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Biomedical subjects

Martin R Zamora

Publications and source records attributed to Martin R Zamora.

7 recordsLinked to original sources
PubMed2005

Simultaneous LFA-1 and CD40 ligand antagonism prevents airway remodeling in orthotopic airway transplantation: implications for the role of respiratory epithelium as a modulator of fibrosis.

Airway remodeling is a prominent feature of certain immune-mediated lung diseases such as asthma and chronic lung transplant rejection. Under conditions of airway inflammation, the respiratory epithelium may serve an important role in this remodeling process. Given the proposed role of respiratory epithelium in nonspecific injury models, we investigated the respiratory epithelium in an immune-specific orthotopic airway transplant model. MHC-mismatched tracheal transplants in mice were used to generate alloimmune-mediated airway lesions. Attenuation of this immune injury and alteration of antidonor reactivity were achieved by the administration of combined anti-LFA-1/anti-CD40L mAbs. By contrast, without immunotherapy, transplanted airways remodeled with a flattening of respiratory epithelium and significant subepithelial fibrosis. Unopposed alloimmune injury for 10 days was associated with subsequent epithelial transformation and subepithelial fibrosis that could not be reversed with immunotherapy. The relining of donor airways with recipient-derived epithelium was delayed with immunotherapy resulting in partially chimeric airways by 28 days. Partial chimerism was sufficient to prevent luminal fibrosis. However, epithelial chimerism was also associated with airway remodeling. Therefore, there appears to be an intimate relationship between the morphology and level of chimerism of the respiratory epithelium and the degree of airway remodeling following alloimmune injury.

Animals↗
PubMed2004

Emphysema lung tissue gene expression profiling.

Emphysema occurs in a subgroup of patients with chronic obstructive pulmonary disease and patients with the genetic defect of alpha(1)-antitrypsin deficiency who have a smoking history of many years' duration. Emphysema is generally the result of a chronic and progressive destruction of the alveolar structures, which is believed to be driven by chronic inflammation, infections, oxidative stress, and an imbalance of protease and antiprotease activity. Here, we use microarray technology to characterize the gene expression profile of lung tissue samples obtained from patients with advanced emphysema and that obtained from healthy subjects. We hypothesized that the gene expression profile of emphysema lung tissue is distinct when compared with the expression profile of normal lungs. We report that severely emphysematous tissue is characterized by a global decrease in gene expression and by an increased abundance of transcripts encoding proteins involved in inflammation, immune responses, and proteolysis. Whereas the gene expression profile is to some degree shared between "usual" emphysema and alpha(1)-antitrypsin deficiency-related emphysema, there are statistically significant differences in the modulation of groups of genes associated with protein and energy metabolism, and immune function, which allow distinction between these two emphysema types on the lung tissue level.

Adolescent↗
PubMed2004

Cytomegalovirus and lung transplantation.

Cytomegalovirus (CMV) infection remains a serious problem in lung transplant recipients. Development of potent oral antiviral agents, molecular techniques for the detection of infection and its response to therapy and the emergence of isolates with antiviral resistance have had significant impacts on the approach to CMV in these patients. This article discusses the following issues as part of a comprehensive CMV management strategy in lung transplant recipients: (1) Prevention strategies in the era of potent oral antiviral agents, (2) the role of new diagnostic techniques in the management of CMV, (3) treatment regimens for established CMV infection or disease, (4) the potential impact of treatment of CMV on the indirect effects on long-term allograft function, and (5) the incidence, risk factors for and impact of ganciclovir resistance following lung transplantation.

Antiviral Agents↗
PubMed2004

Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation.

We prospectively determined the safety and efficacy of valganciclovir for prevention of cytomegalovirus (CMV) in at-risk (donor positive/recipient negative [D+/R-] or R+) lung transplant recipients. We also determined the length of prophylaxis required to significantly decrease both CMV infection and disease. Consecutive lung transplant recipients surviving >30 days (n = 90) received combination prophylaxis with intravenous (i.v.) ganciclovir (GCV) 5 mg/kg/day and cytomegalovirus immune globulin (CMV-IVIG) followed by valganciclovir (450 mg twice-daily) to complete 180, 270 or 365 days of prophylaxis. This group was compared to a historical group (n = 140) who received high-dose oral acyclovir following i.v. GCV and CMV-IVIG. CMV disease was significantly lower in patients receiving valganciclovir compared to acyclovir (2.2% vs. 20%; p < 0.0001). Freedom from CMV infection and disease was significantly greater (p < 0.02) in patients receiving 180, 270 or 365 days of prophylaxis (90%, 95% and 90%, respectively) compared to those receiving 100-179 days (64%) or < 100 days (59%). No patient receiving valganciclovir died during the study. Following prophylaxis with i.v. GCV and CMV-IVIG, valganciclovir is safe and effective for prevention of CMV infection and disease in at-risk lung transplant recipients. The required length of prophylaxis was at least 180 days.

Antiviral Agents↗
PubMed2003

Lobar torsion complicating bilateral lung transplantation.

We report a case of left lower lobe torsion in a patient who had undergone bilateral lung transplantation for alpha(1)-antitrypsin deficiency. The patient experienced acute pulmonary hypertension and hypoxemia on post-operative Day 3 and the chest X-ray showed bilateral alveolar infiltrates and a new focal consolidation of the left lower lobe. Fiberoptic bronchoscopy showed complete obstruction of the left lower lobe bronchus and abnormal rotation of the left upper lobe bronchus suggesting torsion, which was confirmed by pulmonary angiography and ultimately at thoracotomy. The possibility of acute lobar torsion should be considered in lung transplant recipients who demonstrate evidence of acute respiratory insufficiency in the early post-operative period.

Humans↗
PubMed2002

The value of polymerase chain reaction for the diagnosis of viral respiratory tract infections in lung transplant recipients.

BACKGROUND: Respiratory viruses cause severe infections in lung transplant recipients, which require rapid and accurate diagnosis for appropriate management. OBJECTIVES: To evaluate the added benefit of a multiplex PCR for respiratory viruses (influenza [FLU] A and B, respiratory syncytial virus [RSV] A and B and parainfluenza virus [PIV] 1, 2, and 3) complementing rapid respiratory viral culture (RRV) and FLU-A antigen detection (EIA) in this transplant population. RESULTS: Over 6 months, 116 nasal washes and bronchoalveolar lavages, obtained from 72 lung transplant recipients with symptoms of upper or lower respiratory tract infections, were tested in real time by RRV and FLU-A EIA, and batched frozen by PCR. One or more methods recognized a respiratory virus in 31 (27%) specimens, including 15 FLU-A, nine RSV and seven PIV. PCR identified 26 of 31 positive samples demonstrating a sensitivity of 84%, higher than RRV (67%) or EIA (54%). PCR, RRV and EIA detected 60, 80 and 54%, respectively, FLU-A samples. PCR and RRV were equivalent for RSV-A, PIV-2 and 3, but PCR found a significantly higher number of RSV-B and PIV-1. CONCLUSIONS: These data indicate that routine use of PCR will enhance the number and speed with which viral respiratory tract infections are diagnosed in lung transplant recipients.

Adult↗