- Critical Care Medicine
- Pulmonology (Lung) and Critical Care
- Internal Medicine
Professor - Med Center Line, Medicine - Pulmonary & Critical Care Medicine
Medical Director, Stanford Medical Center Respiratory Care Services, Stanford Medical Center (2004 - Present)
Medical Director, Stanford Medical Center Transfer Center, Stanford Medical Center (2003 - Present)
Clinical Chief, Pulmonary and Critical Care Medicine Division, Department of Medicine (2010 - Present)
Internship:University of Connecticut-School of Medicine (1982) CT
Fellowship:UCSF Medical Center (1991) CA
Residency:Va Medical Center - Boston (1985) MA
Board Certification: Internal Medicine, American Board of Internal Medicine (1984)
Residency:Boston University Medical Center/Framington (1984) MA
Medical Education:University of Washington School of Medicine (1981) WA
MD, University of Washington, Medicine (1981)
Current Research and Scholarly Interests
We have an active collaborative project examining basic and clinical aspects of non-tuberculous mycobacterial (NTM) lung infection in non-immune compromised adults. Studies have examined possible cellular immune mechanisms for increased susceptibility to these infections, and are also investigating aspects of optimal diagnosis and treatment. In addition, a clinical and translational research program is investigating the causes and genetic factors underlying the evolution of bronchiectasis. Projects include genetic susceptibility in bronchiectasis, as well as therapy projects for adults with pulmonary NTM infections.
Safety and Efficacy of Saracatinib In Subjects With Lymphangioleiomyomatosis
This study is being done to determine if there is a potential benefit of saracatinib in LAM subjects. Based on the information of this trial, additional clinical development trials will be needed. The study will also test the tolerability of 125 mg of saracatinib given once daily over a 9 month period.
- 3B. Personal History: Have You Ever Had Excessive Shortness of Breath or Fatigue with Exercise beyond What Is Expected for Your Level of Fitness? CURRENT SPORTS MEDICINE REPORTS 2015; 14 (3): 259-260
Acute cellular insulin resistance and hyperglycemia associated with hypophosphatemia after cardiac surgery.
A & A case reports
2015; 4 (2): 22-25
Successful glycemic control reduces morbidity and mortality in cardiac surgery patients. Protocols that include insulin infusions are commonly followed to achieve target blood glucose levels. Insulin resistance has been reported and linked to low serum phosphate levels in animal models and studies in diabetic outpatients, but not in postoperative patients. The following case series is a retrospective observational review of 8 cardiac surgery patients who developed insulin resistance early after surgery; this resistance was reversed by correcting serum hypophosphatemia. We discuss the multiple underlying mechanisms causing hypophosphatemia.
View details for DOI 10.1213/XAA.0000000000000112
View details for PubMedID 25611002
Diagnosing invasive fungal disease in critically ill patients
CRITICAL REVIEWS IN MICROBIOLOGY
2011; 37 (4): 277-312
Fungal infections are increasing, with a changing landscape of pathogens and emergence of new groups at risk for invasive disease. We review current diagnostic techniques, focusing on studies in critically ill patients. Microbiological cultures, the current "gold standard", demonstrate poor sensitivity, thus diagnosis of invasive disease in the critically ill is difficult. This diagnostic dilemma results in under- or over-treatment of patients, potentially contributing to poor outcomes and antifungal resistance. While other current diagnostic tests perform moderately well, many lack timeliness, efficacy, and are negatively affected by treatments common to critically ill patients. New nucleic acid-based research is promising.
View details for DOI 10.3109/1040841X.2011.581223
View details for Web of Science ID 000295616800001
View details for PubMedID 21749278
The International LAM Registry: A Component of an Innovative Web-Based Clinician, Researcher, and Patient-Driven Rare Disease Research Platform
LYMPHATIC RESEARCH AND BIOLOGY
2010; 8 (1): 81-87
A relative inability to capture a sufficiently large patient population in any one geographic location has traditionally limited research into rare diseases.Clinicians interested in the rare disease lymphangioleiomyomatosis (LAM) have worked with the LAM Treatment Alliance, the MIT Media Lab, and Clozure Associates to cooperate in the design of a state-of-the-art data coordination platform that can be used for clinical trials and other research focused on the global LAM patient population. This platform is a component of a set of web-based resources, including a patient self-report data portal, aimed at accelerating research in rare diseases in a rigorous fashion.Collaboration between clinicians, researchers, advocacy groups, and patients can create essential community resource infrastructure to accelerate rare disease research. The International LAM Registry is an example of such an effort. 82.
View details for DOI 10.1089/lrb.2009.0028
View details for Web of Science ID 000277870500011
View details for PubMedID 20235890
Tuberculosis in Liver Transplant Recipients: A Systematic Review and Meta-Analysis of Individual Patient Data
2009; 15 (8): 894-906
Mycobacterium tuberculosis (MTB) causes substantial morbidity and mortality in liver transplant recipients. We examined the efficacy of isoniazid latent Mycobacterium tuberculosis infection (LTBI) treatment in liver transplant recipients and reviewed systematically all cases of active MTB infection in this population. We found 7 studies that evaluated LTBI treatment and 139 cases of active MTB infection in liver transplant recipients. Isoniazid LTBI treatment was associated with reduced MTB reactivation in transplant patients with latent MTB risk factors (0.0% versus 8.2%, P = 0.02), and isoniazid-related hepatotoxicity occurred in 6% of treated patients, with no reported deaths. The prevalence of active MTB infection in transplant recipients was 1.3%. Nearly half of all recipients with active MTB infection had an identifiable pretransplant MTB risk factor. Among recipients who developed active MTB infection, extrapulmonary involvement was common (67%), including multiorgan disease (27%). The short-term mortality rate was 31%. Surviving patients were more likely to have received 3 or more drugs for MTB induction therapy (P = 0.003) and to have been diagnosed within 1 month of symptom onset (P = 0.01) and were less likely to have multiorgan disease (P = 0.01) or to have experienced episodes of acute transplant rejection (P = 0.02). Compared with the general population, liver transplant recipients have an 18-fold increase in the prevalence of active MTB infection and a 4-fold increase in the case-fatality rate. For high-risk transplant candidates, isoniazid appears safe and is probably effective at reducing MTB reactivation. All liver transplant candidates should receive a tuberculin skin test, and isoniazid LTBI treatment should be given to patients with a positive skin test result or MTB pretransplant risk factors, barring a specific contraindication. Liver Transpl 15:894-906, 2009. (c) 2009 AASLD.
View details for DOI 10.1002/lt.21709
View details for Web of Science ID 000268739200010
View details for PubMedID 19642133
Successful pregnancy and cesarean delivery via noninvasive ventilation in mitochondrial myopathy
JOURNAL OF PERINATOLOGY
2009; 29 (2): 166-167
We report a case study of a 22-year-old woman with mitochondrial thymidine kinase 2 deficiency and chronic respiratory failure due to severe neuromuscular weakness requiring noninvasive positive pressure ventilation (NIPPV) since 12 years of age. During pregnancy and cesarean delivery, she was successfully supported with NIPPV. A multidisciplinary team approach should be used in pregnant patients with these disorders with specific attention to management of pulmonary complications, selection of route of delivery, anesthesia, and analgesia.
View details for DOI 10.1038/jp.2008.178
View details for Web of Science ID 000263492700016
View details for PubMedID 19177045
Coexistence of primary adenocarcinoma of the lung and Tsukamurella infection: a case report and review of the literature.
Journal of medical case reports
2008; 2: 207-?
A major diagnostic challenge in the evaluation of a cavitary lung lesion is to distinguish between infectious and malignant etiologies.We present the case of an elderly man presenting with fever, hemoptysis and a left upper lobe cavitary lesion. Serial sputum cultures grew Tsukamurella pulmonis, a rare pathogen associated with cavitary pneumonia in immunocompromised patients. However, despite clinical improvement with antibiotic therapy targeted to the organism, concomitant discovery of a papillary thyroid carcinoma led to a needle biopsy of the cavitary lesion, which showed evidence of primary lung adenocarcinoma.This is the first description of Tsukamurella infection in the setting of primary lung carcinoma. The report also illustrates the potential complex nature of cavitary lesions and emphasizes the need to consider the coexistence of malignant and infectious processes in all patients, especially those with risk factors for malignancy that fail to improve on antibiotic therapy.
View details for DOI 10.1186/1752-1947-2-207
View details for PubMedID 18554413
The safety and effects of the beta-blocker, nadolol, in mild asthma: An open-label pilot study
PULMONARY PHARMACOLOGY & THERAPEUTICS
2008; 21 (1): 134-141
Beta-blockers are currently contraindicated in asthma because their acute administration may be associated with worsening bronchospasm. However, their effects and safety with their chronic administration are not well evaluated. The rationale for this pilot study was based on the paradigm shift that was observed with the use of beta-blockers in congestive heart failure, which once contraindicated because of their acute detrimental effects, have now been shown to reduce mortality with their chronic use. We hypothesized that certain beta-blockers may also be safe and useful in chronic asthma therapy. In this prospective, open-label, pilot study, we evaluated the safety and effects of escalating doses of the beta-blocker, nadolol, administered over 9 weeks to 10 subjects with mild asthma. Dose escalation was performed on a weekly basis based on pre-determined safety, lung function, asthma control and hemodynamic parameters. The primary objective was to evaluate safety and secondary objectives were to evaluate effects on airway hyperresponsiveness, and indices of respiratory function. The escalating administration of nadolol was well tolerated. In 8 out of the 10 subjects, 9 weeks of nadolol treatment produced a significant, dose-dependent increase in PC20 that reached 2.1 doubling doses at 40 mg (P<0.0042). However, there was also a dose-independent 5% reduction in mean FEV1 over the study period (P<0.01). We conclude that in most patients with mild asthma, the dose-escalating administration of the beta-blocker, nadolol, is well tolerated and may have beneficial effects on airway hyperresponsiveness. Our findings warrant further testing in future larger trials.
View details for DOI 10.1016/j.pupt.2007.07.002
View details for Web of Science ID 000262943300020
View details for PubMedID 17703976
Lung transplantation in the management of patients with lymphangioleiomyomatosis: Baseline data from the NHLBI LAM registry
JOURNAL OF HEART AND LUNG TRANSPLANTATION
2007; 26 (12): 1293-1299
In 1997, the National Heart, Lung, and Blood Institute of the National Institutes of Health established a Registry to better characterize the demographic, clinical, physiologic and radiographic features of patients with lymphangioleiomyomatosis (LAM). Herein we report data collected at enrollment from patients who had either undergone transplant prior to enrollment, underwent transplant during the 5-year study, or were evaluated/wait-listed for lung transplant during the 5-year study.The LAM Registry enrolled patients from six clinical centers between August 1998 and October 2001. On entry, patients filled-out questionnaires covering their medical history, symptoms, treatment and quality of life (SF-36 and St. George's Respiratory Questionnaire). Enrollees underwent blood laboratory work and testing for arterial blood gases and pulmonary function. Follow-up was done at 6-month and/or yearly intervals. Diagnoses were confirmed by biopsy or typical clinical presentation plus computerized tomography (CT) findings confirmed by independent expert radiologists. A total of 243 women were enrolled. Of these, 13 (5.3%) had been transplanted at time of entry (Group A), 21 (8.6%) were transplanted during the study (Group B), and 48 (19.8%) were either wait-listed for transplant or underwent evaluation after enrollment during the study period (Group C). The remaining 161 (66.3%) registrants were neither considered for nor listed for transplant during the Registry period (Group D).One-third of patients in a large sample of LAM patients had either been transplanted or were being considered for transplant. At enrollment, patients who had already been transplanted and those not in need of transplant (Groups A and D) had better pulmonary function and quality-of-life scores compared with patients who subsequently underwent lung transplant during the Registry period (Group B).In this large Registry of LAM patients, lung transplantation appears to be associated both with significantly improved lung function and quality of life compared with patients with advanced disease.
View details for DOI 10.1016/j.healun.2007.09.013
View details for Web of Science ID 000251993500010
View details for PubMedID 18096481
Aerosolized amikacin for treatment of pulmonary Mycobacterium avium infections: an observational case series.
BMC pulmonary medicine
2007; 7: 2-?
Current systemic therapy for nontuberculous mycobacterial pulmonary infection is limited by poor clinical response rates, drug toxicities and side effects. The addition of aerosolized amikacin to standard oral therapy for nontuberculous mycobacterial pulmonary infection may improve treatment efficacy without producing systemic toxicity. This study was undertaken to assess the safety, tolerability and preliminary clinical benefits of the addition of aerosolized amikacin to a standard macrolide-based oral treatment regimen.Six HIV-negative patients with Mycobacterium avium intracellulare pulmonary infections who had failed standard therapy were administered aerosolized amikacin at 15 mg/kg daily in addition to standard multi-drug macrolide-based oral therapy. Patients were monitored clinically and serial sputum cultures were obtained to assess response to therapy. Symptomatic improvement with radiographic stabilization and eradication of mycobacterium from sputum were considered markers of success. Of the six patients treated with daily aerosolized amikacin, five responded to therapy. All of the responders achieved symptomatic improvement and four were sputum culture negative after 6 months of therapy. Two patients became re-infected with Mycobacterium avium intracellulare after 7 and 21 months of treatment. One of the responders who was initially diagnosed with Mycobacterium avium intracellulare became sputum culture positive for Mycobacterium chelonae resistant to amikacin after being on intermittent therapy for 4 years. One patient had progressive respiratory failure and died despite additional therapy. There was no evidence of nephrotoxicity or ototoxicity associated with therapy.Aerosolized delivery of amikacin is a promising adjunct to standard therapy for pulmonary nontuberculous mycobacterial infections. Larger prospective trials are needed to define its optimal role in therapy of this disease.
View details for PubMedID 17319962
Prospective analysis of cystic fibrosis transmembrane regulator mutations in adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection
2006; 130 (4): 995-1002
Bronchiectasis and pulmonary infection with nontuberculous mycobacteria (NTM) may be associated with disease-causing mutations in the cystic fibrosis transmembrane regulator (CFTR).Fifty adult patients at Stanford University Medical Center with a diagnosis of bronchiectasis and/or pulmonary NTM infection were prospectively characterized by sweat chloride measurement, comprehensive mutational analysis of CFTR, and sputum culture results.A de novo diagnosis of cystic fibrosis (CF) was established in 10 patients (20%). Patients with CF were more likely than those without CF to have mucus plugging seen on chest high-resolution CT, and women with a CF diagnosis were thinner, with a significantly lower mean body mass index than the non-CF subjects. Thirty CFTR mutations were identified in 24 patients (50% prevalence). Sweat chloride concentration was elevated > 60 mEq/dL (diagnostic of CF) in seven patients (14%), and from 40 to 60 mEq/dL in eight patients (16%). The frequency of CFTR mutations was elevated above that expected in the general population: heterozygous DeltaF508 (12% vs 3%), R75Q (14% vs 1%), and intron 8 5T (17% vs 5 to 10%). Other known CFTR mutations identified were V456A, G542X, R668C, I1027T, D1152, R1162L, W1282X, and L183I. Three novel CFTR mutations were identified: A394V, F650L, and C1344S.Mutations in CFTR that alter RNA splicing and/or functional chloride conductance are common in this population, and are likely to contribute to the susceptibility and pathogenesis of adult bronchiectasis and pulmonary NTM infection. Careful clinical evaluation for disease cause should be undertaken in this clinical context.
View details for DOI 10.1378/chest.130.4.995
View details for Web of Science ID 000241265700014
View details for PubMedID 17035430
Factors related to response to intermittent treatment of Mycobacterium avium complex lung disease
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
2006; 173 (11): 1283-1289
Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate. Objectives: To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin.A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000-2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-gamma treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed.Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5-11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7-9.2) and HRCT response by 4.9 times (95% CI, 1.9-13.0). Culture response was 1.5 times (95% CI, 1.1-2.2) higher for older subjects and 2.2 times (95% CI, 1.0-4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1-5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7-11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0-2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times.TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.
View details for DOI 10.1164/rccm.200509-1531OC
View details for Web of Science ID 000237990100018
View details for PubMedID 16514112
Recurrence of pulmonary intravascular bronchoalveolar tumor with mediastinal metastasis 20 years later
2006; 100 (2): 367-370
Pulmonary intravascular bronchoalveolar tumor (IVBAT) also recognized as pulmonary epithelioid hemangioendothelioma, is a rare malignant vascular tumor of unknown etiology. IVBAT is a tumor of multicentric origin and the lungs are rarely involved, with only about 60 cases of pulmonary IVBAT described in the literature. The prognosis is unpredictable, with life expectancy ranging from 1 to 15 years. We report an unusual case of pulmonary IVBAT that recurred in the lung with metastasis to the mediastinum.
View details for DOI 10.1016/j.rmed.2005.05.010
View details for Web of Science ID 000235243000024
View details for PubMedID 15990286
The NHLBI lymphangioleiomyomatosis registry - Characteristics of 230 patients at enrollment
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
2006; 173 (1): 105-111
Pulmonary lymphangioleiomyomatosis is a progressive cystic lung disease that is associated with infiltration of atypical smooth muscle-like cells. Previous descriptions of clinical characteristics of subjects with lymphangioleiomyomatosis have been based on a limited number of patients.To describe the clinical characteristics of subjects with pulmonary lymphangioleiomyomatosis, both sporadic and tuberous sclerosis-related forms.Over a 3-yr period, from 1998 to 2001, 243 subjects with pulmonary lymphangioleiomyomatosis were enrolled into a national registry; 13 subjects who had already undergone lung transplantation were excluded for the purposes of this report.All 230 subjects were women, aged 18 to 76 yr (mean +/- SE, 44.5 +/- 0.65 yr). The average age at onset of symptoms was 38.9 +/- 0.73 yr and at diagnosis was 41.0 +/- 0.65 yr. Tuberous sclerosis complex was present in 14.8% of subjects. Pulmonary manifestations, most commonly spontaneous pneumothorax, were the primary events leading to the diagnosis in 86.5% of cases. Nearly 55% of the subjects were being treated with a progesterone derivative. An obstructive pattern on pulmonary function testing was observed in 57.3% of the subjects, whereas 33.9% had normal spirometric results. Women with tuberous sclerosis-related lymphangioleiomyomatosis were younger and had less impaired lung function compared with those with the sporadic form.The age range of women afflicted with pulmonary lymphangioleiomyomatosis is broader than previously appreciated and the degree of pulmonary function can be quite variable, with one-third of subjects having normal spirometry at enrollment into this registry.
View details for DOI 10.1164/rccm.200409-1298OC
View details for Web of Science ID 000234520400017
View details for PubMedID 16210669
A multiparameter wearable physiologic monitoring system for space and terrestrial applications
IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE
2005; 9 (3): 382-391
A novel, unobtrusive and wearable, multiparameter ambulatory physiologic monitoring system for space and terrestrial applications, termed LifeGuard, is presented. The core element is a wearable monitor, the crew physiologic observation device (CPOD), that provides the capability to continuously record two standard electrocardiogram leads, respiration rate via impedance plethysmography, heart rate, hemoglobin oxygen saturation, ambient or body temperature, three axes of acceleration, and blood pressure. These parameters can be digitally recorded with high fidelity over a 9-h period with precise time stamps and user-defined event markers. Data can be continuously streamed to a base station using a built-in Bluetooth RF link or stored in 32 MB of on-board flash memory and downloaded to a personal computer using a serial port. The device is powered by two AAA batteries. The design, laboratory, and field testing of the wearable monitors are described.
View details for DOI 10.1109/TITB.2005.854509
View details for Web of Science ID 000231747500010
View details for PubMedID 16167692
Smoking cessation: techniques and potential benefits.
Thoracic surgery clinics
2005; 15 (2): 189-194
Smokers have a significantly greater risk of complications during and after operations. Cigarette smoke has significant effects on cardiac function, circulation, and respiratory function. Preliminary studies suggest that smoking cessation for a minimum of 6 to 8 weeks before surgery is required to reduce the perioperative and postoperative risks of smoking. Smoking cessation programs that employ advice, support groups, nicotine replacement therapy, or some anti-depressants have been used successfully in many situations and should be used to discourage smoking preoperatively. Further research is needed, however, to clarify the best approach to smoking cessation for surgical patients.
View details for PubMedID 15999516
Recurrence of pulmonary intravascular bronchoalveolar tumor with mediastinal metastasis 20 years later
AMER COLL CHEST PHYSICIANS. 2004: 961S-961S
View details for Web of Science ID 000224731400736
A dose-response study of acetazolamide for acute mountain sickness prophylaxis in vacationing tourists at 12,000 feet (3630 m)
HIGH ALTITUDE MEDICINE & BIOLOGY
2004; 5 (1): 33-39
The study objective was to determine whether acetazolamide is effective in prophylaxis of acute mountain sickness (AMS) at moderate altitude in ambulatory travelers not undergoing vigorous exercise. Volunteers vacationing in La Paz, Bolivia (3630 m), immediately after arrival from sea level were studied. The design was a double-blind, randomized trial of two doses of acetazolamide (125 mg twice daily, 250 mg twice daily) versus placebo twice daily over a 24-h period. The main outcome measure was AMS score and score trend, using the Lake Louise consensus questionnaire. Nine of 32 subjects (28%) had symptom scoring diagnostic of AMS at 0 h. At 0 and 24 h (respectively), the mean Lake Louise scores were 1.73 and 1.09 for the 11 subjects receiving placebo, 1.45 and 1.36 for the 11 subjects receiving the 125-mg dose, and 2.7 and 0.6 for the 11 subjects receiving the 250-mg dose. The absolute change in these mean scores was not significant for placebo (p = 0.21) or the 125-mg dose (p = 0.88), but was significant for the 250-mg dose (p = 0.008). A comparison of a difference in decline in average AMS score over time showed a statistically significant decline for the 250-mg dosing group versus placebo (p = 0.002). The 250-mg dose of acetazolamide twice daily (but not 125 mg twice daily) was effective in inducing a significant decline in AMS symptoms over the 24-h period after arrival to 3630 m. These results suggest that the dosing of acetazolamide for AMS prevention in nonmountaineering tourists at altitudes below 3700 m should not be lowered below 250 mg twice daily.
View details for Web of Science ID 000220869500005
View details for PubMedID 15072715
- Acute respiratory failure with thrombocytopenia in a 47-year-old woman after hiking in the Sierras CHEST 2003; 124 (2): 754-757
- Cellulose granulomatosis presenting as centrilobular nodules: CT and histologic findings AMERICAN JOURNAL OF ROENTGENOLOGY 2001; 177 (5): 1151-1153
- Nasal-pulmonary relations in allergic fungal sinusitis and allergic bronchopulmonary aspergillosis CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY 2001; 21 (1): 5-15
Case report - Paclitaxel-induced hypersensitivity pneumonitis: Radiographic and CT findings
AMERICAN JOURNAL OF ROENTGENOLOGY
2001; 176 (3): 718-720
View details for Web of Science ID 000167118800027
Plasma vascular endothelial growth factor in acute mountain sickness
2000; 118 (1): 47-52
To investigate the hypothesis that an increase in circulating vascular endothelial growth factor (VEGF) occurs in mountaineers at high altitude, particularly in association with acute mountain sickness (AMS) and/or low hemoglobin oxygen saturation.: Collection of medical histories, AMS scores, plasma samples, and arterial oxygen saturation (SaO(2)) measurements from mountaineers at 1,500 feet (sea level) and at 14,200 feet.Mount McKinley ("Denali"), AK.Sixty-six mountaineers.None.Plasma VEGF at 14,200 feet was not increased in any group. In fact, plasma VEGF was significantly lower in subjects who did not develop AMS (53 +/- 7.9 pg/mL; mean +/- SEM; n = 47) compared to control subjects at sea level (98.4 +/- 14.3 pg/mL; n = 7; p = 0.005). Plasma VEGF at 14, 200 feet for subjects with AMS (62 +/- 12 pg/mL; n = 15) did not differ significantly from subjects at 14,200 feet without AMS, or from control subjects at sea level. Of a small number of subjects with paired specimens at sea level and at base camp (n = 5), subjects who exhibited a decrease in plasma VEGF at 14,200 feet were those who did not develop AMS. Neither SaO(2), prior AMS, AMS symptom scores, or acetazolamide use were correlated with plasma VEGF.Subjects at high altitude who do not develop AMS have lower plasma VEGF levels compared to control subjects at sea level. Plasma VEGF at high altitude is not elevated in association with AMS or hypoxia. Sustained plasma VEGF at altitude may reflect a phenotype more susceptible to AMS.
View details for Web of Science ID 000088284800014
View details for PubMedID 10893358
- Thoracic lymphangiomas, lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2000; 161 (3): 1037-1046
Inhalational anthrax - Epidemiology, diagnosis, and management
1999; 116 (5): 1369-1376
Anthrax, a disease of great historical interest, is once again making headlines as an agent of biological warfare. Bacillus anthracis, a rod-shaped, spore-forming bacterium, primarily infects herbivores. Humans can acquire anthrax by agricultural or industrial exposure to infected animals or animal products. More recently, the potential for intentional release of anthrax spores in the environment has caused much concern. The common clinical manifestations of anthrax are cutaneous disease, pulmonary disease from inhalation of anthrax spores, and GI disease. The course of inhalational anthrax is dramatic, from the insidious onset of nonspecific influenza-like symptoms to severe dyspnea, hypotension, and hemorrhage within days of exposure. A rapid decline, culminating in septic shock, respiratory distress, and death within 24 h is not uncommon. The high mortality seen in inhalational anthrax is in part due to delays in diagnosis. Classic findings on the chest radiograph include widening of the mediastinum as well as pleural effusions. Pneumonia is less common; key pathologic manifestations include severe hemorrhagic mediastinitis, diffuse hemorrhagic lymphadenitis, and edema. Diagnosis requires a high index of suspicion. Treatment involves supportive care in an intensive care facility and high doses of penicillin. Resistance to third-generation cephalosporins has been noted. Vaccines are currently available and have been shown to be effective against aerosolized exposure in animal studies.
View details for Web of Science ID 000083723900041
View details for PubMedID 10559102
Tick-borne pulmonary disease - Update on diagnosis and management
1999; 116 (1): 222-230
Ticks are capable of transmitting viruses, bacteria, protozoa, and rickettsiae to man. Several of these tick-borne pathogens can lead to pulmonary disease. Characteristic clinical features, such as erythema migrans in Lyme disease, or spotted rash in a spotted fever group disease, may serve as important diagnostic clues. Successful management of tick-borne diseases depends on a high index of suspicion and recognition of their clinical features. Patients at risk for tick bites may be coinfected with two or more tick-borne pathogens. A Lyme vaccine has recently become available for use in the United States. Disease prevention depends on the avoidance of tick bites. When patients present with respiratory symptoms and a history of a recent tick bite or a characteristic skin rash, a differential diagnosis of a tick-borne pulmonary disease should be considered. Early diagnosis and appropriate antibiotic therapy for these disorders lead to greatly improved outcomes.
View details for Web of Science ID 000081513200037
View details for PubMedID 10424529
Mycobacterium avium-intracellulare pulmonary infection in HIV-negative patients without preexisting lung disease - Diagnostic and management limitations
1999; 115 (4): 1033-1040
To review the experience of an outpatient pulmonary clinic with Mycobacterium avium-intracellulare (MAI) pulmonary disease in the HIV-negative population without preexisting lung disease.Retrospective clinical series.University medical center.The clinic charts of all patients who fulfilled the current American Thoracic Society criteria for MAI pulmonary infection and who had no preexisting lung disease or immunosuppression were reviewed.Of 31 patients identified, 94% were female, 90% were white, and the median age at diagnosis was 63 years. The median time interval from symptom onset to diagnosis was 10 months. Bronchiectasis or small nodules without predilection for any lobe was found in 93%. Bronchoscopy or open lung biopsy for diagnosis was required in 45% because of nondiagnostic sputum cultures. At > or = 12 months, 50% failed therapy, 86% continued to be symptomatic, and 58% did not tolerate their initial multidrug regimen.These results emphasize the observed chronic nature of MAI pulmonary disease in this population, both before diagnosis and despite therapy. The sensitivity of sputum culture in this population is low, so an aggressive diagnostic approach, including bronchoscopy, should be considered if sputum cultures are negative. Current treatments are suboptimal because of poor drug tolerance and significant failure rates. Last, the preponderance of disease in older white women argues for a genetic or acquired immune deficiency to explain disease susceptibility.
View details for Web of Science ID 000079655900026
View details for PubMedID 10208205
Diaphragmatic paralysis due to Lyme disease
EUROPEAN RESPIRATORY JOURNAL
1999; 13 (3): 700-702
Lyme disease is a tick-borne spirochaete infection which, in a proportion of patients, can lead to neuropathy. This article describes a case of diaphragmatic paralysis due to Lyme disease. A 39-yr-old male presented to the hospital because of an acute left facial palsy. Six weeks prior to admission he had developed a circular rash on his left flank during a camping holiday. He also complained of shortness of breath and arthralgia for 1 week. His chest radiograph demonstrated a raised right hemi-diaphragm. Diaphragmatic paralysis was confirmed by fluoroscopy (a positive sniff test). Serology revealed evidence of recent infection by Borrelia burgdorferi. On the basis of the patient's clinical presentation, a recent history of erythema migrans, and positive Lyme serology, a diagnosis of neuroborreliosis was made. He received oral doxycycline therapy (200 mg x day(-1)) for three weeks. Facial and diaphragmatic palsies resolved within eight weeks. On the basis of this case, a diagnosis of Lyme disease should be considered in patients from endemic regions with otherwise unexplained phrenic nerve palsy.
View details for Web of Science ID 000079849000041
View details for PubMedID 10232450
Analyses of the NRAMP1 and IFN-gamma R1 genes in women with Mycobacterium avium-intracellulare pulmonary disease
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
1998; 157 (2): 377-381
Mycobacterium avium-intracellulare (MAI) pulmonary disease causes substantial morbidity in a population of older, HIV-negative women without preexisting lung disease. The cause for disease susceptibility in these patients is unknown, although their relative phenotypic homogeneity suggests the existence of a common, subtle immune deficiency. An investigation was undertaken to determine if these patients have a defect in their natural resistance-associated macrophage protein (NRAMP1) or interferon gamma receptor 1 (IFN-gammaR1) genes. A point mutation in murine nramp, an autosomal recessive gene controlling resistance to intracellular organisms, correlates with overwhelming Mycobacterium bovis infection in mice. The corresponding region in human NRAMP1, two coding polymorphisms and one promoter NRAMP1 polymorphism, as well as two IFN-gammaR1 polymorphisms, were analyzed to determine if an allele was present to correlate with disease. Genomic DNA was purified from eight women with MAI pulmonary disease and four controls. Regions of interest were amplified by PCR; three sites were analyzed by restriction fragment length polymorphisms, and three were analyzed using denaturing high-performance liquid chromatography. The NRAMP1 promoter polymorphism of 18 additional random controls was analyzed by microsatellite sizing. No allelism was found in NRAMP1 corresponding to the murine mutation, or in the two coding regions. In the NRAMP1 promoter microsatellite, 3 of 8 patients were heterozygous for a dinucleotide sequence insertion, as were 10 of 22 controls. None of the patients had either of the two known IFN-gammaR1 mutations. In conclusion, in women with MAI pulmonary disease, there is no evidence for a genetic defect in NRAMP1 or IFN-gammaR1 to correlate with disease.
View details for Web of Science ID 000071907200004
View details for PubMedID 9476846
- Lymphangioleiomyomatosis: New insights AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 1997; 155 (4): 1183-1186
Pulmonary capillaritis and alveolar hemorrhage - Update on diagnosis and management
1996; 110 (5): 1305-1316
Pulmonary vascular inflammatory disorders may involve all components of the pulmonary vasculature, including capillaries. The principal histopathologic features of pulmonary capillaritis include capillary wall necrosis with infiltration by neutrophils, interstitial erythrocytes, and/or hemosiderin, and interalveolar septal capillary occlusion by fibrin thrombi. Immune complex deposition is variably present. Patients often present clinically with diffuse alveolar hemorrhage, which is characterized by dyspnea and hemoptysis; diffuse, bilateral, alveolar infiltrates on chest radiograph; and anemia. Pulmonary capillaritis has been reported with variable frequency and severity as a manifestation of Wegener's granulomatosis, microscopic polyarteritis, systemic lupus erythematosus, Goodpasture's syndrome, idiopathic pulmonary renal syndrome, Behçet's syndrome, Henoch-Schönlein purpura, IgA nephropathy, antiphospholipid syndrome, progressive systemic sclerosis, and diphenylhydantoin use. In addition to history, physical examination, and routine laboratory studies, certain ancillary laboratory tests, such as antineutrophil cytoplasmic antibodies, antinuclear antibodies, and antiglomerular basement membrane antibodies, may help diagnose an underlying disease. Diagnosis of pulmonary capillaritis can be made by fiberoptic bronchoscopy with transbronchial biopsy, but thoracoscopic biopsy is often employed. Since many disorders can result in pulmonary capillaritis with diffuse alveolar hemorrhage, it is crucial for clinicians and pathologists to work together when attempting to identify an underlying disease. Therapy depends on the disorder that gave rise to the pulmonary capillaritis and usually includes corticosteroids and cyclophosphamide or azathioprine. Since most diseases that result in pulmonary capillaritis are treated with immunosuppression, infection must be excluded aggressively.
View details for Web of Science ID A1996VR83500037
View details for PubMedID 8915239
THROMBIN RECEPTOR POLYMORPHISM IN CHINESE-HAMSTER
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
1995; 215 (3): 974-980
We report the existence of a new Chinese hamster thrombin receptor allele, characterized by an in-frame insertion of three nucleotides at position 250 of the published sequence. As a consequence, an additional proline is inserted into a proline-rich region of the extracellular amino-terminal domain of the receptor. A corresponding proline at this position is also found in the rat thrombin receptor. A silent base-pair change is found in the cytoplasmic tail of the receptor gene. Single-strand conformation polymorphism and sequence analysis indicate this new receptor allele is present in several cell lines derived from different individual Chinese hamsters. Embryonic CHEF IIC9 cells and primary culture cells are homozygous for this new allele. In contrast, the CCL39 lung fibroblast cell line is heterozygous for both the new and old alleles. Both alleles are transcribed into mRNA and code for functional receptors. Given the allelic distribution and sequence alignment with thrombin receptors from other species, we propose that the new sequence represents the actual predominant allele in Chinese hamster.
View details for Web of Science ID A1995TA98200027
View details for PubMedID 7488069
- Mast Cells, Basophils and Eosinophils in the Evolution of Pulmonary Fibrosis Pulmonary Fibrosis (Lung Biology in Health and Disease Series). SH Phan and R Thrall, editors. Marcel Dekker, Inc., New York 1995