Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study

Background:

Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world.

Objectives:

The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years.

Materials and Methods:

In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded.

Results:

The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI.

Conclusions:

Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.     

Replication timing properties, of the humanHPRT locus on active, inactive and reactivated X chromosomes

X chromosome inactivation is associated with a highly asynchronous pattern of DNA replication at most X-linked loci in females. We studied the human HPRT locus, which is subject to X inactivation and expressed from only the active homolog, with the goal of comparing replication properties between the active and inactive homologs in this region using a fluorescence in situ hybridization approach. We found that in normal female lymphoblasts this locus is replicated in a highly asynchronous manner across a broad, discrete 500–600 kb zone with earliest replication appearing at the gene coding sequence. This general timing profile is maintained in normal male lymphoblasts, as well as in hamster x human hybrid cells containing the active human X chromosome. However, the inactive human X chromosome in the hamster cell background does not appear to function in a fully equivalent manner to the normal inactive X chromosome in female cells. Furthermore, reactivation of the inactive human X chromosome in a hamster x human hybrid system by 5-azacytidine treatment and HAT selection restores early replication at the HPRT gene itself, but does not change the overall domain behavior.     

Prevalence and correlates of tobacco use among Russian cancer patients: Implications for the development of smoking cessation interventions at a cancer center in Russia

This study examined the rate of smoking among 399 cancer patients in Russia and assessed correlates of tobacco use and readiness to quit smoking. The results indicated that (a) 41.6% of patients were smokers; and (b) smokers were likely to be male, have lung or colorectal cancer, exhibit low levels of knowledge concerning the negative effects of smoking, report a low level of advantages to quitting smoking and a high level of disadvantages to quitting smoking, show low perceived risk for the adverse effects of smoking, and exhibit high fatalistic beliefs. Though certain findings converge well with data collected from U.S. samples of cancer patients, these results can guide the development of smoking interventions that address the specific needs of Russian cancer patients. In sum, this study fills a critical gap in knowledge concerning the epidemic of tobacco use in Russia and broadens research regarding tobacco use by cancer patients from the United States to the Russian Federation. Support for this study was provided by National Institutes of Health grant CA95678 (R. Schnoll) and by a U.S. federal appropriation to the American-Russian Cancer Alliance.     

Genome‐wide transcriptome analyses reveal p53 inactivation mediated loss of miR‐34a expression in malignant peripheral nerve sheath tumours

Malignant peripheral nerve sheath tumours (MPNSTs) are aggressive soft tissue tumours that occur either sporadically or in patients with neurofibromatosis type 1. The malignant transformation of the benign neurofibroma to MPNST is incompletely understood at the molecular level. We have determined the gene expression signature for benign and malignant PNSTs and found that the major trend in malignant transformation from neurofibroma to MPNST consists of the loss of expression of a large number of genes, rather than widespread increase in gene expression. Relatively few genes are expressed at higher levels in MPNSTs and these include genes involved in cell proliferation and genes implicated in tumour metastasis. In addition, a gene expression signature indicating p53 inactivation is seen in the majority of MPNSTs. Subsequent microRNA profiling of benign and malignant PNSTs indicated a relative down‐regulation of miR‐34a in most MPNSTs compared to neurofibromas. In vitro studies using the cell lines MPNST‐14 (NF1 mutant) and MPNST‐724 (from a non‐NF1 individual) show that exogenous expression of p53 or miR‐34a promotes apoptotic cell death. In addition, exogenous expression of p53 in MPNST cells induces miR‐34a and other miRNAs. Our data show that p53 inactivation and subsequent loss of expression of miR‐34a may significantly contribute to the MPNST development. Collectively, our findings suggest that deregulation of miRNAs has a potential role in the malignant transformation process in peripheral nerve sheath tumours. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The immunological and virological response in human immunodeficiency virus type-1 (HIV-1) infected Indian individuals on HAART therapy: a one-year follow up study

Currently, antiretroviral therapy has become more affordable even in developing countries and it is being used in India. Fifteen HIV-1 infected individuals, who were on highly active antiretroviral therapy (HAART), were followed up for an average period of one year. The plasma viral load and CD4+ T cell estimation done at mean intervals of 5 months and 11 months after initiation of therapy showed a good response to therapy in 14 (93%) individuals.     

Enhanced Th2 immunity after DNA prime-protein boost immunization with amyloid beta (1-42) plus CpG oligodeoxynucleotides in aged rats

Generation and accumulation of fibrillar amyloid beta (Abeta) is widely considered as the pathogenic basis of neurodegeneration in Alzheimer's disease (AD). Both active immunization with fibrillar Abeta and passive immunization with anti-Abeta antibodies in transgenic mouse models of AD result in prevention/dissociation of Abeta plaque formation and restoration of cognitive functions. However, similar immunization studies in humans had to be halted because 6% of the AD patients developed acute meningoencephalitis, likely due to anti-Abeta specific autoimmune Th1 cells. Hence, making Abeta immunotherapy successful requires production of strong antibody responses without Th1-type immunity. In an attempt to develop safer vaccines, we examined the influence of oligodeoxynucleotides as adjuvant on the Th1 and Th2 immune response to Abeta in aged rats. We further investigated whether a DNA prime-protein boost strategy could elicit a more robust Th2 response. The results of the present study showed that all the animals injected with either Abeta peptide alone or Abeta encoding plasmid alone or plasmid DNA prime followed by peptide boost have elicited specific anti-Abeta antibodies. When co-administered, synthetic oligodeoxynucleotides (ODN) further enhanced the anti-Abeta titres. More importantly, the IgG subclasses of the antibodies generated by DNA prime-peptide boost regimen with ODN as adjuvant were primarily of IgG2b and IgG1 isotypes, suggesting that heterologous immunization strategy along with ODN would be advantageous in eliciting more beneficial Th2-type humoral immune response.     

Indium 111-labeled granulocyte scan in the diagnosis and management of acute inflammatory bowel disease

The indium 111 granulocyte scan was used to evaluate 39 individuals known to have or suspected of having inflammatory bowel disease. Twenty-three of these individuals had positive scans and 16 had negative scans. Eighty-seven confirmatory studies, which consisted of barium radiography, endoscopy, operative findings, and histopathology, were performed in 37 of these individuals. The remaining two negative scans corroborated only by clinical course, CBC, and erythrocyte sedimentation rate. In addition, 10 follow-up scans were performed in six of the 39 patients to monitor therapy or investigate a change in symptoms. As an anatomic indicator of acute granulocytic infiltration of the intestinal lamina propria and crypts, the authors found that this scan had a 97 percent rate of sensitivity and 100 percent specificity. Specific indications for the use of the indium 111-labeled granulocyte scan are described. For the authors, in general, this test has become a vital adjunct to endoscopy and radiography in the diagnosis and management of patients with symptoms of inflammatory bowel disease.Read at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989. This paper received the New York Society of Colon and Rectal Surgeons A. W. Martin Marino, Sr., M.D., Award.     

Aneurysm of the membranous ventricular septum in transposition of the great arteries.

In patients with transposition of the great arteries (TGA), both the D- and L- forms, an aneurysm of the membranous ventricular septum (AMS) produces subpulmonic stenosis due to the higher right ventricular pressure which forces the aneurysm to protrude into the left ventricular, i.e., subpulmonic, outflow tract. The clinical signs and symptoms, hemodynamic findings as well as surgical results were analyzed in eight patients with TGA and AMS. The presence of an AMS should be suspected from hemodynamic data consisting of a combination of elevated left ventricular pressure, gradient across the left ventricular outflow tract and presence of a small ventricular septal defect with or without pulmonary artery hypertension. The AMS can be demonstrated by a right ventricular injection in the lateral view. The anomaly needs to be corrected at the time of the Mustard procedure. If uncorrected it may lead to postoperative death or progressive obstruction. In the presence of an aneurysm even small ventricular septal defects should be closed by a patch and the aneurysm should be excised.     

The influence of cholinergic, adrenergic, and serotonergic drugs on the afternoon surge of plasma prolactin in ovariectomized, estrogen-treated rats.

The effects of systemic administration of cholinergic, adrenergic, and serotonergic drugs on the afternoon surge of plasma prolactin was investigated using ovariectomized, polyestradiol phosphate (PEP)-injected rats bearing aortic catheters. Basal prolactin levels were elevated and similar after PEP administration for a period of 5 weeks, and an afternoon surge in plasma prolactin persisted for a period of 3 weeks before the magnitude of the surge diminished. The plasma estradiol levels were significantly higher for the 1100 and 1300 h samples than for the 1500 and 1700 h samples. Cornified vaginal epithelia were predominant in the vaginal smears of all animals throughout the 49-day experimental period. The cholinergic agonists arecoline, nicotine, and carbachol significantly inhibited the afternoon surge of prolactin. The muscarinic antagonist atropine resulted in a partial inhibition of the surge while the nicotinic antagonist mecamylamine did not have any inhibitory effect. The alpha-adrenergic blockers phenoxybenzamine and phentolamine and the beta-blocker propranolol inhibited the prolactin surge, with phenoxybenzamine being most effective. The administration of the serotonergic antagonist methysergide resulted in only a partial blockade of the afternoon prolactin surge. The data suggest that both the adrenergic and serotonergic systems may have a positive input in the afternoon surge of plasma prolactin. It appears that the cholinergic system does not play a significant role in the afternoon surge.     

Unmet Needs of Women Living with Parkinson's Disease: Gaps and Controversies

Personalized medicine considering sex, gender, and cultural context has become the vanguard of delivery of care. However, women's issues in Parkinson disease (PD), especially from a psychosocial standpoint, have been an overlooked field. The key research areas include women-inclusive drug and device studies and genetic and hormonal considerations. Moreover, women with PD need to be educated and empowered on how to communicate their symptoms and needs, get engaged in research, get organized as a community, and support one another. Women with PD need tools to help track and convey their unique motor and nonmotor symptoms and psychological and social support needs. The management of PD needs to be customized to include the unique stages of women's lives, including menstrual cycles, pregnancy, perimenopause, menopause, and postmenopause. Specific guidelines for the use of hormonal treatments and customized dopamine replacement dosing need to be developed. Women need guidance on culturally sensitive wellness and self-care strategies that are customized for them. Basic core competencies in knowledge for all clinicians treating women with PD need to be established, including how to accurately diagnose, proactively identify, and treat the symptoms of PD in women and to ensure timely referral for specialty care, advanced therapies, and research studies. Caregivers and families need guidance on holistically supporting women with PD. The voices of women living with PD must be amplified to catalyze real change in this neglected field. This paper provides an overview of the current knowledge, gaps, and possible strategies to deal with the unmet needs of women living with PD with a focus on the clinical and psychosocial aspects. © 2022 International Parkinson and Movement Disorder Society