Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity

Background  

The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour.     

Post-biopsy arteriovenous fistulas of the native kidneys diagnosed by Doppler US

Two patients with arteriovenous fistulas of the native kidney occurring after needle biopsy were evaluated using duplex and color Doppler ultrasonography. The first patient had a fistula with associated pseudoaneurysm: color Doppler showed the lesion as a small rounded area with whirling flow; spectral analysis allowed recognition of both the afferent artery with low impedance flow and the draining vein with pulsatile, arterialized flow. The second patient had a normal color Doppler study; however, spectral analysis demonstrated signals with low vascular impedance from an intra-parenchymal artery at the lower pole, and a jet of turbulent flow. Following disappearance of clinical findings, such Doppler abnormalities were no longer detectable. When a iatrogenic arteriovenous fistula is considered on clinical grounds, both color and Doppler spectral analysis of waveforms from intra-parenchymal vessels should be performed. Possibly, further advances in color Doppler technology will permit the use of this examination as the first imaging procedure in these clinical situations.Correspondence to: L. E. Derchi     

Deletions of 17p and p53 mutations in preneoplastic lesions of the lung.

Cytogenetic and p53 mutation analysis in two cases of severe dysplasia of the bronchial epithelium in lung cancer patients and p53 immunostaining in a third one are reported. The finding of both chromosomal deletions of 17p and p53 mutation indicates that these changes may take place early in the process of lung carcinogenesis.     

No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement.

BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.     

Risk factors for asthma in adolescents in a large urban region of Brazil.

BACKGROUND: Identify risk factors for asthma in adolescents from S?o Paulo, Brazil. METHODS: total of 528 adolescents (141 asthmatics, 387 control subjects) from the ISAAC study (phase III) were submitted to a complementary questionnaire to evaluate risk factors, through response to questions regarding personal history, environment, and diet and an agreement to undergo the skin prick test (SPT) for aeroallergens. RESULTS: Positive SPT to at least one allergen occurred in 49.4% adolescents. The risk factors for asthma were: prematurity (OR: 3.84, 95% CI: 1.54-9.64), rhinitis (OR: 3.18, 95% CI: 1.71-5.91), positivity in the SPT (OR: 2.81, 95% CI: 1.48-5.32), eczema in characteristic skin-folds (OR: 2.86, 95% CI: 1.13-7.26), and an allergic mother (OR: 2.01, 95% CI: 1.02-3.93). The consumption of cooked vegetables was a protective factor for asthma (OR: 0.37, 95% CI: 0.18-0.79) CONCLUSIONS: Asthma is a multifatorial disease. An allergic mother, aeroallergen sensitization, rhinitis, eczema and prematurity were considered risk factors and the consumption of cooked vegetables was considered a protective factor for asthma in this population.     

In vivo measurements of fibrin formation and degradation in nephrotic patients

Summary Intraglomerular fibrin deposition has been implicated as an important pathogenetic mechanism in patients with glomerular diseases and the nephrotic syndrome. To investigate fibrin formation and degradation in nephrosis, we measured fibrinopeptide A by radio-immunoassay and D-dimer by enzyme-linked immunosorbent assay in the plasma of 30 consecutive adult patients with the nephrotic syndrome; in 10 the serum creatinine was more than 2 mg/dl. Both fibrinopeptide A and D-dimer were abnormally elevated in the majority of nephrotics (P<0.001 vs. healthy controls), providing evidence of increased fibrin generation and lysis “in vivo.” A positive correlation was found between fibrinopeptide A and D-dimer (correlation coefficient 0.64,P<0.001), suggesting a close relationship between fibrin formation and degradation. Calcium heparin, administered to 12 nephrotics, caused a marked decrease in plasma fibrinopeptide A, due to a reduction of in vivo thrombin activity. As enhanced thrombin activity can favor fibrin deposition within the renal parenchyma, as well as vascular complications, it is reasonable to assume that an antithrombotic treatment aimed at controlling thrombin generation may ameliorate the natural history of nephrosis.     

Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents

Aim  

The aim of the present study was to collect and compare cases of drug-induced PML in order to contribute to the debate about the role of the underlying diseases and/or drug immunosuppression in PML occurrence.     

Localization of parathyroid enlargement: experience with technetium-99m methoxyisobutylisonitrile and thallium-201 scintigraphy,ultrasonography and computed tomography

Technetium-99m methoxyisobutylisonitrile (MIBI), like thallium-201, has recently been introduced as a myocardial perfusion agent and is now also showing very promising results in parathyroid scintigrapy. The results of ²⁰¹Tl/^99mTc-pertechnetate and ^99mTc-MIBI/^99mTc-pertechnetate subtraction scintigraphy, ultrasonography and computed tomography are presented in a series of 43 patients operated on for hyperparathyroidism. All four imaging modalities were confirmed to be reliable, scintigraphy being the most accurate. Sensitivities ranged from 81% to 95%, that of ^99mTc-MIBI being the highest. Moreover this tracer, which has more favourable physical and also biochemical properties, yielded images of superior quality. This allowed localization of the lesion by visual inspection only in as many as 86% of the patients with positive ^99mTc-MIBI/^99mTc-pertechnetate subtraction scintigraphy. We believe that the higher sensitivity, superior image quality and lower cost of ^99mTc-MIBI imaging will make ^99mTc-MIBI the new radiopharmaceutical of choice for parathyroid scintigraphy (when one takes into account the stability of labelling with large activities it is possible to perform three or four cardiac studies together with one parathyroid scintigraphic examination using one lyophililzed vial).