inflammation, fibrosis, muscle, pigment, and lumenal macrophages. The dust-exposed group had increased fibrous tissue deposition and goblet cell metaplasia in the membranous bronchioles (p less than 0.05). When the exposed group was divided according to occupation into miners (n = 13) and nonminers exposed in other dusty jobs (n = 12), the pathologic changes were evident in both exposed groups. No differences in pulmonary function were seen between the 2 groups. We conclude that occupational exposure to mineral dust and fume produces structural changes in peripheral airways that are greater than those seen with smoking alone, but these changes were not associated with a greater deterioration in lung function.

Aged↗

PubMed1984

Styloid-stylohyoid syndrome in the differential diagnosis of atypical facial pain.

Differential diagnosis of atypical facial pain can be a perplexing problem. Similarities in symptomatology and nonspecific subjective findings make diagnosis difficult. The astute diagnostician, regardless of his speciality, must be acutely aware of key findings that will differentiate the myriad of chronic pain syndromes in his patients. Accurate correlation of clinical and radiographic findings in patients with "Eagle's syndrome" may assist the clinician in distinguishing this entity from other pain syndromes, such as glossopharyngeal or vagoglossopharyneal neuralgia.

Carotid Artery Diseases↗

PubMed1982

Long-term pain control by direct peripheral-nerve stimulation.

In 1970, we began implanting electrodes for prolonged stimulation of injured peripheral nerves to reduce chronic pain. Thirty-eight peripheral nerves in thirty-five patients have been stimulated with electrodes for a period ranging from four to nine years. Nineteen electrode systems were implanted in the upper extremity (eleven on the median nerve, six on the ulnar nerve, one on the median and ulnar nerves, and one on the median and radial nerves), with successful relief of pain in 52..6 per cent of the patients. Sixteen stimulators have been implanted on the sciatic nerve with a success rate for pain relief of 31 per cent. Failures in the lower extremity were found primarily in lesions of the posterior tibial nerve at the ankle. We speculate that the stress of weight-bearing and the anatomical position of the posterior tibial nerve may partially account for this rate of failure. Use of the electrode-implant systems required careful preoperative assessment by an experienced team, meticulous technique, and a mechanical system that tolerates stress. The location and characteristics of the lesion affect the response to electrical stimulation.

Adult↗

PubMed1981

Effects of hyperbaric oxygen therapy on long-tract neuronal conduction in the acute phase of spinal cord injury.

To study the acute effects of hyperbaric oxygen ventilation (HBO) on long-tract function following spinal cord trauma, the authors employed a technique for monitoring spinal cord evoked potentials (SCEP) as an objective measure of translesion neuronal conduction in cats subjected to transdural impact injuries of the spinal cord. Control animals subjected to injuries of a magnitude of 400 or 500 gm-cm occasionally demonstrated spontaneous return of translesion SCEP within 2 hours of injury when maintained by pentobarbital anesthesia and by ventilation with ambient room air at 1 atmosphere absolute pressure (1 ATA). Animals sustaining corresponding injuries but receiving immediate treatment with HBO at 2 ATA for a period of 3 hours following impact demonstrated variable responses to this treatment modality. Animals sustaining injuries of 400 gm-cm magnitude showed recovery of translesion SCEP in four of five cases, while animals sustaining injuries of 500 gm-cm magnitude responded to HBO treatment by recovery of SCEP no more frequently than did control animals. When the onset of HBO therapy was delayed by 2 hours following impact, there appeared to be no demonstrable protective effect on long-tract neuronal conduction mediated by HBO alone. The observations suggest that HBO treatments can mediate preservation of marginally injured neuronal elements of the spinal cord long tracts during the early phases of traumatic spinal cord injury. These protective effects may be based upon the reversal of focal tissue hypoxia, or by reduction of tissue edema. HBO treatment markedly diminished the protective effects of HBO on long-tract neuronal conduction following traumatic spinal cord injury.

Animals↗

PubMed1981

Instrumentation for styloidectomy.

Instrumentation that prevents injury to the structures of the tonsillar fossa during styloidectomy was presented. We think that by using this instrumentation, in particular the antral curet, the potential hazards are greatly reduced, if not eliminated.

Humans↗