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Biomedical subjects

A Leff

Publications and source records attributed to A Leff.

At least 19 recordsLinked to original sources
PubMed2001

Identification of higher brain centres that may encode the cardiorespiratory response to exercise in humans.

1. Positron emission tomography (PET) was used to identify the neuroanatomical correlates underlying 'central command' during imagination of exercise under hypnosis, in order to uncouple central command from peripheral feedback. 2. Three cognitive conditions were used: condition I, imagination of freewheeling downhill on a bicycle (no change in heart rate, HR, or ventilation, V(I)): condition II, imagination of exercise, cycling uphill (increased HR by 12 % and V(I) by 30 % of the actual exercise response): condition III, volitionally driven hyperventilation to match that achieved in condition II (no change in HR). 3. Subtraction methodology created contrast A (II minus I) highlighting cerebral areas involved in the imagination of exercise and contrast B (III minus I) highlighting areas activated in the direct volitional control of breathing (n = 4 for both; 8 scans per subject). End-tidal P(CO(2)) (P(ET,CO(2))) was held constant throughout PET scanning. 4. In contrast A, significant activations were seen in the right dorso-lateral prefrontal cortex, supplementary motor areas (SMA), the right premotor area (PMA), superolateral sensorimotor areas, thalamus, and bilaterally in the cerebellum. In contrast B, significant activations were present in the SMA and in lateral sensorimotor cortical areas. The SMA/PMA, dorso-lateral prefrontal cortex and the cerebellum are concerned with volitional/motor control, including that of the respiratory muscles. 5. The neuroanatomical areas activated suggest that a significant component of the respiratory response to 'exercise', in the absence of both movement feedback and an increase in CO(2) production, can be generated by what appears to be a behavioural response.

Adult↗
PubMed2000

Noun imageability and the temporal lobes.

We used positron emission tomography to investigate brain activity in response to hearing or reading nouns of varying imageability. Three experiments were performed. Activity increased with noun imageability in the left mid-fusiform gyrus, the lateral parahippocampal area in humans, and in the rostral medial temporal lobes close to or within perirhinal cortex. The left mid-fusiform activation has been observed in previous imaging studies of single word processing. Its functional significance was variously attributed to semantic processing, visual imagery, encoding episodic memories, or the integration of lexical inputs from different sensory modalities. These hypotheses are not mutually exclusive. The more rostral medial lobe response to noun imageability has not been observed previously. However, lesions in perirhinal cortex impair knowledge about objects in non-human primates, and bilateral rostral ventromedial temporal lobe potentials in response to object nouns were observed with human intracranial recordings. Imageable (object) nouns are learnt with reference to sensory experiences of living and non-living objects, whereas acquisition of the meaning of low imageable (abstract) nouns is more dependent on their context within sentences. Parahippocampal and perirhinal cortices are reciprocally connected with, respectively, second and third order sensory association cortices. We conclude that access to the representations of word meaning is dependent on heteromodal temporal lobe cortex, and that during the acquisition of object nouns one route is established through ventromedial temporal cortical regions that have reciprocal connections with all sensory association cortices.

Adult↗
PubMed1999

Outcomes after long-term acute care. An analysis of 133 mechanically ventilated patients.

Long-term acute-care (LTAC) hospitals are facilities exempt from the Medicare prospective payment system and which provide care to patients suffering from prolonged critical illness. From August 1, 1995 to July 31, 1996, we studied the outcomes of 133 mechanically ventilated patients who were consecutively admitted to a large urban LTAC hospital from intensive care units (ICUs) of acute-care hospitals. Survival and functional status within 1 yr after the index admission were measured, and specific patient variables were used to develop a predictive model for survival at 1 yr. Of the 133 patients studied, 66 (50%) died prior to discharge. Of discharged patients, 70% had been successfully liberated from mechanical ventilation. One year after LTAC hospital admission, 103 (77%) of the patients had expired, typically after spending the majority of their days in acute care or long-term care facilities. Eleven 1-yr survivors (8%) were fully functional, whereas the remainder had significantly reduced functional status. Patients older than 74 yr, and patients older than 64 yr and not functionally independent before admission, had a 95% (confidence interval [CI]: 84% to 99%) 1-yr mortality; patients without these characteristics had a 56% (CI: 41% to 71%) 1-yr mortality (p < 0.001). We demonstrate characteristics predicting the poorest prognoses for patients requiring prolonged mechanical ventilation. These characteristics may be identifiable before transfer to an LTAC hospital.

Adult↗
PubMed1998

Outcomes and resource utilization for patients with prolonged critical illness managed by university-based or community-based subspecialists.

We studied 118 patients with prolonged critical illness to determine if there would be a difference in outcome between patients managed by university-based (UB) or community-based (CB) intensivists. Patients consecutively admitted to a long-term acute care hospital were assigned in an arbitrary manner to the UB service or CB service. Patient survival, length of stay, and success and length of time required for liberation from mechanical ventilation (MV) were compared using survival analysis, logistic regression, and analysis of variance techniques. Patients on the UB service were liberated from MV in 32% fewer days (39 versus 57 d, p = 0.02) and were marginally more likely to be liberated from MV (46% versus 30%, p = 0.14). UB physicians were more likely to write do not resuscitate orders (59% versus 33%, p < 0.01) and to withdraw life-sustaining therapy (12% versus 2%, p = 0.09). There were no detectable differences in survival between the two groups. Estimated reimbursement for CB physicians ($6,797/patient) was 46% greater than for UB physicians ($4,651/patient) for discharged patients (p = 0.03). We conclude that patients experiencing prolonged critical illness may experience different outcomes based on their physician provider. In our study, patients were liberated more quickly from MV, were withdrawn from life support more readily, and were managed at lower cost by UB intensivists than by CB intensivists.

Academic Medical Centers↗
PubMed1998

Exclusion of uniparental inheritance of chromosome 15 in a fetus with a familial dicentric (Y;15) translocation.

We present a prenatal case with a 45,X,dic(Y;15) (q11.23;p11.1) karyotype and describe the inheritance pattern of the chromosome 15s. Chromosome 15 has an imprinted region and inheritance of both chromosome 15 from one parent results in either Angelman syndrome (AS) (paternal inheritance) or Prader Willi syndrome (PWS) (maternal inheritance). Parental chromosome studies revealed that the father carried the same dicentric (Y;15) translocation. Since familial chromosome rearrangements can result in aberrant chromosomal segregation during meiosis, we wanted to exclude paternal uniparental inheritance of chromosome 15. By using DNA microsatellite markers at several 15q11q13 loci, we determined that the fetus had inherited his normal non-translocated chromosome 15 from his mother.

Adult↗
PubMed1997

Dose-response relationships in determining the safety:efficacy ratio.

The development of inhaled agonists selective for beta 2-adrenoceptors and high potency corticosteroids has improved the treatment of asthma. The delivery of the drugs to the site of action reduces the systemic exposure and hence reduces adverse systemic events. Together, these factors have resulted in improved toxicity: therapeutic ratios. Long-acting beta 2-agonists, such as salmeterol and formoterol, and high efficacy corticosteroids, such as fluticasone propionate and budesonide, now are available for clinical use. Because suboptimal treatment of asthma causes increased morbidity and mortality, and increased costs to society, these compounds are of particular value. Risk factors associated with fatal and near-fatal asthma have been identified, and it would appear that drug treatment by metered dose inhaler per se does not cause increased asthma fatality as an independent risk factor.

Administration, Inhalation↗
PubMed1992

Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats.

We have previously demonstrated that susceptibility of Lewis (LEW/N) rats to inflammatory disease, compared to relatively resistant Fischer (F344/N) rats, is related to deficient glucocorticoid counter-regulation of the immune response resulting from deficient corticotropin-releasing hormone (CRH) responsiveness to inflammatory and other stress mediators. The GABA/benzodiazepine receptor complex is an important negative modulator of CRH secretion and responsiveness to excitatory stimuli. In this study, we have examined in vitro binding of [3H]flunitrazepam to hypothalamic membrane preparations from LEW/N and F344/N rats. LEW/N rats had significantly more hypothalamic benzodiazepine binding sites (Bmax) than F344/N rats, but there were no differences in benzodiazepine binding affinities (Kd) between these two strains. The differences in benzodiazepine receptor number were consistent with the respective plasma corticosterone levels in the two strains, and with previous work indicating a negative correlation between corticosterone levels and benzodiazepine binding site number. Adrenalectomy of F344/N rats increased benzodiazepine binding to levels comparable to LEW/N animals and treatment of adrenalectomized F344/N rats with DEX resulted in lowering of benzodiazepine Bmax to levels that did not differ significantly from those of intact F344/N rats. There was no significant change in receptor number in either adrenalectomized or DEX-treated LEW/N rats. These findings suggest that basal benzodiazepine receptor differences between these strains may be partially related to strain differences in corticosterone levels, however that additional factors may contribute to maintenance of these differences in LEW/N rats. Since benzodiazepines attenuate hypothalamic CRH secretion through GABAergic inhibition, we suggest that strain differences in receptor number could also augment strain differences in hypothalamic-pituitary-adrenal axis function through differential sensitivity to GABA-mediated feedback.

Adrenalectomy↗
PubMed1988

Diffusing capacity predicts morbidity and mortality after pulmonary resection.

Patients who are considered for major pulmonary resection are normally evaluated by spirometry and clinical assessment. Despite this, the morbidity and mortality rates are high after these operations. We retrospectively reviewed results of lung resection performed during a period of 7.5 years in 237 patients to identify other important predictors of morbidity and mortality. There were 144 male and 93 female patients with a mean age of 59.4 +/- 11.4 years. The indication for operation was lung cancer in 199 (76 stage I, 34 stage II, 89 stage IIIA-B), benign disease in 34, and metastatic disease from other primary tumors in four. Lobectomy or bilobectomy was performed in 164 patients and pneumonectomy in 73. Data on 38 preoperative and operative risk factors were correlated with information on 24 postoperative events grouped into four major categories: death, pulmonary complications, cardiovascular complications, and other problems. Logistic regression analysis and chi 2 analysis were used to identify the relationship of the preoperative risk factors to the grouped postoperative complications. The diffusing capacity of the lung for carbon monoxide was the most important predictor of mortality (p less 0.01) and was the sole predictor of postoperative pulmonary complications (p less than 0.005). This diffusing capacity can reveal the existence of emphysematous changes in the lung, even when spirometric values are acceptable, and it usually should be a part of the evaluation of patients being considered for pulmonary resection.

Adolescent↗
PubMed1987

A lethal presentation of de novo deletion 7q.

Deletion of 7q32----qter is a well defined syndrome which usually arises de novo. The proband we report was the result of an uncomplicated 36 week first pregnancy of non-consanguineous Oriental parents. The male infant died shortly after birth. Chromosome studies of peripheral blood and umbilical cord revealed 46,XY,del(7), apparently (q32----qter). The parents' karyotypes were normal. The observed facial structural abnormalities and hydrocephalus rather than microcephaly are in sharp contrast to the clinically described syndrome. The lethal components, absence of suprarenal glands and hydranencephaly, suggest either an unknown confounding factor or a more proximal deletion with an alternative interpretation of 7q--(q23.1----q36.1) rather than the apparent breakpoint at 7q32.

Abnormalities, Multiple↗
PubMed1987

Canine bronchoconstriction, gas trapping, and hypoxia with methacholine.

The effects of an intravenous methacholine infusion on cardiovascular-pulmonary function were measured in seven mongrel dogs (22.0 +/- 2.8 kg), anesthetized with chloralose and urethan and beta-adrenergically blocked with propranolol. In a volume-displacement plethysmograph, physiological measurements were made at base line and 25 min after establishing a methacholine infusion (0.1-1.0 mg X kg-1 X h-1). Methacholine significantly (P less than 0.05) increased airways resistance (1.9 +/- 0.8 to 8.2 +/- 2.9 cmH2O X l-1 X s), decreased static lung compliance (84.7 +/- 18.5 to 48.2 +/- 9.4 ml/cmH2O), depressed arterial PO2 (81 +/- 17 to 56 +/- 10 Torr), and lowered blood pressure (132 +/- 10 to 69 +/- 18 Torr) and cardiac output (5.7 +/- 1.9 to 4.1 +/- 1.2 l/min). These effects persisted during a further 80 min of methacholine infusion conducted in five of the animals. During the initial 25-min period of methacholine, the end-expired volume (volume-displacement Krogh spirometer) rose in all animals, indicating an increase in functional residual capacity from 997 +/- 115 to 1,623 +/- 259 ml (P less than 0.0005). Analysis of pulmonary pressure-volume curves revealed no change in total lung capacity but an increase in residual volume from 489 +/- 168 to 1,106 +/- 216 ml (P less than 0.001). Thus methacholine caused 617 ml of gas trapping, which was not detected by the Boyle's law principle, presumably because gas was trapped at high transpulmonary pressure. We suggest that intravenous methacholine-induced canine bronchoconstriction, which causes gas trapping and hypoxia, may be a useful animal model of clinical status asthmaticus.

Animals↗
PubMed1987

Immortalization in culture: occurrence at a late stage in the progression of breast cancer.

The properties in culture of 3 breast cancer effusion metastases, obtained over approximately 2 years from the same patient, were examined. Despite repeated attempts with cryopreserved cells, only the last specimen reproducibly exhibited immortality in culture; the first 2 specimens grew initially but failed to develop into cell lines. Each specimen was unique in morphology and growth properties, although karyotypic markers indicated a common origin. Aberrations of chromosomes 1 and 11 marked these near-diploid cells, and further structural alterations of chromosome 11 accompanied the transition of biological properties observed in the third specimen.

Adult↗
PubMed1982

Pathogenesis of asthma. Neurophysiology and pharmacology of bronchospasm.

Asthma results from variable and often sudden changes in airway smooth muscle tone. Allergy is not an essential component of the asthmatic response; however, mediator release plays an important role in the human asthmatic response. Histamine may act directly to cause bronchoconstriction by stimulating the H1-receptor on airway smooth muscle or indirectly by stimulation of afferent vagal fibers in airways. Histamine may also act locally on airways to augment cholinergic and, possibly, alpha-adrenergic constrictor effects, or to antagonize beta-adrenergic relaxation of airway smooth muscle. Cholinergic neural output promotes bronchoconstriction in non-atopic asthma, but parasympathetic reflexes are not a major component of human bronchial responses to inhaled allergen. The physiologic significance of the sympathetic nervous system in relaxing airway smooth muscle is incompletely defined. Recent studies suggest that direct sympathetic innervation of airways is relatively unimportant and that purinergic fibers may be the predominant inhibitory neurons in human airways. Investigations focusing on intracellular calcium metabolism in airway smooth muscle have implicated the adenyl cyclase-cyclic adenosine monophosphate system in the regulation of bronchomotor tone. Cyclic nucleotides may modulate but do not mediate respiratory muscle contraction, and their precise role in regulating bronchomotor tone remains uncertain.

Adult↗
PubMed1980

Pathophysiology and management of the complications resulting from fire and the inhaled products of combustion: review of the literature.

Respiratory dysfunction is a major consequence of smoke inhalation and significant surface burns. Carbon monoxide intoxication, asphyxia, and upper airway obstruction occur early, whereas pulmonary edema and bacterial pneumonia may be delayed for days or weeks. The noxious constituents of smoke are believed to stimulate irritant receptors producing bronchoconstriction and to cause chemical injury to the airway mucosa and the alveolar-capillary membrane producing pulmonary edema. Pneumonia occurs in most patients who survive the initial injury. Thorough history and physical and laboratory examinations may forecast the severity of injury. Treatment includes administration of oxygen, use of bronchodilators, and when necessary, mechanical ventilation. The long-term sequelae of smoke inhalation are unknown.

Asphyxia↗