Newer management options are needed for leprosy control even at present, as it is predicted that new cases of leprosy will continue to appear for many more years in future. This article detail newer methods of clinical grading of peripheral nerve involvement (thickening, tenderness and nerve pain which are subjective in nature) and the advances made in the use of Ultrasonography and Colour Doppler as an objective imaging tool for nerves in leprosy. It also briefly discusses the newer drugs and alternative regimens as therapeutic management options which hold promise for leprosy in future.
Clinical grading of nerve involvement; leprosy-new management options; newer drugs and regimens; ultrasonography and colour doppler imaging of nerves
Emerging evidence indicates that many aspects of alcohol and drug dependence involve changes in glutamate transmission. A number of studies have reported that drugs of abuse, including alcohol and cocaine, alter glutamate transport. Extracellular glutamate is regulated by a number of glutamate transporters in various brain regions. Of these transporters, glutamate transporter (GLT1) is a key player in the removal of most of the extracellular glutamate. Similar to neurodegenerative disease models, in which there is dysfunction of the glutamatergic excitatory system, the role of GLT1 has been tested in drug dependence models that show dysfunction of glutamate transmission. We and others have recently found that ceftriaxone, an FDA-approved drug known to elevate GLT1 expression, attenuates cue-induced cocaine relapse. Moreover, we recently found that alcohol-preferring rats treated with ceftriaxone showed a significant dose-dependent reduction in alcohol consumption. We also demonstrated that ceftriaxone-induced upregulation of GLT1 expression was associated with increases in glutamate uptake in Huntington’s disease mouse model. Importantly, ceftriaxone is currently in clinical trials for the treatment of amyotrophic lateral sclerosis. This review provides information about the potential therapeutic role of GLT1 for the treatment of alcohol abuse and dependence.
GLT1; EAAT2; glutamate; alcohol dependence; alcohol addiction; cocaine; GLAST; EAAT1; glutamate transporters; alcohol-preferring rats; glutamate uptake; cystine-glutamate exchanger; basal extracellular glutamate; nucleus accumbens; prefrontal cortex
High-force lengthening contractions are associated with muscle damage and pain, and the muscle–tendon junction is commonly cited as the primary area where myofiber damage occurs. We induced injury in the rat tibialis anterior muscle and acquired magnetic resonance imaging (MRI) images postinjury. We also assayed membrane damage and quantified the number of centrally nucleated myofibers throughout the injured muscles. Results suggest that myofiber injury occurs primarily in the middle portion of the muscle, with interstitial edema in the middle and distal portions.
eccentric injury; MRI; sarcolemma
In the title complex, [Cu(C13H11N2O)Cl(C6H8N2)], the CuII atom adopts a distorted tetrahedral geometry being coordinated by the phenolic O atom and the azomethine N atom of the Schiff base ligand N-salicylidene 2-aminopyridine, and by the 2-aminopyridine N atom and a Cl atom. The pyridyl N atom of the Schiff base and the imino N atom of the 4-methyl-pyridine-2-ylimino ligand are not involved in the coordination. There is an intramolecular N—H⋯N hydrogen bond involving the pyridine N atom and the amino group of the 2-aminopyridine ligand. In the crystal, molecules are linked via N—H⋯Cl hydrogen bonds, forming chains propagating along .
A neonate with unilateral complete duplex system with congenital giant megaureter of the upper moiety presenting as abdominal lump is reported. A left upper moiety nephroureterectomy was performed. Such an anomaly with this presentation has not been reported in neonates.
Duplex kidney; hydronephrosis; megaureter
The use of magnetic resonance (MR) imaging in conjunction with an endorectal coil is currently the clinical standard for the diagnosis of prostate cancer because of the increased sensitivity and specificity of this approach. However, imaging in this manner provides images and spectra of the prostate in the deformed state because of the insertion of the endorectal coil. Such deformation may lead to uncertainties in the localization of prostate cancer during therapy. We propose a novel 3-D elastic registration procedure that is based on the minimization of a physically motivated strain energy function that requires the identification of similar features (points, curves, or surfaces) in the source and target images. The Gauss–Seidel method was used in the numerical implementation of the registration algorithm. The registration procedure was validated on synthetic digital images, MR images from prostate phantom, and MR images obtained on patients. The registration error, assessed by averaging the displacement of a fiducial landmark in the target to its corresponding point in the registered image, was 0.2 ± 0.1 pixels on synthetic images. On the prostate phantom and patient data, the registration errors were 1.0 ± 0.6 pixels (0.6 ± 0.4 mm) and 1.8 ± 0.7 pixels (1.1 ± 0.4 mm), respectively. Registration also improved image similarity (normalized cross-correlation) from 0.72 ± 0.10 to 0.96 ± 0.03 on patient data. Registration results on digital images, phantom, and prostate data in vivo demonstrate that the registration procedure can be used to significantly improve both the accuracy of localized therapies such as brachytherapy or external beam therapy and can be valuable in the longitudinal follow-up of patients after therapy.
Elastic registration; strain energy minimization; magnetic resonance imaging; prostate; endorectal coil
In the title compound, [Cu(C4H4O4)(C10H8N2)(H2O)]·2H2O, the CuII ion displays a slightly distorted square-pyramidal coordination. The water molecule at the apical position shows a long bond [Cu—O = 2.276 (2) Å]. The basal plane is formed by two N atoms of the 2,2′-bipyridine ligand and two carboxylate O atoms from a malonate group. The five-membered chelate ring is almost planar [maximum deviation = −0.006 (2) Å], while the six-membered chelate ring defined by the malonate ligand adopts a distorted boat conformation. In the crystal, CuII complex molecules and lattice water molecules are connected by O—H⋯O and C—H⋯O hydrogen bonds. The crystal packing is further stabilized by π–π interactions [centroid–centroid distances = 3.563 (2)–3.828 (2) Å].
The art of maxillofacial prosthetics restores esthetics and function in patients with gross developmental or acquired defects of face and helps them to restore hope and ambition to lead a useful life. This valuable service provided by maxillofacial prosthodontist lifts the morale of the patient and thus aids in physical well being and quality of life. Diagnosis and treatment planning should include attention to each detail prior to rehabilitation process. This paper describes a clinical case of mid face defect due to basal cell carcinoma, rehabilitated with facial prosthesis and intraoral obturator.
Acquired mid face defect; Basal cell carcinoma; Orbital prosthesis; Nasal prosthesis; Lip prosthesis; Obturator
Patients with chronic renal failure, especially those on long-term hemodialysis (HD), have a high incidence of premature cardiovascular disease. Oxidative stress, which occurs when there is an excessive free radical production or low antioxidant level, has recently been implicated as a causative factor in atherogenesis. Hourly changes in malondialdehyde (MDA) and antioxidant enzymes, vitamins, lipid profile and ferric reducing ability of plasma (FRAP) were studied with the first use and immediate subsequent reuse of polysulfone dialysis membrane in 27 patients on regular HD treatment. Data were corrected for hemoconcentration and standardized to measure the rate of change. Increase in MDA and erythrocyte catalase along with decrease in plasma vitamin E and FRAP levels and no change in glutathione peroxidase levels were observed as a result of both fresh and reuse dialysis. These findings indicate a net oxidative stress in both fresh as well as dialyzer reuse sessions. There was no significant change in oxidative stress in both fresh and reuse sessions. The oxidative stress with reuse dialysis was less when compared to first use dialysis, but the difference was not statistically significant.
Hemodialysis; oxidative stress; polysulfone membrane; reuse
The purpose of this study is to report two cases of idiopathic uveitis with secondary epiretinal membrane (ERM) formation in order to describe histologic and immunohistochemical features that may help distinguish uveitic from idiopathic ERMs.
The study utilized a clinical case series and histopathological and immunohistochemical findings.
There was no identifiable etiology of inflammation in either case. Histology and immunohistochemistry demonstrated a mixture of abundant inflammatory cells, including lymphocytes, histiocytes, plasma cells, and occasional eosinophils, among a stromal matrix composed of glial elements and condensed vitreous, but no retinal pigment epithelium (RPE) was present. The relative proportions of the various inflammatory cell types were assessed with immunohistochemistry, and among the lymphocyte population, T cells predominated over B cells. In one of the cases, there was an abundance of histiocytes, consistent with granulomatous uveitis, which was later confirmed on histology of the enucleated globe.
Idiopathic ERM formation is thought to be secondary to glial cell migration that may require some involvement of RPE cells. The absence of RPE and abundance of inflammatory cells may be used to identify ERMs as secondary to uveitis.
Epiretinal membrane; Uveitis; Immunohistochemistry; Surgery; Inflammation; Cytokines; Histology
A 4-year-old girl presented with non-bilious vomiting and loss of appetite and weight. At laparotomy, a non-communicating pyloroduodenal duplication cyst was present. Subtotal excision of the cyst and cauterization of the mucosal lining of the common wall was performed. The post-operative recovery was uneventful.
Gastric duplication; gastric outlet obstruction; pyloroduodenal duplication
Patients with chronic obstructive pulmonary disease (COPD) are susceptible to airway malacia, which may be unmasked following mechanical ventilation or tracheostomy decannulation. Dynamic imaging of central airways, a non-invasive test as effective as bronchoscopy to diagnose airway malacia, has increased the recognition of this disorder. We describe a 70-year-old woman admitted with adult respiratory distress syndrome. She had cardiorespiratory arrest on admission, from which she was successfully resuscitated. She had obesity, hypertension, diabetes mellitus, recurrent ventricular tachycardia, sarcoidosis with interstitial lung disease and COPD. She received short-term (18 days) mechanical ventilation with tracheostomy and developed respiratory distress following tracheostomy decannulation.
Adult respiratory distress syndrome; chronic obstructive pulmonary disease; tracheomalacia; tracheostomy
Background & objectives:
There is a need to develop an affordable and reliable tool for hearing screening of neonates in resource constrained, medically underserved areas of developing nations. This study valuates a strategy of health worker based screening of neonates using a low cost mechanical calibrated noisemaker followed up with parental monitoring of age appropriate auditory milestones for detecting severe-profound hearing impairment in infants by 6 months of age.
A trained health worker under the supervision of a qualified audiologist screened 425 neonates of whom 20 had confirmed severe-profound hearing impairment. Mechanical calibrated noisemakers of 50, 60, 70 and 80 dB (A) were used to elicit the behavioural responses. The parents of screened neonates were instructed to monitor the normal language and auditory milestones till 6 months of age. This strategy was validated against the reference standard consisting of a battery of tests - namely, auditory brain stem response (ABR), otoacoustic emissions (OAE) and behavioural assessment at 2 years of age. Bayesian prevalence weighted measures of screening were calculated.
The sensitivity and specificity was high with least false positive referrals for 70 and 80 dB (A) noisemakers. All the noisemakers had 100 per cent negative predictive value. 70 and 80 dB (A) noisemakers had high positive likelihood ratios of 19 and 34, respectively. The probability differences for pre- and post- test positive was 43 and 58 for 70 and 80 dB (A) noisemakers, respectively.
Interpretation & conclusions:
In a controlled setting, health workers with primary education can be trained to use a mechanical calibrated noisemaker made of locally available material to reliably screen for severe-profound hearing loss in neonates. The monitoring of auditory responses could be done by informed parents. Multi-centre field trials of this strategy need to be carried out to examine the feasibility of community health care workers using it in resource constrained settings of developing nations to implement an effective national neonatal hearing screening programme.
Auditory response; neonatal hearing screening; noisemakers; sensitivity; specificity
To determine the outcomes of various ARV (Anti-Retroviral) prophylactic regimes given to HIV positive pregnant mothers, based on time of presentation, for prevention of vertical transmission.
During a four year period, 92 pregnant HIV positive women and their newborn infants received various ARV prophylactic regimes for prevention of vertical transmission. The outcome, in terms of presence of HIV infection in the infants born to these mothers was studied.
The prevalence of HIV infection in the antenatal group studied was 0.62%. Of the 92 HIV positive pregnant mothers who delivered live babies, 91.3% received ARV prophylaxis or HAART, and 95.6% of the 92 live infants received ARV prophylaxis. The risk of vertical transmission was only 3.3%.
Judicious PMTCT regimes, even if they appear complex, are possible in the Indian setting, and can result in significant decline of HIV positive children. Duration of treatment and mode of delivery should be based on the time of presentation of the HIV positive pregnant mother.
HIV; mother-to-child transmission; vertical transmission; zidovudine; nevirapine; ARV prophylaxis
The tuberculosis control program is based on a felt need–oriented basis. The diagnosis is mainly microbiological. However, sputum smear-negative Acid Fast Bacilli (AFB) cases with suspected radiological findings can be problematic in diagnosis.
To confirm the diagnosis of tuberculosis early, in smear-negative AFB cases by using a Fiberoptic Bronchoscope.
Materials and Methods:
We embarked on Fiberoptic Bronchoscopy (FOB) and Spot Scopy smear Microscopy (SSM) for 533 suspected Pulmonary Tuberculosis (PT) cases (sputum smear negative and radiologically suggestive) from February 2007 to May 2010. FOB was performed using a special device, a Trans Oro Pharyngeal Spacer (TOPS), as a conduit.
The yield for positivity for AFB was 341 (64%) out of 533 cases.
Conclusion and Recommendation:
The specimens collected by using the fiberoptic bronchoscope confirmed the disease in the smear-negative cases. Hence, FOB was recommended in smear-negative cases, to avoid delay in the treatment of tuberculosis.
Fiberoptic bronchoscopy; pulmonary tuberculosis; spot scopy smear microscopy; trans oro pharyngeal spacer
Fanconi anemia (FA) results from mutations in the FANC genes and is characterized by bone marrow failure, birth defects and a high incidence of cancer. FANCG is a part of the FA core complex that is responsible for monoubiquitination of FANCD2 and FANCI. The precise role of the FA pathway is not well understood, although it may be involved in homologous recombination (HR), non-homologous end joining (NHEJ) and translesion synthesis (TLS). Fancd2−/− mice have a more severe phenotype than Fancg−/− and other FA core complex deficient mice, although both Fancg and Fancd2 belong to the same FA pathway. We hypothesized that Fancd2 deficiency results in a more severe phenotype because Fancd2 also has a FA pathway-independent function in the maintenance of genomic integrity. To test this hypothesis we determined the level of DNA damage and genomic instability in Fancd2−/−, Fancg−/− and wildtype controls. Fancd2−/− mice displayed a higher magnitude of chromosomal breakage and micronucleus formation than wildtype or Fancg−/− mice. Also, DNA strand breaks were increased in Fancd2−/− but not in Fancg−/− mice. In addition, Fancd2−/− mice displayed an elevated frequency of DNA deletions resulting from HR at the endogenous pun locus. In contrast, in Fancg−/− mice, the frequency of DNA deletions was decreased. Thus, Fancd2 but not Fancg deficiency results in elevated chromosomal/DNA breakage and permanent genome rearrangements. This provides evidence that Fancd2 plays an additional role in the maintenance of genomic stability than Fancg, which might explain the higher predisposition to cancer seen in the Fancd2−/− mice.
Fanconi anemia; mouse; in vivo; homologous recombination; genomic instability
A fractured central venous catheter (CVC) with embolization of the distal fragment may lead to life-threatening complications. We had inserted a right subclavian CVC in a 68-year-old female which upon a follow-up chest X-ray appeared to have been sheared. A guidewire was inserted through the CVC until the J-tip was just beyond the tip of the CVC which were then withdrawn as a single assembly. We suspected that the tip of the guidewire might have been entrapped in the opening of the middle port, which upon withdrawal of the guidewire could have led to CVC folding upon itself and shearing.
The chromosomal band 17q21.31, containing the microtubule-associated protein tau (MAPT) gene, is a hotspot for chromosomal rearrangements. It is known to contain a common inversion polymorphism of approximately 900 kb in populations with European ancestry. The inverted configuration is linked to a distinct MAPT haplotype, H2, which is relatively common in Europeans but nearly absent in Asian and African populations. Recent studies have demonstrated that the H2 haplotype is ancestral in hominoids, and under positive selection in Europeans. This haplotype is also linked to events leading to the 17q21.31 microdeletion syndrome, one of the most common causes of ‘idiopathic’ mental retardation in people of European descent. We performed direct analysis of the chromosome structure by fluorescence in situ hybridization and observed heterozygosity of the inversion status for the H2 chromosomes, but not for the H1 haplotype. Inversion heterozygosity was also observed in a mother homozygous for the H2 haplotype, who transmitted the chromosome with the deletion to a proband with 17q21.31 microdeletion syndrome. Our results highlight an allele-specific sensitivity to chromosome rearrangements and suggest that it is the heterozygosity of inversion status that predisposes to the 17q21.31 microdeletion syndrome.
17q21.31 microdeletion; Genomic disorder; H1 and H2 haplotypes; Inversion polymorphism; Recurrent
A blood transfusion is a life-saving procedure in many instances. An adequate supply of safe blood is ensured by exercising donor deferral criteria and screening for Transfusion Transmitted Infections (TTI). The aim of this paper is to study the profile of blood donors and reasons for donor deferral in coastal South India.
The study was conducted at a tertiary care hospital in Mangalore. All those who donated between 1 January 2008 and 31 December 2008 were included in the study. Data was collected using a pre-tested semi-structured proforma and analysed using SPSS version 11.5.
Most of the donors were under the age of 25 (42.92%).
Donors were predominantly male (95.20%). In terms of occupation, most subjects were students (28.01%) followed by businessmen (18.61%). Slightly more than three-quarters of the donors (77.20%) were replacement donors. The main reasons for deferral were consumption of medication in the past 72 hours (15.15%), hypertension (13.18%), a low haemoglobin level (12.34%) and alcohol intake in the past 72 hours (12.20%). Among the TTIs identified, most samples were positive for Hepatitis B surface Antigen – HBsAg (0.87%) or tested positive for Anti-Hepatitis C (HCV antibodies (0.36%).
From the study it was concluded that the majority of the donor population was young and educated. The reason for donation was mainly replacement rather than voluntary. This issue needs to be addressed by exercising proactive measures to increase the number of voluntary, nonremunerated, low-risk donors.
Blood donors; deferral; transfusion transmitted infections; South India
Rhabdomyosarcomas (RMSs) are primarily paediatric sarcomas that resemble developing skeletal muscle. Our aim was to determine the effects of microRNAs (miRNA) that have been implicated in muscle development on the clinical behaviour of RMSs.
Expression levels of miR-1, miR-206, miR-133a and miR-133b were quantified by RT–PCR in 163 primary paediatric RMSs, plus control tissues, and correlated with clinico-pathological features. Correlations with parallel gene expression profiling data for 84 samples were used to identify pathways associated with miR-206. Synthetic miR-206 was transfected into RMS cell lines and phenotypic responses assessed.
Muscle-specific miRNAs levels were lower in RMSs compared with skeletal muscle but generally higher than in other normal tissues. Low miR-206 expression correlated with poor overall survival and was an independent predictor of shorter survival in metastatic embryonal and alveolar cases without PAX3/7-FOXO1 fusion genes. Low miR-206 expression also significantly correlated with high SIOP stage and the presence of metastases at diagnosis. High miR-206 expression strongly correlated with genes linked to muscle differentiation and low expression was associated with genes linked to MAPkinase and NFKappaB pathway activation. Increasing miR-206 expression in cell lines inhibited cell growth and migration and induced apoptosis that was associated with myogenic differentiation in some, but not all, cell lines.
miR-206 contributes to the clinical behaviour of RMSs and the pleiotropic effects of miR-206 supports therapeutic potential.
rhabdomyosarcoma; microRNA; overall survival; expression profile; cell line