Assessment of transient ischemic dilation (TID) ratio in gated SPECT myocardial perfusion imaging (MPI) using regadenoson, a new agent for pharmacologic stress testing.

BACKGROUND: Abnormal values of the transient ischemic dilation (TID) ratio are associated with severe and extensive coronary artery disease (CAD). The objective of this study was to determine the relationship between TID, determined from stress and rest ventricular volumes during regadenoson gated single-photon emission computed tomography myocardial perfusion imaging (MPI) dual isotope studies, and the extent of CAD found during coronary angiography. METHODS: 195 patients who underwent dual isotope MPI with regadenoson and cardiac angiography between March 2009 and February 2010 were analyzed. TID was calculated using commercially available software, Emory Cardiac Toolbox. Mean TID values were compared across disease types. A threshold for abnormal TID was determined by adding two standard deviations (SDs) to the mean TID of the "non-obstructive CAD" subgroup. RESULTS: In the 195-patient group analyzed, the mean TID ratio for non-obstructive CAD (n = 104) was found to be 1.09 with a SD of 0.15. In a subgroup of patients whose angiogram was within 3 months of MPI (n = 155), the mean TIDs for non-obstructive disease (n = 81), single-vessel disease (n = 35), and multi-vessel disease (n = 39) were 1.09, 1.15, and 1.19 with SDs of 0.16, 0.19, and 0.26, respectively. Those with an abnormal TID had a crude and adjusted odds ratio of 3.4 for multi-vessel disease which was statistically significant. History of diabetes was not found to be a significant confounder, effect modifier, or mediator of the relationship between the TID and the vessel disease. CONCLUSION: The mean TID ratio in patients with multi-vessel disease was 1.19. The threshold for an abnormal TID was 1.39 with specificity of 95% and sensitivity of 15% for determining multi-vessel CAD status. We conclude that the level of TID in gated SPECT MPI using regadenoson is associated with the degree of CAD on angiography.

Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: examining a more efficient trial design.

OBJECTIVE: To use a historical placebo control design to determine whether lithium carbonate slows progression of amyotrophic lateral sclerosis (ALS). METHODS: A phase II trial was conducted at 10 sites in the Western ALS Study Group using similar dosages (300-450 mg/day), target blood levels (0.3-0.8 mEq/L), outcome measures, and trial duration (13 months) as the positive trial. However, taking riluzole was not a requirement for study entry. Placebo outcomes in patients matched for baseline features from a large database of recent clinical trials, showing stable rates of decline over the past 9 years, were used as historical controls. RESULTS: The mean rate of decline of the ALS Functional Rating Scale-Revised was greater in 107 patients taking lithium carbonate (-1.20/month, 95% confidence interval [CI] -1.41 to -0.98) than that in 249 control patients (-1.01/month, 95% CI -1.11 to -0.92, p = 0.04). There were no differences in secondary outcome measures (forced vital capacity, time to failure, and quality of life), but there were more adverse events in the treated group. CONCLUSIONS: The lack of therapeutic benefit and safety concerns, taken together with similar results from 2 other recent trials, weighs against the use of lithium carbonate in patients with ALS. The absence of drift over time and the availability of a large database of patients for selecting a matched historical control group suggest that use of historical controls may result in more efficient phase II trials for screening putative ALS therapeutic agents. CLASSIFICATION OF EVIDENCE: This study provided Class IV evidence that lithium carbonate does not slow the rate of decline of function in patients with ALS over 13 months.

Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS). METHODS: The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. Topics covered in this section include breaking the news, multidisciplinary clinics, symptom management, cognitive and behavioral impairment, communication, and palliative care for patients with ALS. RESULTS: The authors identified 2 Class I studies, 8 Class II studies, and 30 Class III studies in ALS, but many important areas have been little studied. More high-quality, controlled studies of symptomatic therapies and palliative care are needed to guide management and assess outcomes in patients with ALS. RECOMMENDATIONS: Multidisciplinary clinic referral should be considered for managing patients with ALS to optimize health care delivery and prolong survival (Level B) and may be considered to enhance quality of life (Level C). For the treatment of refractory sialorrhea, botulinum toxin B should be considered (Level B) and low-dose radiation therapy to the salivary glands may be considered (Level C). For treatment of pseudobulbar affect, dextromethorphan and quinidine should be considered if approved by the US Food and Drug Administration (Level B). For patients who develop fatigue while taking riluzole, withholding the drug may be considered (Level C). Because many patients with ALS demonstrate cognitive impairment, which in some cases meets criteria for dementia, screening for cognitive and behavioral impairment should be considered in patients with ALS (Level B). Other management strategies all lack strong evidence.

Malnutrition-induced myopathy following Roux-en-Y gastric bypass.

A 42-year-old man developed a myopathy in the setting of malnutrition following Roux-en-Y gastric bypass for the treatment of morbid obesity. No specific vitamin or electrolyte deficiency was identified. Muscle biopsy revealed type II fiber atrophy. He recovered after the initiation of continuous enteral feeding. We suggest that malnutrition was the underlying cause of his myopathy.

Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome.

We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.

Outcome in severe pediatric Guillain-Barré syndrome after immunotherapy or supportive care.

We reviewed duration of illness in 26 children with severe pediatric Guillain-Barré syndrome (GBS) during two contiguous 8-year periods that represent a "non-treatment era" of supportive care alone or a "treatment era" of supportive care plus either plasma exchange or intravenous immunoglobulin intervention. Our findings of similar recovery times in each treatment group suggest that immunotherapy in severe pediatric GBS may be less effective than in adult GBS, or effective only when given to certain patients very early in the course of the illness.

Acetylcholine receptor antibodies in the Lambert-Eaton myasthenic syndrome.

Two patients were initially diagnosed with myasthenia gravis with elevated titers of acetylcholine receptor antibodies. Features including weakness that normalized with sustained contraction, areflexia, autonomic symptoms, and low-amplitude baseline compound muscle action potentials with abnormal increments following brief exercise and high-frequency repetitive stimulation, however, suggested that these patients had Lambert-Eaton myasthenic syndrome. One patient had antibodies directed against presynaptic calcium channels, confirming the diagnosis. The second patient was seronegative for these antibodies but had elevated titers of antistriated muscle antibodies. This shows that serologic studies can conflict with clinical and electrodiagnostic findings in patients with Lambert-Eaton syndrome. These cases also point out that acetylcholine receptor antibodies are not necessarily diagnostic of myasthenia gravis in patients with Lambert-Eaton syndrome. Instead, these antibodies could represent a nonpathogenic epiphenomenon.

Inclusion body myositis: clinical and pathological boundaries.

Inclusion body myositis, polymyositis, and dermatomyositis are three distinct categories of inflammatory myopathy. Some authorities commented on the selective early weakness of the volar forearm muscles, quadriceps, and ankle dorsiflexors in inclusion body myositis. The most important feature distinguishing inclusion body myositis from the other two inflammatory myopathies is the lack of responsiveness to immunosuppressive treatment. Although most patients with inclusion body myositis have characteristic muscle biopsy findings, some cannot be distinguished histologically early from polymyositis. Predicting responsiveness to immunosuppressive medications, independent of muscle histology, would be valuable to clinicians. We retrospectively reviewed the pattern of weakness and other clinical features of 46 patients newly diagnosed with either inclusion body myositis, polymyositis, or dermatomyositis. Asymmetrical muscle weakness with prominent wrist flexor, finger flexor, and knee extensor involvement was specific for inclusion body myositis and unresponsive polymyositis. Male sex, lower creatine kinase levels, slower rate of progression, and peripheral neuropathy were also more common in inclusion body myositis and unresponsive polymyositis than in responsive polymyositis and dermatomyositis patients. Repeat muscle biopsy in 2 patients in the unresponsive polymyositis group demonstrated histological features of inclusion body myositis. We suspect that patients with clinical features of inclusion body myositis but lacking histological confirmation may nonetheless have inclusion body myositis. Our study supports the recently proposed criteria for definite and possible inclusion body myositis.

Tracheobronchial epithelial multinucleation, viral inclusion bodies and malignant disease.

Patients with malignant disease are known to have an increased incidence of multinucleation in their tracheobronchial ciliated epithelial cells as compared with controls matched by age, sex and smoking habit. A seasonal relationship of viral inclusion bodies in the cilated epithelium of asymptomatic subjects has also been shown and is not related to age, sex and smoking habit. We have conducted an epidemiologic study to determine the possible relationships between these factors. Smears from 4,150 patients with a wide variety of pathologic conditions were examined for the presence of viral inclusions and multinucleated, ciliated epithelial cells. High degress of multinucleation were observed least frequenctly in the summer both in patients with and without known malignancy. Cytoplasmic inclusion bodies were also seen least frequently in the summer and autumn both in patients with and without know malignancy. In the presence of cancer, multinucleated epithelial cells and inclusion bodies were seen more frequently regardless of the season. When the seasonal incidence of multinucleated cells in 155 smears containing viral inclusion bodies was analyzed, it was found that patients without cancer had the lowest levels of multinucleation in the summer, whereas cancer patients had a depressed incidence of multinucleation in the winter and spring. Respiratory viruses may have a specific effect on the ciliated epithelium of cancer patients.

Malignant disease and tracheobronchial epithelial multinucleation.

Multinucleation of noncancerous ciliated tracheobronchial epithelial cells seen in smears from 412 patients suffering from malignant tumors originating from a wide variety of organs was found to be 2.03 times more frequent than in a control group without prediagnosed malignant disease, matched by age (decades), sex, and smoking habit (p less than 0.0005). Multinucleation involving at least 3% of cells was seen four times more frequently in patients with invasive tumors without known metastases than in controls. Excessive smoking habit in control females as well as site of origin and stage of tumor influenced statistical significance, otherwise unaffected by age, sex, and smoking habit in males. A prospective study is being planned in which incidence and degree of tracheobronchial epithelial multinucleation will be used in conjunction with biochemical tests for the diagnosis of occult cancer.

Viral inclusion bodies in tracheobronchial epithelium of asymptomatic subjects.

During a survey conducted for the cytodiagnosis of early bronchogenic carcinoma, cytoplasmic viral inclusion bodies were found sporadically in tracheobronchial smears of asymtomatic patients of both sexes (ages ranging from 18 to 80 years) undergoing general endotracheal anesthesia for surgery. A review of 3,049 cases performed to assess the frequency of occurrence of this phenomenon showed a 1.1 percent incidence in all smears studied. There was no relationship between smoking habit, age, or sex and the presence of inclusion bodies; however, there was a marked seasonal incidence, with 60 percent of inclusion-bearing smears being found during the months of January through March.

Tracheobronchial and pulmonary cytologic changes in shock.

Smears were made from tracheobronchial washings of patients undergoing general endotracheal anesthesia for surgery. Morphologically abnormal histiocytes were noticed in specimens obtained from subjects during hemorrhagic shock. These cells were overloaded with Papanicolaou stain (a greenish orange compound) which compressed the nucleus against the cell membrane. Cytochemical staining methods were undertaken to discover the composition of this substance. In secretions suctioned from ten patients in shock, large numbers of histiocytes were found to have ingested inorganic iron detectable by the Prussian blue method. Only two patients from a matched control group had smears in which this phenomenon was discovered. The maximum proportion of histiocytes containing Prussian blue granules was 40% for patients in shock and only 2% in normal controls. Histologic studies conducted on rats submitted to hemorrhagic shock were carried out to investigate this phenomenon. Iron-laden histiocytes were found in the kidneys, spleen, and lungs of both shocked and control animals. However, substantially more histiocytes containing Prussian blue positive granules were discovered in the lungs of rats in shock than in controls. It may, therefore, be that iron is deposited in the lungs in low flow states.

Tracheobronchial epithelial multinucleation in malignant disease.

Multinucleated tracheobronchial ciliated epithelial cells seen in smears from 112 patients suffering from a wide variety of malignant tumors were found to be 2.08 times more numerous than in a control group comparable in sex, age (decades), and smoking habit but without prediagnosed malignancies. The recognition of this phenomenon may lead to the development of a new test for the diagnosis of occult cancer and may open new pathways for investigation of cancer-host relationships.