RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

HIV AND TUBERCULOSIS CO-INFECTION IN A REFERRAL CHEST HOSPITAL

Serving personnel of Armed Forces admitted with tuberculosis between Apr 1996–1999 were evaluated for co-infection of tuberculosis and HIV. Sixty (1.06%) of tuberculosis patients were found to be HIV positive. Initial test was done by spot kits and subsequently confirmed by ELISA on two different samples. Majority of the cases were in sexually active age group 48 (80%). Alcohol and smoking was associated in 80% cases. Thirty six (60%) were sputum smear positive for AFB. Twenty eight (46.7%) gave history of exposure to sex workers. Family members were not available for study. Sero prevalence of HIV in association with tuberculosis is less in Armed Forces compared to civil population.KEY WORDS: HIV, Seroprevalence, Tuberculosis     

Muramyl dipeptide: Not just another brick in the wall

The robust expression of microbial pattern recognition receptors such as TLR4 and Nod2 in intestinal stem cells reflects an active communication dynamic between the host and the gut microbiota. A new study reveals that muramyl dipeptide, the bacterial cell wall peptidoglycan motif, activates Nod2 within crypt base columnar Lgr5-positive stem cells and promotes their survival. Apart from the immediate relevance to the growth of organoids for in vitro experiments, the study raises new questions about the molecular mechanisms whereby gut microbes influence intestinal physiology.     

Hepatoprotective Bile Acid Co-Drug of Isoniazid: Synthesis,Kinetics and Investigation of Antimycobacterial Potential

Pharmaceutical Chemistry Journal - The long-course treatment of tuberculosis with isoniazid (INH) leads to hazardous side effects on liver and poor patient compliance. To overcome these toxic...     

Protracted effects of chronic oral haloperidol and risperidone on nerve growth factor, cholinergic neurons, and spatial reference learning in rats

The primary therapeutic agents used for schizophrenia, antipsychotic drugs, ameliorate psychotic symptoms; however, their chronic effects on cognition (or the physiologic processes of the brain that support cognition) are largely unknown. The purpose of this rodent study was to extend our previous work on this subject by investigating persistent effects (i.e. during a 14 day drug-free washout period) of chronic treatment (i.e. ranging from 45 days to 6 months) with a representative first and second generation antipsychotic. Drug effects on learning and memory and important neurobiological substrates of memory, the neurotrophin, nerve growth factor (NGF) and its receptors, and certain components of the basal forebrain cholinergic system were investigated. Behavioral effects of oral haloperidol (2.0 mg/kg/day), or risperidone (2.5 mg/kg/day) were assessed in an open field, a water maze task, and a radial arm maze procedure and neurochemical effects in brain tissue were subsequently measured by enzyme-linked immunosorbent assays (ELISAs). The results indicated that both antipsychotics produced time-dependent and protracted deficits in the performance of a water maze procedure when compared with vehicle-treated controls, while neither drug was associated with significant alterations in radial arm maze performance. Interestingly, haloperidol, but not risperidone, was detectible in the rodent brain in appreciable levels for up to 2 weeks after drug discontinuation. Both antipsychotics were also associated with reduced levels of NGF protein in the basal forebrain and prefrontal cortex and significant (or nearly significant) decreases in phosphorylated tropomyosin-receptor kinase A (TrkA) protein and the vesicular acetylcholine transporter (depending on the brain region analyzed). Neither antipsychotic markedly affected TrkA or p75 neurotrophin receptor levels. These data in rats indicate that chronic treatment with either haloperidol or risperidone may be associated with protracted negative effects on cognitive function as well as important neurotrophin and neurotransmitter pathways that support cognition.     

Time-dependent cognitive deficits associated with first and second generation antipsychotics: cholinergic dysregulation as a potential mechanism

Although cognitive dysfunction is considered one of the more debilitating symptoms of schizophrenia, there is a fundamental gap in our knowledge of how the primary pharmacologic treatments of this disease, first- and second-generation antipsychotics (FGAs and SGAs, respectively), affect cognition, particularly over extended periods of time. Moreover, it has been known for decades that chronic treatment with FGAs can lead to imbalances in cholinergic function in the striatum that result in movement disorders; however, there is a growing body of evidence to suggest that both FGAs and SGAs can lead to cholinergic alterations in brain areas more traditionally considered as memory-related, such as cortical and hippocampal regions. Data from our laboratories in rodents indicate that some SGAs (if administered for sufficient periods of time) can be associated with impairments in memory-related task performance as well as alterations in the cholinergic enzyme choline acetyltransferase, the vesicular acetylcholine transporter, and nicotinic (alpha(7)) and muscarinic (M(2)) acetylcholine receptors. Given the well documented importance of central cholinergic function to information processing and cognitive function, it is important that the mechanisms for such chronic antipsychotic effects be identified. In this review, two potential mechanisms for long-term antipsychotic-related cholinergic alterations in the central nervous system are discussed: 1) antipsychotic antagonist activity at dopaminergic-D(2) receptors on cholinergic neurons and 2) antipsychotic effects on neurotrophins that support cholinergic neurons, such as nerve growth factor and brain derived growth factor. Novel strategies to optimize the therapeutics of schizophrenia and maintain cognitive function via adjunctive cholinergic compounds and antipsychotic crossover approaches are also discussed.     

Disseminated Fusarium oxysporum neurospinal infection

We report a case of disseminated meningospondylodiscitis in an elderly diabetic patient caused by Fusarium oxysporum. As the clinical presentation was nonspecific, the diagnosis of the condition could only be arrived at after laboratory and imaging studies. The diagnosis of the condition requires a high index of suspicion. Patient underwent thorough surgical debridement along with a short course of variconazole and remained asymptomatic after 36 months of diagnosis. Fusarium is a large genus of filamentous fungi widely distributed in soil and in association with plants. It is known to cause local infections (nail, cornea) in healthy humans and disseminated infection only in the immunocompromised.