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Biomedical subjects

J S Klein

Publications and source records attributed to J S Klein.

At least 19 recordsLinked to original sources

Soluble interleukin 2 and CD8 and CD4 receptors in inflammatory bowel disease.

Serum levels of soluble interleukin 2 receptor (sIL-2R) have been proposed as a clinical marker of inflammatory bowel disease. The source of sIL-2R in patients with Crohn's disease and ulcerative colitis is unknown, and other soluble receptors have not been investigated. In the present study, sIL-2R and soluble CD8 and CD4 levels were measured in plasma and culture supernatants of peripheral blood and intestinal mucosal mononuclear cells from patients with inflammatory bowel disease, surgical controls, and healthy subjects. Level of plasma sIL-2R was significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy volunteers. Intestinal cells always produced more sIL-2R than peripheral cells. Spontaneous sIL-2R production by mucosal cells was significantly elevated in Crohn's disease but not in ulcerative colitis supernatants compared with levels of surgical controls. Soluble CD8 and CD4 were poor indicators of systemic or mucosal immunity. A positive correlation was found between plasma sIL-2R and spontaneous production by intestinal cells of patients with Crohn's disease and surgical control patients, whereas ulcerative colitis plasma sIL-2R correlated with spontaneous production by peripheral cells. The association of plasma or spontaneous sIL-2R levels with the degree of intestinal inflammation was weak, and there was a wide overlap with control values. Therefore, caution should be used before considering sIL-2R an accurate marker of inflammatory bowel disease activity.

Aged

High-resolution CT diagnosis of emphysema in symptomatic patients with normal chest radiographs and isolated low diffusing capacity.

To determine the prevalence of "nonobstructive" (impairment of gas transfer) emphysema in a select population of smokers with dyspnea, a retrospective study of patients with emphysema evident at high-resolution computed tomography (HRCT) was undertaken. Four hundred seventy HRCT studies were reviewed. In 47 cases, centrilobular emphysema was the dominant or sole parenchymal abnormality. Concomitant chest radiographs were available in 41 of these cases; 16 of the 41 lacked radiographic findings of emphysema. Among these 16 patients, pulmonary function testing revealed 10 to have normal flow rates (ratio of forced expiratory volume in 1 second to forced vital capacity and forced expiratory volume in 1 second greater than 80% predicted) and impaired gas transfer (single-breath carbon monoxide diffusing capacity [DLCOSB] less than 80% predicted). With the exclusion of one patient with congestive heart failure from the group of 10, the severity of emphysema at HRCT correlated inversely with DLCOSB (r = -.643). These results indicate that HRCT allows detection of emphysema in symptomatic patients when chest radiographs and pulmonary function tests are nondiagnostic.

Female

Effect of aerosolized pentamidine prophylaxis on the clinical severity and diagnosis of Pneumocystis carinii pneumonia.

To determine if the use of aerosolized pentamidine prophylaxis decreases the clinical severity or the sensitivity of diagnostic tests for Pneumocystis carinii pneumonia (PCP), we conducted a retrospective matched cohort comparison study of patients admitted to San Francisco General Hospital with PCP from August 1, 1989, to June 30, 1990. Patients who had received pentamidine prophylaxis during at least the 2 months prior to the diagnosis of PCP were matched with patients who had not received the drug. Matching was based on the number of prior episodes of PCP, sex, age, and risk factors for human immunodeficiency virus infection. As markers of clinical severity, we chose alveolar-arterial oxygen difference, serum lactate dehydrogenase levels, outpatient versus inpatient treatment, length of hospitalization, length of intravenous anti-pneumocystis treatment, development of respiratory failure, in-hospital mortality, and chest radiographic appearance. Although, of the 27 matched pairs identified, significantly fewer of the pentamidine cohort were treated as inpatients, and significantly more of this cohort had upper lobe dominant disease on chest radiograph, we found no other significant differences between markers of clinical severity for the two cohorts. In addition, we found no significant differences in the rate of sputum or bronchoalveolar lavage positivity for P. carinii between the two cohorts. We conclude that, although hospitalization is less common in patients with a history of prophylactic pentamidine use, aerosolized pentamidine prophylaxis does not decrease the clinical severity or the sensitivities of sputum induction or bronchoalveolar lavage as diagnostic tests for PCP.

AIDS-Related Opportunistic Infections

Chronic hypersensitivity pneumonitis: use of CT in diagnosis.

OBJECTIVE: In its subacute or chronic form, hypersensitivity pneumonitis is often difficult to distinguish clinically and physiologically from other idiopathic diffuse lung diseases. The aim of this study was to identify high-resolution CT features that allow distinction of chronic hypersensitivity pneumonitis from other chronic diffuse parenchymal lung diseases. MATERIALS AND METHODS: Six patients with chronic hypersensitivity pneumonitis were examined with pulmonary function testing, bronchoalveolar lavage, lung biopsy, chest radiography, and high-resolution CT. The chest radiographs and high-resolution CT scans were reviewed independently by three observers without knowledge of the patients' clinical status. Discrepancies between the observers were resolved by consensus. RESULTS: The chest radiographs revealed normal lung volumes with a combination of abnormalities: a mixed alveolar/interstitial pattern in five cases, peribronchiolar thickening in three, a diffuse granular pattern in one, and a linear fibrotic pattern in one. In general, the high-resolution CT scans showed more abnormalities than were apparent on the plain chest radiographs. High-resolution CT revealed centrilobular, peribronchiolar, indistinct nodular opacities, of various numbers, in all cases. Four cases had areas of ground-glass density, three cases had lobular areas of hyperlucency, and one case had areas of pulmonary fibrosis and honeycombing. CONCLUSION: We confirm that high-resolution CT can most clearly show the type and distribution of parenchymal abnormalities in patients with hypersensitivity pneumonitis. Importantly, although not pathognomonic, the high-resolution CT finding of centrilobular, peribronchiolar, indistinct nodules should suggest the diagnosis of chronic hypersensitivity pneumonitis.

Alveolitis, Extrinsic Allergic

Thoracic intervention.

The literature of the past year regarding interventional procedures in the thorax covers aspects of transthoracic needle biopsy, drainage of pleural fluid collections, percutaneous management of lung abscess, and thoracic vascular interventions. Topics in transthoracic needle biopsy include a large retrospective series on fluoroscopically guided biopsy of thoracic masses; several reports reviewing experience with diagnosis of anterior mediastinal masses, including four studies describing the use of real-time ultrasound guidance for this procedure; the description of a new automated cutting needle for consistent tissue sampling; and two studies addressing factors affecting pneumothorax and chest tube insertion rates following transthoracic needle biopsy. Reports on percutaneous management of pleural fluid collections are highlighted by a paper reporting the results of ultrasound-guided drainage and sclerosis of malignant pleural effusions. Ultrasound-guided percutaneous aspiration of lung abscess for isolation of causative bacteria is the basis of two recent papers, and successful CT-guided drainage of lung abscesses is described by a group of researchers that has written extensively on a variety of the interventional thoracic procedures that are currently performed. Finally, the failures and complications associated with bronchial and pulmonary arterial embolization procedures have been reviewed.

Biopsy, Needle

High-resolution computed tomography of the mammalian lung.

High-resolution computed tomography (HRCT) was performed in 21 isolated animal lungs, from 4 mammalian species (pigs, rabbits, dogs, sheep). Gross and subgross central and peripheral lung morphology was determined by HRCT. Three distinct types of lungs can be identified, principally based on the extent of interlobular septal development; the relationship of major vessels to airways; and the thickness of the visceral pleura. Type-I lung is found in pigs, sheep, and cattle; type-II lung is found in rabbits, dogs, cats, and monkeys; and type-III lung is found in human beings and horses. These mammalian lungs were compared with human lungs. The potential use of HRCT to investigate specific human lung diseases in the aforementioned species also was considered.

Animals

Disaster management. Lessons learned.

Our experiences have taught us that practice makes perfect and that it probably is unreasonable to expect everything to be orderly, sane, and appropriate during disaster management. The best we can hope for probably is controlled chaos. We do believe that we have generated an improved plan, that the plan is known, and that it is being revised continuously. We can no longer rely on our goodwill and good intentions to manage mass casualties in a disaster. There are too many factors that can reduce our ability to provide medical care in this situation. Hospital planning is essential. The hospital should be represented on the emergency preparedness committee so it is knowledgeable about the various plans throughout the city. Each plan must be practiced and critiqued to identify potential problems. Hospital staff must be kept current on the various plans to understand the communication, authority, responsibility, security, and medical control for each plan. We have instituted a video program outlining the various tasks for each hospital department for each disaster plan. This format allows the personnel in these departments to review their responsibilities continually in a concise manner and allows practice of disaster preparedness without implementing an entire disaster drill. Table 1 provides a quick review of the areas and questions we found to be problems when implementing our disaster plan.

Accidents, Aviation

The radiologic staging of lung cancer.

The radiographic evaluation and staging of bronchogenic carcinoma remains one of the greatest challenges to the thoracic radiologist and one of his or her most important responsibilities. With lung cancer now the most common malignant tumor in both men and women, there will be a continued need for radiologists to guide clinicians to the appropriate diagnostic and staging procedures, to help plan curative surgery, and to assess the response to therapy or progression of disease. The article reviews the radiographic approach to lung cancer diagnosis and staging with an emphasis on the use of computed tomography and magnetic resonance imaging for the evaluation of the primary tumor and mediastinal and hilar lymph node metastases.

Carcinoma, Bronchogenic

Inferior hilar window.

The authors undertook a study to determine the ability to detect mass or adenopathy in the "inferior hilar window," a normally avascular region inferior to the shadow of the right pulmonary artery and vein and anterior to the descending left pulmonary artery on lateral chest radiographs. Fifty patients with normal results of thoracic computed tomography (CT) and 25 with unilateral or bilateral hilar masses or adenopathy (defined as opacity greater than 10 mm in diameter) were selected retrospectively. Patients with concomitant pulmonary masses or consolidation at CT that might be confused with or obscure an inferior hilar mass or adenopathy were excluded from study. The 75 corresponding lateral chest radiographs were then evaluated blindly. Forty-seven of the 50 normal cases were correctly interpreted (specificity = 94%). The anterior walls of the right and left lower lobe bronchi were seen in 36% and 84% of normal cases, respectively; the average thickness was 2 mm. Of the 25 patients with inferior hilar masses, 22 were recognized as having abnormalities (sensitivity = 88%); two of the three patients with false-negative results had right hilar masses. Overall accuracy was 92%. For only eight (32%) of the 25 patients was the laterality of abnormality correctly diagnosed. Evaluation of the inferior hilar window on lateral chest radiographs is accurate in assessing the presence or absence of inferior hilar mass or adenopathy.

False Negative Reactions

Pathogenesis of pulmonary edema during interleukin-2 therapy: correlation of chest radiographic and clinical findings in 54 patients.

The pathogenesis of pulmonary edema that occurs during interleukin-2 therapy has often been attributed to an increase in pulmonary capillary permeability. However, renal insufficiency, fluid overload, and hypotension also develop in many patients. These manifestations of systemic toxicity may contribute to the development of pulmonary edema during therapy. Understanding the cause of pulmonary edema during interleukin-2 therapy could directly affect patients' care. Therefore, we reviewed the chest radiographs and clinical course of 54 patients who received high-dose interleukin-2 therapy and lymphokine-activated killer cells for advanced carcinoma. The type, frequency, and course over time of pulmonary abnormalities were recorded and correlated with clinical measures of renal function, fluid status, and blood pressure. Focal or diffuse parenchymal lung opacities were found on radiographs in 43 (80%) of 54 patients. Findings of interstitial pulmonary edema were most common, occurring in 76% of patients. Weight gain, hypotension, and elevation of the serum creatinine level were not associated statistically with interstitial edema. Diffuse air-space disease developed in 20% of patients. Focal consolidation, which was associated with positive central venous catheter cultures (p less than .03), developed in 28% of patients. Pleural effusion occurred in 48% of patients and was associated with all types of parenchymal disease. These data suggest that the frequent development of pulmonary edema during interleukin-2 therapy is not due to renal insufficiency, fluid overload, or hypotension, but is more likely the result of an interleukin-2-related increase in pulmonary capillary permeability.

Adult

Radiographic distribution of Pneumocystis carinii pneumonia in patients with AIDS treated with prophylactic inhaled pentamidine.

The radiographic distribution of Pneumocystis carinii pneumonia was studied in 64 consecutive patients with acquired immunodeficiency syndrome to determine the demographic and clinical factors that might be associated with predominance of the disease in the upper zones of the lungs. Twenty-three patients were receiving monthly prophylaxis with 300 mg of aerosolized pentamidine by means of inhalation; the other 41 were not receiving pentamidine and served as a control group. Parenchymal abnormalities were present in 63 of 64 patients. Pleural effusion and cystic lung lesions were uncommon and did not differ between the two groups. Patients receiving aerosolized pentamidine were more likely than control patients to have disease isolated or predominant in the upper lobes (odds ratio = 3.9, confidence interval = 1.1-14.1). After the possible effects of confounding variables were taken into account, prophylaxis remained a significant risk factor. Age and a previous history of P carinii pneumonia were not significant cofactors. The pattern of deposition or retention of the aerosolized pentamidine could be responsible for the finding of predominant P carinii pneumonia in the upper lobes of the lungs.

Acquired Immunodeficiency Syndrome

Phosphorylation and down-regulation of CD4 and CD8 in human CTLs and mouse L cells.

The CD4 and CD8 molecules are rapidly phosphorylated following exposure of CD4+ or CD8+ human cytotoxic T lymphocytes (CTL) clones to B-lymphoblastoid cell lines bearing the relevant target alloantigens. Treatment of CD4+ or CD8+ CTL clones with phorbol myristate acetate (PMA), phytohemagglutinin, or mitogenic combinations of CD2-specific antibodies also resulted in CD4 or CD8 phosphorylation. Down-regulation of the surface expression of these molecules could be demonstrated in both CD4+ and CD8+ clones following exposure to the relevant alloantigen or PMA. Parallel experiments were conducted using mouse L cells in which the human CD4 or CD8 antigens were stably expressed. Exposure of these transfectants to PMA induced rapid phosphorylation of the CD4 and CD8 molecules. As in CD4+ CTL clones, rapid modulation of the CD4 antigen could be demonstrated in L cells following PMA treatment. In contrast, there was no demonstrable down-regulation of the CD8 antigen in PMA-treated CD8+ L cell transfectants. These studies demonstrate a significant differential property of the CD4 and CD8 antigens and suggest that down-regulation of the CD8 antigen may require its expression in a T-cell environment and/or the association of CD8 with the T-cell receptor or other T cell-specific molecules.

Animals

Analysis of the kinetics of natural killer cell activity in mice during an active infection with Pseudomonas aeruginosa.

The present study was designed to determine the effect of Pseudomonas aeruginosa (PA) infection on the activity of natural killer (NK) cells in mice. Following a sublethal injection of the bacterium, increased NK cell activity is evident as early as 24 h and peaks within 72 h, returning to normal levels by 168 h. Interestingly, the route by which PA was administered was very important with respect to increased NK activity. For example, the greatest augmentation of activity was seen in the peritoneal cavity when mice were injected intraperitoneally and in the spleen when injected intravenously. Peripheral blood leukocytes expressed the greatest augmentation in animals which received an intravenous injection of viable PA. In addition, a nonviable preparation of PA was used and found to significantly augment NK cell activity in a dose-dependent manner. To determine whether the presence of the organism is required for augmentation of NK activity, the rate at which PA is cleared from the animals was evaluated. Regardless of the route of injection, PA is effectively cleared within 24 h, thus eliminating the possibility that viable PA is required for augmentation of NK activity. This augmentation is proximal to the route of injection with little systemic effect seen. The data presented in this report illustrate that both viable and nonviable preparations of PA produce a significant increase in NK cell activity. This augmentation may suggest a role for these cells as effectors in natural resistance to infectious disease.

Animals

Bilateral maintenance of rabbit corpora lutea by the feto-placental unit.

The present study was undertaken to determine whether the rabbit feto-placental unit maintains corpora lutea systematically and/or locally and the interrelationships between conceptus number, luteal weight, luteal progesterone concentrations and serum progesterone levels. Thirty-three does were divided into the following treatment groups: (I) bilaterally pregnant, two ovaries; (II) unilaterally pregnant, two ovaries; (III) bilaterally pregnant, one ovary; (IV) unilaterally pregnant, one ovary, contralateral and (V) unilaterally pregnant, one ovary, ipsilateral. Blood samples were obtained from all rabbits on days 6, 9, 12, 15, 18 and 21 post coitum. Does were killed on day 21, and the percentage of viable fetuses, fetal weights, and luteal weights recorded. Blood samples and corpora lutea were analysed for progesterone. Serum progesterone levels were similar for all groups until day 9 post coitum. Levels in groups III, IV and V declined significantly between days 9 and 12 following removal of one ovary at day 9. Fetal viability, fetal weights and luteal progesterone concentrations did not differ among any of the groups. Luteal weights did not differ among groups I, III, IV and V, but luteal weights of animals in group II were lower than those of group I (P less than 0.05). Ratios of viable fetuses to number of corpora lutea ranged from 1:11-10:5. No differences were observed in serum progesterone, luteal weights or luteal progesterone concentrations among animals with two conceptuses and those with seven or more, but serum progesterone levels in does with only one conceptus were lower than those in does with more (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals