Relationship Between Exhaled Carbon Monoxide and Airway Hyperresponsiveness in Asthmatic Patients

The study objectives were to analyze the changes in exhaled carbon monoxide (COex) induced by histamine provocation challenge in asthmatic patients and to evaluate the relationship between COex and airway sensitivity and reactivity. Levels of COex were measured in 105 nonsmoking mildly asthmatic subjects before and after histamine provocation challenge. Dose-response curves were characterized by their sensitivity (PD₂₀) and reactivity. Dose-response slope (DRS), continuous index of responsiveness (CIR), and bronchial reactivity index (BRI) were determined as reactivity indices. Bronchial challenge was positive for 47 subjects and negative for 58. The COex levels rose significantly after bronchial challenge in the positive response group (4.49 ± 0.4 vs. 5.74 ± 0.57 ppm, p = 0.025) and in the negative response group (2.84 ± 0.25 vs 4.00 ± 0.41 ppm, p = 0.000). An inverse relation between basal COex and PD₂₀ was found (r = - 0.318, p = 0.030). In all subjects, a proportional direct relationship between COex and DRS (r = 0.214, p = 0.015), CIR (r = 0.401, p = 0.000), and BRI (r = 0.208, p = 0.012) was observed. On stepwise multiple linear regression analysis, COex only significantly correlated with CIR (multiple r² = 0.174, p = 0.000). In conclusion, exhaled CO determination is a noninvasive inflammatory marker of the respiratory tract, which shows an acceptable association with airway hyperresponsiveness.     

Monotherapy with enoxaparin for the prevention of recurrent venous thromboembolism.

This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38-4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization.     

Diagnostic value of D-dimer in outpatients with suspected deep venous thrombosis receiving oral anticoagulation.

D-dimer has proved a useful diagnostic tool for the exclusion of deep venous thrombosis (DVT). The objective of this paper was to evaluate the diagnostic performance of a diagnostic algorithm combining clinical probability and D-dimer in outpatients receiving oral anticoagulant treatment (OAT) similar to those regularly applied to nonanticoagulated individuals. We enrolled 70 outpatients on OAT who presented with clinically suspected DVT; a standard diagnostic algorithm including clinical evaluation using the modified Wells score and a quantitative immunoturbidimetric D-dimer assay (STA Liatest D-Di; Diagnostica Stago, Asniéres sur Seine, France) was used. A 3-month follow-up period was applied for those patients in whom DVT was initially excluded. The prevalence of DVT was 18.5% (13/70); four of the diagnoses were made during the 3-month follow-up period. The sensitivity, specificity and negative predictive value of D-dimer were 69.2% (95 confidence interval, 42.4-87.3), 47.4% (95% confidence interval, 35.0-60.1) and 87.1% (95% confidence interval, 71.1-94.9), respectively. In conclusion, D-dimer is of limited value in outpatients on OAT presenting with clinically suspected DVT and should be omitted in such individuals; these patients should always undergo compression venous ultrasound, and repeat ultrasonography within 1 week might be warranted in cases with an initial negative examination.     

Composite prostheses for the repair of abdominal wall defects: effect of the structure of the adhesion barrier component

The component of a composite prosthesis, which makes contact with the visceral peritoneum, can be reabsorbable or non-reabsorbable, and laminar or reticular. This study was designed to determine whether the composition of this second, barrier component could improve its behavior at this interface. Abdominal wall defects in rabbits were repaired using a polypropylene prosthesis (PP), or the composites Sepramesh (PP+h) or Vicryl (PP+v). Fourteen days after surgery, the implants were evaluated by light and scanning electron microscopy, and immunohistochemistry. Prosthetic areas occupied by adhesions (PP: 71.08±5.09, PP+h: 18.55±4.96, P+v: 69.69±16.81%), neoperitoneal thickness (PP: 256.17±21.68, PP+h: 83.11±19.63, PP+v:213.72±35.90 μm) and macrophage counts (PP: 8.73±1.16, PP+h: 27.33±4.13, PP+v: 31.24±3.08%) showed significant differences (P<0.05). The tested biomaterials induced an optimal recipient tissue infiltration. Least adhesion formation was observed on the PP+h implants. This suggests that the second component, although reabsorbable, should be smooth in structure.     

Effect of dithranol therapy on membrane, basement membrane and nuclear markers in psoriasis lesions

We investigated the effects of anti-psoriatic therapy with dithranol (1/20-1%) in salicylic acid (0.5%) in white petrolatum on lesional skin. FITC-labeled lectins and pemphigus vulgaris antibodies (PV) served as analytical means to study the glycocalyx. Antibodies of bullous pemphigoid (BP) were used as basal membrane markers. Nuclear antigens were recorded according to the binding of speckled, anti-nuclear antibodies (ANA) as well as antibodies to dsDNA. With some lectins, dithranol therapy resulted in pronounced fluorescence of the lower parts of the basal cells. ConA was fixed by the basal cell layer. To a lesser degree, ANA were fixed by nuclei of keratinocytes. PV antibodies were not fixed at all.     

Conventional and experimental drug therapy in myelofibrosis with myeloid metaplasia

Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (ie, BCR-ABL-negative) myeloproliferative disorder characterized by anemia, multiorgan extramedullary hematopoiesis, constitutional symptoms, and premature death from either leukemic transformation or other disease complications. Stem cell transplantation can be curative, but many patients either are not appropriate candidates or do not choose to accept the significant risks associated with transplantation. Current pharmacologic therapy has been beneficial mainly in terms of palliating disease-associated cytopenias, constitutional symptoms, splenomegaly, and other organ damage from excess myeloproliferation. Novel treatment strategies are under investigation, including targeted inhibition of JAK2^V617F, the activating tyrosine kinase point mutation present in about half of patients with MMM. In this article, we review both the old and new pharmacologic options for MMM.     

Hyper-IgM syndrome with CHARGE association

A girl with coloboma of the iris, sensorineural deafness, growth delay, distinctive face, and cranial nerve dysfunction was diagnosed of CHARGE association in the first year of life. She presented with repeated otitis. At 3 yr of age, the patient suffered a septicemia ( Streptococcus pneumoniae , Corynebacterium sp.). The immunoglobulin G (IgG) and IgA serum levels were decreased, IgM increased and cellular immunity parameters were normal, supporting the diagnosis of hyper-IgM (HIM) syndrome. The sequence of CD40 ligand and cytidine deaminase genes were normal. From then on, she was receiving immunoglobulin intravenously with an excellent outcome . Here, we report the first case of CHARGE association and HIM syndrome in the same patient. Although the cause could not be identified, a non-random link is likely.