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Biomedical subjects

N Berkman

Publications and source records attributed to N Berkman.

At least 19 recordsLinked to original sources

Exhaled nitric oxide and asthma in young children.

Exhaled nitric oxide (eNO) has been used to diagnose asthma in adults and children using either the slow vital capacity method (SVCm) or, in younger children, the tidal breathing method (TBm). Adenosine 5'-monophosphate (AMP) challenge also has been found to be a sensitive and specific test for the diagnosis of asthma. In the present study, we used the AMP provocation concentration that caused wheezing (PCW) to confirm the diagnosis of asthma (PCW < or = 200 mg/mL). We studied 36 children (2-7 years) with mild intermittent asthma, 13 children (3-7 years) with moderate persistent asthma treated with inhaled steroids, 20 nonasthmatic children (2-7 years) with chronic cough and recurrent pneumonia, and 15 healthy children (4-6 years). Expired gas was collected in collection bags by the TBm, and eNO was measured. We evaluated the efficacy of eNO values in diagnosing asthma. The mean eNO level of the mild intermittent asthmatic children (5.6 +/- 0.4 ppb) not receiving inhaled corticosteroids was significantly higher (ANOVA P < 0.0001) than that of the moderate persistent asthmatics who were treated with inhaled steroids, the nonasthmatic children with chronic cough, and the group of healthy children (3.7 +/- 0.6 ppb, P < 0.05; 3.2 +/- 0.3 ppb, P < 0.001; 2.2 +/- 0.2 ppb, P < 0.001, respectively). The points of intersection for sensitivity and specificity curves of eNO to differentiate mild intermittent asthmatics from nonasthmatic children with chronic cough and from healthy children were 77% and 88% for eNO values of 3.8 ppb and 2.9 ppb, respectively. We conclude that eNO collected by the TBm can differentiate steroid-naive young children with intermittent asthma from healthy children, from nonasthmatic children with chronic cough, and from asthmatic children treated with inhaled steroids.

Analysis of Variance↗

Human recombinant interferon-alpha2a and interferon-alphaA/D have different effects on bleomycin-induced lung injury.

BACKGROUND: Bleomycin (Bleo)-induced lung injury in mice serves as an animal model of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis remains unclear, but it comprises both inflammatory and fibrotic components. The cytokine interferon (IFN)-alpha is produced by macrophages and may modulate both fibrogenesis and the determination of T lymphocyte phenotype in pulmonary fibrosis. OBJECTIVE: To investigate the effect of two preparations of recombinant IFN-alpha (IFN-alphaA/D and IFN-alpha2a) on Bleo-induced lung injury in C57BL/6 mice. METHODS: Mice were treated by a single intratracheal (IT) instillation of 0.06 mg of Bleo in 0.1 ml of saline or saline alone. One of two different IFN-alpha preparations, IFN-alphaA/D or IFN-alpha2a in saline, or saline alone were administered by daily intraperitoneal injections starting 1 day prior to IT instillation. The treatment groups were as follows: IT Bleo and intraperitoneal saline; IT Bleo and intraperitoneal IFN-alpha2a; IT Bleo and intraperitoneal IFN-alphaA/D; IT saline and intraperitoneal IFN-alphaA/D or IFN-alpha2a; IT saline and intraperitoneal saline. The animals were sacrificed 14 days after IT instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage (BAL) fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity and fibrosis fraction and by biochemical analysis of lung hydroxyproline content. RESULTS: In Bleo-treated mice, IFN-alpha2a treatment caused a significant rise in BAL lymphocytes and in cellularity and fibrosis fractions in lung tissue. In contrast, IFN-alphaA/D treatment had no effect on Bleo-induced lung injury. CONCLUSION: IFN-alpha may enhance Bleo-induced lung injury but this effect varies with different IFN preparations.

Animals↗

Eotaxin-3 but not eotaxin gene expression is upregulated in asthmatics 24 hours after allergen challenge.

Eotaxin is an important mediator of eosinophil recruitment and activation in the airways of asthmatics. Eotaxin-2 and eotaxin-3 are two recently identified chemokines with activity similar to that of eotaxin. Using quantitative polymerase chain reaction analysis, we determined the messenger RNA (mRNA) expression of eotaxin, eotaxin-2, and eotaxin-3 relative to GAPDH mRNA expression in bronchial biopsies and bronchoalveolar lavage fluid (BALF) cells obtained from subjects with mild asthma, asthmatic subjects 24 h after allergen challenge, and normal control subjects. In bronchial biopsies, gene expression was upregulated in asthmatic subjects as compared with control subjects for eotaxin (log median values 3.18 pg/microg, 95% confidence interval [CI]; 2.27 to 3.79 versus 4.37 pg/microg, 95% CI; 3.97 to 4.65, P = 0.003) and for eotaxin-2 (0.82 pg/microg, 95% CI; 0.08 to 1.72 versus 2.97 pg/microg, 95% CI; 1.97 to 3.45, P = 0.006), but no further increase was observed after allergen challenge. In contrast, eotaxin-3 mRNA expression was not increased in asthmatic compared with control subjects, but was dramatically enhanced 24 h after challenge (median log value 1.93 pg/microg, 95% CI; 0.74 to 3.92 versus 4.62 pg/microg, 95% CI; 3.05 to 6.23, P = 0.036). No significant difference between groups was observed in BALF cell gene expression for any of the chemokines examined. These data suggest that eotaxin-3 rather than eotaxin or eotaxin-2 may account for the ongoing eosinophil recruitment to asthmatic airways in the later stages (24 h) following allergen challenge.

Adult↗

The role of BAL in the diagnosis of pulmonary mucormycosis.

Five patients with pulmonary mucormycosis diagnosed during life are described. All had underlying predisposing conditions: either posttransplant or hematologic malignancies. In all cases, the diagnosis was made using fiberoptic bronchoscopy. In three patients, BAL was diagnostic. In two of these patients, the diagnosis was made by identifying the typical hyphae of mucormycosis in the BAL fluid alone. Transbronchial biopsy was diagnostic in three patients. Treatment was based on IV antifungal chemotherapy together with surgical removal of involved lung tissue whenever feasible. The clinical outcome of these patients was dismal and was determined primarily by the underlying condition.

Adult↗

Successful talc slurry pleurodesis in patients with nonmalignant pleural effusion.

BACKGROUND: Chemical pleurodesis is an effective treatment for malignant pleural effusion and pneumothorax. This mode of therapy is, however, less widely accepted in the treatment of patients with refractory benign or undiagnosed pleural effusion. STUDY OBJECTIVES: To analyze the outcome of talc slurry pleurodesis in patients with nonmalignant pleural effusions. DESIGN: Retrospective and partly prospective analysis of clinical outcome. SETTING: Hadassah University Hospital, Jerusalem, Israel. PATIENTS AND PARTICIPANTS: Between 1992 and 1997, we treated 16 patients with nonmalignant pleural effusion using talc slurry pleurodesis. The cause of effusion was congestive heart failure in 6 patients, liver cirrhosis in 4 patients, yellow nail syndrome in 1 patient, systemic lupus erythematosus in 1 patient, chylothorax in 1 patient, and undiagnosed in 3 patients. INTERVENTIONS: Nine patients were hospitalized, and seven patients received treatment in a day-care setting. Follow-up ranged from 2 months to 3 years. RESULTS: Complete success was observed in 12 cases (75%), partial success in 3 cases (19%), and pleurodesis was ineffectual in 1 case (6%). There were no significant complications after the procedure in any of our patients. A review of the English-language medical literature revealed an additional 110 reported cases of nonmalignant pleural effusion that were treated with chemical pleurodesis. Of these cases, talc was used in 65% with a success rate of nearly 100%. CONCLUSIONS: Chemical pleurodesis, and specifically talc slurry, is an effective treatment for recurrent benign or undiagnosed pleural effusion. This procedure is safe and easily performed and, in selected cases, can be performed in an outpatient day-care setting.

Adult↗

Lactate dehydrogenase isoenzyme analysis for the diagnosis of pleural effusion in haemato-oncological patients.

This study aimed to evaluate the utility of the pleural fluid lactate dehydrogenase (LDH) isoenzyme algorithm for the differential diagnosis of pleural fluid in patients with haematological malignancies. Twenty consecutive haemato-oncological patients with pleural effusion, hospitalized in the Haematology Department during a 2.75-year period, were prospectively and independently evaluated for the cause of effusion by standard methods for the LDH isoenzyme algorithm. The causes of the pleural effusions established during the standard evaluations were compared to the results obtained from the LDH isoenzyme algorithm. Following the standard evaluation, the pleural effusion was attributed to congestive heart failure in one patient, to infection in six, to the underlying malignancy in 12 and to concomitant congestive heart failure and malignancy in one. LDH isoenzyme analysis correctly predicted the cause of pleural effusion in 18 patients (positive predictive value 90%). In haemato-oncological patients, the pleural fluid LDH isoenzyme pattern may be helpful in the differential diagnosis of the most common causes of pleural effusion.

Biomarkers↗

Pulmonary hypertension secondary to neurofibromatosis: intimal fibrosis versus thromboembolism.

Neurofibromatosis has been known to involve blood vessels throughout the body. Pulmonary involvement with interstitial fibrosing alveolitis has been described but no case of pulmonary vascular involvement has been reported to date. A 51 year old patient with cutaneous neurofibromatosis is described who presented with severe pulmonary hypertension and radiographic, scintigraphic, and angiographic evidence of chronic thromboembolic pulmonary hypertension. Severe intimal fibrosis consistent with vascular involvement with neurofibromatosis was found on endarterectomy with no evidence of pulmonary thromboembolism. Neurofibromatosis of pulmonary arteries should be considered as a possible cause of pulmonary hypertension.

Angiography↗

Effect of immunomodulators on bleomycin-induced lung injury.

BACKGROUND: The role of lymphocytes and their subpopulations in lung fibrosis is as yet unclear. OBJECTIVE: To define the role of immunomodulation in bleomycin-induced inflammatory fibrotic lung injury, by testing the effect of two known Th1 inhibitors: linomide and pentoxifylline. METHODS: C57BL/6 mice were treated by a single intratracheal instillation of 0.06 mg bleomycin in 0.01 ml saline or saline alone. Treatment groups included: (1) intratracheal bleomycin and daily treatment with linomide or pentoxifylline; (2) intratracheal bleomycin and daily water; (3) intratracheal saline and daily linomide or pentoxifylline; (4) intratracheal saline and daily water. Linomide and pentoxifylline were available per os in the drinking water from 1 day prior to intratracheal instillation. Animals were studied 14 days after intratracheal instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity, fibrosis fraction and alveolar wall area fraction, and by biochemical analysis of lung hydroxyproline content. RESULTS: Linomide or pentoxifylline did not cause any lung injury in saline-treated control mice. Overt signs of lung injury were apparent in bleomycin-treated mice. These changes were not affected by daily treatment with linomide or pentoxifylline, which were given in the highest tolerable dose. CONCLUSION: This study does not support the use of linomide or pentoxifylline to prevent or ameliorate lung fibrosis and may suggest that drug-induced differentiation of T lymphocytes into Th1/th2 subpopulations does not affect the evolution of bleomycin-induced lung injury.

Adjuvants, Immunologic↗

The role of open lung biopsy in the management and outcome of patients with diffuse lung disease.

BACKGROUND: Open lung biopsy (OLB) has long been considered the gold standard for the diagnosis of parenchymal lung disease. With recent advances in computed tomographic imaging and diagnostic techniques (eg, bronchoscopy), we thought it necessary to reevaluate the role of OLB in the management of patients with interstitial lung disease. METHODS: We carried out a retrospective analysis of 103 OLBs performed at Hadassah University Hospital, Jerusalem, and Carmel Medical Center, Haifa, between 1980 and 1994. Data gathered included demographic information, underlying condition, indications for biopsy, diagnosis before biopsy, final diagnosis, change in therapy, and mortality. "Benefit" was defined as a change in therapy resulting in survival. RESULTS: There were 45 immunocompetent patients (group 1), 39 immunocompromised patients (group 2), and 26 children (group 3), 7 of whom were included in group 2 for analysis. Overall, a diagnosis was reached after OLB in 85% of patients. An unexpected diagnosis was reached in 52%, and a change in therapy was instituted in 46%. The overall mortality rate was 20%. In group 1, the mortality rate was 13%, and "benefit" from OLB was reached in only 18%. In group 2, the mortality rate was 39%, and "benefit" was achieved in 46%, and in group 3, the mortality rate was 12% and "benefit", 50%. CONCLUSIONS: Open lung biopsy is an excellent diagnostic technique. In immunocompetent patients, the "benefit" is relatively low, as therapy (corticosteroids) is frequently used after biopsy. In immunocompromised patients, therapy changes substantially after OLB, but mortality is high. Therefore, OLB should be reserved for patients in whom the diagnosis is likely to lead to a change in therapy and in patients in whom the underlying condition has a reasonable prognosis according to the clinical impression by the attending physician.

Adolescent↗

Use of fiberoptic bronchoscopy in bone marrow transplant recipients.

Bone marrow transplantation (BMT) has become the therapy of choice for a number of malignant and nonmalignant hematologic and nonhematologic disorders. A frequent complication after BMT is pulmonary disease which is associated with a high mortality rate. We examined the results of 79 bronchoscopies performed between May 1991 and May 1995 in 62 patients for the evaluation of pulmonary complications after BMT. In all cases bronchoalveolar lavage (BAL) was performed, in 10% transbronchial biopsy (TBB) was also carried out and in 13% bronchoscopy was followed by open lung biopsy. Positive results were found in 67% of bronchoscopies. Fungal infection (Candida and Aspergillus species) was the most common finding (18%), bacterial infection was found in 13%, mixed (fungal and bacterial) infection in 6%, cytomegalovirus in 11% and Pneumocystis carinii pneumonia in 4%. Diffuse alveolar hemorrhage was detected in 11% of cases. Idiopathic pneumonia syndrome (IPS) was diagnosed by TBB in 3% of procedures. We conclude that BAL is a safe and accurate procedure for the evaluation of pulmonary complications after BMT. TBB should be considered in the absence of thrombocytopenia for the diagnosis of IPS. If bronchoscopy findings are negative, open lung biopsy should be considered.

Adolescent↗

Rehabilitation of hypoxemic patients with COPD at low altitude at the Dead Sea, the lowest place on earth.

BACKGROUND: In patients with COPD, oxygen therapy has been shown to improve exercise capacity and survival. Increase in barometric pressure at low altitude can serve as a simple way to improve arterial oxygenation in hypoxemic patients. We have tried to evaluate the effect of staying at low altitude on arterial oxygenation and exercise performance in patients with COPD. PATIENTS AND METHOD: Eleven patients with COPD (9 male, 2 female) aged 38 to 79 years (mean FEV1, 0.96 L; 36% predicted) with hypoxemia (mean PaO2, 54.2+/-8.9 mm Hg) at Jerusalem (altitude 800 m above sea level) were taken down to the Dead Sea area (altitude 402 m below sea level) for 3 weeks. At both locations we tested arterial blood gases, spirometry, progressive exercise, 6-minute walking distance, and sleep oximetry. The study was repeated 2 weeks after returning to Jerusalem. RESULTS: Spirometry results were unchanged. Mean arterial PaO2 rose from 54.2+/-8.9 mm Hg to 69.5+/-11 at the first week and to 66.6+/-11 at the third week of stay (p<0.001). PaCO2 rose from 43.5+/-9.8 mm Hg to 47.7+/-9 and 49.5+/-8.4 (p<0.006). Six-minute walking distance rose from 337+/-107 m to 449+/-73 and 507+/-91 in the third week (p<0.005). Maximum oxygen consumption (VO2max) rose from 901+/-257 mL/min to 1,099+/-255 and 1,063+/-250 mL/min (p=0.01). Sleep oximetry showed an increase in mean sleep arterial oxygen saturation from 86.0+/-4.3% to 89.9+/-4.2% and 88.3+/-3.0 at 1 and 3 weeks, respectively (p<0.05). Following the return to Jerusalem, arterial gases returned to their baseline levels (PaO2, 52.9+/-9.4 mm Hg) but 6-min walking distance remained significantly high, 453+/-47 (p<0.02), and VO2max remained high as well (1,102+/-357 mL/min), although it did not reach statistical significance. CONCLUSIONS: Decline to low altitude or staving at high oxygen environment improves arterial oxygenation and exercise capacity in hypoxemic patients residing in moderate or high altitude. Low altitude (or pressurized wards) can improve pulmonary rehabilitation of hypoxemic patients with COPD.

Adult↗

Human airway smooth muscle cells express and release RANTES in response to T helper 1 cytokines: regulation by T helper 2 cytokines and corticosteroids.

RANTES is a basic 8-kDa polypeptide of the C-C chemokine subfamily with strong chemotactic activity for eosinophils, lymphocytes, and monocytes. We determined the regulation of RANTES production by human airway smooth muscle cells in culture. While TNF-alpha, but not IFN-gamma, increased RANTES mRNA expression and protein release, the combination of TNF-alpha and IFN-gamma caused a greater degree of expression and release in a time- and dose-dependent manner. Sequential treatment of airway smooth muscle cells with TNF-alpha and IFN-gamma showed that IFN-gamma sensitized the cells to the stimulatory effect of TNF-alpha. Using a modified Boyden chamber technique, RANTES separated by reverse-phase liquid chromatography from cell culture supernatants of airway smooth muscle cells stimulated by TNF-alpha and IFN-gamma showed a strong chemoattractant effect on human eosinophils, an effect inhibited by an anti-RANTES Ab. RANTES production induced by TNF-alpha and IFN-gamma was inhibited partly by the Th2-derived cytokines, IL-4, IL-10, and IL-13, as well as by dexamethasone. Our studies indicate that, in addition to contractile responses and mitogenesis, airway smooth muscle cells have synthetic and secretory potential with the release of RANTES. They may participate in chronic airway inflammation by interacting with both Th1- and Th2-derived cytokines to modulate chemoattractant activity for eosinophils, activated T lymphocytes, and monocytes/macrophages.

Adrenal Cortex Hormones↗

Bleomycin-induced lung injury is enhanced by interferon-alpha.

We have evaluated the effect of intraperitoneal (I.P.) injection of human recombinant interferon-2alpha (IFN-alpha) on Bleomycin-induced pulmonary injury in hamsters. Pulmonary injury was induced by a single intratracheal (I.T.) instillation of Bleomycin (Bleo). Six groups of male Syrian hamsters were treated as follows: 1) I.T. Bleo and daily I.P. injections of low-dose interferon-alpha (2 x 10(4) U), 2) I.T. Bleo and daily I.P. injections of high-dose interferon-alpha (10(5) U), 3) I.T. Bleo and I.P. injections of saline, 4) I.T. saline and I.P. low-dose IFN-alpha, 5) I.T. saline and I.P. high-dose IFN-alpha, 6) I.T. saline and I.P. saline. Animals were sacrificed 28 days after I.T. treatment. Lung injury was evaluated histologically and biochemically. Treatment of hamsters with low-dose but not high-dose IFN-alpha significantly augmented the Bleo-induced lung injury, as determined by a semiquantitative morphological index. Lung hydroxyproline measurements were highest in Bleo-low-dose-IFN-alpha followed by Bleo-high-dose-IFN-alpha and Bleo-Sal as compared to Sal-Sal and Sal-IFN-alpha controls. These results suggest that IFN-alpha augments Bleo-induced lung injury but that this effect is complex and does not follow a simple-dose-response pattern.

Animals↗

Primary non-Hodgkin's lymphoma of the lung presenting as bronchiolitis obliterans organizing pneumonia.

A 44-year-old man presented with fever, dyspnea, and bilateral cavitary lung lesions. Following percutaneous transthoracic CT guided needle biopsy of the lung, a diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) was made and the patient was treated with corticosteroids. Despite a good initial response he developed new lung lesions within six months, associated with a lack of response to corticosteroids. Due to further deterioration and the development of Guillian-Barre' syndrome an open lung biopsy was performed and revealed T-cell rich, B-cell non Hodgkin's lymphoma with BOOP. We suggest that BOOP may be the presenting manifestation of primary lung lymphoma. We recommend that when BOOP has an atypical course or does not respond to corticosteroids open lung biopsy should be performed in order to exclude pulmonary lymphoma.

Adult↗

Clustering of Pneumocystis carinii pneumonia in patients undergoing renal transplantation from living unrelated donors in Iraq and India.

Over the past few years, we have observed a substantial increase in the number of patients followed at our hospital who have undergone renal transplantation from living unrelated donors (LURD). These transplants were all performed in one of two centers: Bagdad, Iraq or Bombay, India. We have observed a parallel increase in the number of cases of Pneumocystis carinii pneumonia (PCP) post-renal transplant. We conducted a ten-year retrospective analysis (1986-1995) of patients who developed PCP post-renal transplant to determine the risk factors associated with the development of this infection, with particular reference to the type of transplant and the center in which the transplant was performed. Over this period, 270 renal transplant patients were followed at this hospital and 10 episodes of PCP were documented (3.7%). Six of these cases occurred within the last 2 years, as compared to only 4 cases in the preceding 8 years. All of the cases observed in the last 2 years occurred in patients who had undergone renal transplantation from LURD in Iraq or in India. During the same period, we observed no cases of PCP in patients who had undergone transplantation in Israel (cadaver or related living donor transplants). We could find no difference between patients undergoing transplant from LURD and those undergoing other transplants in terms of immuno-suppressive therapy, frequency of organ rejection episodes or coexistent CMV infection. All patients were of Arab descent and live in the West Bank. Although we cannot identify any obvious explanation for this association, we believe that these cases represent a true cluster phenomenon. We therefore feel it is warranted for all recipients of renal transplants from living unrelated donors seen in our hospital to receive prophylactic therapy for Pneumocystis carinii pneumonia.

Adult↗