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J E Gottlieb

Publications and source records attributed to J E Gottlieb.

34 records · Page 2Linked to original sources
PubMed1988

Biochemical analysis of the activation of adherent neutrophils in vitro.

The role played by neutrophil oxidative responses in host defense and injury is an area of active investigation. In order to study neutrophil responses in vitro, methods are required for cell purification, enumeration, and quantification of activation responses, which mimic the in vivo situation as closely as possible. In this communication (and its companion paper, Albertine et al., 1988) improved methods for all of these tasks are described and applied to investigate neutrophil structure-function relationships in vitro and in vivo. Human neutrophils were purified by using a series of platelet-poor plasma-Percoll gradients (51, 62, 76 and 80% in Percoll). This modification of previously published procedures results in consistently successful neutrophil purification and has allowed us to purify neutrophils from bronchoalveolar lavage fluid as well as blood. Activation of human and sheep neutrophils (superoxide anion production) was quantitated by the reduction of ferricytochrome c using a microtiter plate reader to measure the increase in absorbance at 550 nm from adherent neutrophils. Adherence of neutrophils was quantitated by measurement of LDH in cells lysed with Triton X-100 using a new method which uses readily available commercial reagents and can quantitate the LDH content of as few as 5000 neutrophils (or the LDH released from 5% of 100,000 neutrophils). Assay conditions for superoxide anion were optimized, limitations both in assay design and instruments used to measure OD were explored and enumerated, and these methods were used to quantitate sheep and human neutrophil activation responses. Using methods described in Albertine et al. (1988) for fixing neutrophils in microtiter wells after assay of their functional capacity, we have studied the same cells functionally and morphologically. We have used these techniques to study blood and alveolar neutrophils from a patient with acute respiratory failure. His alveolar neutrophils displayed 67% of the activation response as peripheral neutrophils (4.31 +/- 0.12 nmol superoxide released per 250,000 neutrophils at 60 min vs. 6.38 +/- 0.18 in blood, P less than 0.01) and structural changes which suggested previous activation in vivo. These studies demonstrate that similar morphological changes are observed in neutrophils activated with phorbol myristate acetate in vitro, as are observed in cells which have been activated by pathophysiologic processes in vivo.

Animals↗
PubMed1988

Morphological analysis of the activation of adherent neutrophils in vitro.

One approach to study the inflammatory potential of neutrophils involves in vitro methods, using either adherent or suspended cells. In order to do structure-function studies, traditional methods require that experiments be done in parallel: one experiment for structure and another for function. In this report new morphological methods for coordinated structure-function studies on the same cells are described. Isolation and biochemical analysis of sheep and human adherent neutrophils were done as described in the companion paper (Cerasoli et al., 1988). Then, at designated time points, the adherent cells were fixed and processed in the microtiter wells for high-resolution light microscopy and transmission electron microscopy. The principal obstacle to the morphological studies was chemical etching of the microtiter wells by the processing solutions and embedding media. Insertion of No. 3 BEEM capsule 'sleeves' (the cap and conical tip were removed) into the wells before processing eliminated the obstacle and provided standard-sized, polymerized blocks for microtomes. Adherent neutrophils activated in vitro with 10(-7) M phorbol myristate acetate developed prominent cytoplasmic vacuoles. Furthermore, the activated cells assumed irregular shapes and cytoplasmic processes. These changes in adherent cell morphology in vitro are similar to those seen in neutrophils which have been activated and fixed in vivo. Thus, the in vitro approach we devised retains the morphologic characteristics of cells in vivo and provides an efficient method to do integrated structure-function studies. Using these techniques, we have studied alveolar neutrophils obtained from a patient with acute respiratory failure. These cells contained conspicuous cytoplasmic vacuoles, few granules, and their border was ruffled. The same morphologic changes observed after activation of peripheral blood neutrophils with phorbol myristate acetate in vitro were seen in the alveolar neutrophils obtained from this patient. Therefore, these studies reveal that similar morphologic changes are seen in neutrophils stimulated in vitro as well as cells which have been activated pathophysiologically in vivo.

Animals↗
PubMed1988

Acquired renal insufficiency in critically ill patients.

We undertook a study to determine the frequency, predisposing factors, and outcome in 315 patients admitted to a medical-surgical ICU, of whom 47 (14.9%) subsequently acquired renal insufficiency (ARI) during their stay in the unit. Four well-recognized risk factors for ARI were present alone or in combination in all episodes: hypotension, sepsis, aminoglycoside antibiotics, and radiocontrast dye. Hypotension was the most prevalent factor, present in 42 (85.8%) episodes, and was the sole factor present in 18 (36.7%). Patients with ARI but without hypotension all survived their ICU stay, while only 13 (33%) of 40 with hypotension survived (p less than .05). Neither initial, peak nor change in BUN or creatinine predicted mortality; oliguria was marginally associated with poor prognosis. Our findings indicate that: a) ARI was a frequent and important contributing factor to mortality in our critically ill patients, b) hypotension was the most common of well-recognized risk factors, and c) conditions that predisposed to ARI also predisposed to mortality, although mortality did not appear to depend on the severity of renal insufficiency.

Acute Kidney Injury↗
PubMed1988

Hyperthermia, rhabdomyolysis, and myoglobinuric renal failure after recreational use of cocaine.

A patient had hyperthermia, rhabdomyolysis, and myoglobinuric renal failure after the recreational use of cocaine. We attribute this to the pyrogenic properties of cocaine and environmental factors. The use of cocaine during summer months or in areas with high ambient temperatures should alert physicians to the development of hyperthermia with or without seizures. Prompt recognition of the ensuing complications including mixed metabolic acidosis, rhabdomyolysis, and renal failure can result in appropriate and effective treatment.

Acute Disease↗
PubMed1988

Effects of cyclo- and lipoxygenase inhibitors on hypoxic vasoconstriction in isolated ferret lungs.

To evaluate the role of leukotrienes in hypoxic pulmonary vasoconstriction, we measured steady-state pressor responses to graded hypoxia in isolated ferret lungs perfused with autologous blood containing 0.001, 0.03, 1, or 3 mM nordihydroguaiaretic acid (NDGA), 1 mM BW 755C, or 0.02-0.05 mM indomethacin. Untreated lungs served as controls. Perfusate concentrations of thromboxane B2 and 6-ketoprostaglandin F1 alpha, measured by radioimmunoassay, were markedly reduced in all treated lungs, indicating inhibition of cyclooxygenase. The maximum pressor response to hypoxia measured at a blood flow of 50 ml.min-1. kg-1 averaged 26.6 +/- 2.4 Torr in untreated lungs and was not affected by BW 755C or 0.001-0.03 mM NDGA. Because BW 755C and NDGA inhibited cyclooxygenase at concentrations that did not affect hypoxic vasoconstriction and because both agents are thought to inhibit lipoxygenase with a potency greater than or equal to that with which they inhibit cyclooxygenase, these results do not support the possibility that hypoxic pulmonary vasoconstriction was mediated by leukotrienes. At concentrations of 1 and 3 mM, NDGA inhibited the maximum hypoxic pressor response by 57 and 95%, respectively. The mechanism of this attenuation is unknown; however, it was apparently not due to cyclooxygenase inhibition, since indomethacin enhanced the maximum hypoxic pressor response by 45%. Nor was it due to blockade of calcium entry or interference with the contractile process in pulmonary vascular smooth muscle, since 1 mM NDGA did not inhibit vasoconstrictor responses to KCl or prostaglandin F2 alpha.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1987

Psychosocial adaptation in juvenile rheumatic disease: a controlled evaluation.

Juvenile rheumatic diseases are serious chronic illnesses potentially capable of disrupting a child's development and functioning. This study examined the psychosocial functioning of 43 children with severe rheumatic disease as compared to that of 52 children with a milder or inactive form of rheumatic disease. Both patient groups also were compared to 93 healthy children from demographically matched families. Data were obtained from parent reports, from physician evaluation, and, for children who were old enough, from self-reports. The severe patient group showed more parent-reported psychological and physical problems than both the mild patient group and the healthy controls. Compared to the mild group, the severe group also missed more days of school due to illness. Older children in the severe group were more likely to miss school due to illness and to participate in fewer social activities with their families and friends than the controls; however, the older children reported comparable mood and functioning in other areas. An expanded model is proposed to examine risk and resistance factors predictive of psychological and social dysfunction among children with severe chronic disease.

Adaptation, Psychological↗
PubMed1987

Hypoxemia with normal chest roentgenogram due to Pneumocystis carinii pneumonia. Diagnostic errors due to low suspicion of AIDS.

Three patients encountered in a single month had insidious development of atypical respiratory or systemic symptoms and were found to be hypoxemic. All had normal chest roentgenograms and were perplexing problems in diagnosis. On initial presentation, none had evidence of pulmonary infection or recognized clinical or social features that suggested acquired immunodeficiency syndrome (AIDS). All received corticosteroids for respiratory distress before the correct diagnosis was made, and all died rapidly of Pneumocystis pneumonia secondary to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Gastrointestinal complications in critically ill patients: the intensivists' overview.

The critical care environment may be characterized by invasive monitoring, vasoactive drugs, and major interventions which may have adverse effects on gastrointestinal function. Furthermore, conditions such as heart failure or sepsis may compromise oxygen delivery to gastrointestinal organs. Life threatening illness from a variety of causes may produce endoscopically evident gastritis or ulceration in up to 100% of patients, and clinically evident bleeding in 20%. Clinical studies suggest that antacids or H2 receptor blockers may reduce the frequency of this complication. Other conditions are associated with a spectrum of hepatic dysfunction ranging from the cholestatic jaundice of reactive hepatopathy during sepsis to centrilobular necrosis and hepatitis of shock liver. Additionally, many drugs used in the critical care setting may adversely affect mesenteric oxygen delivery and result in ischemia or infarction of the bowel. An increased awareness and understanding of these and other gastrointestinal complications in critically ill patients will, it is hoped, lead to earlier detection and better therapy than is now available.

Animals↗
PubMed1984

Adenosine and hypoxic pulmonary vasodilation.

We have previously shown that after exposure to an inspired O2 tension less than 25 Torr, isolated lungs perfused with autologous blood exhibit vasoconstriction followed by dilation. Because adenosine has been implicated as a mediator of hypoxic vasodilation in the systemic circulation and because the concentration of adenosine in the lung has been shown to increase with hypoxia, we tested the hypothesis that adenosine is the mediator of hypoxic pulmonary vasodilation. We first confirmed that adenosine was a vasodilator in isolated lungs of adult male ferrets. Next we added the enzyme adenosine deaminase (ADase), which inactivates adenosine by converting it to inosine, to the perfusate before exposure to one of two levels of hypoxia [inspiratory PO2 (PIO2) 18 or 0 Torr]. In comparison with untreated lungs, the time course of pulmonary arterial pressure at constant flow in lungs treated with ADase (24 mg protein or 6,000 U) was not different; however, when the vessels were constricted at PIO2 25 Torr, ADase prevented vasodilator responses to adenosine administered into either the perfusate or the airways, indicating penetration of active ADase into the interstitium. Unless adenosine released endogenously into the interstitium during hypoxia was somehow protected from the ADase which reached the interstitium, these results indicate that hypoxic pulmonary vasodilation was not mediated by adenosine.

Adenosine↗
PubMed1984

The cold thyroid nodule: an analysis of diagnostic and therapeutic options.

We applied decision analysis to the controversy over the management of the solitary nonfunctioning thyroid nodule. Three standard management plans were considered: immediate subtotal thyroidectomy; a six month trial of thyroid suppression with L-thyroxine, with non-suppressible lesions being removed surgically; and aspiration cytology followed by surgery or thyroid suppression based on the cytologic examination. The literature formed the basis for quantitative assumptions of the analysis, including the consequences of thyroidectomy, the probability of malignancy, the types and prognoses of cancers found at operation, the likelihood of successful suppression adn relapse, and the possible results of aspiration cytology. We used Bayes' rule to revise the probability of cancer on the basis of cytological results. The relative worths of the 59 possible diagnostic and therapeutic outcomes were expressed as quality-adjusted life expectancies. The expected utility of each management plan was determined by "folding back" the decision tree. Although we found that each possible approach yielded a quality-adjusted life expectancy very close to that of the healthy population, aspiration biopsy with cytologic examination appeared slightly superior. Extensive sensitivity analyses demonstrated that either aspiration biopsy or immediate thyroid suppression was the treatment of choice over a wide range of assumptions, although in no case did the benefit exceed 1 year of life. We conclude that all therapies for cold thyroid nodule are essentially equal, viewed in terms of mortality and morbidity. The decision to operate, suppress or aspirate is thus a " tossup ", dependent in the individual case upon such subjective factors as psychological disutility , relative cost, and attitudes toward operative risk and long-term medical therapy. The controversy concerning the "best" management of the cold thyroid nodule is an illusion: quantitative analysis shows the futility of pursuing the debate any further.

Antithyroid Agents↗
PubMed1982

A convenient approximation of life expectancy (the "DEALE"). II. Use in medical decision-making.

We show how to use a bedside approximation of life expectancy in quantitative decision-making. This method, the declining exponential approximation of life expectancy (DEALE), enables the physician to collate various survival data with information on morbidity to determine a quality-adjusted expected survival for a potential management plan. The keystone in the DEALE approach is the approximation of survival by a simple exponential function. This approximation makes it possible to translate data from various literature sources (life expectancy tables, five-year survival rates, survival curves, median survival) into a single, unified mortality scale. In this paper, we use the DEALE method to obtain approximations of quality-adjusted life expectancy and illustrate the application of the method in a quantitative analysis of a clinical decision.

Aged↗
PubMed1977

Dose response evaluation of adriamycin in human neoplasia.

Because patients treated with 60-90 mg/m2 every three to four weeks reach cardiotoxic doses of 550 mg/m2 within 36 weeks, prolonged treatment with Adriamycin is limited. The purpose of this study was to determine whether lower doses could be given over longer periods without loss of efficacy. Good risk patients treated with 75, 60, or 45 mg/m2 had remission rates of 25, 27, and 19%; poor risk patients treated with 50 and 25 mg/m2 had remission rates of 16 and 12% respectively. Although a dose response was identified, there were no statistically significant differences in remission rates, durations of remission, or toxicities in the dose schedules studied. Irreversible congestive heart failure occurred in five patients with cumulative doses of 240-390 mg/m2. Unless rapid remission induction is urgent, we recommend 60 mg/m2 X four doses and measurement of myocardial function if treatment is to continue.

Adult↗
PubMedDate not supplied

The relationship between the angle of the tibial tunnel in the coronal plane and loss of flexion and anterior laxity after anterior cruciate ligament reconstruction.

Tension in an anterior cruciate ligament graft is greater with the knee in flexion when the angle of the tibial tunnel in the coronal plane is vertical or more perpendicular to the medial joint line of the tibia; however, the relationship of the angle of the tibial tunnel to knee function has not been studied. Greater graft tension may limit knee flexion or stretch the graft and increase anterior laxity. Five surgeons treated 119 subjects by reconstructing a torn anterior cruciate ligament using a double-looped semitendinosus and gracilis graft and a standardized technique. The femoral tunnel was drilled through the tibial tunnel. Radiographs were analyzed for tibial tunnel placement and a clinical evaluation was made 4 months postoperatively. Knees were assigned to subgroups according to the angle of the tibial tunnel in the coronal plane (65 degrees to 69 degrees, 70 degrees to 74 degrees, 75 degrees to 79 degrees, 80 degrees to 84 degrees, and 85 degrees to 89 degrees), with the angle of the latter subgroup being most vertical. Loss of flexion increased significantly from 0.5 degrees to 6.5 degrees and anterior laxity increased significantly from 0.5 to 2.2 mm as the tunnel angle was increased. The average angle of the tibial tunnel varied significantly, 11 degrees between surgeons (range, 69 degrees to 80 degrees). We found a tibial tunnel angle of 75 degrees or more is associated with greater loss of flexion and anterior laxity. Surgeons do not drill the angle of the tibial tunnel in the coronal plane accurately. We now routinely drill the tibial tunnel at an angle of 65 degrees to 70 degrees in the coronal plane because it may reduce loss of flexion and anterior laxity.

Adult↗
PubMedDate not supplied

Monoclonal antibody therapy for gram-negative sepsis: principles, applications, and controversies.

Gram-negative sepsis is a common event in hospitalized patients and is a leading cause of death in the United States. Endotoxin (lipopolysaccharide, LPS), a component of the cell wall of gram-negative microorganisms, is responsible for the cascade of events leading to the sepsis syndrome consisting of fever, tachycardia, tachypnea, and evidence of organ hypoperfusion. The lipid A region of endotoxin produces most of these biologic and toxic effects. Monoclonal IgM antibodies directed against the lipid A portion of endotoxin (anti-LPS MoAb) have been developed for the treatment of gram-negative sepsis. Results of two large-scale clinical trials suggest that these antibodies offer clinically and statistically significant reductions in mortality by a factor of about one-third. However, in both trials, this apparent beneficial effect was limited to particular subsets of patients, and no overall benefit was seen. These considerations, in addition to the likely high cost of the agents, pose questions about their ultimate use in the treatment of patients with gram-negative sepsis. Nevertheless, the logic of the approach, the demonstration of efficacy in disease models, and the advances in modern techniques of molecular biology all suggest that these or other closely related products will play a significant role in the treatment of this disorder.

Antibodies, Monoclonal↗