Biomedical subjects
D A Cortese
Publications and source records attributed to D A Cortese.
Primary biliary cirrhosis: relation between hepatic function and pulmonary function in patients who never smoked.
We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steady-state diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sjögren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatopulmonary syndrome: an evolving perspective in the era of liver transplantation.
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Effect of bleomycin on hematoporphyrin derivative phototherapy of solid tumors.
Hematoporphyrin derivative phototherapy (HpD-PT) has been successfully used to localize and treat superficial squamous cell cancers. Bleomycin sulfate is a glycopeptide antibiotic that has antineoplastic properties against squamous cell cancers. Because both HpD-PT and bleomycin chemotherapy are accepted forms of treatment for squamous cell cancer and their cytotoxicity is mediated by singlet oxygen and oxygen radicals, we studied the possibility of enhancing the response of solid tumors to HpD-PT by combining this modality with systemic bleomycin chemotherapy in a murine tumor model. Bleomycin did not enhance HpD-PT significantly. Also, we are not confident that HpD-PT alone or in combination with other agents can eradicate solid tumors; it certainly did not in this syngeneic murine tumor model.
A prospective pilot study evaluating the effectiveness of secretory IgA measurements in bronchoalveolar lavage to detect non-small cell lung cancer.
Previous studies have described significant elevations in the concentrations of secretory immunoglobulin A (sIgA) in bronchial washings obtained from cancerous lungs. To date, there have been no prospective investigations examining the predictive value of sIgA measurements in clinically relevant settings. Our goal was to determine if measurement of sIgA in bronchoalveolar lavage (BAL) at the time of bronchoscopic evaluation of potentially malignant lung nodules might prospectively predict the presence of cancer. We observed no significant increase in the sIgA obtained from eight BALs obtained from cancerous lungs as compared with BALs taken from these same patients' contralateral cancer-free lungs. We also saw no significant difference in BAL (sIgA) obtained from patients eventually found to have cancer (N = 8) as compared with those found to have noncancer diagnoses (N = 6). In light of these findings, we think it unlikely that measurement of sIgA will be clinically useful in the diagnosis of pulmonary malignant neoplasms.
Intrapulmonary vascular dilatations (IPVD) in liver transplant candidates. Screening by two-dimensional contrast-enhanced echocardiography.
Intrapulmonary vascular dilatations (IPVD) are extrahepatic complications of acute and chronic liver disorders that can result in severe hypoxemia. Contrast-enhanced (CE) echocardiography provides a noninvasive method to detect right-to-left shunting associated with IPVD. We prospectively studied 40 consecutive liver transplant candidates to determine the relationship between CE echocardiography, arterial blood gases, and standard pulmonary function tests. Two patients had technically unacceptable results of echocardiographic studies. Thirty-eight patients had acceptable results of studies; seven (18.4 percent) of 38 were hypoxemic (PaO2 less than 70 mm Hg). Thirty-one patients (81.6 percent) had PaO2 greater than or equal to 70 mm Hg. Positive CE echocardiograms suggesting IPVD were found in five (13.2 percent) of 38. Three (9.7 percent) of the 31 patients with PaO2 greater than or equal to 70 mm Hg had positive CE echocardiograms. Two (28.6 percent) of the seven hypoxemic patients had positive CE echocardiography. Mean PaO2 and pulmonary function parameters were not significantly different between those with positive CE echocardiogram compared with those with normal CE echocardiograms. We conclude that for our group of liver transplant candidates, (1) IPVD as suggested by CE echocardiography were not uncommon (13.2 percent), and (2) positive CE echocardiography could be documented in patients who were not hypoxemic (9.7 percent).
Hepatopulmonary syndrome.
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Localization of hematoporphyrin. Derivative to human colorectal cancer.
This study documents the affinity of hematoporphyrin derivative (HpD) for human colorectal cancer by analysis of surface fluorescence. Ten patients undergoing elective surgery for primary colorectal cancer received intravenous HpD (2-5 mg/kg) either 3 or 72 hours preoperatively. Fluorescent photographs were taken of freshly resected specimens and analyzed using a computerized videodensitometric technique. This technique subtracted contaminating non-HpD fluorescence and facilitated estimation of HpD tissue levels. The HpD-specific fluorescence localized to tumors in all cases, and the mean HpD concentration was six-fold greater in malignant tissue than in surrounding normal mucosa (0.6 microgram/g versus 0.1 microgram/g, P less than 0.001). The authors conclude that HpD preferentially localizes to human colorectal cancer and this is relevant to the photodetection and phototherapy of colorectal neoplasia.
Severe hypoxemia and liver disease.
Severe hypoxemia and orthodeoxia in patients with chronic liver disease is uncommon, but, when present, it is incapacitating. The purpose of this study was to determine the distribution of alveolar ventilation-perfusion (VA/Q) in six patients with mild liver disease and severe hypoxemia (PaO2 at rest in sitting or standing position ranged from 35 to 67 mm Hg). Orthodeoxia was documented with improvement in PaO2 in the supine position in each patient (PaO2 at rest in supine position ranged from 46 to 75 mm Hg). VA/Q distribution was measured by the multiple inert gas elimination technique. The dispersion of VA/Q was increased with small portions of the cardiac output (0.5 to 14.8%) perfusing low VA/Q areas (O less than VA/Q less than 0.1). Another major finding was a large right-to-left shunt (VA/Q less than 0.005) that ranged from 4 to 28%. The VA/Q mismatching and the right-to-left shunt both contributed to the hypoxemia. The predicted PaO2 was 5.5 mm Hg (p less than 0.01) larger than the measured PaO2. In each patient, the mean pulmonary artery pressure was low and the cardiac output was elevated. These results show that the low PaO2 in these patients was due to both increased right-to-left shunt and VA/Q mismatching, but impaired diffusion could not be ruled out.
Bronchoscopic localization and treatment of occult lung cancer.
The flexible fiberoptic bronchoscope is currently the standard tool for localization of radiographically occult carcinomas of the tracheobronchial tree. It allows direct inspection of proximal airways and can establish the location of most occult lung cancers. A small percentage of patients present with bronchoscopically as well as radiographically occult carcinoma, particularly challenging because definitive localizations is required before a therapeutic plan can be outlined. Selective cytologic brushing of each lobar segment, taking random biopsy specimens, has been used to assist in localization of these early cancers. Recently, fluorescent compounds have been used to assist in localizing early lung cancers and in the treatment of radiographically occult carcinoma. We review the current methods of bronchoscopic localization and treatment of radiographically occult lung cancer.
Pulmonary aspects of liver disease and liver transplantation.
This article has summarized the liver-lung relationships from a clinical perspective. The physiology, biochemistry, and molecular biology that link the two organs are of great importance in that many disorders described affect young patients. Indeed, pulmonary abnormalities in patients with hepatic disorders are frequent, and both the pulmonary and hepatic problems may be reversible in the current era of organ transplantation.
Combined effects of hematoporphyrin derivative phototherapy and adriamycin in a murine tumor model.
Hematoporphyrin derivative phototherapy (HpD-PT) is currently being used experimentally in the treatment of various malignancies. The effectiveness of HpD-PT appears to be limited to superficial malignancies because of its inability to penetrate more than 0.5-1 cm. The mechanism of action has been demonstrated to result from the formation of toxic singlet oxygen and other oxygen radicals. Preliminary work suggested that the addition of other chemical agents known to produce toxic oxygen radicals may enhance the effect of HpD-PT. To test this hypothesis, we examined the effectiveness of HpD-PT in the Walker 256 carcinosarcoma with and without Adriamycin. Tumor kill was estimated by calculating the area of necrosis on photomicrographic sections. From this area, a radius of tumor necrosis was determined and compared among various control and experimental groups. HpD-PT was effective in this model when compared to control groups (radius of necrosis 3.79 +/- 0.97 mm vs. 2.60 +/- 1.26 mm, P less than .05). The addition of Adriamycin significantly increased the radius of necrosis when compared to HpD-PT (4.57 +/- 1.70 mm vs. 3.69 +/- 0.97 mm, P less than .01). From this work we conclude that HpD-PT demonstrates effective tumor killing in this murine model. The addition of Adriamycin significantly increased tumor kill.
Management of malignant airway compromise with laser and low dose rate brachytherapy. The Mayo Clinic experience.
Between January 1983 and October 1985, 65 patients with malignant airway compromise have had 93 flexible bronchoscopic placements of a nylon afterloading catheter for low dose rate iridium-192 temporary intraluminal brachytherapy. All patients received prior (59 patients) and/or concurrent (13 patients) external beam irradiation to "tolerance" and were not candidates for surgery. Forty of these patients also received neodymium-YAG laser treatment prior to brachytherapy in a planned combined approach to provide immediate symptomatic relief and facilitate catheter placement. A dose of 3,000 cGy is prescribed to 5 mm and 10 mm radii over 20-40 hours in the bronchus and trachea, respectively. Of 59 patients treated with palliative intent, 40 patients (68 percent) have had follow-up bronchoscopy, 18 patients have had clinical follow-up only, and one patient was lost to follow-up. Of 40 patients examined by bronchoscope in follow-up, 24 (60 percent) responded, eight were stable, and eight progressed. Lack of progression after prior external beam radiation for periods of greater than 12 months, six-12 months and less than six months yielded response rates to brachytherapy in 83 percent, 50 percent and 31 percent, respectively. Most patients with clinical follow-up only expired at early intervals with airway palliation from extra-airway disease progression. Four of five patients treated with curative intent are disease-free at a median of 16 months. Eleven patients have experienced fistula and/or hemorrhage, of which seven instances (11 percent of all patients) appear to be treatment-induced. This brachytherapy technique is simple, well tolerated, and convenient for the patient providing airway palliation in the significant majority of patients with acceptable risk.
Complications of Nd:YAG laser therapy.
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Bronchoscopic phototherapy with hematoporphyrin derivative for treatment of localized bronchogenic carcinoma: a 5-year experience.
Between December 1980 and April 1986 at our institution, 38 patients with cancer that involved the tracheobronchial tree (a total of 40 carcinomas) completed at least one course of hematoporphyrin derivative phototherapy. A complete response occurred in 13 patients (with 14 carcinomas). Eleven of these carcinomas did not recur during follow-up periods that ranged from 3 to 53 months. Three carcinomas recurred at 9, 12, and 35 months, respectively. For 26 carcinomas, the response was less than complete, and alternative therapy was necessary. The carcinomas in patients with a complete response were radiographically occult, were less than 3 cm2 in surface area, and appeared superficial at bronchoscopy. Our experience supports the use of hematoporphyrin derivative phototherapy as an alternative to surgical resection in carefully selected patients.
Monitoring and analysis of oxygenation and ventilation during rigid bronchoscopic neodymium-YAG laser resection of airway tumors.
Neodymium-YAG (yttrium-aluminum-garnet) laser resection of obstructing and inoperable tumors of the large airways is used as palliative therapy to improve the quality of survival in patients by alleviating airway obstruction. Rapid changes in oxygenation and ventilation can occur during these procedures. In a study of 14 patients, transcutaneous oxygen (PtcO2) and carbon dioxide (PtcCO2) monitors responded slowly to these changes and frequently provided misleading values. Pulse oximetry (SNO2) accurately reflected arterial oxygen saturation but did not indicate severe desaturation until arterial oxygen tension approached dangerously low values. Thus, we did not find PtcO2 or PtcCO2 monitoring to be clinically useful during neodymium-YAG laser resection of airway tumors through a rigid bronchoscope. SNO2 was clinically useful and accurate; however, a large decrement in oxygenation may occur before changes in oxygen saturation ensue and are detected.
Severe hypoxemia associated with liver disease: Mayo Clinic experience and the experimental use of almitrine bismesylate.
Severe hypoxemia associated with chronic liver disease is an uncommon disorder most likely due to an intrapulmonary vascular abnormality that has characteristics of both ventilation-perfusion mismatching and diffusion limitation. Anatomically, the intrapulmonary vascular abnormalities can occasionally be detected by angiography. Physiologically, the gas exchange abnormalities can be substantiated by contrast-enhanced two-dimensional echocardiography. Although orthodeoxia and platypnea have frequently been found in these patients, echocardiographic data suggest that vascular abnormalities can exist in the absence of orthodeoxia. We describe 11 patients who had severe hypoxemia and chronic liver disease and review their pulmonary angiographic, contrast echocardiographic, and arterial blood gas findings. Among five of these patients who were given almitrine bismesylate, an experimental medication thought to alter ventilation-perfusion relationships in patients with chronic obstructive pulmonary disease, one had improved oxygenation. We recommend that patients with hypoxemia associated with chronic liver disease have detailed studies to rule out reversible forms of hypoxemia and that those with severe hypoxemia undergo testing to determine the existence of intrapulmonary vascular abnormalities, especially if liver transplantation is considered.
A two-year experience with the neodymium-YAG laser in endobronchial obstruction.
In the first two years after the introduction of neodymium-yttrium-aluminum-garnet (Nd: YAG) laser therapy to our practice, 116 patients were treated 176 times. One hundred six patients (91.4 percent) were treated with the flexible fiberoptic bronchoscope. General anesthesia was used in 89.7 percent of treatments; there were four transient anesthetic complications. Three deaths from massive hemorrhage occurred in the first 59 treatments (first 30 patients). After laser power settings were reduced from 90 to 40 W, there were no further incidences of massive hemorrhage or death in the subsequent 117 treatments. The airway caliber was improved in 83.4 percent of treatments. The trachea, mainstem bronchi, and bronchus intermedius airway calibers were improved more often than those of the lobar bronchi. With lower laser power settings, Nd:YAG laser therapy is a safe and effective means of relieving airway obstruction. Thirty-six percent of patients were alive at one year. The median time to retreatment or death was 130 days.