What Should Define Optimal Correction of Metabolic Acidosis in Chronic Kidney Disease?

Correction of metabolic acidosis is an important goal in the management of patients with chronic kidney disease (CKD). However, there is no consensus as to what constitutes an optimal correction of metabolic acidosis in this setting – various expert groups from around the world have set different goals for serum bicarbonate levels for patients with CKD. Accumulating evidence seems to indicate that achieving an arterial pH closer to the upper limit of the reference range may have even greater benefits than maintaining the arterial pH closer to the lower limit of the reference range. This benefit seems to be particularly relevant for patients with protein‐energy wasting and we present a review of the evidence that supports this argument. Routine measurement of arterial pH, however, is not feasible in clinical practice; using the Henderson equation, a high‐normal arterial pH is generally expected to be associated with a serum bicarbonate level of 24–30 mEq/l and should be the therapeutic goal for chronic kidney disease patients with protein‐energy wasting.     

The spindle checkpoint, aneuploidy, and cancer

Cancer cells contain abnormal number of chromosomes (aneuploidy), which is a prevalent form of genetic instability in human cancers. Defects in a cell cycle surveillance mechanism called the spindle checkpoint contribute to chromosome instability and aneuploidy. In response to straying chromosomes in mitosis, the spindle checkpoint inhibits the ubiquitin ligase activity of the anaphase-promoting complex or cyclosome (APC/C), thus preventing precocious chromosome segregation and ensuring the accurate partition of the genetic material. We review recent progress toward the understanding of the molecular mechanism of the spindle checkpoint and its role in guarding genome integrity at the chromosome level.     

Foix-Alajouanine syndrome: an uncommon cause of myelopathy from an anatomic variant circulation

Foix-Alajouanine syndrome is a rare cause of myelopathy caused by dural arteriovenous malformation of the spinal cord, mostly lower thoracic and lumbar. Patients are usually over 50 years of age and can present with acute lower extremity dysesthesias or intermittent sciatica. Progression to paraplegia may be slow. Spinal angiography is needed for definitive diagnosis, based on the clues provided by the symptoms. If diagnosed early, vascular embolization or neurosurgical excision may be curative.     

Directly observed treatment for tuberculosis

Directly Observed Treatment-Short Course (DOTS) has been a successful strategy in the global control of tuberculosis (TB) in adults. However, reports of implementation are scantily available in pediatric context. Present article reviews diagnostic uncertainties of TB in children commonly faced by physicians on account of the vague clinical presentations, unreliable tuberculin tests or TB score charts, non-specific hematological, biochemical or radiological evidence, difficulty in sputum expectoration and non-availability or ill-affordability of specialised tests. It also describes therapeutic problems arising due to the physician’s inexpertise, child’s incomprehensibility and parental anxiety. DOTS was found to be highly effective in 930 Indian children having TB over the 6-year study period, during which, a rise in number of cases with adult pattern of disease was also noted. The trend change in pediatric TB scenario is thought to have taken place due to malnutrition so widely prevalent in this country. Irrespective of the changing trend, DOTS strategy was found to be effective for all types of pediatric TB. A need, therefore, exists for quick resolution of the programme issues related to pediatric drug dispensing‘ physicians’ reservations about acceptance of strategy in this age-group, service-utilisation of DOTS providers for the selected cases unable to visit DOTS centres and giving executional priority to children during ongoing expansion of Revised National TB Control Programme (RNTCP) in country.     

Peripheral blood and pleural fluid mononuclear cell responses to low-molecular-mass secretory polypeptides of Mycobacterium tuberculosis in human models of immunity to tuberculosis

A total of 104 polypeptides were purified from the low-molecular-mass secretory proteome of Mycobacterium tuberculosis H(37)Rv using a combination of anion exchange column chromatography and high resolution preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electroelution. The goal of this study was to identify polypeptides from a low-molecular-mass secretory proteome recognized by human subjects infected with M. tuberculosis and to ascertain the differences in specificity of antigen recognition by the peripheral blood mononuclear cells (PBMCs) and pleural fluid mononuclear cells (PFMCs) of these individuals. The study identified CFP-8 (Rv0496), CFP-11 (Rv2433c), CFP-14.5 (Rv2445c), and CFP-31 (Rv0831c) as novel T-cell antigens apart from previously characterized ESAT-6, TB10.4, CFP10, GroES, MTSP14, MTSP17, CFP21, MPT64, Ag85A, and Ag85B on the basis of recognition by PBMCs of tuberculosis contacts and treated tuberculosis patients. Further, polypeptides prominently recognized by PFMCs of tuberculous pleurisy patients were the same as those recognized by PBMCs of healthy contacts and treated tuberculosis patients. The results of our study indicate the homogeneity of antigenic target recognition by lymphocytes at the site of infection and at the periphery in the human subjects studied and the need to evaluate these antigenic targets as components of future antituberculous vaccines.