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Biomedical subjects

K Ghosh

Publications and source records attributed to K Ghosh.

At least 19 recordsLinked to original sources

Iatrogenic duodenal perforations caused by endoscopic biliary stenting and stent migration: an update.

Endoscopic biliary stenting is the preferred method of decompression in obstructive jaundice. Duodenal perforations caused during stenting and stent migration are rare but life-threatening complications, and require judicious management. With the increasing use of therapeutic endoscopy, an awareness of these complications is becoming important in our surgical practice. Advances in interventional radiology, endoscopy, and laparoscopy have enhanced the scope and reduced the morbidity of both conservative and surgical treatments of these perforations. This article presents an update on the current state of our knowledge on the science and the management of this complication.

Biliary Tract↗

Extreme rank selections for linkage analysis of quantitative trait loci using selected sib-pairs.

It is well known that linkage analysis using simple random sib-pairs has relatively low power for detecting quantitative trait loci with small genetic effects. The power can be substantially increased by using samples selected based on their trait values. Usually, samples that are obtained by truncation selection consist of random samples from a truncated trait distribution. In this article we propose an alternative method using extreme ranks for linkage analysis with selected sib-pairs. This approach approximates the truncation selection. With similar screening sizes and the same sample size of selected sib-pairs, the extreme rank selection and truncation method have similar power performance, both of which are substantially more powerful than when using random sib-pairs. Simulation results on the comparison of powers between the truncation selection and the extreme rank selection and/or random selection for linkage analysis are reported.

Genetic Linkage↗

Clinical approach to breast disorders: A primer for internists.

Women with breast disorders often present first to their internists for evaluation. A delay in accurate diagnosis could often result in worsening of prognosis for the patient. Common diagnostic problems include evaluation of a breast lump, nipple discharge and breast pain. Internist now has a choice of several diagnostic modalities to evaluate breast disorders. An evidence-based approach to common breast symptoms and advances in breast diagnostic techniques has been described to enable early diagnosis of breast cancer, thereby reducing the need for intensive treatments and improve patient satisfaction and clinical outcome.

Breast Diseases↗

A possible mechanism of zero-crossing detection using the concept of the extended classical receptive field of retinal ganglion cells.

The extended classical receptive field (ECRF) of retinal ganglion cells has been modelled as a combination of three zero-mean Gaussians at three different scales that has been shown to be equivalent to a Biharmonic or Bi-Laplacian of Gaussian filter. It has also been shown that the ECRF can be approximated by a combination of Laplacian of Gaussian (LoG) and the Dirac-delta function. Zero-crossings detected with this operator are more informative than those detected by the traditional filters like LoG or Difference of Gaussians (DoG) that had been devised using the classical receptive field of the ganglion cells. We have also explained that such an additional information processing is not in contradiction with the recent experimental findings on the physiology of retinal ganglion cells.

Animals↗

Evaluation of markers of endothelial damage in cases of young myocardial infarction.

The pathogenesis of arterial thrombotic disease involves multiple genetic and environmental factors related to atherosclerosis and thrombosis. The endothelium is a monolayer of polygonal cells that extend continuously over the luminal surface of the entire vasculature. Injury to the endothelium leads to dysfunction. The causes of injury include lipids, immune complexes, microorganisms, smoking, hypertension, aging, diabetes mellitus and trauma. Studies have been done to evaluate the role of different adhesion molecules on the endothelial membrane in the pathogenesis of atherosclerosis. These molecules are intercellular adhesion molecule type-1 (ICAM-1), vascular cell adhesion molecule type-1 (VCAM-1), platelet/endothelial cell adhesion molecule-1 (PECAM-1), soluble P-selectin (sP-selectin) and soluble E-selectin (sE-selectin). One-hundred and twenty patients of myocardial infarction (age below 40 years) were recruited from the out-patients department of Department of Cardiology, KEM Hospital, Mumbai. All the patients were recruited 8-10 weeks after stabilization after MI. We estimated the levels of sP-selectin, sE-selectin, sPECAM-1 and serum homocysteine. Healthy age and sex-matched controls and family controls were also recruited in the present study. The levels of sP-selectin, sE-selectin and sPECAM-1 did not differ significantly in cases as compared to controls (p>0.05). Hyperhomocysteinemia was significantly associated with MI in comparison with controls (p<0.001) with an odds ratio of 6.26 (95% confidence limits 3.11-12.76). Folic acid was able to correct hyperhomocysteinemia in a large majority of the cases. Although the levels of sP-selectin, sE-selectin and sPECAM-1 decreased after folic acid therapy, it was only sE-selectin which was significantly reduced (p<0.05). Thus, folic acid had a dual effect in that it reduced hyperhomocysteinemia and sE-selectin which showed a significant reduction on folate supplementation for 15 days.

Adult↗

Immunogenetic association in patients with antineutrophil cytoplasmic antibodies (ANCA) from Mumbai, Maharashtra, India.

Considerable genetic evidence exit for ANCA-associated vasculitis and pathogenesis. HLA A and B alleles identified serologically from 84 ANCA-positive patients were compared with 101 controls. Further subtyping were done in the 27 "pauci-immune" vasculitis patients using the polymerase chain reaction based PCR-SSOP technique and compared with controls (67). The results revealed that HLA A1 (OR=4.00; p value 2.72E-05), B17 (OR=3.38; p value 0.0008) and HLA B40 (OR=2.74; p value 0.001) were significantly increased among ANCA-positive patients when compared with the controls. Further, the molecular subtypes A*0101 (OR=5.04; p value 0.0005), B*5801 (OR=4.47; p value 0.0002) and haplotype A*0101-B*5801 (OR=4.47; p value 0.0001) were significantly increased among the autoimmune patients. The study revealed that HLA A1, B17 and B40 alleles are associated in production of antineutrophil autoantibodies and A*0101-B*5801 haplotype is significantly associated with autoimmune diseases and they may be invariably involved in disease pathogenesis in India.

Antibodies, Antineutrophil Cytoplasmic↗

Co-existence of Bernard Soulier syndrome and factor XI deficiency in a family: a unified pathology?

Bernard Soulier syndrome (BSS) is an autosomal recessive disorder of platelet function. Factor XI deficiency leads to a variable bleeding tendency and the defect is also inherited in an autosomal recessive manner. In this paper we describe a case of BSS with severe deficiency of factor XI. The patient had both BSS and factor XI deficiency. The sister and both the parents were heterozygous for BSS and had factor XI deficiency. The brother is normal for both BSS and factor XI levels. Apart from the patient, no other family members had any history of bleeding in spite of having a deficiency of factor XI, which suggests that low level of factor XI in this family was not responsible for bleeding. Curiously, although the index patient inherited both Bernard Soulier syndrome and factor XI deficiency (FXI: C = 1.3%), he had mild bleeding symptoms restricted only to ecchymoses and petechiae. Detailed review of the pedigree showed that all the members who inherited the BSS phenotype, also inherited abnormal factor XI gene. Karyotype of the affected members of the family using standard Giemsa banding technique showed a normal picture. Considering the fact that the genes causing both BSS and factor XI are both on widely different chromosomes, their coinheritance in four members of the family without any unusual translocation suggest a unified pathology probably on the basis of a common transcription factor defect or a common post translational processing defect. This is the first case of coinheritance of BSS and factor XI deficiency reported in the English literature.

Bernard-Soulier Syndrome↗

Frequency distribution of human platelet antigens in the Indian population.

This study was undertaken with an aim of establishing the frequency distribution of various human platelet antigens (HPA) in Indian populations by means of DNA-based technology. A total of 1164 people belonging to various population groups were studied for the frequency distribution of HPA. DNA extraction was performed from peripheral venous blood samples. Polymerase chain reaction allele-specific amplification technique was used for HPA genotyping. The HPA bands were visualized by using ethidium bromide-stained agarose gel, after electrophoresis. The homozygosity of the HPA-1b/1b genotype was found to be significantly higher (P < 0.05) in the Parsi population group and Vatalia Prajapati population group, compared to Maharashtrians. Frequency distribution of HPA-1b in our populations was found to be slightly lower than that reported in some western populations. This study has established a DNA technique to diagnose cases of NAITP definitively and to treat these cases during the neonatal period, and also gives the frequency distribution of HPA in some of the Indian population.

Antigens, Human Platelet↗

Intracranial haemorrhage in severe haemophilia: prevalence and outcome in a developing country.

Intracranial haemorrhage (ICH) is a common cause of morbidity and mortality in haemophilic patients all over the world. From 1995 to 2004, we have investigated 37 patients with 43 episodes of ICH at our Comprehensive Haemophilia Care Center from a total of 600 registered patients. Diagnosis of ICH in the patients was confirmed by clinical, haematological and computed tomographic imaging data. Three patients died despite replacement therapy while one child who had a ventriculo-atrial shunt for acute hydrocephalus also died before further intervention. One of the four patients who died also had severe aplastic anaemia for 6 years in addition to severe haemophilia. Detailed history obtained from 143 families with haemophilia attending the Genetic Diagnosis Clinic at our Center showed a positive history of cerebral bleed in 39 episodes in 37 patients. Sixteen families gave a history of death in the family of haemophilic patients due to ICH, while in the remaining 21 families, the patients had survived the episode after treatment elsewhere. However, the ICH was not confirmed by image data in these cases. The treatment protocols were also not available in these cases. Conservative factor replacement therapy 100% correction for 3 days followed by 50-60% correction for 7 days) coupled with the epsilon amino caproic acid, the antifibrinolytic agent at least for 30 days led to a mortality (10.8%) similar to that of the western countries and almost no morbidity. Surgery was not required in any of these patients except in one elderly patient with HIV infection on antiretroviral therapy.

Adolescent↗

Mutations in GPIIIa molecule as a cause for Glanzmann thrombasthenia in Indian patients.

BACKGROUND: Glanzmann thrombasthenia (GT) results from a quantitative or qualitative defect of GPIIb-IIIa complex, the fibrinogen receptor on platelets, which plays a very important role in platelet aggregation. In this report we describe the molecular studies on 22 patients with Glanzmann Thrombasthenia at our institute. OBJECTIVES: The main objective was to identify the mutations present in our GT population in order to establish a strategy for genetic counseling and antenatal diagnosis. METHODS: Twenty-two patients with GT were included in the present study. Complete blood count (CBC), platelet aggregation, flow cytometry, Western blot, single strand conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE) were performed in all the patients. The patients showing an abnormal migration pattern in SSCP or DGGE were sequenced further on an automated sequencer. RESULTS: Of the 22 patients studied, mutations were detected in 12 individuals. Of these, 11 were novel mutations and one mutation Y115C was reported earlier. Flow cytometric analysis showed the absence of receptors in type I GT, highly reduced levels in type II GT and normal levels in type III GT. The DGGE analysis and SSCP analysis of the patients showed different migration patterns. Sequencing was performed in all patients showing an abnormal migration pattern. Of the 22 cases studied mutations could be detected in 12 cases of GT. We could detect six patients with point mutations, four patients with insertions and five patients with deletion mutations. Exon 4 has been found to be the most common site for mutations in our patients. CONCLUSION: This study has shown a wide array of mutations present in our GT patients which would be extremely useful in genetic counseling and prenatal diagnosis, essential in preventing these disorders in succeeding generations.

DNA Mutational Analysis↗

Molecular diversity of HLA-Cw alleles in the Maratha community of Mumbai, Maharashtra, western India.

Recent advances suggest a significant role for the HLA-C locus as a target of alloreactions after bone marrow transplantation. The biological importance of products of the HLA-C locus, both as transplant antigens and as ligands for natural killer (NK) cells, is well established. A total of 10 different serologically defined HLA-Cw antigen specificities (Cw1-Cw10) are encoded by the C locus; however, there are now 151 different alleles that can be identified by molecular methods. Serological definition of Cw alleles therefore includes 20-50% blanks, which cannot be detected by the available antisera. We used the molecular method of polymerase chain reaction (PCR)-based sequence-specific amplification and probe hybridization to define Cw alleles in 91 individuals from the Maratha community, and compared the data with data for 92 serologically typed Maratha individuals from India. We identified Cw*12, Cw*14, Cw*15, Cw*16 and Cw*18, along with the serologically identified Cw*01, Cw*02, Cw*03, Cw*04, Cw*06 and Cw*07 alleles. The HLA-Cw blank allele frequency in the Maratha was reduced from 0.5706 to 0.00. Furthermore, by using a molecular technique, it was possible to identify novel allele subtypes, such as Cw*0104, Cw*0203 and Cw*0707, and a high frequency of Cw* 1801 in the Maratha community compared with other Indian and world populations. Our results will have clinical implications in related and unrelated HLA-matched bone marrow transplantation in India.

Alleles↗

ANCA: serology in Wegener's granulomatosis.

BACKGROUND AND OBJECTIVES: Wegener's granulomatosis (WG) is being increasingly diagnosed in India, which exists in two forms, the 'limited Wegener's granulomatosis' (LWG) having upper respiratory tract (URT) and lower respiratory tract (LRT) involvement and the 'classical Wegener's granulomatosis' (CWG), with the triad of URT, LRT involvement along with kidney involvement. Cytoplasmic ANCA (C-ANCA) or anti-Proteinase3 (anti-PR3), which is highly diagnostic for WG, rarely perinuclear ANCA (P-ANCA) may exist. AIMS: To detect anti-neutrophil cytoplasmic antibodies (ANCA) and correlate it with serological, hematological parameters, and the Birmingham Vasculitis Activity Score (BVAS). SETTINGS AND DESIGN: Twenty-three clinically and histopathologically proven WG (16 CWG, 7 LWG) were studied. MATERIAL AND METHODS: C-ANCA and P-ANCA patterns were identified by immunofluorescence and specificities were confirmed by 'alpha granule' enzyme linked immunosorbent assay (ELISA), anti-PR3, anti-MPO (myeloperoxidase) and anti-Lactoferrin (anti-LF) by ELISA. RESULTS: LRT involvement was seen in 91.3%, URT in 78.3%, and renal manifestations in 69.6% cases. The BVAS in CWG was significantly higher than BVAS in the LWG. Decreased hemoglobin, increased WBC counts, ESR, CRP and Creatinine were seen in CWG as compared to LWG. The C-ANCA was present in 65.2% patients and P-ANCA in 13% cases. Anti-PR3 was seen in 69.6% patients and anti-LF in 17.4% cases. Severity of disease and ANCA was higher in CWG than in LWG. CONCLUSIONS: Vasculitis syndromes are known to overlap and many go undetected; therefore ANCA testing, along with the clinical and histopathological observations may be helpful in early detection and management of WG cases.

Antibodies, Antineutrophil Cytoplasmic↗

Maternal origin of extra marker chromosome 1Q31.1-qter and 13pter-q12.12 in a child with dysmorhic features.

Maternal origin of extra marker chromosome Iq31.l-qter and 13pter-q12.12 in a child with dysmorphic features: We describe a twenty-days-old female child with dysmorphic features and chromosomal analysis with GTG-banding revealed an extra marker chromosome. Fluorescence in situ hybridization (FISH) study of extra marker chromosome confirmed to be maternal der(13) chromosome, contained 1q31.1-qter and 13pter-q11 chromosomal material and resulted from a maternal balanced translocation t(1;13)(q31.1; q12.12). The child had the majority of trisomy 1q clinical features: dysmorphic features, micropthalmia, high arched palate, long philthrum, micrognathia, hypertelorism, low set ears, short sternum, overlapping fingers, valgus of wrists, right knee and ankle joints were in flexion contractures. This is the first case of trisomy 1q with an extra marker chromosome which also contained chromosome 13pter-q12.12 material.

Abnormalities, Multiple↗

Purification, substrate specificity, and N-terminal amino acid sequence analysis of a beta-lactamase-free penicillin amidase from Alcaligenes sp.

A beta-lactamase-free penicillin amidase from Alcaligenes sp. active against various beta-lactams was purified to homogeneity. The enzyme can hydrolyze penicillin G to 6-amino penicillanic acid (6-APA) and furnish penicillin G from 6-APA and phenyl acetic acid by condensation. The penicillin amidase is a heterodimer of subunit masses of 63 kDa and 22 kDa, respectively. Its isoelectric point is at pH 8.5. Cephalothin was found to be the best substrate. This is a novel type II penicillin amidase which shares the properties of both type II and type III enzymes. It is thermostable and, unlike penicillin amidase from A. faecalis, its stability remains unperturbed even in presence of reductant. An inhibition study by 2-hydroxy-5-nitro benzylbromide indicated the involvement of tryptophan in catalysis by the enzyme.

Alcaligenes↗

Role of epsilon amino caproic acid in the management of haemophilic patients with inhibitors.

We managed bleeding crisis in 10 consecutive severe haemophilic patients with inhibitors (eight had an inhibitor level of >5 BU mL(-1)) mainly with the antifibrinolytic agent, i.e. epsilon amino caproic acid (EACA). EACA was used by local, oral or intravenous routes either in combination or separately. Five patients developed inhibitors postoperatively and among the remaining five, four had recurrent haemarthrosis or soft tissue bleeds and one patient presented with severe gastrointestinal bleeding without demonstrable lesion. In all the patients, addition of EACA to their management protocol resulted in stoppage and/or reduced frequency of bleeding. In six of 10 patients, the results were excellent; of these six patients, five developed inhibitors postoperatively. Although a reduction in the frequency of bleeding was observed in patients with haemarthrosis and soft tissue bleed, it was not spectacular and the patients required additional therapy. Hence the results could be described as poor. No patient needed to stop the medicine because of the side-effect of EACA. Symptoms like mild nausea and vertigo were seen as the side-effects of this medicine when high intravenous dosage was administered. EACA thus appears to be an excellent adjuvant therapy for haemophilic patients with inhibitors. Besides its well-recognized antifibrinolytic activity, EACA may have additional mechanisms of action in haemophilic patients with inhibitors. More extensive use of this cheap and safe product is warranted in haemophilic patients with inhibitors. If larger studies confirm this observation, then using antifibrinolytics will allow substantial reduction of FEIBA or activated prothrombin complex (APCC) usage in such patients without necessarily increasing the thrombotic complications or reduction of the clinical efficacy, when compared with higher dosage of FEIBA or APCC alone. This will lead to substantial financial savings in countries where up to 35% of severe haemophilia A patients develop inhibitors.

Adolescent↗