The IgG autoimmune response in postpartum acquired hemophilia A targets mainly the A1a1 domain of FVIII

Summary. Background: Acquired hemophilia A (AHA) is a severe life‐threatening autoimmune disease due to the development of autoantibodies that neutralize the procoagulant activity of factor VIII (FVIII). In rare cases, AHA occurs in the postpartum period as a serious complication of an otherwise normal pregnancy and delivery. Due to its rarity, little is known about the features of the antibody response to FVIII in AHA. Objectives: Our study wanted to (i) determine the epitope specificity and the immunoglobulin (Ig) subclasses of anti‐FVIII autoantibodies in plasma samples from a large cohort of AHA patients, and (ii) compare the epitope specificity of anti‐FVIII autoantibodies in plasma samples from postpartum AHA and other AHA patients. Patients/Methods: Seventy‐three plasma samples from patients with postpartum AHA (n = 10) or associated with malignancies (n = 16) or autoimmune diseases (n = 11) or without underlying disease (n = 36) were analyzed with three multiplexed assays. Results and Conclusions: Our results showed a stronger response against the A1a1‐A2a2‐B fragments of FVIII and more specifically against the A1a1 domain in patients with postpartum AHA than in the other AHA groups (P < 0.01). Moreover, although IgG₄ was the predominant IgG subclass in all groups, anti‐A1a1‐A2a2‐B and anti‐A1a1 domain autoantibodies of the IgG₁ and IgG₃ subclasses were more frequently detected in postpartum AHA than in the other AHA groups. These findings support the involvement of the Th1‐driven response in the generation of autoantibodies in women with postpartum AHA compared with the other groups of AHA patients in whom production of Th2‐driven IgG₄ was predominant.     

QTc Dispersion in Hyperthyroidism and Its Association with Pulmonary Hypertension

Background: Several studies have reported that hyperthyroidism is associated with prolonged QT interval corrected by the heart rate (QTc) and pulmonary hypertension (PHT). Methods: Forty‐seven patients with newly diagnosed overt hyperthyroidism and 20 healthy people were enrolled in the study. Transthoracic echocardiography, 12‐lead surface electrocardiogram, and thyroid hormone levels were studied at the time of enrollment and after achievement of euthyroid state with propylthiouracil treatment. Results: Baseline clinical characteristics were similar. However, heart rate (90.5±19.6 vs 79.2±13.7 bpm, P = 0.024), pulmonary artery systolic pressure (PASP) (26.0±12.0 vs 10.6±4.0 mmHg, P < 0.001), E deceleration time (DT) (191.8±25.6 vs 177.0±10.7 ms, P = 0.016), isovolumetric relaxation time (IVRT) (91.38±12.3 vs 79.6±10.5 ms, P < 0.001), and QTc dispersion (QTcD) (50.3±17.2 vs 38.9±11.6 ms, P = 0.009) were significantly higher in hyperthyroid patients compared to control group. Heart rate (to 74.1±13.8, P < 0.001), QTcD (to 37.3±10.1 ms, P < 0.001), DT (to 185.3±19.7 ms, P = 0.008), IVRT (to 88.6±10.3 ms, P = 0.056), and PASP (23.1±10.1 mmHg P < 0.001) were significantly decreased after achievement of euthyroid state. Although PHT was present in 16 patients before treatment only six patients still had PHT during euyhyroid state. Compared to patients with normal PASP, QTcD was significantly longer in patients with PHT (56.5±15.8 vs 37.9±12.8 mmHg P < 0.001). There were also significant correlations between QTcD and presence of PHT (r = 0.516, P < 0.001) and PASP (r = 0.401, P = 0.009). Conclusions: Hyperthyroidism is a reversible cause of PHT and diastolic dysfunction. Increased QTcD observed in hyperthyroidism may be associated with PHT and diastolic dysfunction. These abnormal findings in hyperthyroidism often normalize with the achievement of euthyroid state.     

New concept parameters of RigiScan in differentiation of vascular erectile dysfunction: Is it a useful test?

BACKGROUND: The aim of this study is to investigate the value of new nocturnal penile tumescence recording parameters, such as tumescence activity unit and rigidity activity unit values, total erection number and erection times, in differentiating between psychogenic erectile dysfunction and organic erectile dysfunction. We also aimed to determine the role of these parameters in differentiating arterial erectile dysfunction from veno-occlusive dysfunction. METHODS: Eighty-seven consecutive patients were allocated into three groups as psychogenic, arterial and venous erectile dysfunction after investigations. Nocturnal penile tumescence recording parameters between psychogenic and vascular erectile dysfunction and arterial and veno-occlusive dysfunction were compared. Mann-Whitney U-test, Pearson's chi2 test and correlation coefficient tests were used for statistical analysis. RESULTS: Depending on intracavernous injection, penile Doppler ultrasonography and cavernosometry tests, 37 patients (43%) had psychogenic impotence while 50 (57%) had organic pathologies. Of the 50 patients diagnosed with vascular impotence, 29 (48%) had arterial failure and 21 (42%) had veno-occlusive dysfunction. Nocturnal penile tumescence recording revealed psychogenic erectile dysfunction in 34 patients (39%) and vascular erectile dysfunction in 53 patients (61%). Nocturnal penile tumescence recording has been regarded as the gold standard and, in our series, it showed 90.6% sensitivity and 88.2% specificity in differentiating the cause of erectile dysfunction. Values of rigidity activity unit and tumescence activity unit were significantly higher in patients with psychogenic impotence (P < 0.001), when compared with vascular impotence. In patients with a vascular cause, no difference was found between arterial failure and veno-occlusive dysfunction with regard to tip tumescence activity unit, base tumescence activity unit, tip rigidity activity unit, base rigidity activity unit and erection time (P > 0.001). However, patients with arterial failure had less erection than patients with veno-occlusive dysfunction (P < 0.001). CONCLUSION: New recording parameters of nocturnal penile tumescence can differentiate organic and psychogenic erectile dysfunction more precisely. However, these recording parameters cannot distinguish subgroups with a vascular cause of erectile dysfunction.     

Some effects of furazolidone on the testis and plasma levels of testosterone, luteinizing hormone and prolactin in mature male turkeys

Adult male turkeys were treated orally with furazolidone at doses of 1, 2.5, S or 20 mg/kg for 14 days and their plasma analysed for luteinizing hormone (LH), testosterone and prolactin (PRL) concentrations before, during and after treatment. At 20 mg/kg the drug produced a significant decrease in the plasma levels of LH and testosterone at the end of treatment, whereas at 5 mg/kg the drug had no significant effect. Prolactin concentrations were unaffected by any of the drug doses used. Intramuscular injection of luteinizing hormone releasing hormone (LHRH) at a dose of 5 μg/kg produced after 30 min a significant rise in plasma levels of LH, an effect that was decreased significantly by treatment with 20 mglkg furazolidone. Incubation of normal turkey semen with graded doses of furazolidone or nitrofura-zone for up to 30 min resulted in a dose- and time-dependent decrease in sperm motility. At a concentration of 20 mg/ml a complete absence of sperm motility was observed after incubation with either drug, although, on the whole, nitrofurazone seemed more potent than furazolidone as a sperm-immobilizing agent. Histological changes occured in the 20 mg/kg group and consisted of a decrease in spermatocyte production, corrugation of sperm cell nuclear envelopes and distention of the endoplasmic reticulum of elongate spermatids. It is concluded that furazolidone depresses pituitary LH output but may, in addition, directly affect spermatogenesis and sperm motility.     

Neuromuscular and Microvascular Changes Associated with Chronic Administration of an Extract of Teucrium stocksianum in Mice

This work examines the effect on the weights of vital body organs, on blood biochemical variables, on neuromuscular coordination and on cerebral microcirculation of aqueous extracts of Teucrium stocksianum, given to mice in drinking water at concentrations of 2 and 4% for 56 days. The treatment caused progressive impairment of neuromuscular coordination, as evidenced by the time spent on the rota-rod. After photochemical challenge, the time for first observable platelet aggregation in arterioles was shorter than for the control group by 22 and 45% in the 2 and 4% T. stocksianum-treated groups, respectively. Platelet aggregation on the venular side was not affected by the treatment nor were microvascular diameters. Treatment with the plant extract produced no statistically significant effect on the plasma biochemical variables that are considered indices of liver and kidney function. Histologically, brains obtained from mice treated with T. stocksianum showed loss of cerebellar Purkinje cells. Although it is likely that the accelerated platelet aggregation might have contributed to an ischaemic effect which could, at least in part, have caused the cytotoxicological changes, this does not exclude the possibility of a direct cytotoxicological effect of the plant extract. Further pharmacological and toxicological investigations on Teucrium species seem warranted.     

The use of preoperative lidocaine to prevent stridor and laryngospasm after tonsillectomy and adenoidectomy

The most important complications from tonsillectomy and adenoidectomy are bleeding, stridor, and laryngospasm. This controlled, double-blind study was designed to investigate the effects of topical and intravenous lidocaine on stridor and laryngospasm. A total of 134 patients scheduled for elective tonsillectomy and/or adenoidectomy were randomly separated into four groups. In the topical lidocaine group 4 mg/kg of 2% lidocaine was applied to subglottic, glottic, and supraglottic areas before endotracheal intubation. Normal saline solution was used topically for the first control group. In the intravenous lidocaine group, patients were given 1 mg/kg of 2% lidocaine before extubation, and the same amount of 0.9% NaCl was given to the second control group. Postoperative stridor, laryngospasm, cyanosis, bleeding, sedation degree, and respiratory depression were observed, and plasma lidocaine levels were measured. Both topical and intravenous lidocaine groups revealed less stridor and laryngospasm than the control groups, and no difference was found between the topical and intravenous lidocaine groups except the higher sedation scores in the early postoperative period for the intravenous lidocaine group. (Otolaryngol Head Neck Surg 1998;118:880-2.)     

Efficacy of pollen immunotherapy in seasonal allergic rhinitis

BACKGROUND: The efficacy of subcutaneous pollen immunotherapy has been documented in published double-blind, placebo-controlled studies related to treatment of seasonal allergic rhinitis. In the present study, subjective (symptom scores) and objective (nasal peak inspiratory flow, nasal smear, nasal biopsy) parameters were used to study the efficacy of pollen immunotherapy. METHODS: Forty-eight patients (32 male), mean +/- SE age 13.6 +/- 2.8 years allergic to grass-pollen participated in the present study. Patients were divided into three groups: group I, 24 patients who did not receive pollen immunotherapy; group II, 12 patients who received the build-up phase of pollen immunotherapy; and group III, 12 patients who had just finished pollen immunotherapy. With regard to objective and subjective parameters these three groups were compared. RESULTS: When group I was compared to groups II and III, the patients who had not received any immunotherapy were found to have a high daytime nasal symptoms score (P < 0.01), high daytime eye symptoms score(P < 0.01) and high night-time symptoms score (P < 0.01). In objective parameters, it was found that group I had low nasal peak inspiratory flow (P < 0.05), and a high eosinophil count in nasal smears (P < 0.05) and peripheral blood (P < 0.05). It was also demonstrated that there was an increased eosinophil infiltration (P < 0.01) and mast cell infiltration (P < 0.05) in nasal biopsy in group I. There was no significant difference between group II and group III according to these results (P > 0.05). CONCLUSIONS: Immunotherapy leads to a better clinical and histopathological prognosis in children with seasonal allergic rhinitis.