Anthony Montanaro

Results of the First U.S. Double-Blind, Placebo-Controlled, Multicenter Clinical Study in Asthma with Pranlukast, a Novel Leukotriene Receptor Antagonist

Pranlukast (SB 205312; ONO-1078), a potent, orally active selective cysteinyl-leukotriene receptor antagonist (LTRA), was developed in Japan for the treatment of asthma. This article reports results of the initial U.S. clinical evaluation of pranlukast. The primary objective of this multicenter study was to evaluate the safety and tolerability of pranlukast administered at doses of 337.5 mg b.i.d. and 450 mg b.i.d. in 65 patients with mild to moderate asthma. Pranlukast, a novel LTRA, is safe and well tolerated at doses of 337.5 mg b.i.d. and 450 mg b.i.d. Pranlukast has demonstrated clinical activity in patients with asthma.

Sporotrichosis in the acquired immunodeficiency syndrome

Kaposis sarcoma and disseminated sporotrichosis of the skin and joints developed simultaneously in a homosexual man with antibodies to human immunodeficiency virus. There was no identified source of exposure to Sporothrix organisms. Sporotrichosis may be a presenting opportunistic infection associated with acquired immunodeficiency syndrome and tends to be disseminated at the time of diagnosis.

Individual patient variations in the kinetics of intravenous immune globulin administration

Subjects with primary immunodeficiency received modified immune serum globulin (IGIV) intravenously at various dose levels in long-term therapeutic studies. Therapy was effective and essentially free from adverse reactions. Two pertinent observations were made relating to the attained levels of serum IgG. Over a dose range of 100-225 mg/kg, the serum IgG level directly reflects the dosage administered. Sequential analysis of serum levels of IgG demonstrated three patient populations in 14 subjects receiving 150 mg/kg. The largest group, nine patients, had progressive reduction of serum IgG values compatible with the half-life of the reagent, with a return to the original serum IgG level in four weeks. A second population of four patients had a slower reduction of serum IgG over the four-week period. IgG values were significantly elevated over baseline values at the time of the next due infusion. In one subject serum IgG values varied greatly with rapid drops and elevations unrelated to the infusion.

Allergies to sulfonamide antibiotics and sulfur-containing drugs.

OBJECTIVE To provide a literature review and clinical summary of the evaluation and management of sulfonamide drug reactions. DATA SOURCES Published English-language medical literature. STUDY SELECTION Selected trials of drug desensitization protocols. RESULTS Obtaining a detailed history is invaluable in assessing a history of reactions to sulfonamide medications, because allergy to these drugs remains a clinical diagnosis at present. Numerous efficacious drug desensitization protocols for management have been published and are reviewed in detail. CONCLUSIONS The term sulfa allergy is imprecise and misleading and therefore should be discouraged. There are important distinctions between sulfonylarylamines (antimicrobial sulfonamides), nonarylamine (nonantimicrobial) sulfonamides, and sulfones, with regard to allergic and other adverse drug reactions. Most reactions to sulfonylarylamines probably result from multifactorial immunologic and toxic metabolic mechanisms, whereas less is known about the precise mechanisms of reactions to other sulfur-containing drugs.

Prolonged interval high-dose intravenous immunoglobulin in patients with primary immunodeficiency states

Intravenous immunoglobulin can be a very effective form of treatment for patients with primary immunodeficiency states. Recommendations for intravenous dosing previously have been empirically derived. In order to determine the potential prolongation of intervals between infusions following the administration of 500 mg/kg of intravenous immunoglobulin, 11 patients were studied. This high-dose therapy was well tolerated and resulted in a modest prolongation of therapeutic IgG levels when compared with lower-dose 150 mg/kg regimens. Significant variability among individual patients was observed. Implications of this high-dose therapy are discussed.

Protein-losing enteropathy in systemic lupus erythematosus - Diagnosis and monitoring immunosuppressive therapy by alpha-1-antitrypsin clearance in stool

SummaryEnteric protein loss resulting in profound hypoalbuminemia and anasarca is an uncommon manifestation of systemic lupus erythematosus and only rarely is the initial presentation of disease. A few patients with SLE and protein-losing enteropathy in the absence of increased central venous pressure or intestinal lymphangiectasia have been reported. We describe the utility alpha-1-antitrypsin clearance in stool for diagnosing and monitoring enteric protein loss during successful immunosuppressive drug therapy in a patient who presented with massive enteric protein loss as the initial manifestation of systemic lupus erythematosus.

An outbreak of acute hepatitis C among recipients of intravenous immunoglobulin

BACKGROUND An association between therapy with intravenous immunoglobulin (IVIG, Gammagard, Baxter Healthcare Corp) and acute hepatitis C (HCV) was reported by the manufacturer in 1994. OBJECTIVE We sought to describe those patients at risk at our institution who developed HCV infection after IVIG (Gammagard) treatment(s). MATERIALS An inception cohort study of patients with exposure to contaminated IVIG in a university tertiary care institution. Twenty-three patients received suspect IVIG and presented to be screened for HCV via ELISA II and polymerase chain reaction techniques. We describe the demographics and clinical characteristics of patients diagnosed with hepatitis C infection from IVIG. RESULTS Ten of 23 (44%) patients who had received immunoglobulin (2 g/kg) for neurologic or immunologic disorders and were tested for anti-HCV were positive. All were also HCV-RNA positive by polymerase chain reaction. None had other HCV risk factors; all but two had normal aminotransferases documented prior to therapy. The patients had received monthly therapy for periods ranging from 2 to 60 months. Four patients were asymptomatic and the others had mild symptoms. One patient spontaneously became PCR negative within 12 months after exposure. CONCLUSION Patients who received intravenous immunoglobulin (Gammagard, Baxter Healthcare Corp) between March, 1993, and February, 1994, are at risk for acute hepatitis C. The initial sequellae appear to be mild and spontaneous remission is possible.

Recurrent Wegener's granulomatosis: a case report and review.

BACKGROUND Wegeners granulomatosis is a granulomatous systemic necrotizing vasculitis with prominent upper airway involvement. Complete remissions can be induced with aggressive management. Despite successful treatment, relapses and recurrences of active disease may occur. OBJECTIVE We present a patient who presents with histologically confirmed active disease 17 years following successful therapy. METHODS A case report of a 72-year-old man who initially presented at age 50 with necrotizing vasculitis of the upper and lower respiratory tract. Eighteen years following his initial therapy he presented with isolated retroorbital disease. Following re-institution of cytotoxic therapy he appears to be disease-free. RESULTS Following re-treatment with cytoxan and prednisone, a second remission was induced. The patient is currently entirely well 1 year off therapy. CONCLUSION Wegeners granulomatosis may recur many years following apparent successful and aggressive cytotoxic and anti-inflammatory therapy.

Chemically induced nonspecific bronchial hyperresponsiveness

ConclusionIn summary, it is clear that in some instances, inhalant exposure to irritating chemicals can result in nonspecific bronchial hyperresponsiveness. The physiologic mechanisms underlying the induction of nonspecific bronchial hyperresponsiveness in this setting are poorly understood. Although inflammation is the pathologic hallmark of nonspecific bronchial hyperresponsiveness in asthma, it has not been well demonstrated in chemically-induced nonspecific bronchial hyperresponsiveness. This article has highlighted the observation that despite the large number of individuals exposed to respiratory irritants in our society in and away from industrial settings, very few develop obvious nonspecific bronchial hyperresponsiveness. Further study is necessary in this important area.

SJOGREN'S SYNDROME

Sjogrens syndrome is a chronic systemic inflammatory disorder characterized by the presence of dry eyes and dry mouth. Dryness in the eyes and mouth are secondary to diminished glandular production secondary to lymphocytic and plasma cell infiltration. Because of the prominent autoimmune features of this condition, Sjogrens syndrome has recently been referred to as an autoimmune exocrinopathy. 32 Although there is no universally accepted definition of Sjogrens syndrome, the diagnostic triad of keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth) associated with the presence of a connective tissue disorder is commonly employed. 7 Dry eyes may occur with or without lacrimal gland enlargement. Dry mouth may occur with or without salivary gland enlargement. Both primary and secondary forms of this disorder are recognized. Although primary Sjogrens syndrome may be a distinct disorder in the absence of another known connective tissue disease, the most frequent association of Sjogrens syndrome and a connective tissue disorder is with rheumatoid arthritis. Approximately one half of all patients with rheumatoid arthritis will present with Sjogrens syndrome whereas a less frequent association is seen with less common connective tissue disorders such as systemic lupus erythematosus or scleroderma. 30,49 It is important to distinguish these patients from patients that present with sicca complex, which includes only the presence of ocular and oral dryness. Because patients with primary sicca do not appear to have the systemic disease associations that are discussed in this article, they clearly would have a more favorable prognosis. Historically, features of Sjogrens syndrome have been recognized for over a decade. In 1892, Mikulicz reported the findings of bilateral parotid and lacrimal gland enlargement associated with significant round cell inflammation. 24 Although numerous reports appeared between 1883 and 1933 regarding patients with Mikuliczs syndrome, it was not until 1933 that Heinrich Sjogren described the syndrome that bears his name. 31 It is now generally accepted that Sjogrens syndrome and Mikulitzs disease are in fact variants of the same disorder. 25 It is important for the clinician to consider the diagnosis of Sjogrens syndrome in a patient who presents with suspected allergic disease. Patients with Sjogrens syndrome may present not only with dry eyes and dry mouth but may have prominent respiratory and ocular manifestations that are suspected to be of allergic origin. Because Sjogrens syndrome is suspected to affect 2 to 3 million individuals in the United States alone, 46 it is considered to be in fact the most common autoimmune disease process. Given its reasonably frequent occurrence and its potential for associated lymphoid malignancies, it is crucial that the clinician be aware of the manifestations of this disorder.