Production of granulocyte-macrophage colony-stimulating factor in a patient with metastatic chest wall large cell carcinoma

Recent reports of cancers that produce colony-stimulating factors (CSF) and which are associated with leukocytosis indicate that most are granulocyte CSF-producing tumors. A 71-year-old man with metastatic chest wall tumors from large cell lung cancer with marked leukocytosis and eosinophilia was reported. His maximal leukocyte count was 48300/microliter with 37.5% eosinophils. Granulocyte-macrophage CSF (GM-CSF) activity detected by enzyme-linked immunosorbent assay (ELISA) in serum was 112 pg/ml (normal range < 2.0 pg/ml), but G-CSF was normal. Immunohistochemical detection of GM-CSF protein on a chest wall tumor sample was positive. Irradiation of the chest wall tumor was performed and the leukocyte count decreased temporally. However, he died of respiratory failure due to progressive tumor growth 56 days after admission. Based on these results it appears that autocrine production of GM-CSF is a possible cause of this leukemoid reaction.     

Black/white differences in leukocyte subpopulations in men

BACKGROUND: Although counts of leukocytes differ substantially between blacks and whites, and are predictive of ischaemic heart disease (IHD), racial differences in counts of leukocyte subpopulations have received less attention. METHODS: We examined black/white differences in leukocyte subpopulations among 3467 white and 493 black 31-45 year-old-men who had previously served in the US Army. Laboratory determinations were performed at a central location during 1985-1986. RESULTS: Black men had an 840 cell/microliter (or 15%) lower mean total leukocyte count than did white men, largely due to a 960 cell/microliter (or 25%) lower mean neutrophil count. Although black men also had a 20% lower mean monocyte count (= 70 cells/microliter) than did white men, their mean lymphocyte count was 10% higher (approximately = 200 cells/microliter). Counts of various leukocyte subpopulations were associated with cigarette smoking, haemoglobin levels, platelet counts, and several other characteristics, but black/white differences in counts of neutrophils, lymphocytes, monocytes and other subpopulations could not be attributed to any of the examined covariates. CONCLUSIONS: Despite the relatively low counts of leukocytes and neutrophils among black men, their lymphocyte counts are generally higher than those among white men. It is possible that black/white differences in counts of various cell types may influence race-specific rates of IHD, and future studies should attempt to assess the importance of leukocyte subpopulations in the development of clinical disease.     

Myositis caused by hydroxyurea in a patient with chronic myelogenous leukemia

A 59-year-old man with chronic myelogenous leukemia (CML) had a white-blood-cell (WBC) count of 55,400/microliter when admitted in July 1997, and was placed on oral hydroxyurea (HU) of 1,500 mg/day. Treatment with 600 MU/day of interferon alpha (IFN alpha) was started on August 5. HU was discontinued when the patient's WBC count dropped to 8,100/microliter on August 18. However, HU was resumed about a month later, after his WBC count increased to 10,100/microliter, but discontinued when the patient started to complain of chills, high fever, and bilateral femoral pain. HU treatment was initiated again one week later, after the patient's WBC count had begun rising but ceased again after he experienced chills, high fever, and bilateral femoral pain. The patient's myogenetic enzymes were found to be increasing the following day, and a lymphocyte stimulation test (LST) with HU showed a high stimulation index of 41.7%. The elevation of myogenetic enzymes and the results of the LST suggested that myositis due to HU was the cause of the patient's clinical manifestations. His myositis spontaneously disappeared after HU was discontinued. Although the patient is no longer receiving HU, IFN alpha has brought his CML under control. To our knowledge, this is the first reported case of myositis caused by HU.     

Left ventricular function during respiratory failure

Indirect measures of left ventricular function were studied in seven patients with respiratory failure secondary to chronic obstructive pulmonary disease to determine if there were a relationship between left ventricular function and treatment of the pulmonary disease. All patients were studied during acute episodes while in respiratory failure having arterial Pco2 (Paco2) values greater than 49 torr with no clinical evidence of left ventricular failure. Indirect methods to evaluate left ventricular function included the use of the Swan-Ganz catheter for pulmonary capillary wedge pressure measurement, systolic time intervals, and cardiac output. There was improvement in left ventricular function with treatment of the respiratory failure manifested by decreases in the wedge pressure and pre-ejection period/left ventricular ejection time ratio, and an increase in the dp/dt/pulmonary capillary wedge pressure with treatment of the chronic obstructive pulmonary disease. The improvement in left ventricular function suggests that there is a depression of left ventricular function in respiratory failure. The depressed function improved with therapy of the lung disease without additional medication directed at cardiac function.     

Risk modeling in acute renal failure requiring dialysis: the introduction of a new model

Predicting patient outcome in acute renal failure has become increasingly important as technology advances and ethical questions arise concerning life supporting therapies. We propose a new model which uses mortality as an endpoint and may be applied to the acute renal failure patient in the ICU setting who requires dialysis. This model is based on our ICU acute renal failure registry and has been prospectively validated for our institution. Our registry for the purposes of developing this model consists of data from 512 ICU patients requiring acute dialysis from 1988 until 1992. The model was developed by testing a variety of potential risk factors for mortality in a univariate analysis (Student's t-test and Chi square), and those factors found to be significant (p < 0.05) were subsequently tested in a multivariate fashion. The factors found significant included male gender, respiratory failure requiring intubation, hematologic dysfunction (platelet count < 50,000, leukocyte count < 2,500, or bleeding diathesis), bilirubin < 2.0 mg/dl, the absence of surgery, serum creatinine on the first dialysis treatment day, an increasing number of failed organ systems, and an increased BUN from the time of admission. Weights are assigned to each variable based on the odds ratio, and a score is generated with a range of 0 to 20. The initial data for the registry demonstrates good fit using the Hosmer and Lemeshow goodness-of-fit table. The model is next validated in 88 patients from 1993 through February 1994, then prospectively tested in 35 additional patients using a standard data collection form, and the model continues to demonstrate good fit. Although this model has been prospectively validated at our institution, this model or any such predictive model should be used with caution if not independently validated at any institution which proposes its use.     

Respiratory failure based on pulmonary tuberculosis sequelae and its management

According to the complexity of pathological change of pulmonary tuberculosis sequelae (TB seq), on which respiratory failure based shows the higher incidence of marked degree of hypoxemia and hypercapnia than that based on chronic pulmonary emphysema (CPE). In TB seq, pulmonary artery mean pressure is higher, nocturnal oxyhemoglobin desaturation is much lower than in CPE. Also hypoxemia on exercise is lower, and oxygen inhalation for this hypoxemia is more effective than in CPE. The most effective therapy is continuous oxygen therapy. Home oxygen therapy has improved the prognosis and quality of life (QOL) of patients with respiratory failure based on TB seq. Artificial positive pressure ventilation (TIPPV) with intubation or tracheotomy is carried out for patients with severe hypercapnia and respiratory acidosis. Recently, early application of nasal mask ventilation (NPPV) on patients with TB seq has prohibited acute exacerbation of chronic respiratory failure. And also for patients with severe hypercapnia, NPPV with BIPAP method is effective for their QOL. Comprehensive respiratory rehabilitation is also successfully applied for their management.     

Apoptosis of undifferentiated progenitors and granule cell precursors in the postnatal human cerebellar cortex correlates with expression of BCL-2, ICE, and CPP32 proteins

This article reviews the literature of noninvasive positive pressure ventilation (NPPV) in patients with acute respiratory failure. The article divides acute respiratory failure into the categories of primary ventilation failure and oxygenation failure, and examines various diagnostic groups within these categories. Although the use of NPPV for patients with acute respiratory failure of other etiologies requires further study, the authors conclude that there is sufficient evidence to support the use of NPPV in acute, severe exacerbations of chronic obstructive pulmonary disease.     

Comparison of CD4 cell count by a simple enzyme-linked immunosorbent assay using the TRAx CD4 test kit and by flow cytometry and hematology

Measurement of CD4 T-lymphocyte levels is clinically useful in monitoring immune status in a number of conditions, including human immunodeficiency virus (HIV) infection, in which the absolute CD4 count is used to guide therapy. The absolute CD4 count is obtained by multiplying the results of the leukocyte count and the differential with a hematology cell counter and the percentage of CD4+ T lymphocytes determined by flow cytometry. These techniques require expensive, complex instrumentation, and interlaboratory results are difficult to standardize and reproduce. The rapid growth of HIV infection worldwide has increased the need for more-reproducible and cost-effective methods for CD4 T-cell monitoring. The TRAx CD4 test kit is based on a novel adaptation of conventional enzyme-linked immunosorbent assay (ELISA) and permits the simple quantitation of total CD4 protein from whole-blood lysates. In this study, the relationship between total CD4 protein measured in units per milliliter (TRAx) and in cells per microliter (flow cytometry and hematology) was defined in a multisite clinical study using linear regression analysis. Data from 230 HIV-seronegative and 321 HIV-seropositive specimens were used to calibrate the TRAx assay recombinant CD4 standards and controls in equivalent CD4 T lymphocytes per microliter (cells per microliter). The calibration of the TRAx CD4 assay in cells per microliter was validated with a second group of specimens from 17 healthy volunteers and 20 HIV-seropositive patients which were collected and tested under strictly controlled conditions intended to minimize the effects of specimen aging on the results of the reference method. These data were also used to estimate the variability of absolute CD4 count by cytometric methods as well as the precision of the TRAx CD4 result after it was calibrated in cells per microliter. Overall, correlations between the two methods ranged from 0.87 to 0.95. Additional studies demonstrated that the contribution of CD4 protein from monocytes and any soluble CD4 in sera are negligible in the TRAx assay and do not significantly affect results. This new method represents a promising alternative to absolute CD4 T-cell enumeration by flow cytometry and hematology.     

Immunocytologic detection of isolated tumor cells in bone marrow of patients with squamous cell carcinomas of the head and neck region

Methimazole 5 mg three times daily was prescribed in 1994 spring to a woman, aged 53 years, with relapsed hyperthyroidism. The drug was discontinued six weeks after initiation because of leukopenia. Two weeks still later, the patient developed chills, high fever, and a sore throat. The leukocyte count was 1,100/mm3 with 23% granulocytes, 76% lymphocytes and 1% monocytes. The granulocyte count stopped decreasing only three weeks after the drug was discontinued when the recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given; the patient recovered uneventfully. Thus we recommend that the peripheral leukocyte count of patients who receive methimazole therapy must be carefully monitored during the first three months. Furthermore, the use of rhG-CSF for methimazole-induced agranulocytosis abbreviates the period required for marrow recovery after cessation of this offensive drug.     

Systemic sclerosis with pulmonary involvement and right ventricular failure in a child

We report a very rare case of systemic sclerosis in a 6-year-old girl. She presented with diffuse scleroderma, Raynaud's phenomenon, pulmonary interstitial fibrosis, pulmonary hypertension, and right ventricular failure. The diagnosis was confirmed by skin manifestations, high resolution computed tomography, cardiac catheterization, and anti-nuclear antibodies. Nifedipine, prednisolone, digoxin, and furosemide were given. There was remission of the right ventricular failure and dyspnea, and the skin showed partial improvement. The patient remained asymptomatic for a year. The symptoms of respiratory and right heart failure developed again after an episode of lower respiratory tract infection and she eventually died. We discuss the clinical manifestations, treatment, and outcome.     

Outcomes of noninvasive positive-pressure ventilation in patients with acute hypercapnia complicating chronic respiratory failure]

We used noninvasive positive-pressure ventilation to treat hypercapnea due to acute exacerbations of chronic respiratory failure (21 episodes in 19 patients; COPD, 4; pulmonary tuberculosis sequelae, 4; silicosis, 3; silicotuberculosis, 3; bronchiectasis, 3; others, 2). All patients had acute onsets of severe hypercapnea (PaCO2 > 45 Torr), acute decreases in pH (< 7.35), and tachypnea, paradoxical breathing or both. During the first 2 to 4 hours of bi-level positive airway pressure, PaCO2 decreased from 72 to 61 Torr (p < 0.0005), pH increased from 7.26 to 7.31 (p < 0.001), and respiratory rate decreased from 30 to 25 breaths/min (p < 0.005). In three cases leakage of air through the mouth prevented improvement in the patients' conditions, but in two of those a face mask was then used successfully. In 17 of the 21 episodes (81%) gas exchange improved and intubation was not necessary. In those 17, the mean duration of noninvasive positive-pressure ventilation was 6.3 days. We conclude that noninvasive positive-pressure ventilation can improve gas exchange in patients with acute hypercapnea complicating chronic respiratory failure.     

Noninvasive ventilation in acute respiratory failure

Noninvasive PPV has been employed for decades in patients with chronic respiratory failure. Increasing use in patients with acute respiratory failure is a more recent phenomenon, mainly because of advances in noninvasive interfaces and ventilator modes. Noninvasive PPV delivered by nasal or oronasal mask has been demonstrated to reduce the need for endotracheal intubation, decrease lengths of stay in the ICU and hospital, and possibly reduce mortality. In the acute care setting, evidence now demonstrates the efficacy of noninvasive PPV for acute exacerbations of COPD, pulmonary edema, pulmonary contusions, and acute respiratory failure in patients who decline or who are not believed to be candidates for intubation. No firm conclusions can yet be made regarding patients with respiratory failure due to other causes, but studies suggest that noninvasive PPV may also be of benefit in patients with postoperative respiratory insufficiency, chest wall disease, and cystic fibrosis. Several factors are vital to the success of this therapy, including careful patient selection, properly timed intervention, a comfortable, well-fitting interface, patient coaching and encouragement, and careful monitoring. Noninvasive ventilation should be used as a way to avoid endotracheal intubation rather than as an alternative. Accordingly, a trial of noninvasive ventilation should be instituted in the course of acute respiratory failure before respiratory arrest is imminent, to provide ventilatory assistance while the factors responsible for the respiratory failure are aggressively treated. Moreover, the authors favor conservative management with expeditious intubation in patients who have other conditions that place them at risk during use of noninvasive ventilation or in patients failing to respond to noninvasive PPV. Noninvasive PPV clearly represents an important addition to the techniques available to manage patients with acute respiratory failure; however, because most studies have been retrospective and uncontrolled, many issues remain unresolved. Further controlled studies are needed to confirm the safety and efficacy of noninvasive PPV, evaluate the most appropriate selection of patients and timing of intervention, define the best type of interface, and assess the costs of noninvasive PPV in comparison with conventional therapy.     

Respiratory failure sometimes is due to a cardiac cause

In two women aged 65 and 49 years and a man aged 64 years, severe respiratory failure developed and a pulmonary disease was suspected. They also had a minor systolic murmur. At further investigation no pulmonary cause for the disease could be established. Pulmonary artery catheterization revealed increased pulmonary artery and wedge pressures and transthoracic and transoesophageal echocardiography revealed mitral valve insufficiency. Two patients had valve surgery, the third received medication. Respiratory failure is a common problem in an intensive care unit. If this condition is caused by mitral valve insufficiency the clinical picture is not always that of acute left ventricular failure with hydrostatic pulmonary oedema due to backward failure. In patients with respiratory failure due to mitral valve pathology initial diagnostic problems may be overcome by combining the findings of pulmonary artery catheterization and transthoracic and transoesophageal echocardiography.     

Effects of support pressure ventilation with facial mask in patients with chronic respiratory failure in acute decompensation

BACKGROUND: In previous nonrandomized studies the efficacy of ventilation with back up pressure with face mask (BUPM) in the treatment of patients with chronic obstructive pulmonary disease (COPD) in acute decompensation has been demonstrated. This study analyzes the acute effects and the clinical efficacy of BUPM in a group of patients with COPD in acute respiratory failure comparing the same with conventional therapy (CONV). METHODS: A prospective randomized study including patients with COPD in acute decompensation was carried out comparing treatment with BUPM (n = 9) with CONV treatment (n = 9). Back up pressure was fixed at 20 cmH2O. Acute gasometric effects were analyzed as well as the need for intratracheal intubation, mortality and hospital stay. RESULTS: No clinical or gasometric differences were found between either group of patients upon admission. Only the patients of the BUPM group presented a significant improvement from gaseous exchange and respiratory frequency from the first hour of treatment. Three of the nine patients (33%) of the BUPM group and nine of the CONV group of patients (100%) required intubation and mechanical ventilation (p = 0.001). CONCLUSIONS: Back up pressure face mask is the technique of choice in patients with chronic obstructive pulmonary disease in acute decompensation given that this technique leads to a rapid and significant improvement of gaseous exchange and avoids the need for intubation and mechanical ventilation in most of these patients.     

Clinical effects of low-dose and long-term erythromycin in diffuse panbronchiolitis with chronic respiratory failure

We studied the effects of erythromycin (EM) in diffuse panbronchiolitis (DPB) with chronic respiratory failure. Seventeen patients with DPB or sinobronchial syndrome receiving home oxygen therapy (HOT) were treated with EM of 400-600 mg/day for twelve months. Five patients discontinued HOT, and hypoxemia was improved in five other patients. Clinical effects were evident at one month after the start of EM administration, and a stable state was achieved after six months of EM therapy. FEV1 was significantly increased in pulmonary function tests. Factors which influenced the effects of EM included the period between onset of clinical symptoms and commencement of HOT and/or between commencement of HOT and administration of EM. EM was effective for patients with obstructive, but not constrictive impairment in pulmonary function tests. These findings indicate that EM is effective for DPB even in patients with chronic respiratory failure.     

Acute transformation of chronic myelomonocytic leukemia with t(1;3) (p36;q21) abnormality

A 66-year-old man was given a peripheral blood test because of low grade fever. Leukocytosis was detected, and the blood and bone marrow findings were consistent with those of chronic myelomonocytic leukemia. Three months later the hematological findings were: WBC 58,800/microliter (19% blastoid cells, 22% monocytes), Hb 9.0 g/dl, and a platelet count of 116 x 10(4)/microliters. A bone marrow examination revealed the presence of 52.6% blastoid cells and dysmegakaryocytopoiesis, including micromegakaryocytes. Serum and urinary lysozyme levels were elevated. Karyotypic analysis detected t(1; 3) (p36;q21), but not major bcr/abl mRNA. The patient was given a diagnosis of acute transformation of chronic myelomonocytic leukemia. Despite treatment, he died about 3 months later. t(1;3) is occasionally observed in cases of myelodysplastic syndrome (MDS) and leukemia. Patients with t(1;3) often exhibit dysmegakaryocytopoiesis; furthermore, acute leukemia develops more readily in those who also have MDS. Cases of long-term survival are rare.     

Allogeneic peripheral blood stem cell transplantation in 30 patients with hematologic disorders

Thirty patients (median age of 32 years; range, 6-61) with hematologic disorders received unmanipulated peripheral blood stem cell transplants from HLA-matched or one-antigen-mismatched related donors following myeloablative therapy for acute lymphoblastic leukemia (7), acute myelogenous leukemia (6), chronic myelogenous leukemia (8), myelodysplastic syndrome (3), or other disorders (6). Granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells were collected from donors in 1 to 3 aphereses. The apheresis products contained mean counts of 11.3 x 10(8) (range, 3.8-17.2) nucleated cells/kg and 6.7 x 10(6) (range, 1.3-16.7) CD34+ cells/kg. Graft-versus-host-disease (GVHD) prophylaxis consisted of cyclosporin A plus methotrexate, or FK506 plus methotrexate. All patients received G-CSF following their transplant. Although 1 patient died of pneumonia 6 days after transplantation, the others demonstrated rapid engraftment. Median days to recovery to 500/microliter neutrophils and 20,000/microliter platelets were 13 (range, 8-21) and 14 (range, 1-23) days, respectively. The incidence of acute GVHD grade II-IV was 33%; chronic GVHD developed in 57% of the assessable patients. There were no episodes of graft failure or rejection. Nineteen patients (63%) were alive and in complete remission from 147 to 839 days following their transplant (median follow-up of 560 days). Further follow-up study will be required to assess the incidence of chronic GVHD and graft-versus-leukemia (GVL) effects.     

3 years of long-term home oxygen therapy in the Czech Republic

BACKGROUND: Long-term domiciliary oxygen therapy was introduced in the Czech Republic as a standard therapeutic method in patients with chronic respiratory failure in October 1992. As a source of oxygen almost exclusively oxygen concentrators are used which are allocated to the patients according to criteria elaborated by the European Respiratory Society. METHODS AND RESULTS: From October 1, 1992 to October 1, 1995 the mean number of installed concentrators is 10,24/100000 population. From a total of 1064 patients by October 1, 1995 3.8% were treated for three years, 20.7% for two years and 34.4% for more than one year. In the course of three years a total of 490 patients died. The mean survival period of patients treated for prolonged periods by domiciliary oxygen therapy was 8.88 months. The high mortality rate is due to the fact that patients in a very serious state are treated. On account of chronic pulmonary disease oxygen therapy was indicated in 93.4%, on account of interstitial pulmonary processes (KFA and other fibroses) in 3.9, on account of kyphoscoliosis in 2.4% and on account of cystic fibrosis in 0.3% of the group. The mean costs of treatment were 114.40 K?/day which is a third of the costs when the patient is hospitalized. CONCLUSIONS: Domiciliary oxygen therapy proved effective and economical in patients with chronic respiratory failure.     

Respiratory failure in ANCA-associated vasculitis

OBJECTIVE: To assess the prevalence, clinical manifestations, and course of respiratory failure in all patients who tested positive for antineutrophil cytoplasmic autoantibodies (ANCA) in our clinics in the period between January 1985 and January 1993. DESIGN: Case-series analysis. SETTING: Three teaching hospitals in the Netherlands. PATIENTS: Two hundred twenty consecutive patients suspected of having vasculitis and/or glomerulonephritis who tested positive for ANCA by indirect immunofluorescence and enzyme-linked immunosorbent assay. RESULTS: Sixty-two patients had pulmonary involvement. Acute respiratory failure developed in nine. Respiratory failure was related to infections in two of them and to ANCA-associated vasculitis in seven. These seven patients uniformly presented with pulmonary hemorrhage and diffuse pulmonary infiltrates. The diagnosis of systemic vasculitis was supported by the presence of a pulmonary-renal syndrome in all patients, and by detection of antibodies to the proteinase 3 or myeloperoxidase antigen in all but one patient. Antiglomerular basement membrane antibodies were absent. The mortality was high due to hypoxic respiratory failure, pulmonary superinfections, and concomitant renal failure. CONCLUSIONS: Acute respiratory failure due to vasculitis developed in one of every nine patients with ANCA-associated pulmonary disease. Patients usually present with pulmonary infiltrates and hemoptysis. A diagnosis of vasculitis may be further supported by analysis of the urinary sediment and determination of the ANCA target antigen. It remains to be proved that early detection of ANCA favorably affects the outcome.     

Partial characterization of a cell-directed inhibitor of leukotaxis in human serum

A leukotactic defect is described in a man with a low cerebrospinal fluid leukocyte count in the presence of an acute listeria meningitis. On the basis of subsequent studies with his serum and normal human serum, a leukotactic inhibitor has been identified. This inhibitor, termed the cell-directed inhibitor (CDI), is relatively heat stable and nondialyzable. By ultracentrifugal analysis in sucrose density gradient, the inhibitor has been resolved into two activities with estimated sedimentation coefficients of 7 and 10 S. It interacts directly with neutrophils and monocytes to render them chemotactically defective. CDI also impairs the phagocytic function of neutrophils. Evidence is presented that an antagonist to the inhibitor is present in normal serum. CDI and its antagonist are probably normally occurring regulators of leukotaxis. In the patient studied, an elevated CDI serum level may be related to the development of the listeria infection and failure of cutaneous response to skin test antigens.