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1.  Sitagliptin, sitagliptin and metformin, or sitagliptin and amitriptyline attenuate streptozotocin-nicotinamide induced diabetic neuropathy in rats 
Journal of Biomedical Research  2012;26(3):200-210.
Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide-streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly improved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 (P < 0.001). Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 (P < 0.001). Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.
PMCID: PMC3596070  PMID: 23554750
diabetic neuropathy; nicotinamide-streptozotocin; metformin; pioglitazone; glimipiride; sitagliptin; amitriptyline
2.  Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury 
Journal of Biomedical Research  2012;26(1):24-36.
The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide.
PMCID: PMC3596077  PMID: 23554727
Allium sativum Linn.; ischemic preconditioning; cardioprotection; adenosine; nitrite
3.  Typhoid Intestinal Perforation: 24 Perforations in One Patient 
Intestine perforation is one of the most dreaded and common complication of typhoid fever remarkably so in developing world; it usually leads to diffuse peritonitis, requiring early surgical intervention. Despite various measures such as safe drinking water supply and safe disposal of waste, intestinal perforation from salmonellosis remains the most common emergency surgery performed. The incidence continues to rise, so also the mortality, despite new antibiotics and improvement in surgical technique. More disturbing is that we now see increasing number of ileal perforations and colonic involvement. We hereby present a case report of 35-year-old male with multiple (24) intestinal perforation in the Ileum and Cecum.
PMCID: PMC3853607  PMID: 24349848
Asia; Multiple ileal perforations; Salmonellosis
4.  Does multiplex Polymerase Chain Reaction increase the diagnostic percentage in osteoarticular tuberculosis? A prospective evaluation of 80 cases 
International Orthopaedics  2011;36(2):255-259.
Multiplex Polymerase Chain Reaction (MPCR) is a technique in which two or more gene targets are amplified in a single reaction. This has increased sensitivity of diagnosis as a single gene target may be absent in some Mycobacterium tuberculosis strains.
MPCR using two target genes specific for Mycobacterium tuberculosis, that is, IS6110 and MPB 64, ZN staining and Mycobacterial culture were performed on synovial fluid/pus samples of 80 (three confirmed, 77 suspected) patients of osteoarticular tuberculosis and 25 non tuberculosis patients.
MPCR had a sensitivity of 100% in confirmed cases and 81.8% in clinically suspected cases. AFB was positive in one patient and Mycobacterial culture was positive in three patients. MPCR also had 100% specificity; MPB64 was positive in five patients in which IS6110 was negative whereas IS6110 was positive in two patients in which MPB64 was negative.
MPCR is a sensitive and specific method for diagnosis of paucibacilliary conditions such as osteoarticular tuberculosis.
PMCID: PMC3282846  PMID: 21442201
5.  Analysis of 3′-Terminal Region of Bean common mosaic virus Strains Infecting Common Bean in India 
Four strains (NL-1, NL-1n, NL-7 and NL-7n) of Bean common mosaic virus (BCMV) prevalent on common bean (Phaseolus vulgaris) in Himachal Pradesh, a north-western Himalayan state of India were compared at the 3′ terminal region of the viral genome to elucidate variation and relationship among these strains. 3′ terminal region comprising of partial nuclear inclusion b (NIb) (171–233 bp), complete coat protein (CP) (860 bp) and 3′ untranslated region (UTR) (208–244 bp) shared 96–98% nucleotide and 96–99% amino acids identity among various strains of BCMV. Multiple alignment as well as cluster dendrograms of the 3′ terminal region placed the test isolates in BCMV species of genus Potyvirus. Phylogenetic analysis of complete CP as well as 3′ UTR also showed Indian strains to be distinct strains. Sequence homology, multiple alignment and evolutionary divergence of 3′ terminal region could not differentiate the pathogenic strain groups, thereby establishing least role of this region in strain characterization of the virus. Comparisons of CP and 3′ UTR region of BCMV strains and other members of genus Potyvirus clearly indicated the little utility of 3′ terminal region in distinction of virus strains. Implications of coat protein region in viral strain distinction are also discussed.
PMCID: PMC3550725  PMID: 23637500
BCMV; Common bean; Strains; Coat protein; Variability
6.  Synthesis and Characterisation of Some New Aluminium Derivatives of Schiff Bases Containing N, O and S Donor Atoms and the Anti Fertility Activity of the Derivative Al[SC6H4N:C(CH3)CH2COCH3]3  
Some new compounds of aluminium having the general formula AI[SC6H4N:C(R) CH2 C(O)R’]3 where R = CH3, R' = CH3 (1); R' = CH3, R' = C6H5 (2); R = CF3, R’ = -C = CH - CH = CHS (3); R = CF3, R’ = C6H5 (4) have been synthesised by the reactions of Al(OPri)3 and the corresponding ligands in 1:3 molar ratios in benzene. Elemental and spectroscopic (IR, 1H, 13C, and 27AI NMR) characterisation of these monomeric compounds reveals monofunctional bidentate behaviour of ligand moiety and the octahedral geometry around aluminium atom. Compound (1), AI[SC6H4N:C(CH3)CH2COCH3], has been tested for its antifertility activity in male albino rats. The oral administration of this compound at the dose level 6.5 rag/rat/day reduced the weights of testes and epididymides. Significant decrease in sperm motility as well as sperm density resulted in the reduction of male fertility by 100%. Production of primary spermatocytes (preleptotene and pachytene), secondary spermatocytes and step-19 spermatids declined by 56.10%, 44.42 %, 63.35 % and 64.57 % respectively. These results indicate that the administration of compound (1) in male rats brought about an interference with spermatogenesis which ultimately caused infertility.
PMCID: PMC2267056  PMID: 18365055
7.  Irrational Fixed Dose Combinations & Need for Intervention: Understanding of Dental Clinicians and Residents 
Context: There is a growing concern about ever-burgeoning list of irrational fixed dose combinations (FDCs) which have flooded pharmaceutical market recently in India. Till date no structured study has evaluated the level of understanding among the dental clinicians and residents about these concepts. The present study is designed to fulfil that lacuna.
Objective: To evaluate the knowledge, attitude and practice, regarding the use of FDCs by the dental residents and dental clinicians in a tertiary care teaching dental hospital.
Materials and Methods: The present study was carried out among postgraduate students and dental clinicians working at Rajasthan Dental College, a tertiary care teaching dental hospital, in Jaipur, India. Sixty residents and 77 dental clinicians from the departments of Orthodontics, Prosthodontics, Oral Medicine, Periodontology, Conservative Dentistry & Endodontics, Oral & Maxillofacial Surgery, Pedodontics who gave their informed consent were enrolled. A prevalidated questionnaire regarding knowledge, attitude and prescribing practice of fixed dose combinations was filled up. Data was analysed with suitable statistical tests.
Results: Out of the 60 residents and 77 dental clinicians recruited for the study, none of them were aware about all of the advantages and disadvantages of FDCs. On an average, only 47% of residents and 61% dental clinicians were aware of FDC included in WHO Essential Medicines List (EML). Only 47% residents and 58% dental clinicians could recall a single banned FDC in India. Common sources of information about FDCs were Monthly Index of Medical Specialities (MIMS), medical representatives and internet. The most commonly prescribed irrational FDC was diclofenac + paracetamol combination, 42% residents and 41% dental clinicians and residents believed that regular Continuous Medical Education (CMEs) stressing upon rational use of medicine could reduce the magnitude of this problem.
Conclusion: It is the need of the hour to reduce the magnitude of this problem by sensitizing dental residents and prescribers regarding the efficacy, safety, suitability, rationality and cost benefit of FDCs available for patient use.
PMCID: PMC4316337  PMID: 25654031
Dental clinicians; Essential medicines list; Irrational fixed dose combinations; Residents
8.  Insulinoma: A Comprehensive Summary of Two Cases 
Pancreatic endocrine tumours are rare in occurrence. They may present with a baffling range of symptoms which pose a diagnostic dilemma. Two cases of pancreatic insulinoma are presented herewith. Both presented with neuro-psychiatric complaints and were treated symptomatically for depression, anxiety, seizures etc. The diagnosis in these patients was missed for years. Insulinoma being a great diagnostic challenge, requires reasonably high clinical suspicion, accurate biochemical diagnosis and radiological localization to avoid extensive surgery. The aim is to highlight the occurrence of this rare tumour at a tertiary care hospital.
PMCID: PMC4225896  PMID: 25386444
Insulinoma; Neuropsychiatric presentation; Spontaneous hypoglycaemia
9.  Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design: In Vitro and In Vivo Evaluation  
BioMed Research International  2014;2014:156010.
The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167–318 d·nm, PDI below 0.441, and −18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of 21.7 ± 1.3% with prolonged drug release of 69.5 ± 0.8% from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway.
PMCID: PMC4122152  PMID: 25126544
10.  Lymphadenopathic form of solid variant of alveolar rhabdomyosarcoma: A rare case report 
Lymph node enlargement due to metastatic rhabdomyosarcoma, without an obvious primary tumor, is rare. We report a fine-needle aspiration diagnosed and histopathologically confirmed case of solid variant of alveolar rhabdomyosarcoma in a 13-year-old female. She presented with right cervical lymphadenopathy, followed by a diffuse swelling in right forearm 2 months later.
PMCID: PMC4274531  PMID: 25538389
Lymphadenopathic form; rhabdomyosarcoma; solid variant
11.  mtDNA G10398A variation provides risk to type 2 diabetes in population group from the Jammu region of India 
Meta Gene  2014;2:269-273.
Mitochondrion plays an integral role in glucose metabolism and insulin secretion. Mitochondrial electron-transport chain (ETC) is involved in adenosine triphosphate (ATP) generation and ATP mediated insulin secretion in pancreatic β-cells. β-cell dysfunction is a critical component in the pathogenesis of type 2 diabetes (T2D). The mtDNA G10398A variation (amino acid change: Alanine → Threonine) within the NADH dehydrogenase (ND3) subunit of complex I of mtDNA ETC, has emerged as a variation of clinical significance in various disorders including T2D. This variation is supposed to result in altered complex I function, leading to an increased rate of electron leakage and reactive oxygen species (ROS) production, which might cause β-cell damage and impaired insulin secretion. The aim of the study was to explore the association of mtDNA G10398A variation with T2D in a total of 439 samples (196 T2D cases and 243 healthy controls) belonging to the Jammu region of Jammu and Kashmir (J&K). The candidate gene association analyses showed significant association of mtDNA G10398A variant with T2D and the estimated odds ratio (OR) was 2.83 (1.64–4.90 at 95% CI) in the studied population group. The extent of genetic heterogeneity in T2D and diversity of the Indian population groups, make such replication studies pertinent to understand the etiology of T2D in these population groups.
PMCID: PMC4287871  PMID: 25606409
T2D; Jammu; mtDNA; ND3 gene
12.  Genetic polymorphism of glutathione S-transferase P1 (GSTP1) in Delhi population and comparison with other global populations☆ 
Meta Gene  2014;2:134-142.
Glutathione S-transferases (GSTs) belong to a super family of phase II detoxification enzymes, which play an important role in protecting cells from damage caused by endogenous and exogenous compounds by conjugating reactive intermediates with glutathione to produce less reactive water-soluble compounds. In the present study, we determined the frequencies of two polymorphisms in exon 5 and exon 6 of GSTP1 gene in 500 normal individuals from Delhi. GSTP1 polymorphism was analysed by PCR-RFLP using amplification refractory mutation system (ARMS) assay. Two polymorphic sites in GSTP1 (Ile105 → Val105; Ala114 → Val114) have been analysed simultaneously, which results in four alleles: GSTP1*A (wild-type Ile105; Ala114), GSTP1*B (Val105; Ala114), GSTP1*C (Val105; Val114) and GSTP1*D (Ile105; Val114). The GSTP1 allele frequency in Delhi population was 0.663, 0.248, 0.069, and 0.020 for GSTP1*A, GSTP1*B, GSTP1*C, and GSTP1*D respectively. The frequency of Ile105 and Val105 allele was 0.683 and 0.317 respectively and it was calculated for the purpose of comparison with published data where all the four alleles were not analysed. GSTP1 alleles from Delhi population were compared with reported frequencies from all over India, and from other ethnic groups worldwide. This study would provide a basic database for future genetic studies.
PMCID: PMC4287809  PMID: 25606397
GST polymorphism; GSTP1; North Indians; ARMS assay; Glutathione S-transferase
13.  Dark Age Vampires or Our Poor Patients 
PMCID: PMC3778832  PMID: 24082237
14.  Evidence based herbal drug standardization approach in coping with challenges of holistic management of diabetes: a dreadful lifestyle disorder of 21st century 
Plants by virtue of its composition of containing multiple constituents developed during its growth under various environmental stresses providing a plethora of chemical families with medicinal utility. Researchers are exploring this wealth and trying to decode its utility for enhancing health standards of human beings. Diabetes is dreadful lifestyle disorder of 21st century caused due to lack of insulin production or insulin physiological unresponsiveness. The chronic impact of untreated diabetes significantly affects vital organs. The allopathic medicines have five classes of drugs, or otherwise insulin in Type I diabetes, targeting insulin secretion, decreasing effect of glucagon, sensitization of receptors for enhanced glucose uptake etc. In addition, diet management, increased food fiber intake, Resistant Starch intake and routine exercise aid in managing such dangerous metabolic disorder. One of the key factors that limit commercial utility of herbal drugs is standardization. Standardization poses numerous challenges related to marker identification, active principle(s), lack of defined regulations, non-availability of universally acceptable technical standards for testing and implementation of quality control/safety standard (toxicological testing). The present study proposed an integrated herbal drug development & standardization model which is an amalgamation of Classical Approach of Ayurvedic Therapeutics, Reverse Pharmacological Approach based on Observational Therapeutics, Technical Standards for complete product cycle, Chemi-informatics, Herbal Qualitative Structure Activity Relationship and Pharmacophore modeling and, Post-Launch Market Analysis. Further studies are warranted to ensure that an effective herbal drug standardization methodology will be developed, backed by a regulatory standard guide the future research endeavors in more focused manner.
PMCID: PMC3751117  PMID: 23822656
Diabetes; Standardisation; Herbal drugs; Drug development
15.  Thoracic extraosseous, epidural, cavernous hemangioma: Case report and review of literature 
A 40-year-old male presented with mid-thoracic backache and progressive, ascending, spastic, paraparesis for one year. Magnetic resonance imaging demonstrated an extraosseous, extradural mass, without any bone invasion at the T2-T4 vertebral levels, located dorsal to the thecal sac. The spinal cord was compressed ventrally. The lesion was totally excised after a T2-T4 laminectomy. Histopathological examination revealed a cavernous hemangioma. The authors reported this case and reviewed the literature, to explain why extraosseous, extradural, cavernous hemangiomas should be considered in the differential diagnosis of extradural thoracic compressive myelopathy.
PMCID: PMC3821420  PMID: 24250167
Cavernous hemangioma; epidural; magnetic resonance imaging; myelopathy; thoracic spine
16.  Designed Chemical Intervention with Thiols for Prophylactic Contraception 
PLoS ONE  2013;8(6):e67365.
Unlike somatic cells, sperm have several-fold more available-thiols that are susceptible to redox-active agents. The present study explains the mechanism behind the instant sperm-immobilizing and trichomonacidal activities of pyrrolidinium pyrrolidine-1-carbodithioate (PPC), a novel thiol agent rationally created for prophylactic contraception by minor chemical modifications of some known thiol drugs. PPC, and its three derivatives (with potential active-site blocked by alkylation), were synthesized and evaluated against live human sperm and metronidazole-susceptible and resistant Trichomonas vaginalis, in vitro. Sperm hexokinase activity was evaluated by coupled enzyme assay. PPC irreversibly immobilized 100% human sperm in ∼30 seconds and totally eliminated Trichomonas vaginalis more efficiently than nonoxynol-9 and metronidazole. It significantly inhibited (P<0.001) thiol-sensitive sperm hexokinase. However, the molecule completely lost all its biological activities once its thiol group was blocked by alkylation. PPC was subsequently formulated into a mucoadhesive vaginal film using GRaS excipients and evaluated for spermicidal and microbicidal activities (in vitro), and contraceptive efficacy in rabbits. PPC remained fully active in quick-dissolving, mucoadhesive vaginal-film formulation, and these PPC-films significantly reduced pregnancy and fertility rates in rabbits. The films released ∼90% of PPC in simulated vaginal fluid (pH 4.2) at 37°C in 5 minutes, in vitro. We have thus discovered a common target (reactive thiols) on chiefly-anaerobic, redox-sensitive cells like sperm and Trichomonas, which is susceptible to designed chemical interference for prophylactic contraception. The active thiol in PPC inactivates sperm and Trichomonas via interference with crucial sulfhydryl-disulfide based reactions, e.g. hexokinase activation in human sperm. In comparison to non-specific surfactant action of OTC spermicide nonoxynol-9, the action of thiol-active PPC is apparently much more specific, potent and safe. PPC presents a proof-of-concept for prophylactic contraception via manipulation of thiols in vagina for selective targeting of sperm and Trichomonas, and qualifies as a promising lead for the development of dually protective vaginal-contraceptive.
PMCID: PMC3694959  PMID: 23826278
17.  Multiplex PCR for Rapid Diagnosis of Gastrointestinal Tuberculosis 
Rapid and specific diagnosis of gastrointestinal tuberculosis (GITB) is of utmost importance.
To evaluate Multiplex PCR (MPCR) using MPB64 and IS6110 primers specific for M. tuberculosis for rapid diagnosis of GITB.
Materials and Methods:
MPCR was performed on colonoscopy biopsy specimens on 11 GITB confirmed (culture/AFB/histopathology was positive), 29 GITB suspected and 30 Non GITB (control group) patients.
MPB64 PCR had sensitivity and specificity of 90% and 100% for confirmed GITB cases. In 29 clinically diagnosed but unconfirmed GITB cases, MPCR was positive in 72.41%. MPCR was negative in all control group patients. The overall sensitivity and specificity of microscopy, culture, histopathology and MPCR was 5%, 2% 20% and 77.5% and 100%, 100%, 100% and 100% respectively.
MPCR has good sensitivity and specificity in diagnosing gastrointestinal tuberculosis.
PMCID: PMC3703210  PMID: 23853431
Gastrointestinal tract; Multiplex PCR; Tuberculosis
18.  Novel multi-targeted polymerase chain reaction for diagnosis of presumed tubercular uveitis 
The objective of this study was to report the use of multi-targeted polymerase chain reaction (PCR) in the diagnosis of presumed tubercular uveitis. Multi-targeted PCR using three targets specific for Mycobacterium tuberculosis, i.e., IS6110, MPB64, and protein b, was performed on intraocular fluid samples of 25 subjects. Nine had presumed tubercular uveitis, six had intraocular inflammation secondary to a nontubercular etiology (disease controls), and ten had no evidence of intraocular inflammation (normal controls). As described previously, response to antitubercular therapy was considered as the gold standard.
Multi-targeted PCR was positive in seven out of nine patients with presumed tubercular uveitis and negative in all normal and disease controls. The sensitivity and specificity were 77.77% and 100%, respectively. For the diagnosis of presumed tubercular uveitis, multi-targeted PCR had a positive predictive value of 100% and a negative predictive value of 88.88%.
Multi-targeted PCR can be a valuable tool for diagnosing presumed tubercular uveitis.
PMCID: PMC3605072  PMID: 23514226
Uveitis; Tubercular; Polymerase chain reaction; Multi-targeted PCR
19.  Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy in tertiary care hospitals of Jammu 
To study whether the administration of recombinant human erythropoietin increases the amount of autologous blood that can be collected before orthopaedic surgery.
Materials and Methods:
We conducted a randomized controlled trial of recombinant human erythropoietin in 68 adults scheduled for elective orthopedic procedures. The patients received either erythropoietin 600 units/kg of body weight or placebo intravenously every 5th day prior to each phlebotomy for 21 days during which time up to 5 units of blood was collected. Patients were excluded from donation when their hematocrit values were less than 33%. All patients received iron sulphate 325mg orally 3 times daily. The mean number of units collected per patient was 4.33 ± 0.4 for erythropoietin group and 3.05± 0.71 for the placebo group.
The mean packed red cell volume donated by patients who received erythropoietin was 32% greater than that donated by patients who received placebo (196.3 vs. 169.4 ml, p<0.05). 68% in the placebo group and 9% of patients treated with erythropoietin were unable to donate ≥4 units. No adverse effects were attributed to erythropoietin. While participating in the study, complications developed in 2 patients one in each group necessitating their removal from the study.
We conclude that recombinant human erythropoietin increases the ability of the patients about to undergo elective surgery to donate autologous blood units.
PMCID: PMC3613661  PMID: 23559764
Autologous blood; preoperative; recombinant human erythropoietin
20.  Paraneoplastic Pemphigus: A Paraneoplastic Autoimmune Multiorgan Syndrome or Autoimmune Multiorganopathy? 
Paraneoplastic pemphigus (PNP), a clinically and immunopathologically distinct mucocutaneous blistering dermatosis, is a severe form of autoimmune multiorgan syndrome generally associated with poor therapeutic outcome and high mortality. This IgG-mediated disease is initiated by an obvious or occult lymphoproliferative disorder in most cases. Clinically severe mucositis, and polymorphic blistering skin eruptions, and histologically acantholysis, keratinocyte necrosis and interface dermatitis are its hallmark features. A 58-year-old female presented with recurrent, severe, recalcitrant stomatitis and widespread erosions/blistering lesions of one-year duration. Treatment with repeated courses of systemic corticosteroids at a peripheral center would provide temporary relief. She also had fever, productive cough, odynophagia and poor oral intake, herpes zoster ophthalmicus, pain in the abdomen, and watery diarrhea. An array of investigations revealed chronic lymphocytic leukemia (CLL), mediastinal and para-aortic lymphadenopathy, bronchiolitis obliterans, and vertebral osteoporosis/fractures. With the diagnosis of CLL-associated PNP she was managed with dexamethasone-cyclophosphamide pulse (DCP) therapy for 3 cycles initially, followed by COP regimen (cyclophosphamide, vincristine, and prednisolone) for 5 cycles. Remission is being maintained with chlorambucil and prednisolone pulse therapy once in 3 weeks with complete resolution of skin lesions and adequate control of CLL.
PMCID: PMC3535815  PMID: 23316398
21.  Metastatic Basal Cell Carcinoma: A Biological Continuum of Basal Cell Carcinoma? 
Basal cell carcinoma (BCC) accounts for 80% of all nonmelanoma skin cancers. Its metastasis is extremely rare, ranging between 0.0028 and 0.55 of all BCC cases. The usual metastasis to lymph nodes, lungs, bones, or skin is from the primary tumor situated in the head and neck region in nearly 85% cases. A 69-year-old male developed progressively increasing multiple, fleshy, indurated, and at places pigmented noduloulcerative plaques over back, chest, and left axillary area 4 years after wide surgical excision of a pathologically diagnosed basal cell carcinoma. The recurrence was diagnosed as infiltrative BCC and found metastasizing to skin, soft tissue and muscles, and pretracheal and axillary lymph nodes. Three cycles of chemotherapy comprising intravenous cisplatin (50 mg) and 5-florouracil (5-FU, 750 mg) on 2 consecutive days and repeated at every 21 days were effective. As it remains unclear whether metastatic BCC is itself a separate subset of basal cell carcinoma, we feel that early BCC localized at any site perhaps constitutes a biological continuum that may ultimately manifest with metastasis in some individuals and should be evaluated as such. Long-standing BCC is itself potentially at risk of recurrence/dissemination; it is imperative to diagnose and appropriately treat all BCC lesions at the earliest.
PMCID: PMC3523573  PMID: 23304569
22.  Congenital Insensitivity to Pain with Anhidrosis (HSAN Type IV), Extremely Rare Syndrome that Can Be Easily Missed by Bone and Joint Surgeons: A Case Report 
Iranian Journal of Pediatrics  2012;22(4):559-563.
Congenital insensitivity to pain with anhidrosis is an extremely rare disorder in which injuries can often be missed by patient, parents and even by orthopedic surgeon. Pain and tenderness, on which a trauma team so much depends to make a clinical diagnosis and to decide whether to go for radiological evaluation can be misleading in this rare syndrome. So complete clinical examination still forms the corner stone to avoid misdiagnosis and pick up the rare disorders.
Case Presentation
We present a 5 year old girl child, who was brought to us as a case of one and a half month old neglected trauma left leg and was diagnosed to be suffering from congenital insensitivity to pain with anhidrosis (HSAN Type IV).
Congenital insensitivity to pain with anhidrosis is extremely rare entity, in which patients are subjected to repeated injuries which are often neglected. There is no specific treatment but patient training and parent education are key to avoid further neglect and damage.
PMCID: PMC3533163  PMID: 23429452
Congenital Insensitivity to Pain with Anhidrosis; Hereditary sensory autonomic neuropathy; Anhidrosis; Osteoacrolysis; Hyperpyrexia
23.  OA01.05. Role of prabhakara vati and lekhana basti treatment in the management of coronary artery disease (Hridroga) 
Ancient Science of Life  2012;32(Suppl 1):S5.
The present study was conducted on 30 clinically diagnosed and confirmed patients of Coronary Artery Disease (C.A.D.). Patients having C.A.D. with specific conditions were not registered. The study was conducted with an objective of evaluating the role of Prabhakara Vati and Lekhana Basti in the management of C.A.D. on various scientific parameters.
30 patients were randomly divided into three groups. It was a randomised, comparative, open ended, pre and post design, clinical trial. Out of the three groups, 10 patients were administered Tab. Dilzem 30 mg TDS for one month, 10 patients of second group were administered Prabhakara Vati 500 mg (two tablets) bd for one month and 10 patients were administered Lekhana Basti (for 15 days) along with Prabhakara Vati 500 mg (two tablets) bd for one month.
During present trial it was observed that there was significant improvement in clinical manifestations of stable angina after the therapy with Prabhakara Vati and Lekhana Basti. The level of S. Cholesterol, L.D.L., V.L.D.L. and Serum Triglycerides decreased and the level of H.D.L. increased considerably after the therapy.
Prabhakara Vati and Lekhana Basti possesses potent antianginal and cardio protective activities and it can be used effectively in the management/to slow down the progress of pathogenesis of atherosclerosis leading to various Hridrogas (C.A.D.) specially stable angina.
PMCID: PMC3800929
24.  Comparative Efficacy and Safety of Various Anti-Microbials in Patients of Acute Rhinosinusitis at Tertiary-Care Hospital in Uttarakhand (UK) 
To compare the efficacy of gatifloxacin, azithromycin with amoxicillin as positive control for the treatment of Acute rhinosinusitis (ARS). To monitor adverse drug reaction profile of amoxicillin, azithromycin and gatifloxacin in patient of ARS. An open randomized trial of comparative efficacy and safety of amoxicillin, azithromycin and gatifloxacin in patients with ARS. Patients were randomized into three groups as under: group 1: patients on oral amoxicillin 500 mg TDS for 10 days; group 2: patients on oral azithromycin 500 mg OD for 5 days; group 3: patients on oral gatifloxacin 400 mg OD for 10 days. Patients were evaluated for signs and symptoms at day 1, day 7 (for group 2), on day 12 (for group 1, 3) as primary end points and 28 days after post therapy as secondary end point. All the three antimicrobial drugs i.e., amoxicillin, azithromycin and gatifloxacin were effective in reducing symptoms of acute sinusitis on visual analogue scale scoring. Azithromycin showed significant improvement radiographically on day 7 (P < 0.01) and on day 35 (P < 0.01). Gatifloxacin elicited very highly significant improvement radiographically on day 40 (P < 0.001) and significant improvement on day 12 (P < 0.01) when compared with amoxicillin. Azithromycin, the ketolide was associated with lesser adverse effects as compared to amoxicillin. All the three antimicrobial drugs i.e., amoxicillin, azithromycin and gatifloxacin were effective in reducing symptoms of acute sinusitis on visual analogue scale scoring. Gatifloxacin was found to be most effective drug both in terms of improvement in signs and symptoms on visual analogue scale and radiographic scoring and was associated with least adverse events in comparison to rest of two drugs under study.
PMCID: PMC3227819  PMID: 23024943
Acute rhinosinusitis (ARS); Gatifloxacin-respiratory fluoroquinolone, ketolide-azithromycin; Aminopenicillin-amoxicillin
25.  sushruta-samhitA: A critical review Part - 2: Few new additions 
Ayu  2012;33(4):491-498.
In this part importace and specialize of sushruta are specified. In Part – 1 all the translation works in all the available languages is narrated. After studying all those books and keeping in to mind about a comprehensive work of sushruta it is necessary to elaborate in this present text. This part is divided into 5 sections. (A) All available commentaries taken in to consideration for this part is written, (B) Specialities of sushruta are most important as he has narrated all eight sections of Ayurveda elabroted widely where as caraka has only narrated mainly selected part of kAya-cikitsA and left other sections for other authors e.g., “atra dhAnavantareyaNAM adhikArah” etc., Specifying a list of all sections and chapters with the numbers of prose + poetery, (C) None of the translator or commentator touched the importance of sushruta in the literature of samskRta, where as sushruta was a great poet. Giving similar resemblance of common use by mass, he tried to explain the tough subject in simpler mode of knowledge for proper understanding to all public. He has specifically selected the prosody for the specified subject. Examples are given in this section. (D) sushruta has written prosody in14 metres and long sentences too in samskRta that shows his ability and wast knowledge in the literature. All references of each and every metre is noted from all sections of sushruta with complete reference numbers. And no where this subject is published till now- (E) A challenging word regarding the work of sushruta “shArIre sushruto naSTah” is turned back while quoting various references of shArIra-sthAnam and placing its world wide importance by various writers.
PMCID: PMC3665190  PMID: 23723665
Ayurveda; caraka; sushruta; sushruta samhitA

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