Characterization of a highly polymorphic marker adjacent to the SLC4A1 gene and of kidney immunostaining in a family with distal renal tubular acidosis.

BACKGROUND: Mutations in the human SLC4A1 (AE1/band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain unclear. Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation. METHODS: One CA repeat region was identified in a phage P1-derived artificial chromosome (PAC) clone containing most of the human AE1 gene and the upstream flanking region. We determined its heterozygosity value in multiple populations by PCR analysis. Genotyping of one family with dominant dRTA identified the AE1 R589H mutation, and family member genotypes were compared with the CA repeat length. AE1 and vH(+)-ATPase polypeptides in kidney tissue from an AE1 R589H patient were examined by immunocytochemistry for the first time. RESULTS: This CA repeat, previously reported as D17S1183, is approximately 90 kb upstream of the AE1 gene and displayed considerable length polymorphism, with small racial differences, and a heterozygosity value of 0.56. The allele-specific length of this repeat confirmed co-segregation of the AE1 R589H mutation with the disease phenotype in a family with dominant dRTA. Immunostaining of the kidney cortex from one affected member with superimposed chronic pyelonephritis revealed vH(+)-ATPase-positive intercalated cells in which AE1 was undetectable, and proximal tubular epithelial cells with apparently enhanced apical vH(+)-ATPase staining. CONCLUSIONS: The highly polymorphic dinucleotide repeat adjacent to the human AE1 gene may be useful for future studies of disease association and haplotype analysis. Intercalated cells persist in the end-stage kidney of a patient with familial autosomal dominant dRTA associated with the AE1 R589H mutation. The absence of detectable AE1 polypeptide in those intercalated cells supports the genetic prediction that the AE1 R589H mutation indeed causes dominant dRTA.     

Muscle weakness and intolerance to exercise in mitochondrial myopathies

Muscle weakness and intolerance to exercise are two of the main features commonly shown by patients affected by mitochondrial myopathies. In order to obtain an objective and quantitative evaluation of muscle weakness and endurance, we studied an evaluation protocol devoted to the assessment of 1) muscle strength by the isokinetic ergometer and 2) the metabolic aspects of exercise by means of Maximal Oxygen Consumption and endurance by a Steady State Submaximal exercise evaluation. The protocol has been applied to the study of patients affected by mitochondrial diseases and proved to be a reliable method to quantitate the defect in the oxidation pathways, either before or during the therapeutic follow-up.     

A multimedia database system for thermal ablation therapy of brain tumors

A prototype multimedia medical database is described for supporting thermal ablation therapy of brain tumors. Its design is motivated by the major need to manage and access multimedia information on the progress and reaction of tumors to various therapy protocols. The database links images to patient data in a way that permits the user to view and query medical information using alphanumeric, temporal, and feature-based predicates. Visualization programs permit the user to view or annotate the query results in various ways. These results support the wide variety of data types and presentation methods required by neuroradiologists to manage thermal ablation therapy data. The database satisfactorily meets the requirements defined by thermal ablation therapy. A similar approach is being undertaken for supporting different therapies of other types of tumors, thus showing the generality of our approach.     

Treatment of deep brain abscesses by stereotactic implantation of an intracavitary device for evacuation and local application of antibiotics

Summary Complete recovery from deep brain abscesses was achieved in four patients treated by a specialized stereotactic method. In one patient the lesion was in the right thalamus, in two patients within the brain stem and in one case in the right rolandic cortex. The technique consists in the stereotactic implantation of a chronic intracavitary catheter connected to a subcutaneous reservoir to allow postoperative multiple evacuations and local antibiotic irrigations. Serial CT scan examinations guided the timing of intracavitary treatment and the removal of the catheter. No recurrence developed. The diagnostic and therapeutic advantages of this stereotactic technique are emphasized.     

Identification of High-Risk Groups among Node-Positive Patients with Stage IB and IIA Cervical Carcinoma

The purpose of the present study was to identify a subset of high-risk patients among surgically treated node-positive patients with stage IB and IIA cervical carcinoma. From 1982 through 1991, 334 patients underwent radical hysterectomy for FIGO stage IB and IIA cervical carcinoma. In 68 patients pathological analysis of the surgical specimen revealed positive pelvic nodes. In this group, a Cox proportional hazard analysis was performed to examine the prognostic significance of clinicopathological variables. Only for adenocarcinoma (P= 0.002) and parametrium infiltration (P= 0.003) was evidence of an association with prognosis found. Based on these two factors, patients with positive pelvic nodes were categorized into a low-risk group (squamous cell carcinoma without parametrium infiltration,N= 33) and a high-risk group (squamous cell carcinoma with parametrium infiltration or adenocarcinoma,N= 34). The 5-year disease-specific survival in the low-risk group was 94% compared with 60% in the high-risk group (P= 0.003). For patients in the high-risk group, there is an urgent need for alternative adjuvant treatment to improve outcome.     

Is it possible to stabilize the trunk using rhythmic stabilization in the upper limb? A cross-sectional study of asymptomatic individuals

Objective: The study aim was to evaluate the immediate effect of rhythmic stabilization on local and distant muscles involved in a functional reach. Method: Prospective, observational cross-sectional study. Eight right-handed and non-impaired individuals (4 females and 4 males) aged 18–24 years (21.5 ± 1.58 years) were evaluated. Bilateral electromyographic recording of the biceps brachii, triceps brachii, multifidus lumbar, and rectus abdominis muscles was performed during three different tasks. Task 1 involved functional reach, while Task 2 involved rhythmic stabilization followed by a functional reach. Task 3 was similar to Task 2, but with 3 repetitions before a functional reach. Results: The results showed no difference between the tasks or sides. However, an interaction was observed between each side and muscles, with greater activation of the right multifidus lumbar muscle. Conclusion: Rhythmic stabilization during the task of reaching promotes an increase of multifidus activity ipsilateral to its application. Thus, this particular technique of proprioceptive neuromuscular facilitation can be useful for improving stability of the trunk and can be used in clinical practice for this purpose. Level of Evidence: 5.     

Value of automated segmental motion analysis in the assessment of aortic stenosis severity

BACKGROUND AND AIMS OF THE STUDY: Left ventricular (LV) contraction is slowed in patients with aortic stenosis (AS). Although the possible role of LV systolic function abnormalities in the assessment of AS severity has been evaluated, current echocardiographic techniques cannot offer precise quantification of LV motion velocity. The study aim was to evaluate an automated segmental motion analysis (ASMA) system to assess AS severity. METHODS: Twenty-two patients with AS, sinus rhythm and preserved LV ejection fraction were studied prospectively. Patients underwent both conventional Doppler echocardiography to measure transaortic gradient and aortic valve area by the continuity equation, and ASMA of the interventricular septum. The ASMA line graph mode displays changes in area through the cardiac cycle. The RR interval and time from the R-wave to peak maximum area shortening were measured, and an ASMA index was calculated. RESULTS: A significant and strong inverse correlation was found between aortic valve area and ASMA index (r = -0.78; 95% CI -0.90 to -0.55; p <0.001). The area under the ROC curve in the diagnosis of severe AS (aortic valve area < or =0.8 cm2) was 0.97 (95% CI 0.90-1.0). Sensitivity, specificity, positive and negative predictive values and overall accuracy for an ASMA index >0.40 were 100, 91.7, 92.3, 100 and 95.8%, respectively. CONCLUSION: The ASMA system may be valuable in evaluating AS, as it offers a strong correlation with aortic valve area calculated by the continuity equation, and very high sensitivity and specificity in the diagnosis of severe AS.