Hydroxychloroquine-induced toxic myopathy causing respiratory failure.

Chloroquine and hydroxychloroquine (HCQ) are commonly prescribed antimalarial agents used for a variety of systemic diseases. HCQ neuromyotoxicity is a rare complication characterized by proximal muscle weakness, normal creatinine kinase levels, and characteristic ultrastructural changes on muscle biopsy of curvilinear body formation. In this report, we describe a patient with rheumatoid arthritis and respiratory failure associated with proximal myopathy secondary to HCQ. Characteristic changes on muscle biopsy were present. Patients treated with HCQ in whom proximal myopathy, neuropathy, or cardiomyopathy develop should be evaluated for possible HCQ toxicity. Clinicians should be aware of this unusual complication of antimalarials, as discontinuation of the agent may result in clinical improvement.

Malignant pleural effusions in lymphoproliferative disorders.

In order to determine variables that correlate with malignant pleural effusion and mortality in patients with lymphoproliferative disorders and pleural effusion, a retrospective study was performed. Clinical data of hospitalized patients with a lymphoid malignancy and pleural effusion who underwent thoracentesis from January 1993 to December 2002 were collected. A logistic regression analysis was carried out to determine prognostic variables that predict malignant pleural effusion and hospital mortality. There were 86 patients who were admitted on 91 occasions. The median age was 70 years (range 4 - 92) and the male:female ratio was 44:42. Sixty-four patients (74%) had advanced disease, 43 (50%) had received prior chemotherapy and 9 (10%) were in remission. Of 91 cases of pleural effusions, 44 (48%) were bilateral, 80 (88%) were exudates and 48 (53%) were due to malignant involvement of pleura. In multivariate analysis, symptomatic pleural effusion (odds ratio 10.3, 95% confidence interval 1.7 - 98.3), pleural fluid mesothelial cell count < 5% (odds ratio 8.0, 95% confidence interval 1.4 - 58.2), pleural fluid:serum lactate dehydrogenase (LDH) > or =1 (odds ratio 6.4, 95% confidence interval 1.2 - 45.6) and pleural fluid lymphocyte percentage > or =50 (odds ratio 6.4, 95% confidence interval 1.2 - 50) were significantly correlated with malignant effusion. A secondary cancer (odds ratio 11.9, 95% confidence interval 2.3 - 88.8), pleural fluid:serum LDH > or =1 (odds ratio 10.9, 95% confidence interval 2.6 - 64.9), and pneumonia (odds ratio 6.4, 95% confidence interval 1.7 - 28.6) were significantly correlated with hospital mortality. In conclusion, malignant pleural effusion is the common etiology of pleural effusion in patients with lymphoid malignancy. Many clinical and cytochemical markers have discriminatory values in identifying malignant effusion. A high pleural fluid to serum LDH level correlates with malignant pleural involvement and hospital mortality.

Lack of physician concordance with guidelines on the perioperative use of beta-blockers.

BACKGROUND: The American College of Physicians recommends perioperative use of beta-blockers for certain patients to improve outcomes after surgery. Study of physician behavior with respect to guidelines and recommended practices have shown that beta-blockers have been underutilized after myocardial infarction. We evaluated physician concordance with the perioperative use of beta-blockers along with a specialty-related difference in the frequency of perioperative beta-blocker use. METHODS: To determine perioperative use of beta-blockers, we retrospectively analyzed the medical charts of adult patients who underwent open cholecystectomy at a tertiary care medical center from December 1997 through December 2001. Patients met criteria for perioperative beta-blocker use if they had a history of coronary artery disease or if they had the presence of 2 or more of the following risk factors: 65 years or older; history of hypertension, diabetes mellitus, or hypercholesterolemia; or current smoking. RESULTS: Among the 336 cases of cholecystectomy reviewed, criteria for beta-blocker use were met in 146 patients (43%) who did not have emergency operations and/or contraindications to beta-blocker use. Of these 146 patients, 123 (84%) had a documented preoperative medical evaluation by a physician in the medical chart. There were 44 patients (30%) receiving beta-blockers prior to admission, and 102 patients (70%) were not receiving beta-blockers. Of those 102 patients not receiving beta-blockers at admission but who meet criteria for their use, 94 (92%) were not started on beta-blocker therapy preoperatively. Of the 18 patients evaluated by a cardiologist, 4 (22%) were started on beta-blocker therapy compared with 3 (6%) of 47 patients evaluated by a noncardiologist physician (P =.08). CONCLUSION: Perioperative beta-blocker therapy is underutilized in patients with risk factors for coronary artery disease despite evidence that its use in appropriate individuals may be lifesaving.

Legionella micdadei infection presenting as severe secretory diarrhea and a solitary pulmonary mass.

Sixty percent of infections with non-pneumophila species of Legionella are caused by Legionella micdadei. Although diarrhea is a common symptom of legionellosis, including that due to L. micdadei infection, severe, life-threatening diarrhea is rare. We describe a patient with profound secretory diarrhea (secretion rate, up to 8 L/day) that was secondary to culture-proven L. micdadei pneumonia. In addition, a 3-cm pulmonary nodule was detected, which completely resolved after proper treatment for Legionella infection. Resolving pulmonary nodules have been previously reported in association with treatment of L. micdadei infections.

Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease.

Bronchial-associated lymphoid tissue (BALT) lymphoma is a distinct subgroup of low-grade B-cell extranodal non-Hodgkin's lymphoma, classified as marginal-zone lymphoma. This study was performed in order to assess the natural history of this rare entity. We evaluated retrospectively the clinical data of 22 patients with biopsy-proven BALT lymphoma at two tertiary-care institutions from 1996 to 2002. Immunophenotyping was done to confirm the abnormal populations of B-lymphoid cells in all cases, and clonality was determined by flow cytometry or molecular studies. There were 11 men and 11 women in the sample, median age 61 years (range 21-80 years); nine were asymptomatic at diagnosis. All 13 symptomatic patients had non-specific pulmonary complaints. On computed tomographic examination of the chest, 11 patients had bilateral disease, 12 had lung nodules, and 10 had a mass or air-space consolidation. In all but one case the disease was localised to the lung at diagnosis and none had peripheral blood or bone marrow involvement. Out of 22 patients, 20 received treatment in various combinations, 12 had chemotherapy and/or rituximab, six had surgery, and two received radiation therapy as primary treatment. A complete response (CR) was achieved in nine patients and a partial response was obtained in 10 patients. Seven of 10 patients who had unilateral disease achieved a CR. The estimated progression-free survival was 53 months. All patients were alive during the median follow-up period of 36 months (range 12-76 months). It appears that BALT lymphoma tends to be localised to lung at the time of diagnosis, responds well to local or systemic therapy, and has a favourable prognosis.

Paradoxical arterial emboli causing acute limb ischemia in a patient with essential thrombocytosis.

Acute arterial occlusion can be the result of acute thrombosis or systemic embolism. Paradoxical embolism of a venous thrombosis through a right-to-left shunt is an important cause of acute limb ischemia. We describe a young patient with acute limb ischemia who was found to have multiple deep venous thromboses causing arterial embolization through a patent foramen ovale. Essential thrombocytosis was found to be the risk factor for venous thromboses in this patient. The patient was managed with embolectomy and anticoagulation along with chemotherapeutic cytoreduction of platelet count. This case illustrates the importance of considering the systemic embolism as a cause of acute arterial occlusion. The presence of a hypercoagulable status such as chronic myeloproliferative disorder does not eliminate the possibility of systemic embolism in the event of acute arterial occlusion. Patients presenting with acute limb ischemia should be evaluated for embolic sources. The presence of deep venous thrombosis in such a patient should prompt the evaluation for a patent foramen ovale.

Prolonged activated partial thromboplastin time in pregnancy: a brief report.

BACKGROUND: Limited data are available regarding causes of prolonged activated partial thromboplastin time (aPTT) in otherwise normal pregnancies. We retrospectively evaluated clinical data of pregnant women in whom an elevated aPTT was noted on routine prenatal testing. Our intent was to identify various causes of prolonged aPTT and to evaluate whether the pregnancies were adversely affected. METHODS: A retrospective review of medical records of 36 pregnant patients with a prolonged aPTT as the sole abnormal coagulation test seen in the outpatient department of a tertiary care hospital over a period of 4 years. RESULTS: Patients' median age was 26 (range, 19-41) years and median duration of gestation period was 19 (range, 8-38) weeks. Fifteen patients were primigravida. Of 36 patients, repeated aPTT values were normal in 24 (67%) patients, whereas 12 (33%) patients had persistently elevated aPTT values. Factor XI deficiency was found in 5 patients, lupus anticoagulant in 3 patients, elevated anticardiolipin antibody in 2 patients, and low von Willebrand Factor level in 1 patient. Overall, 23 patients delivered. No patients experienced excessive bleeding or thromboembolism. CONCLUSION: Factor XI deficiency and antiphospholipid antibody were 2 major abnormalities identified in patients with prolonged aPTT. These coagulopathies were not associated with excessive bleeding or thromboembolism. Repeat normal aPTT in approximately 2 thirds of patients suggests that proper sample collection and processing are important for coagulation assays to avoid erroneous clotting times.

Hemoglobin oxygen saturation discrepancy using various methods in patients with sickle cell vaso-occlusive painful crisis.

OBJECTIVE: To evaluate agreement among various methods for measuring oxyhemoglobin (O2Hb) saturation in adult hypoxic patients with sickle cell disease (SCD) during painful vaso-occlusive crisis and to compare those results with a control group. PATIENTS AND METHODS: The hemoglobin oxygen saturation was determined simultaneously by pulse oximetry (SpO2), co-oximetry [SO2 (functional oxyhemoglobin saturation) and FO2Hb (oxyhemoglobin fraction)] and by calculation (SaO2) using a normal O2Hb dissociation curve in 18 adult patients with SCD during vaso-occlusive crisis and 12 non-SCD patients with various cardiopulmonary diagnoses. The method proposed by Bland and Altman was used to evaluate agreement of various methods in each of the two groups. RESULTS: Mean differences between various methods in patients with SCD were significantly larger than the control group. Limits of agreement (LOA) were also wider in the SCD group than in the control group. Mean bias between SpO2 and SO2, and SpO2 and FO2Hb in patients with SCD were -3.1 +/- 4.4 (LOA: -11.9 to 5.7) and 2 +/- 4.1 (LOA: -6.2 to 10.2) respectively, compared with -1.4 +/- 1.4 (LOA: -4.2 to 1.4) and 1.2 +/- 1.5 (LOA: -1.9 to 4.3) in the control group. A mean bias of -4.5 +/- 4 (LOA: -12.5 to 3.5) between SpO2 and SaO2 was noted in patients with SCD compared with -0.1 +/- 2.1 (LOA: -4.3 to 4.1) in the control group. The width of LOA for various methods in patients with SCD ranged from 9.8 to 17.6 compared with 1.3 to 8.4 in the control group. CONCLUSION: Patients with SCD during vaso-occlusive crisis have discrepancies in O2Hb saturation measurements by various methods. Abnormal pulse oximetry values in these patients should be interpreted cautiously and supplemented by arterial blood gas analysis and co-oximetry.

Ventilator strategy for status asthmaticus in pregnancy: a case-based review.

Asthma is a common and potentially serious condition complicating pregnancy. However, the literature available on the management of severe asthma in pregnancy is limited. We describe two episodes of respiratory failure due to asthma in pregnant women and discuss their management in the context of a review of the literature. In both patients, adequate oxygenation was maintained by using controlled hypoventilation with a permissive hypercapnia strategy. Both patients received aggressive steroid therapy, aerosolized bronchodilators, sedation, and paralysis. Aggressive asthma treatment as in a nongravid female is recommended.

Acute pancreatitis during sickle cell vaso-occlusive painful crisis.

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to microvascular occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease.

Pulmonary complications in chronic lymphocytic leukemia.

BACKGROUND: Although pulmonary complications account for significant morbidity and mortality in patients with chronic lymphocytic leukemia (CLL), to the authors' knowledge there are sparse data available in published literature. The authors evaluated pulmonary complications in patients with CLL and identified prognostic variables that predict hospital mortality in these patients. METHODS: Clinical data were analyzed retrospectively from patients with CLL who required hospitalization for a respiratory illness at a tertiary care institution from January 1993 to December 2001. A logistic regression analysis with a backward elimination procedure was carried out to determine prognostic variables that predict hospital mortality. RESULTS: There were 110 patients who were admitted on 142 occasions with a pulmonary complication. The median age was 75 years (range, 43-97 years), and the male:female ratio was 1.7:1.0. Among 142 admissions, 68% were high risk according to the Rai criteria, 68% of patients admitted had received prior therapy for CLL, and 35% had received treatment within 3 months of admission. The most common pulmonary complications were pneumonias (75%), malignant pleural effusion/and or lung infiltrate due to CLL (9%), pulmonary leukostasis (4%), Richter transformation or nonsmall cell lung carcinoma (3%), and upper airway obstruction (2%). Forty-four of 110 patients (40%) died. In multivariate analysis, admission absolute neutrophil counts /= 20 mg/dL (odds ratio, 3.0; 95% CI, 1.1-8.3) were correlated significantly with mortality. CONCLUSIONS: Pneumonia was the major pulmonary complication in hospitalized patients with CLL. Severe neutropenia and high BUN levels were correlated significantly with increased mortality.

Prognostic variables in newly diagnosed childhood immune thrombocytopenia.

Immune thrombocytopenia (ITP) has a favorable prognosis in children. Only a small number of children go on to develop chronic ITP. However, at the time of diagnosis, it is not possible to predict the course of the disease. In order to determine prognostic factors that could predict the disease course at diagnosis, we retrospectively evaluated various clinical variables in 103 pediatric patients with newly diagnosed ITP at our institution from 1995 to 2001. Sixty-eight (66%) patients had a mean platelet volume (MPV) of <8 fL on admission. Of 72 patients who had a follow-up period of at least 6 months, 54 (75%) achieved a durable remission within 6 months and 18 (25%) developed chronic ITP. In univariate analysis, a low admission MPV (<8), history of viral prodrome, and a low admission platelet count (<10 x 10(9)/L) predicted for a favorable outcome. Age and sex did not correlate with remission. In multivariate analysis, a low admission MPV and a history of a viral prodrome were the only independent factors correlated with a durable CR. The adjusted odds ratio for achieving a durable remission was 8.9 (95% CI: 1.54-51.8) for history of a viral prodrome and 14 (95% CI: 2.52-83.3) for low admission MPV value. In conclusion, our study showed that a majority of the children with newly diagnosed ITP presented with a low MPV value. A history of viral illness and a low admission MPV were found to be independent prognostic variables that predicted for the achievement of a durable CR in childhood ITP.

Echocardiographic abnormalities in sickle cell disease.

Echocardiographic abnormalities in patients with sickle cell disease (SCD) were determined, and pulmonary arterial systolic pressure (PASP) was estimated. Clinical data and echocardiograms of 38 adult hospitalized patients with SCD at two tertiary care hospitals were reviewed. Fisher's exact test was performed to determine correlation between pulmonary hypertension and various clinical variables. Pulmonary hypertension was the most common abnormality identified in 22 (58%) patients. The estimated mean PASP was 37.5 +/- 10.9 mmHg. Older age and prior history of acute chest syndrome were significantly correlated with an increased prevalence of pulmonary hypertension (P < 0.05). Patients with hemoglobin levels <8 g/dL had PASP 43.2 +/- 0.5 compared to a mean PASP of 33.3 +/- 6.0 in patients with hemoglobin > or =8 g/dL (P = 0.01). Eight (21%) patients had evidence of a hyperdynamic left ventricle. Left heart abnormalities included dilated atrium in 14 (37%), dilated ventricle in 5 (13%), ventricle hypertrophy in 5 (13%), and ventricle dysfunction in 3 (9%) patients. Right heart abnormalities included dilated atrium in 9 (24%), dilated ventricle in 6 (16%), and ventricle dysfunction in 3 (9%) patients. Despite an increased incidence of abnormal flow across the valves on Doppler analysis, no patient had structurally abnormal valves. A majority of patients with SCD had evidence of pulmonary hypertension, which correlated with older age and history of acute chest syndrome. Other structural and functional echocardiographic abnormalities were less common.

Effect of low-dose warfarin on D-dimer levels during sickle cell vaso-occlusive crisis: a brief report.

OBJECTIVE: To evaluate the activation of clotting systems in patients with sickle cell disease (SCD) by measuring the plasma D-dimer level and to determine the effect of low-dose warfarin on D-dimer level during vaso-occlusive crisis. METHODS: Plasma D-dimer level was measured in 65 blood samples of 37 adult patients with SCD who were hospitalized for vaso-occlusive painful crisis. D-dimer level of patients who were on low-dose warfarin was compared with those patients who were not on any anticoagulation treatment. Analysis of variance (anova) was carried out to determine factors significantly associated with low D-dimer level in patients with SCD. The following factors were included in the anova model; warfarin, homozygous hemoglobin S, history of blood transfusion in past 3 months, hydroxyurea, hemoglobin S%, hemoglobin F%, white blood cell counts, hemoglobin level, platelet count, and plasma fibrinogen level. RESULTS: Overall median D-dimer level in 65 samples was 2.7 microg fibrinogen equivalent units (FEU)/mL (0.34-4). Patients who were on low-dose warfarin had a median D-dimer level of 0.81 microg FEU/mL (0.34-1.8) compared with 3.1 microg FEU/mL (0.94-4) in those patients who were not on anticoagulation treatment. Using anova to model D-dimer levels, only warfarin was significantly correlated with low D-dimer levels after controlling for other variables. CONCLUSIONS: Patients with SCD during vaso-occulsive painful crisis have an elevated D-dimer level. Low-dose anticoagulation treatment is associated with a significant reduction in the D-dimer levels.