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F J Martinez

Publications and source records attributed to F J Martinez.

At least 73 records · Page 4Linked to original sources

Substrate specificity of human aldose reductase: identification of 4-hydroxynonenal as an endogenous substrate.

Aldose reductase, which catalyzes the reduction of glucose to sorbitol as part of the polyol pathway, has been implicated in the development of diabetic complications and is a prime target for drug development. However, aldose reductase exhibits broad specificity for both hydrophilic and hydrophobic aldehydes, which suggests that aldose reductase may also be a detoxification enzyme. Several series of structurally related aldehydes were compared as substrates in order to deduce the structural features that result in low Michaelis constants. Aldehydes that contain an aromatic ring are generally excellent substrates, consistent with crystallographic data which suggest that aldose reductase possesses a large hydrophobic substrate binding site. However, there is little discrimination among different aromatic aldehydes. In addition, small hydrophilic aldehydes exhibit low Km values if the alpha-carbon is oxidized. Analysis of the binding of NADPH by fluorescence quenching techniques indicates that aldose reductase exhibits higher affinity for NADPH than NADP, suggesting that this enzyme is normally primed for reductive metabolism. Thus aldose reductase appears to have evolved to catalyze the reduction of a very broad range of aldehydes. Structural features of substrates that bind to aldose reductase with low Km values were used to identify potential endogenous substrates. 4-Hydroxynonenal, a reactive alpha-beta unsaturated aldehyde produced during oxidative stress, is an excellent substrate (Km = 22 microM, kcat/Km = 4.6 x 10(6) M-1 min-1). Reductive metabolism of endogenous aldehydes in addition to glucose, catalyzed by aldose reductase, may play an important role in the development of diabetic complications.

Aldehyde Reductase↗

Influence of sample number and biopsy site on the histologic diagnosis of diffuse lung disease.

BACKGROUND: Although open biopsy is considered the optimal method for obtaining lung tissue for the diagnosis of diffuse infiltrative pulmonary disorders, there are no universally established guidelines concerning biopsy site selection and the ideal number of tissue samples. Relatively few investigations have been devoted to the influence exerted by the site and number of biopsy samples on the histologic diagnosis. METHODS: Seventy-seven open biopsy samples obtained from different lobes of 28 patients with idiopathic pulmonary fibrosis were analyzed. The histopathologic features were evaluated semiquantitatively and the results from each sample compared with those of the other samples obtained from each patient. RESULTS: Statistically significant differences in histopathologic features were not observed between samples. CONCLUSIONS: A single generous (2 cm or greater diameter) sample, obtained from a representative region of the radiographically most involved lobe, will suffice for diagnostic and evaluation purposes.

Adult↗

Inotropic and chronotropic effects of 4-(4'-n-butylaniline)-7,8- dimethoxy-5H-pyrimido[5,4-b]indole in guinea-pig atria.

Cardiotonic effect of 4-(4'-n-butylaniline)-7,8-dimethoxy- 5H-pyrimido[5,4-b]indole (B11) was investigated in isolated cardiac tissue preparations. The action of this agent on force of contraction, beating frequency and cyclic nucleotide phosphodiesterase (PDE) activity was studied. Amrinone was used for comparison. B11 produced concentration-dependent (5 x 10(6)-1 x 10(-4)M) positive inotropic and positive chronotropic responses in guinea-pig atrial tissues. The potency of B11 was greater than that of amrinone. The cardiotonic effects of B11 were not modified by beta-adrenoceptor blockade. Carbachol inhibited the positive inotropic effect of B11. The activity of B11 was increased in desensitized left atrial tissues. B11 inhibited the activities of PDE isoenzymes (type I, II, IV and V) from dog heart ventricle and PDE type IV from guinea-pig heart ventricle nonselectively. It is concluded that B11 possesses potent positive inotropic activity in guinea-pig atria, and the effect is probably mediated by a non-selective inhibition of PDE activity.

3',5'-Cyclic-AMP Phosphodiesterases↗

Stenosis of the central airways: evaluation by using helical CT with multiplanar reconstructions.

PURPOSE: To assess the accuracy of helical computed tomography (CT) with multiplanar reconstructions (MPRs) in the evaluation of stenoses of the central airways. MATERIALS AND METHODS: Thin-section axial CT and helical CT with MPRs were used to examine the central tracheobronchial tree for the presence of stenosis in 27 patients who underwent lung transplantation and 17 nontransplantation patients. The findings from these modalities were then compared with the findings obtained at conventional tomography and bronchoscopy, when available. RESULTS: Axial CT alone was 91% accurate in depicting stenosis, CT with MPRs was 94% accurate, and conventional tomography was 89% accurate in the evaluation of bronchial anastomosis in transplant recipients. CT and CT scans with MPRs were each 91% accurate in depicting stenosis in nontransplantation patients; the single false-negative finding showed focal tracheomalacia at bronchoscopy. CONCLUSION: CT with MPRs may be more accurate than thin-section axial CT in the demonstration of mild stenosis, the length of a stenosis, and horizontal webs.

Anastomosis, Surgical↗

Increased interleukin-1 receptor antagonist in idiopathic pulmonary fibrosis. A compartmental analysis.

Idiopathic pulmonary fibrosis (IPF) is a poorly understood interstitial disease that usually proves refractory to therapy and results in irreversible tissue scarring and pulmonary dysfunction. Previous investigations have suggested a number of possible mediators of inflammation and fibrosis that typify IPF. We report increases in lung interleukin-1 receptor antagonist protein (IRAP) content in patients with IPF, as compared with normal control subjects. Importantly, this increase in IRAP was not accompanied by concomitant increases in interleukin-1 beta (IL-1 beta), resulting in a local environment that may be profibrotic. Tissue homogenates and bronchoalveolar lavage fluid from patients with IPF both demonstrate elevated IRAP content compared with that in normal subjects. Immunohistochemical staining and in situ hybridization localize IRAP to hyperplastic type II pneumocytes, macrophages, and local stromal cells. Finally, in vitro studies utilizing fibroblasts isolated from patients with IPF demonstrated no difference in constitutive IRAP production compared with that in normal subjects, but they revealed an exaggerated response to stimulation with transforming growth factor-beta (TGF-beta). These findings suggest that the fibrotic tissue changes of IPF and possibly other chronic interstitial lung diseases may result in part from the local effects of IRAP, and they also demonstrate that pulmonary nonimmune cells may influence local tissue changes through the elaboration of IRAP.

Bronchoalveolar Lavage Fluid↗

Cardiopulmonary exercise testing following allogeneic lung transplantation for different underlying disease states.

OBJECTIVES: To assess the exercise response to single lung transplantation in chronic airflow obstruction (CAO), idiopathic pulmonary fibrosis (IPF), and pulmonary vascular disease (PVD) vs double lung transplantation at well-defined time points after transplantation, and to define the change in exercise response in SLT and DLT over the first year after transplantation. DESIGN: Prospective study. SETTING: Tertiary referral hospital. PATIENTS: Fourteen stable SLT recipients (6 with CAO, 4 with IPF, 4 with PVD) and 11 stable DLT recipients. MEASUREMENTS: Spirometry, lung volumes, diffusion lung capacity for carbon monoxide (DLco) and MVV measured prior to exercise at 3 months (n = 25) then at 3-month intervals up to a maximum of 12 months post-transplantation (n = 18 [12 SLT and 6 DLT]). Symptom-limited cardiopulmonary exercise tests at same time points (n = 25 at 3 months, n = 18 [12 SLT and 6 DLT] at 3-month intervals up to 12 months). Breathlessness was estimated by visual analogue scale prior to exercise and at peak exercise. RESULTS: At 3 months, FEV1 percent predicted was lower for SLT-CAO and SLT-IPF vs DLT (p < or = 0.05). Mean FEV1/FVC was lower for SLT-CAO vs all other groups (p < or = 0.05). The FVC, MVV, and DLco/VA were similar for all groups. The TLC and RV were higher for the SLT-CAO group compared with all others. The TLC was lower for SLT-PVD compared with DLT. Exercise responses were similar in all groups studied without a statistically significant difference in achieved VO2, work rate, O2 pulse, anaerobic threshold, heart rate response, respiratory rate, VE/MVV, and VT/VC. The change in O2 saturation during exercise was the least in recipients of DLT. Maximal achieved VO2 rose from 3 to 6 months after SLT but dropped by 9 to 12 months after transplantation. Maximal achieved VO2 trended up from 3 to 6 months after DLT but dropped by 9 to 12 months after transplantation. Maximal achieved work rate rose in both SLT and DLT from 3 to 9 to 12 months after transplantation. There was no significant difference in breathlessness at rest and peak exercise measured between recipients of SLT or DLT. CONCLUSIONS: Minor differences in pulmonary function and change in O2 saturation occur between recipients of SLT and DLT during the first posttransplant year. These differences are most pronounced when comparing SLT-CAO with DLT. However, there is no significant difference in exercise capacity between SLT for CAO, IPF, PVD, and DLT. The rise in maximum achieved VO2 over the first 6 months after transplantation may reflect the effects of exercise training and should be taken into account when examining aerobic response after transplantation.

Anaerobic Threshold↗

The sensitivity of high-resolution CT in detecting idiopathic pulmonary fibrosis proved by open lung biopsy. A prospective study.

OBJECTIVES: To assess the sensitivity of high-resolution chest computed tomography (HRCT) in detecting idiopathic pulmonary fibrosis proved by biopsy specimen. To determine the degree of physiologic and pathologic abnormalities in patients with idiopathic pulmonary fibrosis who have a false-negative HRCT. DESIGN: Prospective 2-year study. SETTING: Tertiary care university hospital. PATIENTS: All patients with dyspnea and suspected interstitial lung disease referred to the University of Michigan for enrollment in the Idiopathic Pulmonary Fibrosis Specialized Center of Research (SCOR) protocol were included; 25 underwent open lung biopsy and formed the final study group. MEASUREMENTS: All patients underwent physiologic (pulmonary function, gas exchange, and exercise testing), radiologic (chest x-ray film and HRCT), and pathologic assessments (bronchoscopic and open lung biopsy). The results of HRCT were prospectively compared with results of standard pulmonary function tests, cardiopulmonary exercise testing, and open lung biopsy. RESULTS: Of 25 patients who had both HRCT and open lung biopsy, 3 patients (12%) had HRCTs that demonstrated no evidence of interstitial lung disease. These three patients had less severe disease based on clinical, radiographic, and physiologic (CRP) scores, gas exchange abnormalities, and pathologic scoring of open lung biopsy specimens, compared with those with an abnormal HRCT. CONCLUSION: We conclude that in the evaluation of patients with dyspnea and abnormal results of pulmonary function studies, a normal HRCT does not exclude early and clinically significant interstitial lung disease. In our patient population, physiologic testing was more sensitive than HRCT in detecting mild abnormalities in patients with idiopathic pulmonary fibrosis proved by biopsy specimen.

Adult↗

Preoperative examination of lung transplant candidates: value of chest CT compared with chest radiography.

OBJECTIVE: The purpose of our study was to determine the usefulness of CT in examining candidates for lung transplantation to detect cancer not visible on plain chest radiographs (a finding that would exclude a patient from transplantation) and to determine which lung is more severely diseased to aid in the decision of which side to transplant. MATERIALS AND METHODS: We reviewed the chest radiographs and CT scans of 190 transplant candidates during a 3-year period for findings suggestive of neoplasm, including lung nodules and atelectasis; we also reviewed the symmetry of disease. In the latter category, patients with primary pulmonary hypertension, Eisenmenger's complex (pulmonary vascular, not parenchymal, disease), and cystic fibrosis (for which bilateral transplantation is performed) were excluded. A total of 190 plain chest radiographs, 180 thin-section CT scans, and 31 standard CT scans were reviewed retrospectively. RESULTS: Plain chest radiographs revealed 20 noncalcified nodules; 13 were 8 mm or more in diameter, and 7 were less than 8 mm. CT scans revealed 66 noncalcified nodules; 37 were 8 mm or more in diameter, and 29 were less than 8 mm. Eight non-calcified nodules seen on plain chest radiographs were either absent on CT scans (and follow-up plain chest radiographs) or appeared calcified on CT scans. Solitary nodules in three patients proved to be bronchogenic carcinomas; two of these lesions were identified only on CT scans. CT prompted a change in the determination of which lung was more severely diseased from that made on the basis of plain radiography for 27 of 169 patients (16%) evaluated. Of the 45 patients who subsequently underwent transplantation, CT prompted a change in the determination of which side to transplant from that made on the basis of plain radiography for 4 patients (9%). CONCLUSION: CT provides additional information to supplement plain radiography in the examination of lung transplant candidates. This information can alter patient management, particularly when bronchogenic carcinoma is detected, and enable a better determination of which lung is more severely diseased to aid in the decision of which lung to transplant for single-lung transplantation.

Adolescent↗

High-resolution CT detection of lacerations in the transplanted lung after transbronchial biopsy.

Relatively large tissue samples may be obtained from the lung with the "Alligator" biopsy forceps. We report the radiographic and high-resolution computed tomography (HRCT) appearances of six pulmonary lacerations in the transplanted lungs of three asymptomatic patients after transbronchial biopsy with this large caliber biopsy forceps. All patients had undergone transbronchial biopsy from 4 to 10 days before HRCT that was performed as part of routine surveillance after transplantation. The site and histopathologic findings of lung biopsies and negative microbiologic studies on bronchoalveolar washings correlated accurately with each pulmonary lesion seen. Laceration size varied from 9 to 20 mm (mean 14 mm) on HRCT. A thickened wall or surrounding alveolar reaction related to bronchoalveolar lavage or biopsy-induced hemorrhage was seen in five lesions. These simulated the appearance of lung abscess or invasive fungal disease. Only nonspecific alveolar opacities were noted on chest radiographs. The Alligator biopsy forceps may cause pulmonary lacerations in transplanted lungs that are detectable on HRCT but not on chest radiographs. Differentiation from opportunistic infection by CT criteria alone is difficult in these immunocompromised patients. CT studies in this population should be performed prior to transbronchial biopsy whenever possible.

Adult↗

High-fructose feeding elicits insulin resistance, hyperinsulinism, and hypertension in normal mongrel dogs.

To determine whether chronic high-fructose feeding causes insulin resistance and hypertension in normal dogs, we fed 10 male dogs a normosodic diet containing 60% of the calories as fructose for 20 to 28 days; a control group of 8 dogs was fed a similar diet containing dextrose instead of fructose. In the fructose-fed group, (1) fasting triglyceridemia increased from 35.3 +/- 0.63 to 91.9 +/- 11.55 mg/dL after 25 days (P < .001); (2) fasting insulinemia increased from 19.0 +/- 1.9 to 58.9 +/- 7.22 microU/mL after 25 days (P < .001); (3) insulin resistance, which was estimated by steady-state glycemia during an insulin suppression test, increased from 105.8 +/- 21.5 to 187.8 +/- 32.6 mg/dL after 15 days (P < .001), whereas steady-state insulinemia did not change; (4) mean arterial pressure increased from 100.4 +/- 1.6 to 122.6 +/- 2.3 mm Hg after 28 days (P < .01); and (5) cumulative sodium balance was increased on days 7 through 11 (111.60 +/- 4.44 mEq on day 8, P < .01), returning to normal for the rest of the experiment. All these parameters were similar between the fructose-fed and dextrose-fed groups before the diets were started and remained constant in the dextrose-fed group. Neither group showed any change in body weight, fasting plasma glucose, atrial natriuretic factor, or endothelin-1 levels. We conclude that chronic high-fructose feeding elicits hypertriglyceridemia, insulin resistance, hyperinsulinemia, hypertension, and a transient sodium retention in dogs without fostering fasting hyperglycemia or weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Limitations of spirometry in detecting rejection after single-lung transplantation.

Pulmonary function testing has been extensively studied in the heart-lung transplant (HLT) population and has been advocated as a screening test for rejection or infection; however, few data are available in the single-lung transplant (SLT) population. The effect of acute episodes of infection, rejection, and bronchiolitis on the pulmonary function of 30 SLT patients with varying underlying disease states was prospectively evaluated. The native disease process was obstructive in 17 (SLT-OBS), restrictive in six (SLT-IPF), and pulmonary vascular in seven (SLT-PVD). Rejection was associated with a drop in FVC from 71 +/- 15 to 62 +/- 14% of predicted, with a significant drop seen in all three subgroups. Statistically significant drops in FEV1 were also seen in the SLT-OBS and SLT-PVD subgroups but not in the SLT-IPF subgroup. A drop in FEV25-75% was seen only in SLT-PVD. The greatest fall in FVC, FEV1, and FEF25-75% was seen with bronchiolitis, followed by acute rejection. The sensitivity and specificity of spirometry as a predictor of infection or rejection were significantly lower than those previously reported for HLT, with SLT-PVD having the most and SLT-OBS the least clinically useful values. We conclude that a fall in spirometry is seen in infection and rejection in SLT and that the underlying disease state has a significant influence on the diagnostic utility of specific spirometric indices.

Adult↗

Graded comprehensive cardiopulmonary exercise testing in the evaluation of dyspnea unexplained by routine evaluation.

The evaluation of dyspnea is problematic when a cause is inapparent after initial diagnostic studies. We examined the results and role of cardiopulmonary exercise testing (CPET) in 50 patients with a mean 23 months of dyspnea and normal FEV1 and FVC. The CPET studies were interpreted by a panel and a consensus reached. Subsequent tests ordered by the primary physician were reviewed, and a final diagnosis was agreed on by the panel. Seven of 50 patients had cardiac limitation, 17 of 50 had pulmonary limitation, 14 of 50 had obesity and/or deconditioning, 1 of 50 had gastroesophageal reflux, and 16 of 50 had either psychogenic dyspnea or no identifiable disease. Five patients had more than one clinical diagnosis accounting for 55 diagnoses in the 50 patients. Those with a normal CPET had a higher VO2max and O2 pulse than those with cardiac disease, deconditioning, or hyperactive airways disease (HAD) (p < 0.05). Electrocardiographic changes identified cardiac disease while studies demonstrating ventilatory limitation identified a pulmonary process. In 24, deconditioning could not be distinguished from cardiac limitation. Of these, 14 responded to exercise training and/or weight loss, whereas 3 had cardiac disease, 7 had HAD, and 4 had psychogenic dyspnea (4 had more than one clinical diagnosis). In the 13 patients with normal CPET results, one had gastroesophageal reflux, two had HAD, four had psychogenic dyspnea, and six had no identifiable disease. We conclude that a diagnosis can be made in most patients with chronic dyspnea; however, further studies including bronchoprovocation are often required. Cardiopulmonary exercise testing is useful in identifying a cardiac or pulmonary process, but it is insensitive in distinguishing cardiac disease from deconditioning.

Adult↗

Dyspnea in a patient years after severe poliomyelitis. The role of cardiopulmonary exercise testing.

Dyspnea after polio can occur for a variety of reasons, including neuromuscular disease and upper airway abnormalities resulting from prolonged intubation, including tracheal stenosis, tracheomalacia, and vocal cord paralysis. Routine studies such as spirometry and maximum voluntary ventilation (MVV) measurements can give similar results in these conditions. We present a 50-year-old woman who as a child developed poliomyelitis that required tracheostomy and negative pressure ventilation. Thirty-nine years later, she developed breathlessness with normal spirometry but decreased MVV. The flow volume loop showed flattening of the inspiratory and expiratory limbs, consistent with a fixed upper airway obstruction or neuromuscular weakness. Exercise testing with measurement of exercise flow volume loops and respiratory pressures was performed. The patient was ventilatory limited with increasing end-expiratory lung volume through exercise. Flow volume loops confirmed flow limitation. Respiratory pressures did not change after maximal exercise. Further evaluation confirmed left vocal cord paralysis and tracheomalacia. This patient demonstrates that the causes of dyspnea after poliomyelitis can be multifactorial, and that routine evaluation may fail to elucidate the limiting factor. In this case, exercise testing provided valuable insight into the limiting factor for this patient and provided useful data for counseling and for further management.

Anaerobic Threshold↗

Recurrence of sarcoidosis following bilateral allogeneic lung transplantation.

We report the first case of recurrent sarcoidosis manifested by clinical symptoms, radiographic abnormalities, and pathologic changes in a patient following sequential double allogeneic lung transplantation. A 40-year-old male patient underwent bilateral allogeneic lung transplantation for end-stage pulmonary sarcoidosis. Thirteen months posttransplantation, he developed fatigue, shortness of breath, and bilateral upper lobe pulmonary infiltrates. Transbronchial biopsy specimens revealed noncaseating granulomata. The patient's symptoms and radiographic abnormalities resolved with an increased dose of oral prednisone.

Adult↗

Increased resistance of hygroscopic condenser humidifiers when using a closed circuit suction system.

OBJECTIVES: To examine a hygroscopic condenser after clinical use and to describe the interaction of a hygroscopic condenser and a closed circuit suction system used simultaneously. DESIGN: Prospective evaluation of hygroscopic condensers used clinically, and laboratory investigation of a hygroscopic condenser used with a closed circuit suction system. SETTING: Tertiary referral centers. MEASUREMENTS AND MAIN RESULTS: The hygroscopic condenser used during mechanical ventilation was removed and peak inflation pressure was measured by delivering a standard tidal volume and inspiratory flow across the isolated hygroscopic condenser while recording the peak inflation pressure. In the laboratory, four 10-mL aliquots of saline were instilled via closed circuit suction system into a test lung with fresh hygroscopic condensers (n = 15) inline. At baseline and after each instillation, the hygroscopic condenser was weighed and the peak inflation pressure was measured while in five condensers, peak expiratory flow rate was also measured. In these five devices, hygroscopic condenser resistance was measured with 100 L/min of constant gas flow while measuring the pressure drop across the hygroscopic condenser. In 11 hygroscopic condensers used for 27.5 +/- 11.9 hrs with no closed circuit suction system, the peak inflation pressure was 3.74 +/- 0.58 cm H2O. In the laboratory, instillation of saline via closed circuit suction system was associated with an increase in hygroscopic condenser weight. Peak inflation pressure increased in a quadratic fashion with the increase in hygroscopic condenser weight, while peak expiratory flow rate decreased in a linear fashion. After four saline instillations, hygroscopic condenser resistance increased from 5.66 +/- 0.31 to 13.9 +/- 2.42 cm H2O/L/sec. CONCLUSIONS: Clinical use of a hygroscopic condenser alone is not associated with a significant increase in peak inflation pressure. We caution the use of a hygroscopic condenser and a closed circuit suction system simultaneously, as an increase in hygroscopic condenser resistance may develop and may be poorly tolerated in patients with marginal ventilatory reserve.

Aged↗

Pleuropulmonary manifestations of systemic lupus erythematosus.

The pleuropulmonary manifestation of systemic lupus erythematous (SLE) are pleuritis, acute lupus pneumonitis, chronic interstitial lung disease with fibrosis, alveolar hemorrhage, respiratory muscle and diaphragmatic dysfunction, atelectasis, bronchiolitis obliterans, pulmonary vascular disease with pulmonary hypertension, and pulmonary embolism. This article reviews these specific pleuropulmonary consequences of SLE while focusing on clinical, pathologic, and therapeutic considerations.

Bronchiolitis Obliterans↗

Pulmonary function in single lung transplantation for chronic obstructive pulmonary disease.

The primary determinants of pulmonary function after heart-lung or double lung transplantation are the volume and compliance of the recipient's thoracic cage. This study evaluated the influence of recipient chest wall factors on static and dynamic lung volumes after single lung transplantation for chronic obstructive pulmonary disease. Fourteen patients with chronic obstructive pulmonary disease received 15 single lung transplants (one retransplant). Posttransplantation follow-up data at 3 and 6 months, in the absence of infection or rejection, were available in nine patients. Overall pulmonary function at 6 months improved from preoperative levels to 55% to 65% of predicted values (forced vital capacity 38% to 55%, forced expiratory volume at 1 second 18% to 55%, maximum voluntary ventilation 21% to 65%), and allograft-specific pulmonary function improved to nearly normal predicted single-lung values (forced vital capacity 89%, forced expiratory volume at 1 second 90%, maximum voluntary ventilation 105%). Postoperative pulmonary function in these patients correlated significantly with preoperative thoracic volume measured by planimetry of chest radiographs. No correlation between postoperative pulmonary function was demonstrated with either the estimated volume of donated lung tissue or relative donor-to-recipient size matching. These findings support the concept that recipient chest wall factors determine postoperative pulmonary function in patients undergoing single lung transplantation for chronic obstructive pulmonary disease. Furthermore, the allograft lung functions at a normal level for the recipient and does not appear to be constrained by hyperinflation of the contralateral lung.

Adult↗