Adaptive Support Ventilation as the sole mode of ventilatory support in chronically ventilated patients.

OBJECTIVE: To describe the outcome of patients admitted to a new private facility for chronically ventilated patients in the Ashdod area of Israel. METHODS: On arrival, all patients were placed on Adaptive Support Ventilation (ASV) at 90% of target minute ventilation for lean body weight, reducing progressively in weekly decrements of 10% down to 60% of target minute ventilation if adequate spontaneous ventilation was maintained by the patient. RESULTS: Almost half (12/27) of these patients admitted in the first 12 months following establishment of the facility were successfully weaned from mechanical ventilation within 2 weeks to 2 months of admission. CONCLUSIONS: The cost effectiveness of this form of closed loop mechanical ventilation in achieving weaning automatically, without the need for respiratory therapists or continuous attendance by intensive care specialists to conduct weaning trials is demonstrated by these results.

Successful talc slurry pleurodesis in patients with nonmalignant pleural effusion.

BACKGROUND: Chemical pleurodesis is an effective treatment for malignant pleural effusion and pneumothorax. This mode of therapy is, however, less widely accepted in the treatment of patients with refractory benign or undiagnosed pleural effusion. STUDY OBJECTIVES: To analyze the outcome of talc slurry pleurodesis in patients with nonmalignant pleural effusions. DESIGN: Retrospective and partly prospective analysis of clinical outcome. SETTING: Hadassah University Hospital, Jerusalem, Israel. PATIENTS AND PARTICIPANTS: Between 1992 and 1997, we treated 16 patients with nonmalignant pleural effusion using talc slurry pleurodesis. The cause of effusion was congestive heart failure in 6 patients, liver cirrhosis in 4 patients, yellow nail syndrome in 1 patient, systemic lupus erythematosus in 1 patient, chylothorax in 1 patient, and undiagnosed in 3 patients. INTERVENTIONS: Nine patients were hospitalized, and seven patients received treatment in a day-care setting. Follow-up ranged from 2 months to 3 years. RESULTS: Complete success was observed in 12 cases (75%), partial success in 3 cases (19%), and pleurodesis was ineffectual in 1 case (6%). There were no significant complications after the procedure in any of our patients. A review of the English-language medical literature revealed an additional 110 reported cases of nonmalignant pleural effusion that were treated with chemical pleurodesis. Of these cases, talc was used in 65% with a success rate of nearly 100%. CONCLUSIONS: Chemical pleurodesis, and specifically talc slurry, is an effective treatment for recurrent benign or undiagnosed pleural effusion. This procedure is safe and easily performed and, in selected cases, can be performed in an outpatient day-care setting.

The role of BAL in the diagnosis of pulmonary mucormycosis.

Five patients with pulmonary mucormycosis diagnosed during life are described. All had underlying predisposing conditions: either posttransplant or hematologic malignancies. In all cases, the diagnosis was made using fiberoptic bronchoscopy. In three patients, BAL was diagnostic. In two of these patients, the diagnosis was made by identifying the typical hyphae of mucormycosis in the BAL fluid alone. Transbronchial biopsy was diagnostic in three patients. Treatment was based on IV antifungal chemotherapy together with surgical removal of involved lung tissue whenever feasible. The clinical outcome of these patients was dismal and was determined primarily by the underlying condition.

Prognostic value of CYFRA 21-1, TPS and CEA in different histologic types of non-small cell lung cancer.

The prognostic value of the tumor markers CYFRA 21-1, tissue polypeptide specific antigen (TPS) and carcinoembryonic antigen (CEA) was investigated in three histologic subtypes of non-small cell lung cancer. Pretreatment serum marker levels were measured in 38 patients with adenocarcinoma (AC), in 43 patients with squamous cell carcinoma (SQC) and in 35 patients with large cell carcinoma (LCC). Univariate analysis in AC showed significant lower survival of patients with elevated levels of TPS, CYFRA 21-1 and CEA. In LCC, elevated levels of TPS and CEA were found to predict lower survival, while in SQC--only TPS was a predictor. A multivariate analysis of survival identified CEA (Relative Risk-5.5; p = 0.004), CYFRA 21-1 (RR-3.4; p = 0.008) and TPS (RR-3.0; p = 0.02) as independent prognostic factors in AC. In SQC, only TPS (RR-2.3; p = 0.03) was such a factor whereas in LC--none of the markers studied retained statistical significance. Thereafter, the combinations of the two strongest prognostic factors in the AC group--CEA and CYFRA 21-1 were explored to divide this group into subsets with different prognosis. In cases where both markers were positive, the relative risk of death was 10.5 times higher as compared to cases where both markers were negative (p = 0.002).

Cytokeratin markers in malignant pleural mesothelioma.

Previously available serum tumor markers had a low clinical value in malignant pleural mesothelioma (MPM). The recently developed tissue polypeptide-specific antigen (TPS) and CYFRA 21-1 assays identify the soluble cytokeratin 18 and 19 fragments, respectively. In MPM these cytokeratins are expressed and may therefore be used as serum tumor markers. In this preliminary study, TPS and CYFRA 21-1 assays were evaluated to determine their potential for management of patients with MPM. Carcinoembryonic antigen (CEA) was evaluated as an additional marker. The study group consisted of 95 patients with benign lung and pleural diseases (BLPD), 14 patients with MPM, 41 patients with adenocarcinoma of lung (AC), and 40 patients with squamous cell carcinoma of lung (SQC). The utilized cutoff points corresponded to a 95% specificity for patients with BLPD. In MPM, TPS showed greater sensitivity (64.3%) than CYFRA 21-1 (50.0%), while CEA showed no sensitivity. In SQC, the marker CYFRA 21-1 had the highest sensitivity (52.5%), whereas in AC the most sensitive marker was CEA (56.1%). Significantly lower levels of CEA were found in MPM compared with BLPD (p < 0.001) or AC and SQC (p < 0.0001). Conversely, TPS levels in MPM were significantly higher than in SQC (p < 0.05). Close correlation of various individual pretreatment marker levels was observed only between TPS and CYFRA 21-1, both in MPM (r = 0.84; p < 0.001) and in non-small cell lung cancer (NSCLC) (r = 0.71; p < 0.001). In serial determinations of the markers during chemotherapy of MPM (n = 10), TPS and CYFRA 21-1 were shown to demonstrate more or less the same pattern of reactivity, although the changes in the TPS levels better reflected the clinical response to therapy. In conclusion, TPS seems to be a more sensitive marker than CYFRA 21-1.

Evaluation of tissue polypeptide specific antigen, CYFRA 21-1, and carcinoembryonic antigen in nonsmall cell lung carcinoma: does the combined use of cytokeratin markers give any additional information?

BACKGROUND: Recently developed tissue polypeptide specific antigen (TPS) and CYFRA 21-1 assays determine the soluble cytokeratin 18 and 19 fragments, respectively, in serum. The authors compared the value of TPS, CYFRA 21-1, and carcinoembryonic antigen (CEA) for the diagnosis, staging, prognosis, and monitoring of patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The study included 85 patients with benign lung diseases and 94 patients with NSCLC. TPS, CYFRA 21-1, and CEA serum levels were measured with commercial kits. RESULTS: The following were demonstrated: 1) CYFRA 21-1 and TPS levels, but not CEA levels, differed significantly between NSCLC patients with operable disease (Stages I-IIIA) and those with inoperable disease (Stages IIIB-IV). 2) The correlation coefficient between CYFRA 21-1 and TPS increased with the progression of NSCLC from Stages I-IIIA (r = 0.41, P = 0.04) to Stages IIIB-IV (r = 0.70, P < 0.001). 3) Multivariate analysis identified TPS and CYFRA 21-1 as significant predictors of survival, with relative risks of 2.57 (P = 0.001) and 2.05 (P = 0.01), respectively. For cases in which both cytokeratin markers were positive, the relative risk was 6.4 (P < 0.0001) compared with cases in which both were negative. 4) For the group with inoperable disease, the combined use of TPS and CYFRA 21-1 allowed for the definition of 3 sets of patients with significantly different median survival times (14.3 months vs. 7.4 months vs. 2.6 months). 5) The percentages of marker evaluations concordant with results of clinical assessments of response to therapy were 75.0%, 72.2%, and 61.1% for CYFRA 21-1, TPS, and CEA, respectively. CONCLUSIONS: These findings suggest that, for NSCLC patients, CYFRA 21-1 and TPS are significant prognostic factors and effective monitors of therapy. The combined use of these cytokeratin markers may provide additional information for prognosis.

Use of fiberoptic bronchoscopy in bone marrow transplant recipients.

Bone marrow transplantation (BMT) has become the therapy of choice for a number of malignant and nonmalignant hematologic and nonhematologic disorders. A frequent complication after BMT is pulmonary disease which is associated with a high mortality rate. We examined the results of 79 bronchoscopies performed between May 1991 and May 1995 in 62 patients for the evaluation of pulmonary complications after BMT. In all cases bronchoalveolar lavage (BAL) was performed, in 10% transbronchial biopsy (TBB) was also carried out and in 13% bronchoscopy was followed by open lung biopsy. Positive results were found in 67% of bronchoscopies. Fungal infection (Candida and Aspergillus species) was the most common finding (18%), bacterial infection was found in 13%, mixed (fungal and bacterial) infection in 6%, cytomegalovirus in 11% and Pneumocystis carinii pneumonia in 4%. Diffuse alveolar hemorrhage was detected in 11% of cases. Idiopathic pneumonia syndrome (IPS) was diagnosed by TBB in 3% of procedures. We conclude that BAL is a safe and accurate procedure for the evaluation of pulmonary complications after BMT. TBB should be considered in the absence of thrombocytopenia for the diagnosis of IPS. If bronchoscopy findings are negative, open lung biopsy should be considered.

Clustering of Pneumocystis carinii pneumonia in patients undergoing renal transplantation from living unrelated donors in Iraq and India.

Over the past few years, we have observed a substantial increase in the number of patients followed at our hospital who have undergone renal transplantation from living unrelated donors (LURD). These transplants were all performed in one of two centers: Bagdad, Iraq or Bombay, India. We have observed a parallel increase in the number of cases of Pneumocystis carinii pneumonia (PCP) post-renal transplant. We conducted a ten-year retrospective analysis (1986-1995) of patients who developed PCP post-renal transplant to determine the risk factors associated with the development of this infection, with particular reference to the type of transplant and the center in which the transplant was performed. Over this period, 270 renal transplant patients were followed at this hospital and 10 episodes of PCP were documented (3.7%). Six of these cases occurred within the last 2 years, as compared to only 4 cases in the preceding 8 years. All of the cases observed in the last 2 years occurred in patients who had undergone renal transplantation from LURD in Iraq or in India. During the same period, we observed no cases of PCP in patients who had undergone transplantation in Israel (cadaver or related living donor transplants). We could find no difference between patients undergoing transplant from LURD and those undergoing other transplants in terms of immuno-suppressive therapy, frequency of organ rejection episodes or coexistent CMV infection. All patients were of Arab descent and live in the West Bank. Although we cannot identify any obvious explanation for this association, we believe that these cases represent a true cluster phenomenon. We therefore feel it is warranted for all recipients of renal transplants from living unrelated donors seen in our hospital to receive prophylactic therapy for Pneumocystis carinii pneumonia.

[Pulmonary thrombo-endarterectomy].

Chronic pulmonary thromboembolism is an underdiagnosed condition with major morbidity and mortality. Over the past year and a half, we diagnosed 6 new cases of which 3 underwent successful, pulmonary thrombo-endarterectomy (2 in San Diego, 1 in Jerusalem). All recovered fully and returned to normal, active life. We conclude that pulmonary thrombo-endarterectomy is a viable option for patients with chronic pulmonary thromboembolism.

Somatostatin-receptor scintigraphy of subcutaneous and thyroid metastases from bronchial carcinoid.

We present a case of bronchial carcinoid tumor with multiple metastases in the retina, subcutaneous tissues and thyroid gland. These metastatic lesions were detected by 111In-pentetreotide scintigraphy 15 yr after removal of the primary tumor. The extensive metastatic involvement documented on scintigraphy spared the patient unnecessary total thyroidectomy and directed the attention of the primary physician to previously unknown and potentially more important foci of metastatic disease.

Radiation-induced pulmonary veno-occlusive disease.

Late occurrence of radiation-induced pulmonary pneumonitis and fibrosis is well documented. We report an unusual case of radiation induced veno-occlusive disease (VOD) occurring six years following mantle irradiation for Hodgkin's lymphoma. The patient developed severe pulmonary hypertension and cor pulmonale. A left lung transplantation was performed successfully and pathologic examination of the explanted lung showed severe changes compatible with VOD. In the absence of exposure to alternate therapeutic or toxic agents that may cause VOD, it is likely that radiation caused damage to the venular endothelium and caused progressive obliteration of the pulmonary vessels. Review of the literature reveals only a few similar reports of VOD mostly following radiation for bone marrow transplantation. We conclude that previous irradiation (even several years earlier) should be considered as a possible cause of pulmonary VOD.

Obstructive solitary bronchial non-Hodgkin's lymphoma--a rare presentation of primary extranodal disease.

Endobronchial involvement by non-Hodgkin's lymphoma (NHL) is uncommon and usually occurs in the presence of more generalised disease. Solitary endobronchial lymphoma in the absence of disease elsewhere is extremely rare. In this report we describe a patient with an obstructing endobronchial mass which was the initial manifestation of NHL. The patient was treated initially with radiotherapy followed by cyclic combination chemotherapy with initial complete resolution of the endobronchial disease. However, he subsequently developed widespread lymphoma. This unusual presentation of NHL is discussed and the relevant literature is reviewed.

Cardiopulmonary assessment in beta-thalassemia major.

Thalassemia patients succumb at a young age to congestive heart failure. Hitherto, attention has been focused on left ventricular function. This report emphasizes right ventricular dysfunction and abnormal pulmonary function. We performed cardiopulmonary evaluation, including echo-Doppler, spirometry, CO diffusion (DCO), and blood gas analyses in 35 patients with homozygous beta-thalassemia maintained by multiple blood transfusions. Six autopsy lung specimens were studied. Thalassemia patients exhibited pulmonary dysfunction, characterized by hypoxemia (85 percent of the patients were outside the 95 percent confidence limits), reduced lung volumes (51 percent), flow rates (63 percent) and DCO (50 percent). Right ventricular dysfunction was more prevalent than left ventricular dysfunction. Furthermore, 75 percent of the patients had evidence of pulmonary hypertension consistent with more frequent right ventricular rather than left ventricular dysfunction. Our findings suggest that in thalassemia patients, complex cardiopulmonary abnormalities precede the final outcome of congestive heart failure.

Utility of bronchoalveolar lavage in the assessment of diffuse pulmonary infiltrates in nonAIDS immunocompromised patients.

The efficacy of bronchoscopy with bronchoalveolar lavage for diagnosing 32 episodes of diffuse pulmonary infiltrates was studied in 30 nonAIDS immunocompromised patients. Bronchoalveolar lavage had an overall diagnostic yield of 84% (27 of 32 episodes). Bronchoalveolar lavage was noncontributive in five episodes of pneumonitis: drug induced in one, nonspecific in three and pneumonitis of unestablished etiology in one. Overall, the procedure is safe and did not miss diagnoses for which conventional treatment was available. Our data support the use of bronchoscopy with bronchoalveolar lavage as the primary diagnostic procedure in immunocompromised patients with diffuse pulmonary infiltrates.

Interstitial pneumonitis in T cell-depleted bone marrow transplantation.

The incidence of interstitial pneumonitis (IP) was reviewed in 80 consecutive patients who received allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) for malignant and non-malignant diseases. Pretransplant conditioning used in malignant disorders included total lymphoid irradiation (TLI) 150 cGy x 4, total body irradiation (TBI) 200 cGy x 6, and cyclophosphamide (CY) 120 mg/kg. In non-malignant diseases conditioning included no TBI, but adjusted doses of TLI in addition to CY (severe aplastic anemia) or CY and busulfan (severe beta-thalassemia major). In the malignant group only one patient developed graft-versus-host disease (GVHD) grade I; IP developed in 12 out of 61 patients (19.7%) and IP-associated fatality occurred in five patients (8.2%). Cytomegalovirus (CMV) was associated with only two of the five fatal IP. In the non-malignant group there was no GVHD; one patient out of 19 (5.2%) had IP, which was fatal and not associated with CMV. These data indicate that fatal IP may appear in the absence of GVHD. The relatively low incidence of IP-related mortality in recipients of allogeneic T lymphocyte-depleted BMT suggests that although prevention of GVHD and elimination of drugs used for GVHD prevention may reduce the incidence of fatal pulmonary complications, other approaches have to be investigated for complete prevention of IP which still represents a major complication in patients with malignant hematologic disorders treated by allogeneic BMT.

Endotracheal neurofibroma in a patient with von Recklinghausen's disease.

Benign neurogenous tumours arising in the trachea are rare. We report on a patient with von Recklinghausen's disease who presented with shortness of breath caused by endotracheal neurofibroma.

Thrombocytosis in chronic eosinophilic pneumonia.

Thrombocytosis has not yet been described in chronic eosinophilic pneumonia. A typical patient with chronic eosinophilic pneumonia is described. The patient's thrombocyte count was up to 900,000 per cu mm, which returned to normal under steroid therapy. Thrombocytosis may be associated with chronic inflammation and should not require further investigations such as lung biopsy, in an otherwise usual case of chronic eosinophilic pneumonia.

Post-pneumonectomy syndrome. Surgical correction using Silastic implants.

A post-right pneumonectomy syndrome is described which manifests symptoms of exertional dyspnea and inspiratory stridor on rapid inspiration. These symptoms were associated with marked rightward and posterior deviation of the trachea, over-distention of the left lung with its herniation into the right side of the chest and kinking of the left lower lobe bronchus. At the time of surgery, the tracheal deviation, lung herniation and the kink in the left lower lobe bronchus were immediately corrected by releasing the adhesions between the malpositioned structures and the right chest wall. To maintain the corrected positions, Silastic implants totalling a volume of 990 ml were placed into the space created in the right chest. Following surgery, exertional dyspnea was present with only extraordinary activity, and inspiratory stridor was eliminated. The patient remains asymptomatic three years following surgical correction, and is able to carry on a normal and productive life. We conclude that a syndrome associated with marked exertional dyspnea and inspiratory stridor might develop in situations of marked tracheal shift and overdistention of the remaining lung following right pneumonectomy.

Unusual amyloid bodies in human liver. Ultrastructural and freeze-etching studies.

An unusual presentation of amyloidosis in the liver is described in two patients with chronic pulmonary disease. Amyloid bodies, ranging from 3 to 20 microns in diameter and staining positive for Congo red, were found to be deposited between or within hepatocytes and, therefore, to be in a more direct spatial relationship to epithelial than to Kupffer or sinusoidal lining cells. The freeze-etching technique revealed that the average diameter of the amyloid fibrils was 15 nm and not 7 to 10 nm. This may be due to the fact that this technique avoids shrinkage artefacts which follow fixation and dehydration.

Application of the cilia dyskinesis test in the diagnosis of cystic fibrosis in an adolescent.

In certain cases of obscure chronic lung disease, the possibility of a genetic disorder, such as cystic fibrosis of the pancreas, should be considered. When the genetic defect fails to cause pancreatic involvement, the partial expression of cystic fibrosis is encountered. Elevation of sweat electrolyte levels is not sufficient to confirm the diagnosis of cystic fibrosis in adults since normal levels vary widely in both adolescents and adults. Other tests should, therefore, be utilized. The cilia dyskinesis test is positive in both homozygous and heterozygous patients with cystic fibrosis. Utilization of this technique in a family study confirmed the diagnosis of partial expression of cystic fibrosis in an adolescent female.