Central sleep apnea and atrial fibrillation: A review on pathophysiological mechanisms and therapeutic implications.

Precipitating factors and chronic diseases associated with atrial fibrillation (AF) are detailed in the literature. Emerging evidence over the last several decades suggests a potential causal relationship between central sleep apnea (CSA) and AF. Mechanisms including apnea-induced hypoxia with intermittent arousal, fluctuating levels of carbon dioxide, enhanced sympathetic/neurohormonal activation and oxidative stress causing inflammation have been implicated as etiologic causes of AF within this subpopulation. CSA affects the efficacy of pharmacologic and catheter-based antiarrhythmic treatments, which is why treating CSA prior to these interventions may lead to lower rates of AF. Subsequently, a reduction in the AF burden with transvenous phrenic nerve stimulation (TPNS) has become a topic of interest. The present review describes the relationship between these conditions, pathophysiologic mechanisms implicating the role of CSA in development of AF, and emerging therapeutic interventions.

The association between obstructive sleep apnea syndrome and microvascular complications in well-controlled diabetic patients.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) may promote hyperglycemia and insulin resistance. OBJECTIVE: We studied the link between sleep apnea and microvascular diabetic complications in veterans with type 2 diabetes mellitus (DM-2). DESIGN: A retrospective electronic chart of all veterans referred for sleep studies over a 1-year period was reviewed. Ninety-eight patients with a glycosylated hemoglobin < 6.5% were included in the study. The degree of glycemia (HbA1c) and presence of macro- and microvascular complications were compared with OSAS variables. METHOD: Statistical analysis examined bivariate associations between OSAS variables and metabolic syndrome parameters. RESULTS: The apnea hypopnea index was significantly related to diabetic microvascular complications, particularly retinopathy. Oxygen desaturation was significantly and inversely related to microalbuminuria, microvascular complications, retinopathy, and HbA1c. CONCLUSIONS: Sleep apnea is associated with microvascular complications even in well-controlled DM-2 veterans. CLINICAL IMPLICATIONS: Screening for OSAS should be considered in patients with DM-2.

The occurrence of stiff person syndrome in a patient with thymoma: case report and literature review.

Stiff-person syndrome (SPS) is a rare disorder that affects the central nervous system, being characterized by intermittent episodes of muscle spasms, rigidity, and a significant increase in morbidity and mortality. We report a 29-year-old patient, with left-sided chylothorax and thymoma, who presented with truncal, lower extremities stiffness and painful cramps alleviated by diazepam and opiates. His clinical picture was suggestive of SPS secondary to invasive thymoma. This syndrome is best approached by its early recognition and prompt treatment since a missed diagnosis can have deleterious outcome. An intensive search for the underlying etiology is of utmost importance in the management of SPS. A review of the current literature is also included in this manuscript.

Respiratory failure in a 70-year-old veteran.

In Western countries the incidence of amyotrophic lateral sclerosis (ALS) is 1.89 per 100,000 per year and the prevalence is 5.2 per 100,000. The incidence of ALS is lower among African, Asian, and Hispanic ethnicities when compared to Caucasians. The mean age of onset for sporadic ALS is about 60 years and there is a slight male predominance (male to female ratio of 1.5 to 1). Approximately two thirds of patients with ALS have the spinal form of the disease with symptoms presenting in the extremities. Patients typically have evidence of both lower motor neuron degeneration (atrophy, weakness, and fasciculations) and upper motor neuron degeneration (spasticity, weakness, and hyperreflexia). Patients with limb onset ALS typically complain of focal muscle weakness and wasting. The symptoms may start either distally or proximally in the upper and/or lower limbs. Gradually spasticity develops in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS typically present with dysarthria and dysphagia for solid or liquids. Limb symptoms can develop simultaneously with bulbar onset. In the vast majority of patients, limb weakness will occur within 1-2 years of bulbar onset ALS symptoms. A case of bulbar and sporadic limb ALS in a 70-year-old veteran, presenting with right diaphragmatic paralysis and respiratory failure, is presented.

Reduction of amiodarone pulmonary toxicity in patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

BACKGROUND: Amiodarone (AM) is a widely used anti-arrhythmic medication. Its utility is, however, limited by adverse side effects. The mechanism of amiodarone-induced toxicity (APT) in the lungs is attributed primarily to stimulation of the angiotensin enzyme system leading to lung cell apoptosis and cell death. This mechanism has been demonstrated by in vitro and in vivo experimental animal studies. To date, however, no in vivo human studies have confirmed this mechanism for APT. PURPOSE: This study was undertaken to determine whether angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) offer a protective effect against APT in humans. Demonstration of a protective effect of an ACE-I or ARB would suggest that stimulation of the angiotensin enzyme system may be a key process in APT. DESIGN: An 8-year retrospective analysis of all patients on AM therapy at the James H. Quillen Veterans Affairs Medical Center was undertaken. RESULTS: A total of 1000 patients on AM were identified. One-hundred-and-seventeen were excluded from the study. Five-hundred-and-twenty-four patients were simultaneously on an ACE-I or ARB. The remaining 359 patients were not. Pulmonary toxicity attributed to AM was identified in five and 14 patients with and without concomitant ACE-I or ARB therapy, respectively. The APT rate for the entire patient sample was 2.2%. APT occurred in 1% of patients on an ACE-I or ARB and in 3.9% of patients not taking an ACE-I or ARB. This observed difference in percentage of APT was statistically significant. CONCLUSION: The concomitant use of ACE-I or ARB in patients taking AM appears to offer a protective effect against APT. This observation suggests that the stimulation of the angiotensin enzyme system may play an important role in APT in humans.

Peritoneal tuberculosis: modern peril for an ancient disease.

Extrapulmonary manifestations of Mycobacterium tuberculosis (MTB) in general, and tuberculous peritonitis (TBP) in particular, have posed complex diagnostic challenges for centuries. Peritoneal tuberculosis is a very rare manifestation of MTB with subtle clinical findings that may result in a significant diagnostic delay, often of more than four months. As the incidence of tuberculosis is declining in developed nations, clinicians may overlook the need to establish an early diagnosis and prompt therapy for this disorder. We present a case of peritoneal tuberculosis and a review of the literature.

Adalimumab-induced acute myelogenic leukemia.

Newer biological treatment strategies have been developed in the last decade with some promising outcomes. Their safety, however, has been questioned lately with multiple reports of increased risk for malignancies and infectious complications. These reports render their use suboptimal. We report a 44-year-old woman receiving adalimumab (Humira) for advanced juvenile rheumatoid arthritis who then developed acute myelogenic leukemia.

Fatal iatrogenic hyperphosphatemia.

Hypertonic sodium phosphate enemas are available for relief of constipation. They are widely used as colorectal laxatives because of their efficacy and because most patients tolerate the preparation well. Nevertheless, their use has been associated with decreases in intravascular volume as well as measurable changes in serum phosphorus and calcium levels. Usually these effects are transient and cause no ill effects. Severe toxicity may occur when the osmotically active hypertonic phosphate enema is retained or when it is administered to a patient with a decreased glomerular filtration rate. We report an elderly patient with previously normal renal function who developed severe hyperphosphatemia, hypocalcemia, and cardiac arrest after the administration of hypertonic sodium phosphate enemas for the treatment of an ileus. We review the patient characteristics that increase the risk of adverse effects from hypertonic sodium phosphate enemas and emphasize the danger that moderate dehydration poses when considering the use of these cathartics.

IgA nephropathy and small cell lung carcinoma.

The occurrence of glomerular disease as a paraneoplastic manifestation of malignancy is well documented in the medical literature. The strongest association is between membranous glomerulonephritis and solid tumors. We report a patient with IgA nephropathy associated with small cell lung cancer. To our knowledge, this is the second documented occurrence of an IgA nephropathy with a casual association with small cell bronchogenic cancer. This observation leads to the hypothesis that IgA nephropathy might be a paraneoplastic manifestation of this histiologic type of lung cancer.

Ascaris lumbricoides: a travel joke?

Intestinal nematodes affect more than a billion people worldwide. They are commonly found in regions with poor fecal sanitation, such as developing countries. Although most of the nematode infections are non-fatal diseases, they contribute to significant morbidities such as loss of work capacity and malnutrition. We are presenting an 80-year-old male who was diagnosed with Ascaris Lumbricoides after a return from recent travel to Greece, with some clinical endoscopic images.

Marked bilateral parotid enlargement in metabolic syndrome: a case report and review of the literature.

Bilateral non inflammatory salivary gland enlargement (sialadenosis) is seen with a diverse number of diseases. It is commonly recognized in alcoholism, anorexia and bulimia nervosa and HIV infections. The association between diabetes mellitus and sialadenosis has been reported rarely in the last three decades. We report a patient with sialadenosis in association with metabolic syndrome. We discuss the clinical implications of this novel association including possible regression of salivary gland enlargement with intensive glycemic and lipid control.

Nodular pulmonary histoplasmosis in Cushing's disease: a case report and literature review.

Opportunistic infections are well documented in states of steroid excess. To our knowledge, histoplasmosis has not been previously reported in Cushing's disease, and has rarely been reported in patients with exogenous glucocorticoid use. We report a novel presentation of Histoplasmosis as pulmonary nodules in a patient with Cushing's disease. A 45-year-old man with a pituitary macroadenoma and Cushing's disease was treated with transsphenoidal hypophysectomy and radiation therapy. He was receiving Ketoconazole and basal steroid replacement, when he presented with dyspnea. Chest radiograph showed nodular lesions and subsequent biopsy revealed Histoplasma capsulatum. Itraconazole was administered and the patient recovered. The case not only demonstrates the protean manifestations of Histoplasmosis in patients with glucocorticoid excess but it also emphasizes the importance of intensive control of the hypercortisolemia in achieving a favorable outcome.

The Dapsone hypersensitivity syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations.

4,4'-Diaminodiphenylsulphone (Dapsone) is widely used for a variety of infectious, immune and hypersensitivity disorders, with indications ranging from Hansen's disease, inflammatory disease and insect bites, all of which may be seen as manifestations in certain occupational diseases. However, the use of dapsone may be associated with a plethora of adverse effects, some of which may involve the pulmonary parenchyma. Methemoglobinemia with resultant cyanosis, bone marrow aplasia and/or hemolytic anemia, peripheral neuropathy and the potentially fatal dapsone hypersensitivity syndrome (DHS), the focus of this review, may all occur individually or in combination. DHS typically presents with a triad of fever, skin eruption, and internal organ (lung, liver, neurological and other systems) involvement, occurring several weeks to as late as 6 months after the initial administration of the drug. In this sense, it may resemble a DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms). DHS must be promptly identified, as untreated, the disorder could be fatal. Moreover, the pulmonary/systemic manifestations may be mistaken for other disorders. Eosinophilic infiltrates, pneumonitis, pleural effusions and interstitial lung disease may be seen. This syndrome is best approached with the immediate discontinuation of the offending drug and prompt administration of oral or intravenous glucocorticoids. An immunological-inflammatory basis of the syndrome can be envisaged, based on the pathological picture and excellent response to antiinflammatory therapy. Since dapsone is used for various indications, physicians from all specialties may encounter DHS and need to familiarize themselves with the salient features about the syndrome and its management.

Marked insulin resistance in pregnancy: a case report and literature review.

Pregnancy is usually accompanied by insulin resistance; however, severe insulin resistance in pregnancy requiring massive doses of insulin is rare. We report a case of a 14-year-old with acanthosis nigricans and a strong family history of Type 2 diabetes who exhibited marked insulin resistance during pregnancy. Her treatment included terbutaline for pre-term labor and dexamethasone for fetal lung maturity. Shortly after these interventions, her insulin requirements escalated to 130 units per hour. Multiple insulin regimens were used in her treatment. Investigations were negative for antinuclear antibodies, islet cell IgG auto-antibodies (GAD65 Antibody assay) and insulin antibodies. Her thyroid-stimulating hormone was within normal limits and her C-peptide level elevated at 18 ng/dL [1.1-4.8 ng/L]. A week following cessation of the dexamethasone and terbutaline, her insulin requirements dramatically decreased. We conclude that in pregnant patients with underlying insulin resistance and strong family history of diabetes, the use of agents that antagonize insulin action, such as dexamethasone and terbutaline, can result in massive insulin resistance.

Hepatitis C virus and the lung: implications for therapy.

Hepatitis C virus (HCV) infection is a chronic blood-borne disease that affects > 4,000,000 individuals in the United States. The majority of individuals with HVC infection acquire a chronic hepatitis that predisposes them to the complications of cirrhosis and hepatoma. Chronic HCV infection is, however, associated with multiple extrahepatic manifestations as well, including recently recognized effects on the lung. These include primary effects on lung function, as well as secondary effects in the settings of progressive liver disease and drug treatment for HCV. In this article, we discuss the emerging clinical data that support a role for HCV infection in lung disease, describe the multiple pulmonary manifestations of this viral infection, and outline the therapies available for specific pulmonary complications of chronic HCV infection.

Actinomycosis esophagitis in a patient with persistent dysphagia.

Many causes of esophagitis exist in immunocompromised patients. Uncommon pathogens must be considered to facilitate timely and appropriate therapy. A limited number of cases of esophageal actinomycosis have been reported. This report describes an unusual case of esophageal actinomycosis in a patient with persistent dysphagia. The broad differential may have delayed definitive diagnosis in the case study patient. Biopsy and culture are essential for accurate diagnosis. Although actinomycosis is a rare disease, it should be included in the differential diagnosis of patients presenting with oral or esophageal complaints. It may also be considered as an opportunistic infection in immunocompromised patients. The treatment of choice is parenteral penicillin G, 18 to 24 million units for 2 to 6 weeks followed by oral therapy for 6-12 months.