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 inhibition of fatal graft-versus-host disease by immunization of donor or host with bacillus Calmette-Guérin cell walls.

F1 mice receiving sublethal whole-body x-irradiation (300 rads) or treatment with cyclophosphamide prior to the i.p. inoculation of parental spleen cells developed fatal graft-versus-host disease (GVHD). A greater survival rate was obtained when the inoculated parenteral spleen cells were obtained from BCGcw-preimmunized donors. The immunization of the F1 host with bacillus Calmette-Guerin cell walls (BCGcw) also increased host survival. The combined treatment of preimmunizing the host with BCGcw and of using spleen cells from BCGcw-immunized parental donors to initiate the GVHD resulted in producing the least severe GVHD and the greatest overall survival. The systemic transfer of x-irradiated spleen cells from BCGcw-immunized parental mice inhibited the fatal GVHD induced by the inoculation of normal parental spleen cells. These studies show that BCGcw immunization of the host or obtaining parental spleen cells from BCGcw-immunized animals resulted in improving the overall survival rate in graft-versus-host disease. BCGcw immunization induces suppressor cells and the decrease of graft-versus-host disease that was observed was most likely due to the induction of suppressor cells.

Cytosolic calcium in T lymphocytes from the spontaneously hypertensive rat.

To gain further insight into the possible generalized nature of intracellular calcium-related alterations in hypertension we measured free cytosolic calcium (iCa2+) in lymphocytes obtained from the spleen and the blood of the spontaneously hypertensive rat (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats. By monitoring Fura-2 fluorescence at an excitation wavelength of 340 nm and an emission wavelength of 510 nm we estimated; Ca2+. In peripheral lymphocytes from the SHR iCa2+ was increased as compared to those from WKY rats (146 +/- 14 and 112 +/- 6.0 nm, respectively, P less than .025). In contrast, in lymphocytes obtained from the spleen, iCa2+ was not different between SHR and WKY rats (93 +/- 7.0 and 96 +/- 8.0 nm, respectively). When spleen cells were subjected to selective B lymphocyte depletion to generate a preparation of predominantly T lymphocytes, iCa2+ was found to be higher in SHR than in WKY rats (149 +/- 23 and 89 +/- 12 nm, respectively, P less than .05). The finding that iCa2+ is elevated in peripheral lymphocytes and spleen cells subjected to B cell depletion but not in untreated spleen cells indicates that T, but not B, lymphocytes have increased iCa2+ in the SHR. This observation may be related to existing evidence that T lymphocyte function is impaired in the SHR. An increase in iCa2+ is not a phenomenon generalized to all cells of this model of genetic hypertension.

Multiple QTL mapping in related plant populations via a pedigree-analysis approach.

QTL mapping experiments in plant breeding may involve multiple populations or pedigrees that are related through their ancestors. These known relationships have often been ignored for the sake of statistical analysis, despite their potential increase in power of mapping. We describe here a Bayesian method for QTL mapping in complex plant populations and reported the results from its application to a (previously analysed) potato data set. This Bayesian method was originally developed for human genetics data, and we have proved that it is useful for complex plant populations as well, based on a sensitivity analysis that was performed here. The method accommodates robustness to complex structures in pedigree data, full flexibility in the estimation of the number of QTL across multiple chromosomes, thereby accounting for uncertainties in the transmission of QTL and marker alleles due to incomplete marker information, and the simultaneous inclusion of non-genetic factors affecting the quantitative trait.

Acute theophylline overdose treated with whole bowel irrigation.

Case report of massive overdose of TheoDur treated with Whole Bowel Irrigation (WBI) with Colite. Theophylline levels and clinical symptoms decreased as soon as WBI was completed. Colite is inexpensive, safe to administer and easy to store. It may be lifesaving if administered promptly during transport to a secondary treatment facility.

Isolated transection of the common duct.

A patient with complete transection of the common bile duct after blunt trauma from a steering wheel presented with severe right-sided lower chest pain. Based on results of physical examination, blood and urine analysis and chest x-ray films, he was discharged after suture of a lip laceration. Five days later upon his return for suture removal, the appearance of jaundice and mild symptoms of abdominal distention prompted hospitalization and exploratory surgery. At surgery, avulsion of the common bile duct was the only injury. In the few previously reported cases of this injury, jaundice and mild symptoms of abdominal distention appeared three to four days after injury. The minimal findings of a potentially fatal lesion emphasize the need for securing appropriate follow-up medical care for patients with a history of blunt trauma to the chest and/or abdomen.