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Biomedical subjects

M Beaulieu

Publications and source records attributed to M Beaulieu.

At least 55 records · Page 3Linked to original sources

Thoracoplasty: its forgotten role in the management of nontuberculous postpneumonectomy empyema.

The role of thoracoplasty in the management of empyema complicating pneumonectomy is controversial because alternative techniques, such as pedicled muscle transplants or open-space sterilization, have now replaced the conventional collapse procedures. Among 46 patients treated for postpneumonectomy empyema during the years 1975 to 1984, 17 underwent space-reducing thoracoplasty as the final step in pleural space management. Technical considerations, critical in the success of the operation, were: (a) single-stage extramusculoperiosteal resection of the second to the seventh rib, (b) sparing of the first rib to maintain integrity of the neck and shoulder girdle, (c) intercostal muscle closure of large fistulas and (d) adequate drainage of pleural and extrapleural spaces. Immediate control of the empyema was obtained in 15 (88%) patients. Fourteen patients were alive at the time of follow-up (mean 4.5 years) and none had major thoracic deformity or residual infection. Our data show that thoracoplasty is an excellent therapeutic option for patients with chronic postpneumonectomy empyema. Adherence to strict surgical principles ensures that the space is obliterated and the cosmetic result is satisfactory.

Adult↗

Transmitter-replacement therapy in Alzheimer's disease using intracerebroventricular infusions of receptor agonists.

Neurotransmitter replacement therapy in Alzheimer's Disease is currently being attempted using bethanechol chloride (Urecholine) infused intracerebroventricularly with an Infusaid continuous infusion pump. The rationale of this therapy is based on the severe cortical pre-synaptic cholinergic deficit in the presence of relatively normal post-synaptic muscarinic receptor density. Patients are selected on the basis of strict clinical criteria at a functional stage 4 or 5 of Reisberg. A cortical biopsy at the time of pump and catheter implantation confirms the diagnosis by histological and biochemical examination. Pre-operative, post-operative and serial mental status assessments combined with functional ADL assessments monitor changes in behavior. A 6 months double-blind treatment period is done in every patient, who is then free to continue if he has improved on active treatment. This specific study is part of a multi-centre trial. Other therapeutic trials using somatostatin analogs, such as Sandostatin, could then be done. The biological effects of the latter compound are being studied currently in adult Green Vervet monkeys, prior to its use in Alzheimer patients. Furthermore autoradiography of bethanechol and peptides labeled with 14C administered in these animals by intracerebroventricular infusion will allow a better knowledge of their pharmacological site of action.

Alzheimer Disease↗

D-2 dopaminergic agonists and adenosine 3',5'-monophosphate directly regulate the synthesis of alpha-melanocyte-stimulating hormone-like peptides by cultured rat melanotrophs.

When placed in short term (2-day) tissue culture, the melanotrophs from the intermediate lobe of the rat pituitary gland synthesize a proopiomelanocortin-like material (POMC-LM). Exposure of these cells to bromocriptine (CB 154), an agonist upon their D-2 dopamine receptor, reduces the synthesis of POMC-LM; spiroperidol, an antagonist of the D-2 receptor, prevents this effect of CB 154. Cultured melanotrophs secrete an alpha MSH-like material. The amount of this alpha MSH-like material, either stored intracellularly or secreted into the culture medium, can be quantified in a specific RIA; the material identified in this manner is designated immunoreactive alpha MSH (IR-alpha MSH). CB 154 inhibits the secretion of IR-alpha MSH from these cells. Either spiroperidol or 8-bromo-cAMP prevent this inhibitory effect of CB 154. The capacity of these cells to synthesize alpha MSH-like molecules and release them into the culture medium can be assessed by incubation in the presence of [3H]tyrosine, followed by immunoprecipitation with an antibody directed against alpha MSH. This newly synthesized immunoprecipitable material is designated immunoprecipitable alpha MSH (IP-alpha MSH) and should be distinguished from IR-alpha MSH. Both CB 154 and quinpirole, a selective D-2 agonist (but not SKF 38393, a selective D-1 agonist), inhibit the synthesis and secretion of IP-alpha MSH. YM-09151-2, a selective D-2 antagonist (but not SCH 23390, a selective D-1 antagonist), blocks the inhibitory effects of quinpirole. Several compounds affecting cAMP metabolism (cholera toxin, forskolin, 8-bromo-cAMP, and 3-isobutyl-1-methylxanthine) can also prevent the inhibitory effect of CB 154 on the synthesis of IP-alpha MSH. We conclude the following. The D-2 receptor in the intermediate lobe directly regulates the synthesis and secretion of IP-alpha MSH. cAMP can regulate either the synthesis of POMC-LM or the processing of this substance into alpha MSH-like peptides.

1-Methyl-3-isobutylxanthine↗

Long-term clinical and functional results of sleeve lobectomy for primary lung cancer.

Sleeve lobectomy is a lung-saving operation in which a portion of main bronchus is removed in continuity with the involved lobe to preserve distal parenchyma. Current controversies relate to indication and safety of the procedure, adequacy as a cancer operation, and contribution of the reimplanted lobe to overall remaining lung function. Between 1975 and 1985, sleeve lobectomy was done electively in 72 patients with lung cancer. There were no operative deaths, but major complications occurred in 10% of patients. Most resected carcinomas were squamous (65/72). Complete resection was performed in all but five patients. A minimum of 1 year's follow-up information was available for all patients. For patients with N0 disease (n = 34) the cumulative 5 year survival rate was 67%, and for patients with N1 status (n = 34) it was 60%. Although postoperative pulmonary function studies at 5 years (n = 19) show subnormal values, they were not severely altered with regard to percent of predicted (forced vital capacity, 85.9% +/- 17.5%; forced expiratory volume in 1 second, 74.9% +/- 19.4%). Regional function was determined by ventilation/perfusion isotope scanning methods. For 15 patients with right lung bronchoplasties, perfusion ratios were 41.1% right lung/58.9% left lung. For four patients with left sleeve operations, these ratios were 29.3% left lung/51.7% right lung. Washout curves show comparable ventilation between the reimplanted lobe and the contralateral lung. The data show that sleeve lobectomy is a safe and adequate operation for patients with resectable lung cancer. The reimplanted lobe or lobes contribute significantly to the overall remaining lung function.

Actuarial Analysis↗

Role of mediastinoscopy in pretreatment staging of patients with primary lung cancer.

Since the introduction of mediastinoscopy, there has been a great deal of discussion regarding indications for this technique and the significance of positive findings. We undertook this study to determine the role of clinical staging and the value of routine mediastinoscopy in the treatment selection of patients with primary lung cancer. From 1975 to 1983, 1,259 consecutive patients with proven and operable lung cancer underwent preresection mediastinoscopy. Nodes were sampled at three levels, and findings were recorded by location, invasiveness, and histology. There were no operative deaths, but 3 patients had a major complication. Mediastinoscopy was positive in 339 (27%) patients and negative in 920 (73%). In the group with positive findings, 303 patients had no operation because a curative resection was not possible (extranodal metastases, 180; location, 76; histology, 47). No patient survived 5 years, and only 4% survived 2 years. Of the 36 patients considered to have operable disease, 28 underwent resection with a projected 5-year survival of 18%. In the group with negative findings, 89% had a curative resection with a hospital mortality of 3.2% and 5-year survival of 53%. When results of mediastinoscopy were correlated with findings at thoracotomy, the sensitivity of the test was 93% on nodes in the superior mediastinum and the specificity, 100%. This study shows that mediastinoscopy is safe and is an accurate indicator of the presence or absence of tumor in superior mediastinal nodes. If positive nodes are found, a curative resection is generally not possible, thoracotomy is avoided, and the overall survival is low.

Adult↗

High-flow catheter ventilation during major tracheobronchial reconstruction.

Anesthetic management during tracheobronchial reconstruction is a concern to the anesthetist, who must maintain satisfactory gas exchange while ensuring adequate exposure to the trachea. The technique for high-flow catheter ventilation was first described for bronchoscopy, and it involves positive-pressure breathing with a high flow (40 to 60 L/min) of oxygen. This flow is directed to a semirigid catheter inserted in the endotracheal tube and around which the tracheobronchial anastomosis can be done without interruption. The value of the technique was tested in 18 patients undergoing tracheobronchial reconstructions. Patients' ages ranged from 22 to 69 years and the average duration of catheter ventilation was 35 minutes. Regardless of the duration of high-flow catheter ventilation good arterial blood gas values were maintained in all patients. In six patients, the average oxygen tension (measured at 5 minute intervals) was 416 mm Hg and the average carbon dioxide tension was 34 mm Hg. One patient developed surgical emphysema during the procedure. The high-flow catheter ventilation provides specific advantages during tracheobronchial procedures: avoidance of endotracheal manipulations, unobstructed field during surgical reconstruction, and good oxygenation throughout the procedure.

Adult↗

N,N-disubstituted 2-aminotetralins are potent D-2 dopamine receptor agonists.

Mono- and di-N-substituted 2-amino-5-hydroxytetralins stimulate the D-2 dopamine receptor, 2-(N-n-propyl-N-phenylethylamino)-5-hydroxytetralin being the most potent D-2 agonist encountered to date. In contrast, 2-amino-5-hydroxytetralins only marginally stimulate the D-1 receptor; however, 2-(di-N-n-propylamino)-5, 6-dihydroxytetralin is equipotent with dopamine as a D-1 agonist. The results are discussed within the context of the two dopamine receptor hypothesis.

Adenylyl Cyclases↗

The chemical basis for the blockade of the D-1 dopamine receptor by SCH 23390.

SCH 23390 (R(+)-7-chloro-8-hydroxy-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3 -benzazepine) is a potent, relatively selective antagonist of the D-1 dopamine receptor ( Iorio et al., J. Pharmacol. Exp. Ther. 226, 462). Because SKF 75670, the 7-OH analogue of SCH 23390, is a partial D-1 agonist, we conclude that the 7-Cl substituent of SCH 23390 contributes to its D-1 antagonist activity. Because SKF 83509, the desmethyl analogue of SCH 23390, is a selective D-1 antagonist, we conclude that the N-methyl substituent of SCH 23390 is not essential for its D-1 antagonist activity.

Adenylyl Cyclases↗

Institutional objectives for medical education that relates to the community.

The graduate of most medical schools in North America is described as an "undifferentiated physician", but there is no universally agreed upon definition of the term. With the proliferation of subspecialties during the past 30 years, each division or department has its own concept of the undifferentiated physician. The result is strong pressure on curriculum committees to increase curriculum content. The medical faculty of the University of Ottawa used an approach to developing institutional objectives for medical schools that was based on the premise that graduates should possess the knowledge, skills and attitudes of a primary care practitioner in the community, and they accepted an institutional goal and 10 institutional objectives after five revisions of the original proposal. An essential element in the development of the objectives was the use of a list of common medical problems, ranked in order of frequency, as guidelines. The resulting institutional objectives are relevant to current community needs and may be used to project the future needs of the community.

Academic Medical Centers↗

Pharmacological and biochemical evidence for the existence of two categories of dopamine receptor.

Evidence supporting the validity of the 'two dopamine receptor' hypothesis is presented. The availability of the 'first generation' of selective agonists and antagonists of the D-1 and the D-2 dopamine receptors provides pharmacological support for the hypothesis. The demonstration that stimulation of the D-2 receptor either inhibits or has no effect upon adenylate cyclase activity while stimulation of the D-1 receptor enhances cAMP formation provides biochemical support for the hypothesis. Finally, binding assays demonstrating two affinity states for the D-1 and the D-2 receptors are briefly discussed.

Animals↗

Development of central neurotransmitter-specified neuronal systems: implications for pediatric neuro-psychiatric disorders.

An increasing focus on the mechanism of synaptic neurochemistry in pediatric neurology, may lead to a better understanding of the pathophysiology of many disorders and result in a more rational approach to their pharmacotherapy. With the burgeoning list of putative neurotransmitters in brain, and the growing evidence of co-localization of many of these neurotransmitters, chemical neurotransmission likely involves a higher degree of complexity than appreciated heretofore. The potential role of neurotransmitter dysfunction in the pathophysiology of neurologic and behavior disorders of children, should not be considered as restricted to those disorders that involve selective neuronal loss, but may encompass a much wider spectrum of syndromes due to metabolic abnormalities, as well as disturbances of the finer features of chemical neurotransmission.

Afferent Pathways↗

Bromocriptine-induced changes in the biochemistry, physiology, and histology of the intermediate lobe of the rat pituitary gland.

Treatment of rats with 2-Br-alpha-ergocryptine (bromocriptine; CB 154) elicits biochemical, physiological, and histological changes in the intermediate lobe (IL) of the rat pituitary gland, suggesting a decrease in activity in the IL. CB 154 treatment decreases 1) the capacity of the IL to synthesize proopiomelanocortin (POMC), 2) the content of mRNA directing the synthesis of POMC, and 3) the capacity of the IL to synthesize the peptides desacetyl alpha MSH, N,O-diacetyl alpha MSH, and alpha MSH. CB 154 treatment also causes a 40% loss of IL protein and an atrophy of the IL. CB 154 treatment has a biphasic effect upon the IL content of alpha MSH-like peptides; the drug first increases and then diminishes the content of these molecules. Control experiments using CB 154-treated IL tissue suggest that these effects of CB 154 are not a toxic effect of CB 154 on the IL. Spiroperidol reverses the effects of CB 154 on POMC synthesis and POMC mRNA content; by itself, spiroperidol increases the IL synthesis of POMC, the IL content of POMC mRNA, and the capacity of the IL to synthesize immunoreactive alpha MSH. Stalk section of rat pituitary gland also results in an increase in the capacity of the IL to synthesize POMC. These results suggest that a D-2 dopamine receptor mediates a tonic inhibition of the function of the IL.

Adrenocorticotropic Hormone↗

Postnatal development of aminergic projections to frontal cortex: effects of cortical lesions.

The effects of lesions induced by fetal treatment with methylazoxymethanol acetate (MAM) on the developmental synaptic chemistry of the frontal cortex of rats were examined. Treatment at 14 days' gestation (DG) resulted in a 50% decrease in frontal cortical mass whereas treatment at 15 DG caused a 40% decrement. No difference in concentration between MAM and control rats was observed in the postnatal development of the GABA-ergic markers, glutamate decarboxylase, and GABA. In contrast, the concentrations of the presynaptic markers for the dopaminergic, noradrenergic, and serotonergic terminals were generally elevated in the MAM lesioned frontal cortex throughout postnatal development. The effects of MAM lesion on cholinergic markers were mixed, with minimal alterations in concentration during the first 2 postnatal weeks followed by an increasing disparity thereafter. The results of this study provide additional evidence in support of the differential impact of the cortical hypoplasia on intrinsic neurons as contrasted to aminergic afferents.

Animals↗

alpha-Melanocyte-stimulating hormone-like peptides in the intermediate lobe of the rat pituitary gland: characterization of content and release in vitro.

Reverse phase high performance liquid chromatography (HPLC) followed by RIA of the chromatographic fractions was used to separate and quantify, respectively, the alpha MSH-like peptides stored in the intermediate lobe (IL) of the rat pituitary gland and released from IL cells in vitro. Immunoreactive material eluting with the same HPLC retention time as N,O-diacetyl alpha MSH accounted for approximately 80% of the total immunoreactive alpha MSH (IR-alpha MSH) in either the neurointermediate lobe or dispersed IL cells. The remainder of the IR-alpha MSH coeluted with either synthetic desacetyl alpha MSH or alpha MSH. Furthermore, the predominant alpha MSH-like compound released in vitro from dispersed IL cells eluted from the HPLC column with the same retention time as synthetic N,O-diacetyl alpha MSH. Treatment of dispersed IL cells with drugs known to enhance (l-isoproterenol or A 23187) or to inhibit (apomorphine or lisuride) the release of IR-alpha MSH revealed that N,O-diacetyl alpha MSH was the primary form released. Finally, an evaluation of the stability of the alpha MSH-like peptides indicated that N,O-diacetyl alpha MSH was readily converted to alpha MSH in the presence of 0.1 N hydrochloric acid.

Adrenocorticotropic Hormone↗

Fetally-induced noradrenergic hyperinnervation of cerebral cortex results in persistent down-regulation of beta-receptors.

Methylazoxymethanol acetate (MAM)-induced cortical hypoplasia resulted in a 2-fold increase in the concentration of norepinephrine and its metabolite, 3-methoxyl-4-hydroxyphenylglycol sulfate, and a 26% decrease in the Bmax for the beta-receptor ligand, [3H]dihydroalprenolol (DHA) in the rat cortex. Chronic treatment with desmethylimipramine did not further decrease DHA-labeled sites although prior lesion of the noradrenergic terminals with 6-hydroxydopamine markedly increased the number in the MAM-lesioned cortex.

Animals↗

Diagnosis and long-term follow-up of major bronchial disruptions due to nonpenetrating trauma.

From 1966 through 1978, 13 patients were treated for major bronchial disruptions due to nonpenetrating trauma. In 10 patients the diagnosis was made early, and operation was carried out in all of them. Four of the 6 patients with main bronchus avulsion had primary repair and all 4 patients with lobar rupture underwent lobectomy. One patient had a pneumonectomy. There was 1 operative death. In 3 patients the diagnosis was made more than a month after the injury. A bronchoplastic repair was done in every patient. All 7 patients who had repair of a transected main bronchus were assessed 2 to 14 years after operation (average, 7 1/2 years). Flow-volume curves on air and air-helium were normal, indicating no major airway obstruction; this finding was confirmed by clinical and bronchoscopic examinations. Pulmonary diffusing capacity for carbon monoxide was also normal in all patients. Volume measurements by closed circuit method and by body plethysmography showed restriction in 1 patient but no major air trapping. Perfusion/ventilation scans showed homogeneous distribution of air and blood flow in the lung.

Adolescent↗