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Biomedical subjects

J Greif

Publications and source records attributed to J Greif.

At least 19 recordsLinked to original sources

Induced sputum-retrieved matrix metalloproteinase 9 and tissue metalloproteinase inhibitor 1 in granulomatous diseases.

Matrix metalloproteinases (MMPs) capable of degrading various components of connective tissue matrices, and tissue inhibitor metalloproteinases (TIMPs) are considered important in lung parenchymal remodeling and repair processes in pulmonary diseases. Induced sputum (IS) is a reliable noninvasive method to investigate pathogenesis, pathophysiology and treatment of lung disease. This study was designed to determine whether IS-MMP9/TIMP1 levels demonstrate lung parenchymal remodeling in sarcoidosis (SA) and Crohn's disease (CRD) patients. Sputum was induced and processed conventionally in 13 SA patients, 18 CRD patients and 9 controls. Two-hundred cells were counted on Giemsa-stained cytopreps, and T lymphocytes subsets (CD4 = T helper and CD8 = T suppressor cytotoxic cells) were analysed by FACS using monoclonal antibodies.MMP-9 and TIMP-1 were measured using commercial ELISA kits. MMP-9 concentrations, but not those of TIMP-1, were significantly greater in the sputum supernatant in SA and CRD patients compared to controls (P = 0.018 and P = 0.0019, respectively). The molar ratio, MMP-9/TIMP-1, was significantly higher in SA and CRD patients compared to controls (P = 0.008 and P = 0.024, respectively). Gelatinase species having a molecular weight similar to that of MMP-9 were demonstrated by zymographic analysis. MMP-9 levels were highly correlated with the CD4/CD8 ratio and DLCO capacity in SA but less in CRD patients. MMP-9 levels in IS provide a sensitive marker for pulmonary damage.

Adult↗

Correlation between c-erbB-4 receptor expression and response to gemcitabine-cisplatin chemotherapy in non-small-cell lung cancer.

BACKGROUND: While the overexpression of c-erbB gene family in several malignancies is associated with poorer prognosis, the association between the expression of the cellular markers and the response to chemotherapy is not yet clear. In this study we investigated the expression of c-erbB-4 receptor in NSCLC and correlated it with the response to gemcitabine-cisplatin combination chemotherapy. PATIENTS AND METHODS: Forty-three NSCLC patients with histologically or cytologically proven disease were treated with gemcitabine-cisplatin combination chemotherapy. Immunohistochemical stains for c-erbB-4 receptor were performed in 20 cases on paraffin sections using the avidin-biotin-peroxidase method. RESULTS: Two patients achieved complete response (5%), and 16 achieved partial response (37%) yielding an overall objective response rate of 42%. Minimal response was observed in seven patients (16%) and disease stabilization in 7%. Immunohistochemical stain was positive for the presence of c-erbB-4 receptor in 25% of patients, and negative in 75%. No response was documented in c-erbB-4 positive patients (0 of 5) while an objective response (complete, partial or minimal) was seen in 11 of 15 (73%) c-erbB-4 negative patients. Negative stain for c-erbB-4 significantly favored response to gemcitabine-cisplatin combination (P < 0.01). CONCLUSION: C-erbB-4 expression status showed no correlation with survival and cannot be accepted at this time as a guiding factor for therapeutic management. These interesting results deserve further evaluation in a large-scale prospective trial before treatment recommendations on the basis of c-erbB-4 presence can be finally made.

Adult↗

Severe allergic bronchopulmonary aspergillosis in an infant with cystic fibrosis and her asthmatic father.

An infant with cystic fibrosis and her asthmatic father were diagnosed as suffering from allergic bronchopulmonary aspergillosis (ABPA). Cystic fibrosis was diagnosed in the infant at 6 weeks of age, and gene mutations were W1282X/G542X. She was diagnosed definitively as suffering from ABPA at age 3.5 years, but had suggestive symptoms from age 11 months. This may be the youngest age described to date for ABPA. The child responded well to systemic steroid therapy, but remained steroid-dependent over the next 4 years. Treatment with itraconazole enabled a marked reduction in steroid dosage. The father was an asthmatic, and a heterozygote for the cystic fibrosis transmembrane regulator (CFTR) mutation W1282X. He had a normal sweat test, atopy, and moderate reversible airway obstruction. There was no proven exposure to Aspergillus in the home environment. The importance of considering the diagnosis of ABPA even in infancy, the therapeutic dilemmas, and the possible role of abnormal CFTR function in the development of ABPA are discussed.

Adult↗

Eosinophil influx into the airways in patients with exercise-induced asthma.

Exercise-induced asthma is a common phenomenon, the mechanism of which is undetermined. Eosinophils have been suggested as playing a role in its occurrence. We studied the effect of exercise-induced asthma on the cellular and mediator composition of spontaneously obtained sputum. Twenty-five patients with bronchial asthma were investigated by studying sputum spontaneously obtained before and following challenge. One group with (n=9) and one without (n=9) exercise-induced asthma performed exercise challenge. A third group (n=7) performed methacholine challenge. The sputum was analysed using Giemsa staining for differential cell count, measuring eosinophil cationic proteins and mixtures of leukotrienes (D4, E4 and C4) in the liquid phase using ELISA. The group with exercise-induced asthma had a mean drop of 23.7+/-7.4% in FEV1, significantly (P=0.001) higher than the group without it. Following challenges, there were significant increases in sputum eosinophils only in the group with exercise-induced asthma (from 8.1+/-13.9% to 18.3+/-20.2%, P=0.0017) and not in control groups (from 0.9+/-0.9% to 1.5+/-15%) or in those who had methacholine challenge (from 23.6+/-27.2% to 22.3+/-23.8%). Eosinophil cationic proteins did not change significantly in any group. In the liquid phase of the sputum, the amount of leukotrienes increased following exercise in six of the seven patients with exercise-induced asthma in whom it was measured. The influx of eosinophils to the airway in patients who develop exercise-induced asthma can be partially explained by the leukotrienes in the airways of those patients.

Adolescent↗

Correlative study of preoperative transthoracic core cutting needle biopsy of focal thoracic lesions and thoracotomy findings.

We conducted a retrospective study to determine the clinical utility of percutaneous core needle biopsy (PCNBx) in 36 patients with peripheral focal chest lesions who later underwent thoracic surgery for diagnostic or therapeutic purposes. PCNBx provided adequate material in 31/36 cases, giving an overall sample yield of 86.1%. PCNBx diagnosis was confirmed by surgery in 27/31 patients, giving a sensitivity of 91.6% and a specificity of 87.5%. In 4 patients, the lesions were misdiagnosed by PCNBx. In 5 patients with benign processes, surgical intervention could have been avoided, according to PCNBx results. The rate of PCNBx-induced pneumothorax was 11%. Radiologically guided PCNBx is an easy and safe procedure that can provide important preoperative diagnostic information and can circumvent the need for exploratory diagnostic surgery in cases of benign lesions. PCNBx also allows better preoperative planning in cases of malignancy.

Adult↗

Selected abstracts

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Journal Article↗

Percutaneous core needle biopsy in the diagnosis of mediastinal tumors.

OBJECTIVE: to determine the contribution of percutaneous core cutting needle biopsy (PCNB) in the diagnosis of mediastinal tumors. DESIGN: retrospective review of 70 patients with mediastinal lesions who underwent CT-guided PCNB between 1988 and 1996. RESULTS: PCNB provided adequate material in 62/70 cases, giving a total sample rate of 88.6%. Of these 62 patients, 57 were diagnosed correctly by PCNB whereas 5/62 were misdiagnosed as nonspecific inflammation, providing an overall sensitivity of 91.9%. PCNB established a specific histologic diagnosis in 90.3% of the patients, mainly in cases of lymphoma, bronchogenic carcinoma, and thymoma. Pneumothorax was the most commonly encountered complication (11%). Hemoptysis (30-50 ml) occurred in only one (1.6%) of the patients. CONCLUSION: CT guided PCNB is an easy and safe procedure which can provide a precise diagnosis in the majority of mediastinal tumors and can obviate the need for exploratory thoracic surgery in cases which are medically treatable or non-resectable.

Adult↗

Induced sputum compared to bronchoalveolar lavage for evaluating patients with sarcoidosis and non-granulomatous interstitial lung disease.

Bronchoalveolar lavage (BAL), an important tool for evaluating interstitial lung diseases (ILDs), has limited utility due to its invasiveness and the difficulty of performing it in clinically contraindicated patients. We compared BAL with the induced sputum (IS) technique to analyse cells and T lymphocytes in patients with sarcoidosis (SA) and non-granulomatous ILD (NG-ILD). Pulmonary function tests and BAL were performed by conventional methods. IS induction was done 20 sec after inhalation of 3.5% saline with an ultrasonic nebulizer. Giemsa-stained cytopreps were differentially counted. T lymphocyte subsets were analysed by flow activated cell sorter (FACS). Patients with NG-ILD had impaired total lung capacity (TLC). Transbronchial biopsy demonstrated lung fibrosis in NG-ILD and non-caseating granuloma in SA. The differential cell count in both groups demonstrated a significantly lower percentage of neutrophils and a significantly higher percentage of macrophages in BAL than in IS. The IS samples of patients with SA were significantly richer in metachromatic cells and eosinophils, but had a lower percentage of lymphocytes, compared to the BAL samples. The profiles of T cell subsets showed the same pattern, in both samples, in both groups. A CD4/CD8 ratio of 2.5 or greater had a sensitivity of 100% and a specificity of 81.2%, with a positive predictive value of 81.2% to distinguish SA from NG-ILD. IS is an effective non-invasive technique to identify CD4+ inflammation which distinguishes sarcoidosis from other NG-ILDs.

Adult↗

Tattooing and body piercing. Body art practices among college students.

Tattooing and body piercing are increasing, especially among college students. A study of 766 tattooed and/or body-pierced college students in 18 universities across the United States and one in Australia was conducted to discover the demographic characteristics, motivational factors, and health concerns. The traditional college time of 18 to 22 years of age (69%) was when they obtained their tattoo (73%) and/or body piercing (63%). More frequent health problems and impulsive decision making were noted for those with body piercing when compared to those tattooed. Three cases of hepatitis were reported. Health professionals should openly discuss body art with students, convey a nonjudgmental attitude, and assist with informed decision-making information to either reduce risks or dissuade. Open communication and applicable health education will be very important.

Adolescent↗

Assessment of hazardous dust exposure by BAL and induced sputum.

OBJECTIVES: BAL, an important tool in assessing occupational lung diseases, is unsuitable for screening programs, exposure evaluation, or monitoring hazardous dust because it is an invasive technique. The results of induced sputum (IS) analysis were compared with BAL and evaluated as a possible alternative. METHODS: We compared BAL with IS analysis of 5 workers exposed to asbestos and 14 exposed to silica and hard metals. Pulmonary function tests and BAL were performed by conventional methods. IS induction was performed after a 20-min inhalation of 3.5% saline solution with an ultrasonic nebulizer. Giemsa-stained cytopreparations were differentially counted. T-lymphocyte subsets were analyzed by flow-activated cell sorter, and messenger RNA (mRNA) was transcribed by reverse transcriptase-polymerase chain reaction. Mineralogic particles were analyzed by scanning electron microscopy and polarizing light microscopy and quantified by an analyzer. RESULTS: The percentage of neutrophils was significantly lower in BAL fluid than in IS specimens, whereas no differences were found in the percentage of lymphocytes and subsets profile. Asbestos fibers were found in BAL but not in IS samples from workers exposed to asbestos. Polarizing particles were found in both samples. Similar mineral elements were found in qualitative analysis by scanning electron microscopy. Quantitative studies showed similar size distribution with a small shift toward larger particles in sputum; mRNA showed the same cytokine profile. CONCLUSIONS: A comparison of BAL and IS specimens in the evaluation of the study population yielded similar quantitative and qualitative results. Further research is needed to evaluate the hypothesis that IS, being a noninvasive technique, may be useful in monitoring exposed workers.

Adult↗

Percutaneous core cutting needle biopsy compared with fine-needle aspiration in the diagnosis of peripheral lung malignant lesions: results in 156 patients.

BACKGROUND: The authors attempted to determine the utility of percutaneous core needle biopsy (PCNB) compared with fine-needle aspiration (FNA) in the diagnosis of peripheral lung carcinoma. METHODS: A retrospective review was undertaken of 156 computed tomography (CT)-guided PCNBs and FNAs of malignant lung lesions between 1988-1996. Both CT-guided FNA and PCNB biopsies were performed sequentially at the same visit for each subject. RESULTS: The authors reviewed 156 malignant lesions whose specific diagnosis was obtained by FNA in 133 cases (85.3%) and by PCNB in 121 cases (77.6%) (P < 0.05). PCNB confirmed the FNA diagnosis in 90 patients (57.7%), provided additional information in 17 patients (10.9%), and was less informative than FNA in 35 patients (22.4%), mostly those with nonsmall cell carcinoma. The PCNB was marginally superior to FNA only in cases of metastatic carcinoma. The only significant complication encountered was a 24% rate of pneumothorax, which is comparable to the reported rate for FNA alone-induced complications. CONCLUSIONS: PCNB offers no substantial advantage over FNA in the evaluation of peripheral malignant lung lesions. Therefore, the authors recommend the use of FNA biopsy as the initial diagnostic procedure in all cases of suspected malignancy. The use of the PCNB technique is recommended when the diagnosis of malignancy by FNA is uncertain, or when a more detailed characterization of the lesion is required.

Adult↗

Evaluation of workers exposed to dust containing hard metals and aluminum oxide.

BACKGROUND: Fourteen worker exposed to hard metals and aluminum oxide were evaluated. METHODS: Six heavily exposed workers underwent bronchoscopy and bronchoalveolar lavage, and five workers underwent transbronchial biopsy. RESULTS: Microchemical analysis of transbronchial biopsies showed a high lung burden of exogenous particles, especially metal related to their hard metals exposure. Lung tissue and cellular changes, which were associated with exposure to hard metal and aluminum oxide, corresponded well with the microanalytic test results. CONCLUSIONS: Three workers had at biopsy diffuse interstitial inflammatory changes: two of them were asymptomatic with normal chest X-ray films, and one had clinically evident disease with severe giant cell inflammation. Two other workers showed focal inflammation. The worker showing clinical disease and one asymptomatic worker with interstitial inflammatory changes had evaluated bronchoalveolar lavage fluid-eosinophilia counts. These two were father (with clinical disease) and son (asymptomatic).

Adult↗

Pleuropulmonary metastasis from an intracranial glioblastoma.

We present an unusual case of glioblastoma with intrathoracic and liver metastasis. The clinical diagnosis was confirmed by a percutaneous core needle biopsy from a metastatic lung lesion. The pathogenetic and diagnostic aspects of the case are discussed.

Biopsy, Needle↗

Additional information from percutaneous cutting needle biopsy following fine-needle aspiration in the diagnosis of chest lesions.

OBJECTIVE: To determine the contribution of percutaneous cutting needle biopsy (PNB) subsequent to fine-needle aspiration (FNA) in the diagnosis of chest lesions. DESIGN: A retrospective review of 220 patients who underwent CT-guided FNA followed immediately by PNB performed at our center between 1988 and 1995 was undertaken. Thirty-eight patients were excluded because FNA and/or PNB specimens were nondiagnostic, yielding a study group of 182 patients. RESULTS: A diagnosis of malignancy was made in 141 (77.5%) and nonmalignancy in 41 (22.5%) cases. The yield of histospecific diagnosis due to FNA was marginally higher than PNB in malignant lesions (86.5% vs 78%, respectively). In contrast, PNB was superior to FNA for the histospecific diagnosis of benign lesions (87.8% for PNB vs 31.7% for FNA, p<0.00001) and lymphomas (88% for PNB vs 56% for FNA, p<0.05). In 58.8% of the patients with benign lesions and in 37.5% of the patients with lymphoma, PNB performances altered clinical management, either by avoiding further surgery or allowing specific medical treatment. Pneumothorax occurred in 24.7% of the cases but only five patients (2.7%) required hospitalization. CONCLUSION: PNB is extremely effective for making a specific diagnosis in benign lesions compared with FNA. PNB does not increase the yield of histospecific diagnosis for malignant lesions except for the subset of lymphoma, where it seems to provide important additional information in many instances. We recommend that FNA be performed as the initial procedure, followed by PNB in cases of equivocal diagnosis of carcinoma, for lymphoma and for suspected benign lesions.

Adolescent↗

Predictive value of response to treatment of T-lymphocyte subpopulations in idiopathic pulmonary fibrosis.

T-cell types are important in maintaining immune homeostasis in the lung and their imbalance may be associated with several diseases. We examined the relationship between bronchoalveolar lavage (BAL) T-cell subset profiles and the clinical course of 46 patients with idiopathic pulmonary fibrosis (IPF). A flow cytometry cell sorter (FACS) was used to analyse the T-cell subsets. Pulmonary function tests (PFT) were performed at baseline and 6-12 months later. Patients were divided into two groups according to their CD4/CD8 ratio: CD4/CD8 >1 (group 1, n=21); and CD4/CD8 <1 (group 2, n=25). A lower percentage of lymphocytes, a higher percentage of CD8/S6F1 cells (cytotoxic T-lymphocytes) and a higher percentage of neutrophils were found in the BAL in group 2 compared to group 1 (11+/-7.5% versus 19+/-13.2%; p=0.024 and 29.8+/-17.6% versus 13.3+/-6.9%; p=0.068, respectively for lymphocytes and cytotoxic T-lymphocytes; and 8+/-11% versus 29+/-27%; p=0.003 for neutrophils). Inversely, in the peripheral blood, the distribution of CD8/S6F1 cells was lower in group 1 than in group 2 (8.3+/-6.9% versus 33.4+/-16.5%; p=0.0048). The patients were followed over a period of 1 yr in order to test whether those findings could determine efficacy of therapy. The baseline transfer factor of the lung for carbon monoxide (TL,CO) capacity in group 1 and group 2 was 59+/-22% and 51+/-21%, respectively (p=0.29), but only in group 1 was the TL,CO capacity improved significantly in response to steroids treatment after 6-12 months. IPF patients with a higher percentage of lymphocytes, a lower percentage of neutrophils, CD4/CD8 >1 and a low percentage of CD8/S6F1 may have a more benign course of disease. These parameters may identify an early stage of reversible disease responsive to therapy. We conclude that these measurements may be a useful tool in monitoring response to treatment in patients with idiopathic pulmonary fibrosis.

Bronchoalveolar Lavage Fluid↗