Hereditary Amyloidosis with Recurrent Lung Infiltrates.

BACKGROUND Amyloidosis is a protein conformational disorder characterized by extracellular deposition of amyloid fibrils in extracellular tissue. Lung involvement is most commonly caused by secondary AL amyloidosis. The familial autosomal-dominant senile transthyretin (ATTR) disease manifests mainly as polyneuropathy and restrictive cardiomyopathy denoting the name familial amyloidotic polyneuropathy (FAP). Rarely, this form manifests with clinical and radiologically relevant respiratory tract symptoms and lung involvement. CASE REPORT A 51-year-old male former smoker presented with progressive lower-extremity weakness of several months' duration. He was ultimately diagnosed with chronic demyelinating polyneuropathy and treated with intravenous immunoglobulin therapy. Subsequently, he was admitted with heart failure symptoms and pulmonary infiltrates and his echocardiogram showed a 'myocardial speckled pattern', prompting an endomyocardial biopsy, which showed transthyretin amyloid deposition. He was started on diflunisal. Additionally, serial radiographic imaging of his chest over 3 different admissions for cough, dyspnea, hypoxemia, and lethargy demonstrated recurrent pulmonary infiltrates. A fiberoptic bronchoscopy with trans-bronchial biopsies revealed amyloid deposition in the lung tissue. CONCLUSIONS The clinical presentation of recurrent or persistent pulmonary symptoms and fleeting infiltrates on imaging in a patient with familial amyloidotic polyneuropathy is not common; when present, it should raise the suspicion of respiratory tract involvement.

Efficacy and adverse effects of drugs used to treat adult cystic fibrosis.

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disease and is the most commonly seen monogenetic disease in Caucasians. The disease has various manifestations resulting from the abnormal thick secretions, most common being chronic lung infection and airway obstruction. Many new promising drugs have appeared on the horizon over the years. This review here is an attempt to bring together the various treatments being used to prolong and enhance the quality of life of CF patients. AREAS COVERED: A literature review of published as well as ongoing clinical trials, meta-analysis and systematic reviews regarding the drugs used in CF management was carried out using PubMed and Ovid databases. EXPERT OPINION: New concepts have been formed and some positive results in this direction have already led to the approval of cystic fibrosis transmembrane conductance regulator potentiator drug. Gene therapy and stem cell therapy are under development. The current therapies such as dornase alfa and pancreatic enzymes targeting the symptoms continue to evolve as they play an important complementary role. Development of new simple and cost-effective markers, which help assess the efficacy and safety of these constantly emerging new drugs, is also being investigated.

Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability.

BACKGROUND: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infection. To determine the impact and sustainability of the effect of chlorhexidine bathing on central venous catheter-associated bloodstream infection, we performed a prospective, 3-phase, multiple-hospital study. METHODS: In the medical intensive care unit and the respiratory care unit of a tertiary care hospital and the medical-surgical intensive care units of 4 community hospitals, rates of central venous catheter-associated bloodstream infection were collected prospectively for each period. Pre-intervention (phase 1) patients were bathed with soap and water or nonmedicated bathing cloths; active intervention (phase 2) patients were bathed with 2% chlorhexidine gluconate cloths with the number of baths administered and skin tolerability assessed; post-intervention (phase 3) chlorhexidine bathing was continued but without oversight by research personnel. Central venous catheter-associated bloodstream infection rates were compared over study periods using Poisson regression. RESULTS: Compared with pre-intervention, during active intervention there were significantly fewer central venous catheter-associated bloodstream infections (6.4/1000 central venous catheter days vs 2.6/1000 central venous catheter days, relative risk, 0.42; 95% confidence interval, 0.25-0.68; P<.001), and this reduction was sustained during post-intervention (2.9/1000 central venous catheter days; relative risk, 0.46; 95% confidence interval, 0.30-0.70; P<.001). During the active intervention period, compliance with chlorhexidine bathing was 82%. Few adverse events were observed. CONCLUSION: In this multiple-hospital study, chlorhexidine bathing was associated with significant reductions in central venous catheter-associated bloodstream infection, and these reductions were sustained post-intervention when chlorhexidine bathing was unmonitored. Chlorhexidine bathing was well tolerated and is a useful adjunct to reduce central venous catheter-associated bloodstream infection.

Cardiac sarcoidosis: a comprehensive review.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by noncaseating granulomas in involved organs. Organs involved with sarcoidosis include lymph nodes, skin, lung, central nervous system, and eye. Only 40-50% of patients with cardiac sarcoidosis diagnosed at autopsy have the diagnosis made during their lifetime. Cardiac sarcoidosis can manifest itself as complete heart block, ventricular arrhythmias, congestive heart failure, pericardial effusion, pulmonary hypertension, and ventricular aneurysms. Diagnostic tests such as the electrocardiogram, two-dimensional echocardiography, cardiac magnetic resonance imaging, positron emission tomography scan, radionuclide scan, and endomyocardial biopsy can be helpful in the early detection of cardiac sarcoidosis. Considering the increased risk of sudden death, cardiac sarcoidosis is an indication for early treatment with corticosteroids or other immunosuppressive agents. Other treatments include placement of a pacemaker or implantable defibrillator to prevent sudden death. In refractory cases, cardiac transplantation should be considered.

Lung cancer: the importance of early intervention.

Lung cancer is the leading cause of cancer death in the United States. Fifteen percent of patients are asymptomatic at diagnosis. Symptoms usually indicate advanced disease. Signs include chronic cough, hemoptysis, wheezing, dyspnea, vague chest pain, hoarseness, pleural effusion, cardiac arrhythmias and bone pain. Significant surgical advances have reduced operational mortality rate. Early detection and surgery can increase survival rates for some patients.

Association of lung volumes with nocturnal oxygen saturation in obese persons: a possible role for therapeutic continuous positive airway pressure.

We investigated the association among obesity, nocturnal oxygen saturation, and pulmonary function in 31 obese women and 17 obese men scheduled for bariatric surgery who underwent nocturnal polysomnography and pulmonary function testing. Pearson correlation coefficients showed a significant association between expiratory reserve volume percent and average oxygen saturation (P = 0.027), between body mass index and lowest oxygen saturation (P = 0.034), and between body mass index and average oxygen saturation (P = 0.039). The mean age, body mass index, expiratory reserve volume percent, and functional residual capacity percent were not significantly different between obese women and men. The lowest oxygen saturation was 80 +/- 10% in obese women and 62 +/- 19% in obese men (P = 0.001). The average oxygen saturation was 88 +/- 5% in obese women and 83 +/- 6% in obese men (P = 0.005) Therapeutic nocturnal continuous positive airway pressure may have a role by improving ventilation-perfusion matching and thereby improving nocturnal oxygen saturation in these patients.

Prediction of moderate or severe pulmonary hypertension by main pulmonary artery diameter and main pulmonary artery diameter/ascending aorta diameter in pulmonary embolism.

We investigated the accuracy of computed tomographic measurements of main pulmonary artery diameter (MPAD) and of MPAD/ascending aorta diameter (AAD) in predicting moderate or severe pulmonary hypertension in 190 patients with acute pulmonary embolism. A pulmonary artery systolic pressure of > or = 50 mm Hg measured by Doppler echocardiography was considered moderate or severe pulmonary hypertension. A MPAD of > 28.6 mm and a MPAD/AAD ratio of > or = 1.00 measured by computed tomography were considered abnormal. A MPAD of > 28.6 mm had a 75% sensitivity and specificity, a 52% positive predictive value, a 89% negative predictive value, a 3.0 likelihood ratio for a positive test, and a 0.33 likelihood ratio for a negative test in predicting moderate or severe pulmonary hypertension. A MPAD/AAD ratio of > or = 1.00 had a 59% sensitivity, a 82% specificity, a 55% positive predictive value, a 84% negative predictive value, a 3.3 likelihood ratio for a positive test, and a 0.50 likelihood ratio for a negative test.

Hyponatremia and cerebrovascular spasm in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Hyponatremia develops in approximately a third of patients with aneurysmal subarachnoid hemorrhage (SAH). Studies have been conflicting about the association between hyponatremia and cerebrovascular spasm (CVS). AIMS: To investigate whether hyponatremia can signal the onset of CVS. SETTINGS AND DESIGN: Retrospective chart review of all patients with SAH treated at a tertiary-care university hospital from January to May 2002. MATERIALS AND METHODS: 106 patients were included in the study. Serum sodium levels were recorded from days 1 to 14 of hospitalization. Hyponatremia was defined as serum sodium level<135 meq/l and a fall in sodium level of >4 meq/l from the admission sodium level. The presence of CVS was determined by transcranial doppler sonography. Patients were assigned to one of four groups based on the presence or absence of CVS and hyponatremia. STATISTICAL ANALYSIS: Student's t-test was used for comparison of means. A logistical regression model was constructed and odds ratios (OR) were calculated. RESULTS: 41 patients developed hyponatremia and 44 developed CVS. Among the 41 with hyponatremia, 22 (54%) had evidence of CVS, whereas among the 65 patients without hyponatremia, 22 (34%) had evidence of CVS (P=0.023). Among those with hyponatremia, the mean sodium drop was 7.9 meq/L in those with CVS compared to 7.0 meq/L in those without CVS (P=0.068). More than half of those with hyponatremia and CVS (13/22) developed hyponatremia at least a day before CVS was diagnosed. CONCLUSION: In patients with SAH, hyponatremia is associated with a significantly greater risk of developing CVS and may precede CVS by at least one day.

Prevalence of left ventricular hypertrophy in persons with and without obstructive sleep apnea.

We investigated the prevalence of left ventricular hypertrophy (LVH) in persons with and without obstructive sleep apnea (OSA). Fifty-three persons had a nocturnal polysomnogram to diagnose OSA and 2-dimensional echocardiograms to measure left ventricular mass. OSA was considered mild if the respiratory disturbance index (RDI) was 5 to 15, moderate if the RDI was 15 to 30, and severe if the RDI was >30. LVH was diagnosed if the left ventricular mass index was >110 g/m in women and >134 g/m in men. LVH was present in 21 of 27 persons (78%) with moderate or severe OSA, in 6 of 13 persons (46%) with mild OSA, and in 3 of 13 persons (23%) with no OSA (P < 0.001 comparing moderate or severe OSA with no OSA and P < 0.05 comparing moderate or severe OSA with mild OSA). OSA was a significant independent predictor of LVH after controlling the confounding effects of hypertension with an odds ratio of 3.579 (95% confidence interval, 1.589-8.058).

Association of reduced carbon monoxide diffusing capacity with moderate or severe left ventricular diastolic dysfunction in obese persons.

STUDY OBJECTIVES: To determine the association of reduced diffusing capacity of the lung for carbon monoxide (D(LCO)) with moderate or severe left ventricular diastolic dysfunction (LVDD) in obese persons. DESIGN: We investigated the association of D(LCO) with LVDD in 105 patients with a mean +/- SD body mass index of 49 +/- 5 kg/m2. An abnormal D(LCO) was < 80%. LVDD was investigated by Doppler and by tissue Doppler echocardiography. The Doppler echocardiographic data were analyzed blindly without knowledge of the clinical characteristics or whether the D(LCO) was normal or abnormal. SETTING: A university hospital. PATIENTS: The 105 patients included 19 men and 86 women (mean age, 45 +/- 9 years). RESULTS: An abnormal D(LCO) was present in 62 of 105 patients (59%). Moderate or severe LVDD was present in 35 of 105 patients (33%). Moderate or severe LVDD was present in 25 of 62 patients (40%) with an abnormal D(LCO) and in 10 of 43 patients (23%) with a normal D(LCO) (p < 0.05). CONCLUSION: Obese patients with a decreased D(LCO) have an increased prevalence of moderate or severe LVDD.

Efficacy of unfractionated heparin for thromboembolism prophylaxis in medical patients.

A common mode of deep vein thrombosis prophylaxis in medical inpatients is unfractionated heparin 5000 U subcutaneously (s.q.) twice daily. We examined the evidence in favor of using this dose of heparin in this group of patients. MEDLINE was searched for studies using the words deep vein thrombosis prophylaxis and heparin. All randomized controlled trials comparing heparin and placebo or heparin and a low molecular weight heparin were used. Relative risk was 0.4 (95% confidence interval 0.22-0.73) in studies comparing heparin 5000 U s.q. b.i.d. with placebo. Relative risk was 0.28 (95% confidence interval 0.21-0.38) in studies comparing heparin 5000 units s.q. t.i.d. versus placebo. In studies comparing unfractionated heparin with enoxaparin relative risk was 1.42 (95% confidence interval 0.99-2.05). Heparin 5000 U s.q. b.i.d. is less efficacious than low molecular weight heparins and unfractionated heparin 5000 U s.q. t.i.d.

Role of the 12-lead electrocardiogram in diagnosing pulmonary embolism.

We investigated the role of the standard 12-lead electrocardiogram (ECG) to improve the pretest probability of pulmonary embolism before performing computed tomographic (CT) pulmonary angiography. A retrospective chart analysis was performed on patients who underwent CT pulmonary angiography at a tertiary care hospital during a 30-month period. Comparison of 15 ECG parameters was made between those with CT pulmonary angiograms positive for pulmonary embolism and a matched control group with negative CT pulmonary angiograms. Data were analyzed by chi-squared tests and logistic regression. Sinus tachycardia (39% vs. 24%, P <0.01), an S1 Q3 T3 pattern (12% vs. 3%, P <0.01), atrial tachyarrhythmias (15% vs. 4%, P <0.005), a Q wave in lead III (40% vs. 26%, P <0.02), and a Q3 T3 pattern (8% vs. 1%, P <0.02) were the findings significantly associated with pulmonary embolism. We conclude that 1) standard 12-lead ECG findings can increase the pretest probability of pulmonary embolism before performing CT pulmonary angiography; and that 2) the ECG findings have relatively low likelihood ratios to have clinical use.

Natural history of colonization with vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and resistant gram-negative bacilli among long-term-care facility residents.

OBJECTIVE: To determine the natural history of colonization with vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and resistant gram-negative bacilli among long-term-care facility (LTCF) residents. DESIGN: Observational cohort study. SETTING: A 355-bed LTCF with a ventilator unit and a subacute unit. PARTICIPANTS: Residents with colonization or infection with VRE, MRSA, or resistant gram-negative bacilli housed at the LTCF between December 1, 1999, and February 29, 2000. METHODS: Cultures of clinical and surveillance sites were performed at regular intervals. Charts were reviewed for clinical characteristics associated with clearance of colonization. Kaplan-Meier curves were constructed to analyze the number of days to clearance of colonization. RESULTS: Forty-nine residents had 65 episodes of colonization (27 VRE, 30 MRSA, and 8 resistant gram-negative bacilli). Eighteen (28%) of the episodes cleared. The clearance rate was 2.7 episodes per 1,000 person-days. Clearance occurred significantly more often with resistant gram-negative bacilli colonization compared with VRE or MRSA colonization (6 [75%] vs 12 [21%]; P = .007; relative risk, 4.17; 95% confidence interval, 1.26 to 11.8). There was a trend toward longer use of antimicrobial agents among residents with persistent colonization. Infections occurred most frequently with MRSA. The urinary tract was the most common site of infection. CONCLUSION: Among LTCF residents, colonization with resistant gram-negative bacilli is four times more likely to clear than colonization with VRE or MRSA. Performance of surveillance cultures at regular intervals may reduce the need for contact precautions for LTCF residents with resistant gram-negative bacilli colonization.

Cardiovascular consequences of sleep-related breathing disorders.

Sleep-related breathing disorders (SRBDs) represent a spectrum of abnormalities that range from simple snoring to upper airway resistance syndrome to sleep apnea. The clinical presentation may include obesity, snoring, neuropsychological dysfunction, and daytime hypersomnolence and tiredness. The acute hemodynamic alterations of obstructive sleep apnea include systemic and pulmonary hypertension, increased right and left ventricular afterload, and increased cardiac output. Earlier reports attributed the coexistence of SRBDs with cardiovascular diseases to the shared risk factors such as age, sex, and obesity. However, recent epidemiologic data confirm an independent association between SRBDs and the different manifestations of cardiovascular diseases. Possible mechanisms may include a combination of intermittent hypoxia and hypercapnia, repeated arousals, sustained increase in sympathetic tone, reduced baroreflex sensitivity, increased platelet aggregation, and elevated plasma fibrinogen and homocysteine levels. The strength of the association, its pathogenesis, and the impact of treatment of SRBDs on the health outcome of patients with cardiovascular diseases are issues to be addressed in future studies.