Allan L. Goldman

INHIBITION OF HUMAN PULMONARY PHOSPHODIESTERASE ACTIVITY BY THERAPEUTIC LEVELS OF THEOPHYLLINE

1. To test the hypothesis that inhibition of cyclic nucleotide phosphodiesterase is the major mechanism of the bronchodilator action of theophylline in reversible airways disease, the effects of therapeutic plasma levels of the drug on human pulmonary phosphodiesterase activity were examined.

Bilateral diaphragmatic paralysis complicating local cardiac hypothermia during open heart surgery

Filling the pericardial sac with ice and saline during open heart surgery protects the myocardium during periods of ischemic arrest. Bilateral diaphragmatic paralysis complicated intense local hypothermia in five patients undergoing coronary artery bypass surgery. All complained of severe orthopnea, exertional dyspnea, insomnia, and excessive daytime somnolence. All exhibited paradoxic inward movement of the abdominal wall with inspiration. The diagnosis of bilateral diaphragmatic paralysis was confirmed with upright and supine spirometry and, in one patient, with transdiaphragmatic pressure measurements. Although paralysis has resolved in four patients, all experienced months of disabling impairment. One patient required four months of mechanical ventilatory support prior to her recovery. Alternative methods of intraoperative myocardial preservation that avoid this complication should be developed.

Radiographic Patterns of Drug-Induced Lung Disease1

Drugs which induce lung disease are categorized according to the radiographic pattern of the disease. The five categories are: (a) diffuse interstitial (reticulo-nodular) findings, (b) diffuse air-space consolidation, (c) pleural effusion of fibrosis, (d) hilar or mediastinal widening, and (e) localized areas of consolidation. Information regarding onset, reversibility, fever, eosinophilia, and findings associated with each drug is presented. An extensive list of references is included.

Lithium carbonate in patients with small cell lung cancer receiving combination chemotherapy.

Lithium administration has been shown to attenuate the leukopenia associated with systemic chemotherapy. The results of a randomized trial of lithium in 45 patients with small cell lung cancer who received combination chemotherapy and radiation therapy are reported. Patients randomized to receive lithium were started on 300 mg three times daily for 18 days of every 21 day chemotherapy cycle. Patients who received lithium experienced significantly less mid-cycle leukocyte and neutrophil count depression and spent fewer days with leukopenia and neutropenia than control patients regardless of age or extent of disease. Patients who received lithium spent fewer days hospitalized and fewer days with fever in the presence of severe neutropenia than control patients. The cumulative risk of fever with signs of infection was greater in control patients regardless of age, disease extent or the presence of marrow involvement. Patients who were given lithium received significantly more chemotherapy than control patients. Patient survival was greatest in those with limited disease, in complete responders and in those who received more than 75 percent of their induction chemotherapy although it did not differ between the two study groups. The majority of patients required either reduction or discontinuation of lithium. Those who received lithium continuously demonstrated a higher objective response rate and longer survival than either patients in whom the lithium had to be discontinued or those randomized to the control group. Infection was an important cause of death in the control group and cardiovascular event occurred frequently in the lithium group, but the major cause of death in this patient population remains progressive malignant disease.

Reduced adenosine 3',5'-cyclic monophosphate levels in patients with reversible obstructive airways disease.

1. Patients were grouped into categories of ‘no airways disease’, ‘obstructive airways disease without response to bronchodilator’ and ‘obstructive airways disease with bronchodilator responsiveness’.

The Costs of Training Internal Medicine Residents in the United States

AAIM is the largest academically focused specialty organization representing departments of internal medicine at medical schools and teaching hospitals in the United States and Canada. As a consortium of five organizations, AAIM represents department chairs and chiefs; clerkship, residency, and fellowship program directors; division chiefs; and academic and business administrators as well as other faculty and staff in departments of internal medicine and their divisions.

Altered effector responses

Abstract During neurotransmission the second unit should always be regarded as an effector cell, regardlessof its nervous or non-nervous nature. In the autonomic system there are three types of effector cells: the neurons, the smooth muscle, and exocrine gland cells. These are the principal target cells of the pharmacologic mediators of allergic responses. The mediators of antigen-antibody responses, when viewed from the standpoint of their physiologic function, are among the natural chemical organizers of autonomic action. Denervation or mediator antagonist drugs cause hypersensitivity in the effector cells towards the transmitter in short supply. The hypothalamus has two reciprocally antagonistic divisions: the anterior hypothalamus, which mediates primarily cholinergic responses, and the posterior hypothalamus, the stimulation of which results largely in adrenergic responses. A balance between these divisions is important in maintaining normal autonomic functions (e.g., blood pressure). The posterior hypothalamus is normally suppressed by inhibitory impulses transmitted from the sinoaortic barorecaptors, which, among others, keep the posterior hypothalamus in check. When histamine or acethylcholine is given, blood pressure falls, the sinoaortic tension decreases, causing a shift to sympathetic activity. This leads to the release of catechols, which tends to correct and limit the blood pressure drop. Catecholamines increase blood pressure, which shifts the hypothalamic balance to the cholinergic side. It is possible to produce imbalance of the hypothalamus by applying histamine, acethylcholine, or catecholamines directly on hypothalamic structures; by the electrolytic removal or electrical stimulation of one of the divisions of the hypothalamus and by many other stimuli.

The discovery of immune-neuroendocrine circuitry — A generation of progress

Abstract The recognition of the immunoregulatory role of the hypothalamus in 1951 coincided with the advent of knowledge about some basic aspects of immunology. The nature of antibody diversity occupied the focus of interest in the light of new genetic studies completed. The “instructionist” theories of immune activation have been abandoned on the basis of new knowledge in favour of “selection theories” as advanced by Talmage and Burnet. These theories served as the basis for the elucidation of the genetic and molecular basis of lymphocyte function during immune responses, as we know it today. The recognition that the immune system is highly adaptable through receptor mutation, possesses memory and is capable of responding under in vitro conditions led to the conclusion that it is a virtually autonomous system that defends the body from foreign pathogens. This view is still maintained by many immunologists who see no need or use for additional systemic regulatory intervention. Under these conditions the scientific community at large has ignored the evidence that has accumulated slowly with regards to the interaction of the Neuroendocrine and Immune systems. Neverteless, the significance of this relationship has been re-emphasised in 1966 and it was proposed that immune homeostasis and the homeostasis of the organism are closely linked. Much evidence has accumulated since then to support this hypothesis.

Studies on the hypothalamic regulation of histamine synthesis history and some current information

Abstract As described earlier, L-histidine decarboxylase (HDC) activity in bone marrow is markedly increased on incubation with interleukin-3 (IL-3) or granulocyte macrophage colony stimulating factor (GM-CSF). This is due to the induction of the de novo synthesis of HDC in hemopoietic progenitor cells. Chemical axotomy in adult mice, chemical sympathectomy in neonatal mice or catecholamine depletion in adult rats by 6-hydroxydopamine inhibited the IL-3 or GM-CSF induced histamine synthesis. Stereotaxic lesions of the pre-optic and anterior hypothalamic area (parasympathetic representation) or electric stimulation of the posterior hypothalamus, enchanced the same effect. Likewise, chemical anterior lesions produced by N-methyl-DL-aspartate, or surgical antero-lateral deafferentation show the same result. Conversely, posterior hypothalamic lesions (sympathetic representation) or electric stimulation of the anterior hypothalamus have no effect on HDC synthesis. Thus the de novo synthesis of HDC induced by IL-3 and GM-CSF required β-adrenergic activation of progenitor hemopoietic cells that sensitizes these cells to the cytokines. The β-adrenergic input can be completely replaced in the induction of HDC synthesis by in vitro addition of Interleukin-1α.