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Biomedical subjects

R A Dweik

Publications and source records attributed to R A Dweik.

At least 37 records · Page 2Linked to original sources
PubMed1999

Role of bronchoscopy in massive hemoptysis.

Massive hemoptysis accounts for a minority of all patients with hemoptysis but poses a major challenge for the acute and long-term treatment. Massive hemoptysis can lead to asphyxiation and airway obstruction, shock, and exsanguination. Bronchoscopy plays an integral part in managing massive hemoptysis in diagnosis and treatment (Table 5). Specifically, bronchoscopy allows lateralization and more specific localization of bleeding that is critically important for effective management. Furthermore, acute control of bleeding can sometimes be achieved with instruments and catheters placed through the bronchoscope or by agents instilled into the airways through the bronchoscope.

Bronchoscopy↗
PubMed1999

Role of bronchoscopy in asthma research.

Over the past 15 years, much has been learned about the presence of airway inflammation in asthma through the use of investigative bronchoscopy. It has become quite clear that inflammation is present even in mild asthma. In addition to the eosinophils, T-lymphocytes and a variety of cytokines have been identified to play a prominent role in asthmatic inflammation. The concept of delayed asthmatic response after allergen exposure and its relationship to cellular inflammation and airway hyper-reactivity has become more clearly established. Our understanding of asthmatic airway inflammation, however, is incomplete. As interesting as the database has been so far, investigative FB has not defined a unique profile for patients with asthma. Specifically, lavage or endobronchial biopsy has not identified parameters that help in the diagnosis, assessment of disease severity, prognosis, or likelihood to respond to specific therapies. Also, the exact relationship between parameters in lavage compared with mucosal biopsy and how these are related to airway hyper-reactivity and the clinical syndrome of asthma remains poorly understood. In this regard, it must be confessed that currently FB with lavage and biopsy in asthmatics needs to be considered as a research tool for specimen retrieval to help characterize and express inflammation. Although these techniques have contributed immensely to our understanding of asthma pathogenesis, presently these techniques do not have any practical role or clinical usefulness.

Asthma↗
PubMed1999

Venous thromboembolism in the intensive care unit.

Venous thromboembolic disease has emerged as a significant cause of morbidity and mortality in hospitalized patients. This article reviews the salient features of venous thromboembolism as they pertain to the critically ill. Emphasis is placed on identifying risk factors, diagnostic strategies, prophylaxis, and treatment of this disorder. Deep venous thrombosis and pulmonary embolism, both being manifestations of the same disease processes, are considered together in this discussion of venous thromboembolism.

Adult↗
PubMed1999

High prevalence of hypothyroidism in patients with primary pulmonary hypertension.

PURPOSE: To characterize the prevalence of hypothyroidism in a population with primary pulmonary hypertension (PPH). METHODS: Retrospective record review of 41 patients with PPH seen between 1991 and 1997 at a tertiary care center. Data abstracted included: history of previous thyroid disease, intake of thyroid supplement, and thyroid function tests. Hypothyroidism was defined as a serum thyroid stimulating hormone (TSH) level higher than 5.5 U/L, intake of thyroid supplement, or low serum thyroxine level. RESULTS: Of the 40 patients with PPH included in the study (11 men and 29 women), ages ranged from 11 to 76 years (mean 43.5 years). The mean pulmonary artery pressure was 58.7 mm Hg. Thirty-three patients had normal serum TSH levels (3 of whom were on levothyroxine supplement); 1 had low TSH; 5 had high TSH (range, 6.8-9.9 U/L, mean 8.4 U/L), and 1 had low thyroxine (T4 < 1.0 microg/dL). Nine of 40 patients (22.5%) had evidence of hypothyroidism, which is much more than expected in the general population of similar age range (2.8% in men, 7.5% in women) (p = 0.002). CONCLUSIONS: The prevalence of hypothyroidism in patients with PPH is high (22.5%). Patients with PPH should be investigated for the possibility of coexisting hypothyroidism.

Adolescent↗
PubMed1999

Human vascular endothelial cells express oxytocin receptors.

Pharmacological studies in humans and animals suggest the existence of vascular endothelial vasopressin (AVP)/oxytocin (OT) receptors that mediate a vasodilatory effect. However, the nature of the receptor subtype(s) involved in this vasodilatory response remains controversial, and its coupled intracellular pathways are unknown. Thus, we set out to determine the type and signaling pathways of the AVP/OT receptor(s) expressed in human vascular endothelial cells (ECs). Saturation binding experiments with purified membranes of primary cultures of ECs from human umbilical vein (HUVEC), aorta (HAEC), and pulmonary artery (HPAEC) and [3H]AVP or [3H]OT revealed the existence of specific binding sites with a greater affinity for OT than AVP (Kd = 1.75 vs. 16.58 nM). Competition binding experiments in intact HUVECs (ECV304 cell line) with the AVP antagonist [125I]4-hydroxyphenacetyl-D-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-NH2 or the OT antagonist [125I]D(CH2)5[O-Me-Tyr-Thr-Orn-Tyr-NH2]vasotocin, and various AVP/OT analogs confirmed the existence of a single class of surface receptors of the classical OT subtype. RT-PCR experiments with total RNA extracted from HUVEC, HAEC, and HPAEC and specific primers for the human V1 vascular, V2 renal, V3 pituitary, and OT receptors amplified the OT receptor sequence only. No new receptor subtype could be amplified when using degenerate primers. DNA sequencing of the coding region of the human EC OT receptor revealed a nucleotide sequence 100% homologous to that of the uterine OT receptor reported previously. Stimulation of ECs by OT produced mobilization of intracellular calcium and the release of nitric oxide that was prevented by chelation of extra- and intracellular calcium. No stimulation of cAMP or PG production was noted. Finally, OT stimulation of ECs led to a calcium- and protein kinase C-dependent cellular proliferation response. Thus, human vascular ECs express OT receptors that are structurally identical to the uterine and mammary OT receptors. These endothelial OT receptors produce a calcium-dependent vasodilatory response via stimulation of the nitric oxide pathway and have a trophic action.

Arginine Vasopressin↗
PubMed1998

Nitric oxide synthesis in the lung. Regulation by oxygen through a kinetic mechanism.

In this study, we show that oxygen regulates nitric oxide (NO) levels through effects on NO synthase (NOS) enzyme kinetics. Initially, NO synthesis in the static lung was measured in bronchiolar gases during an expiratory breath-hold in normal individuals. NO accumulated exponentially to a plateau, indicating balance between NO production and consumption in the lung. Detection of NO2-, NO3-, and S-nitrosothiols in lung epithelial lining fluids confirmed NO consumption by chemical reactions in the lung. Interestingly, alveolar gas NO (estimated from bronchiolar gases at end-expiration) was near zero, suggesting NO in exhaled gases is not derived from circulatory/systemic sources. Dynamic NO levels during tidal breathing in different airway regions (mouth, trachea, bronchus, and bronchiole) were similar. However, in individuals breathing varying levels of inspired oxygen, dynamic NO levels were notably dependent on O2 concentration in the hypoxic range (KmO2 190 microM). Purified NOS type II enzyme activity in vitro was similarly dependent on molecular oxygen levels (KmO2 135 microM), revealing a means by which oxygen concentration affects NO levels in vivo. Based upon these results, we propose that NOS II is a mediator of the vascular response to oxygen in the lung, because its KmO2 allows generation of NO in proportion to the inspired oxygen concentration throughout the physiologic range.

Adult↗
PubMed1998

Manifestations of scleroderma pulmonary disease.

Scleroderma is a multisystem disease of unknown cause characterized by synthesis and deposition of excessive extracellular matrix and vascular anti-GBM antibodies, leading to pulmonary hemorrhage and glomerulonephritis with rapidly progressive renal insufficiency. Recent advances in the understanding of disease pathogenesis and diagnosis and treatment have significantly improved our ability to recognize the syndrome, distinguish it from other similar disorders, and offer successful treatment. This article focuses on the pathogenetic features, clinical manifestations, diagnostic strategies, and therapeutic principles of anti-GBM disease.

Humans↗
PubMed1998

iNOS expression in human intestinal microvascular endothelial cells inhibits leukocyte adhesion.

Increased nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) has been associated with intestinal inflammation, including human inflammatory bowel disease. However, NO can downregulate endothelial activation and leukocyte adhesion, critical steps in the inflammatory response. Using primary cultures of human intestinal microvascular endothelial cells (HIMEC), we determined the role of NO in the regulation of HIMEC activation and interaction with leukocytes. Both nonselective (NG-monomethyl-L-arginine) and specific (N-iminoethyl-L-lysine) competitive inhibitors of iNOS significantly increased binding of leukocytes by HIMEC activated with cytokines and lipopolysaccharide. Increased adhesion was reversible with the NOS substrate L-arginine and was not observed in human umbilical vein endothelial cells (HUVEC). Activation of HIMEC significantly upregulated HIMEC iNOS expression and NO production. NOS inhibitors did not augment cell adhesion molecule levels in activated HIMEC but did result in sustained increases in intracellular reactive oxygen species. In addition, antioxidant compounds reversed the effect of NOS inhibitors on HIMEC-leukocyte interaction. Taken together, these data suggest that after HIMEC activation, iNOS-derived NO is an endogenous antioxidant, downregulating leukocyte binding and potentially downregulating intestinal inflammation.

Arginine↗
PubMed1998

Biochemical reaction products of nitric oxide as quantitative markers of primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is a rare and fatal disease of unknown etiology. Inflammatory oxidant mechanisms and deficiency in nitric oxide (NO) have been implicated in the pathogenesis of pulmonary hypertension. In order to investigate abnormalities in oxidants and antioxidants in PPH, we studied intrapulmonary NO levels, biochemical reaction products of NO, and antioxidants (glutathione [GSH], glutathione peroxidase [GPx], and superoxide dismutase [SOD]) in patients with PPH (n = 8) and healthy controls (n = 8). Intrapulmonary gases and fluids were sampled at bronchoscopy. Pulmonary hypertension was determined by right-heart catheterization. NO and biochemical reaction products of NO in the lung were decreased in PPH patients in comparison with healthy controls (NO [ppb] in airway gases: control, 8 +/- 1; PPH, 2.8 +/- 0. 9; p = 0.016; and NO products [microM] in bronchoalveolar lavage fluid [BALF]: control, 3.3 +/- 1.05; PPH, 0.69 +/- 0.21; p = 0.03). However, GSH in the lungs of PPH patients was higher than in those of controls (GSH [microM] in BALF: 0.55 +/- 0.04; PPH, 0.9 +/- 0.1; p = 0.015). SOD and GPx activities were similar in the two groups (p >/= 0.50). Biochemical reaction products of NO were inversely correlated with pulmonary artery pressures (R = -0.713; p = 0.047) and with years since diagnosis of PPH (R = -0.776; p = 0.023). NO reaction products are formed through interactions between oxidants and NO, with the end products of reaction dependent upon the relative levels of the two types of molecules. The findings of the study therefore show that NO and oxidant reactions in the lung are related to the increased pulmonary artery pressures in PPH.

Adult↗
PubMed1997

Interferon gamma and interleukin 4 stimulate prolonged expression of inducible nitric oxide synthase in human airway epithelium through synthesis of soluble mediators.

Human respiratory epithelium expresses inducible nitric oxide synthase (iNOS) continuously in vivo, however mechanisms responsible for maintenance of expression are not known. We show that IFNgamma is sufficient for induction of iNOS in primary human airway epithelial cells (HAEC) in vitro, and IL-4 potentiates IFNgamma-induced iNOS expression in HAEC through stabilization of iNOS mRNA. IFNgamma/IL-4- induced iNOS expression in HAEC was delayed in onset and prolonged with expression up to 1 wk. Removal of overlying culture media resulted in loss of expression, while transfer of conditioned media induced iNOS mRNA in other HAEC. IFNgamma and IL-4 stimulation activated STAT1 and STAT6 in HAEC, but conditioned media transfer to HAEC produced even higher levels of STAT1 activation than achieved by direct addition of cytokines. Although cytokine induction of iNOS was dependent on new protein synthesis, conditioned media induction of iNOS in HAEC was not. Further, removal of overlying culture media from cells at different times after cytokine stimulation demonstrated that mediator synthesis and/or secretion important for induction and maintenance of iNOS occurs early after cytokine stimulation. In conclusion, a combination of IFNgamma/ IL-4, which occurs naturally in the lung epithelial lining fluid, leads to maintenance of iNOS expression in human airway epithelium through production of soluble mediators and stabilization of mRNA.

Adolescent↗
PubMed1997

Inhaled corticosteroids and beta-agonists inhibit oxidant production by bronchoalveolar lavage cells from normal volunteers in vivo.

To study the anti-inflammatory mechanisms of inhaled corticosteroids and beta-agonist therapies, we evaluated basal and stimulus-induced superoxide production by human airway inflammatory cells obtained by bronchoalveolar lavage from normal volunteers before and after 3 weeks of an inhaled corticosteroid (flunisolide) and beta-agonist (metaproterenol). Assay of superoxide production by the bronchoalveolar lavage cells was performed in the presence of media alone or media containing phorbol ester by optical density determination of reduced ferricytochrome c at 550 nm. Interleukin-1 beta released from unstimulated cells and cells stimulated with lipopolysaccharide was quantitated by enzyme immunoassay. Interestingly, phorbol ester-stimulated superoxide production was strikingly inhibited (P < 0.05) by inhaled therapies, while stimulus induced Interleukin-1 beta production was not significantly affected (P = 0.12). Suppression of oxidant production by airway inflammatory cells may be a major mechanism for the beneficial anti-inflammatory effects of inhaled corticosteroids and beta-agonists.

Administration, Inhalation↗
PubMed1997

Alveolar hemorrhage in patients with rheumatic disease.

Alveolar hemorrhage is an uncommon event that is associated with several underlying disorders, many of which are immunologically mediated. Careful evaluation of basic laboratory tests, extrapulmonary physical findings, and serology usually leads to the correct diagnosis. Significant overlap, however, exists, and pathologic (especially immunopathologic) evaluation of pulmonary or renal biopsies may be necessary. An accurate diagnosis is essential because treatment is most helpful when directed at the underlying diagnosis. Supportive therapy may be needed until the underlying disease is diagnosed and specific therapy is initiated.

Algorithms↗
PubMed1996

Analysis of the safety of bronchoscopy after recent acute myocardial infarction.

Acute myocardial infarction (AMI) is generally considered to increase the risk of flexible fiberoptic bronchoscopy (FFB). Currently, to our knowledge, no data in the literature support or challenge this concept. We conducted a retrospective chart review for the years 1986 to 1994 of 20 patients (14 men) who underwent 21 FFBs while hospitalized for an AMI. The mean age was 63.8 years (range, 38 to 83 years). Ten patients underwent revascularization procedures (eight coronary artery bypass grafting and two percutaneous transluminal coronary angioplasty) before FFB. The mean period between the AMI and FFB was 11.7 days (range, 1 to 30 days). Indications for FFB were pulmonary infiltrate (n = 10), hemoptysis (n = 6), atelectasis (n = 4), and to localize a suspected bronchopleural fistula (n = 1). Procedures performed included airway examination (21), BAL (12), transbronchial biopsy (2), endobronchial biopsy (3), and endobronchial brushing (4). No procedure was interrupted as a result of an adverse event, and five patients died during the same hospitalization. Four of the deaths occurred 6 to 15 days postprocedure; 1 patient (who had active ischemia at the time of FFB) died 4 h postprocedure. We conclude that FFB is safe in the immediate post-AMI period as long as the patient does not have active ischemia at the time of the procedure.

Adult↗
PubMed1995

Rare pulmonary manifestation of Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is an inherited disorder of connective tissue with multiple thoracic manifestations. We present an unusual thoracic manifestation of EDS consisting of parenchymal cysts and fibrous and fibroosseous nodules. These manifestations may be related to an abnormal attempt at repair of parenchymal or vascular tears.

Adolescent↗
PubMed1995

Necrosis of the bronchus. Role of radiation.

The effects of radiation on the lung parenchyma and pleura are well described in the literature. Necrosis of the larynx is a known complication of radiation therapy. Necrosis of a part of the tracheobronchial tree following radiation therapy for bronchogenic carcinoma is likely to occur; however, there is little mention in the English-language literature about such an effect. This report describes four cases with total necrosis of a specific bronchus following radiation therapy for squamous cell carcinoma of the lung. All patients received 5,000 to 6,400 rad (50 to 64 Gy) of external-beam radiation. Two patients presented with massive hemoptysis and two with pneumonia. In all four cases, the patients were found to have, by bronchoscopy, necrosis of the bronchus with the involved lobe of the lung replaced by a large cavity lined by tumor tissue. Diagnosis was made 5 to 7 months after radiation therapy was completed. Three of the patients died of exsanguination within weeks following diagnosis of the complication. We suspect that such necrosis occurs as a consequence of radiation therapy in combination with infection in the set up of squamous cell carcinoma, and is a marker of poor prognosis.

Aged↗