Repeat treatment of acute hereditary angioedema attacks with open-label icatibant in the FAST-1 trial.

Hereditary angioedema (HAE) is characterized by potentially life-threatening recurrent episodes of oedema. The open-label extension (OLE) phase of the For Angioedema Subcutaneous Treatment (FAST)-1 trial (NCT00097695) evaluated the efficacy and safety of repeated icatibant exposure in adults with multiple HAE attacks. Following completion of the randomized, controlled phase, patients could receive open-label icatibant (30 mg subcutaneously) for subsequent attacks. The primary end-point was time to onset of primary symptom relief, as assessed by visual analogue scale (VAS). Descriptive statistics were reported for cutaneous/abdominal attacks 1-10 treated in the OLE phase and individual laryngeal attacks. Post-hoc analyses were conducted in patients with ≥ 5 attacks across the controlled and OLE phases. Safety was evaluated throughout. During the OLE phase, 72 patients received icatibant for 340 attacks. For cutaneous/abdominal attacks 1-10, the median time to onset of primary symptom relief was 1·0-2·0 h. For laryngeal attacks 1-12, patient-assessed median time to initial symptom improvement was 0·3-1·2 h. Post-hoc analyses showed the time to onset of symptom relief based on composite VAS was consistent across repeated treatments with icatibant. One injection of icatibant was sufficient to treat 88·2% of attacks; rescue medication was required in 5·3% of attacks. No icatibant-related serious adverse events were reported. Icatibant provided consistent efficacy and was well tolerated for repeated treatment of HAE attacks.

C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks--final results of the I.M.P.A.C.T.2 study.

BACKGROUND: The placebo-controlled study International Multicentre Prospective Angioedema C1-INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U/kg C1 esterase inhibitor (C1-INH) concentrate (Berinert®; CSL Behring, Marburg, Germany) is effective in treating acute abdominal and facial Hereditary Angioedema (HAE) attacks. METHODS: I.M.P.A.C.T.2 was an open-label extension study of I.M.P.A.C.T.1 to evaluate the safety and efficacy of long-term treatment with 20 U/kg C1-INH for successive HAE attacks at any body location. Efficacy outcomes included patient-reported time to onset of symptom relief (primary) and time to complete resolution of all symptoms (secondary), analysed on a per-patient and per-attack basis. Safety assessments included adverse events, vital signs, viral safety and anti-C1-INH antibodies. RESULTS: During a median study duration of 24 months, 1085 attacks were treated in 57 patients (10-53 years of age). In the per-patient analysis, the median time to onset of symptom relief was 0.46 h and was similar for all types of attacks (0.39-0.48 h); the median time to complete resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8-26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type of HAE, intensity of attacks, time to treatment, use of androgens and presence of anti-C1-INH antibodies had no clinically relevant effect on the efficacy outcomes. There were no treatment-related safety concerns. No inhibitory anti-C1-INH antibodies were detected in any patient. CONCLUSIONS: A single dose of 20 U/kg C1-INH concentrate is safe and provides reliable efficacy in the long-term treatment of successive HAE attacks at any body location.

The effect of theophylline on the lower esophageal sphincter pressure.

The effects of theophylline on lower esophageal sphincter pressure (LESP) were studied on four normal volunteers and six asthmatics with symptoms of gastroesophageal reflux (GER). Manometric evaluations of LESP were obtained before and after an intravenous dose of aminophylline. All subjects had therapeutic theophylline levels at the time of the second measurement of LESP and a significant decrease in LESP occurred in normal and asthmatic volunteers.

Laboratory tests in chronic urticaria.

One hundred twenty-five patients with chronic urticaria were evaluated with 11 commonly recommended laboratory and radiologic procedures. Abnormal studies were obtained in 26 (20.8%) of these patients, but the majority of these abnormalities were evident from the initial history and physical examination. These results indicate that, with the possible exception of sinus roentgenograms, these laboratory studies are not likely to be helpful in the evaluation of chronic urticaria unless there are suggestive findings in the history and physical examination. The yield and equivalent charge of diagnosis for each procedure used was also analyzed.

Selective immunoglobulin A deficiency associated with modular lymphoid hyperplasia.

Nodular lymphoid hyperplasia (NLH) has been firmly associated with syndromes of hypogammaglobulinemia but not with selective absence of IgA. We report the case of a 5-yr-old girl with the triad of selective IgA deficiency, NLH of the small bowel, and giardiasis. Results of an extensive immunologic investigation, including immunohistochemical examinations of small bowel biopsies, support the hypothesis that the basic defect responsible for IgA deficiency in this patient was the failure of precursor IgM-bearing lymphocytes to differentiate into IgA-producing plasma cells. Furthermore, the abundance of IgM-bearing cells in biopsy specimens demonstrates the existence of a compensatory mechanism in the intestine to substitute IgM for the absent IgA.

Primary inoculation tuberculosis of the skin. Prosector's paronychia,.

Subsequent to an autopsy of a tuberculotic cadaver, a pathology resident presented with a painless paronychia and axillary adenopathy after surgical incision and broad-spectrum antibiotics had failed to improve his condition. Demonstration by culture of Mycobacterium tuberculosis var hominis, positive smears, and findings of acid-fast organisms in a skin biopsy specimen proved the diagnosis of tuberculosis. Conversion of a previously negative skin test permitted the diagnosis of primary inoculation tuberculosis of the skin. The disease responded well to treatment with isoniazid, rifampin, and pyridoxine hydrochloride.