A rare case of diphyllobothriasis from Pondicherry, South India

Diphyllobothriasis is an intestinal parasitic infection caused by the ingestion of raw fresh-water fish containing the infectious larvae of Diphyllobothrium spp. This infection is uncommon in India. We report a case of diphyllobothriasis that occurred in Pondicherry, India, in a 5-year-old boy hailing from a fishing community. He attended the Pediatric OPD with spontaneous discharge of segments of the adult parasite. The segments (macroscopically and microscopically) were identified as those of Diphyllobothrium latum. The stool examination also revealed characteristic oval eggs.     

Cigarette smoke induces p-benzoquinone-albumin adduct in blood serum: Implications on structure and ligand binding properties

Earlier we had reported that irrespective of the source cigarette smoke (CS) contains substantial amounts of p-benzosemiquinone, which is readily converted to p-benzoquinone (p-BQ) by disproportionation and oxidation by transition metal containing proteins. Here we show that after CS-exposure, p-BQ-protein adducts are formed in the lungs as well as serum albumin of guinea pigs. We also show that serum of human smokers contains p-BQ-albumin adduct. It is known that human serum albumin (HSA) plays a very important role in binding and transport of a variety of ligands, including fatty acids and drugs. We show in vitro that p-BQ forms covalent adducts with free amino groups of all twenty amino acids as well as ?-amino groups of lysine residues of HSA in a concentration dependent manner. When HSA is incubated with p-BQ in the molar ratio of 1:1, the number of p-BQ incorporated is 1. At the molar ratio of 1:60, the number of p-BQ incorporated is 40. The formation of HSA-p-BQ adduct has been demonstrated by absorption spectroscopy, MALDI-MS and MALDI-TOF-TOF-MS analyses. Upon complexation with p-BQ, the secondary structure and conformation of HSA are altered, as evidenced by steady state and time-resolved fluorescence, circular dichroism, 8-anilino-1-napthalenesulfonic acid binding and differential scanning calorimetry. Alteration of the structure and conformation of HSA results in impairment of its ligand binding properties with respect to myristic acid, quercitin and paracetamol. This might be one of the reasons why transport and distribution of lipids and drugs are impaired in smokers.     

Phosphatase and tensin homologue deficiency in glioblastoma confers resistance to radiation and temozolomide that is reversed by the protease inhibitor nelfinavir

Glioblastomas are malignant brain tumors that are very difficult to cure, even with aggressive therapy consisting of surgery, chemotherapy, and radiation. Glioblastomas frequently have loss of the phosphatase and tensin homologue (PTEN), leading to the activation of the phosphoinositide-3-kinase (PI3K)/Akt pathway. We examined whether PTEN deficiency leads to radioresistance and whether this can be reversed by nelfinavir, a protease inhibitor that decreases Akt signaling. Nelfinavir decreased Akt phosphorylation and enhanced radiosensitization in U251MG and U87MG glioblastoma cells, both of which are PTEN deficient. In the derivative line U251MG-PTEN, induction of wild-type PTEN with doxycycline decreased P-Akt expression and increased radiosensitivity to a similar extent as nelfinavir. Combining these two approaches had no greater effect on radiosensitivity than either alone. This epistasis-type analysis suggests that the nelfinavir acts along the Akt pathway to radiosensitize cells. However, nelfinavir neither decreased Akt phosphorylation in immortalized human astrocytes nor radiosensitized them. Radiosensitization was also assessed in vivo using a tumor regrowth delay assay in nude mice implanted with U87MG xenografts. The mean time to reach 1,000 mm(3) in the radiation + nelfinavir group was 71 days, as compared with 41, 34, or 45 days for control, nelfinavir alone, or radiation alone groups, respectively. A significant synergistic effect on tumor regrowth was detected between radiation and nelfinavir. (P = 0.01). Nelfinavir also increased the sensitivity of U251MG cells to temozolomide. These results support the clinical investigation of nelfinavir in combination with radiation and temozolomide in future clinical trials for patients with glioblastomas.     

InVivo Loss of Function Screening Reveals Carbonic Anhydrase IX as a Key Modulator of Tumor Initiating Potential in Primary Pancreatic Tumors

Reprogramming of energy metabolism is one of the emerging hallmarks of cancer. Up-regulation of energy metabolism pathways fuels cell growth and division, a key characteristic of neoplastic disease, and can lead to dependency on specific metabolic pathways. Thus, targeting energy metabolism pathways might offer the opportunity for novel therapeutics. Here, we describe the application of a novel in vivo screening approach for the identification of genes involved in cancer metabolism using a patient-derived pancreatic xenograft model. Lentiviruses expressing short hairpin RNAs (shRNAs) targeting 12 different cell surface protein transporters were separately transduced into the primary pancreatic tumor cells. Transduced cells were pooled and implanted into mice. Tumors were harvested at different times, and the frequency of each shRNA was determined as a measure of which ones prevented tumor growth. Several targets including carbonic anhydrase IX (CAIX), monocarboxylate transporter 4, and anionic amino acid transporter light chain, xc- system (xCT) were identified in these studies and shown to be required for tumor initiation and growth. Interestingly, CAIX was overexpressed in the tumor initiating cell population. CAIX expression alone correlated with a highly tumorigenic subpopulation of cells. Furthermore, CAIX expression was essential for tumor initiation because shRNA knockdown eliminated the ability of cells to grow in vivo. To the best of our knowledge, this is the first parallel in vivo assessment of multiple novel oncology target genes using a patient-derived pancreatic tumor model.     

A technique for the threading of lymph nodes to facilitate excisional biopsy by the single surgeon

Some clinical settings require open lymph node biopsy, even when the expertise for performing fine needle aspiration cytology (FNAC) is available. In many cases, the lymph node biopsy is performed by a junior surgical trainee or intern without any assistant, making the procedure even more difficult and an unpleasant experience for the patient. The author's technique of threading a lymph node facilitates its dissection in less time, thus minimizing discomfort to the patient and a delay in diagnosis. This surgical technique is simple and can be easily adopted by an inexperienced surgeon for self-help, especially when there is no assistant.     

A study on dyslipidaemia in subclinical hypothyroidism

Subclinical hypothyroidism is characterised by elevated serum thyroid stimulating hormone (TSH) concentrations in association with normal free thyroid hormones. The aim of the study was to evaluate the prevalence and pattern of serum lipid alterations in patients with stable subclinical hypothyroidism in comparison to age- as well as sex-matched euthyroid group and also subgroup analysis between them in regard to age of presentation, sex, antithyroperoxidase (anti TPO) positivity, and TSH value. In this study, 100 patients of SCH were recruited, age ranged 17-68 years, majority (78%) being females, presenting mainly with non-specific symptoms and compared with 52 euthyroid control regarding lipid parameters. Of the subclinical hypothyroidism patients, only 10% had goitre and anti TPO was positive in 52% cases. Serum lipoprotein (a) above the age of 20 years, and total cholesterol, triglyceride and low density liporpotein cholesterol in the age group of 40-50 years were significantly elevated. In addition, total cholesterol, triglyceride and low density lipoprotein cholesterol levels in anti TPO positive cases and serum triglyceride and low density lipoprotein cholesterol in anti TPO negative patients showed statistically significant higher levels. In males only lipoprotein (a), but in females total cholesterol, triglyceride, low density lipoprotein cholesterol and liproprotein (a)--all were significantly elevated.     

Outcome of Complex Adult Congenital Heart Surgery in the Developing World

Background. There is scanty information on the outcome of adult congenital heart disease surgery from the developing world. Methods. This was a retrospective chart review of the surgical outcome of 153 adults with congenital heart disease over a 5‐year period. Surgical atrial septal defect closure was considered “simple” while all other surgeries were considered “complex.” Results. There were 102 patients in the “simple” group and 51 in the “complex” group. Only three (2%) patients had prior operations. The “complex” group had longer bypass time and cross clamp time. Intensive care unit stay, ventilation time, and inotrope administration were longer. Major complications were more common and there were two deaths in the “complex” group. Age more than 30 years, cyanosis, and New York Heart Association class more than II were predictors of longer stay in the intensive care unit. Surgical repair of Tetralogy of Fallot in adults tended to have a longer ventilation time and intensive care unit stay with a mortality of 4%. At follow up, all patients were in New York Heart Association class I or II. Improvement of the functional class with negligible adverse events was noted in both groups. Conclusions. A retrospective evaluation of 153 adults with congenital heart disease who underwent open heart surgery at a single center in India showed strikingly fewer reoperations compared with large European studies. There was a similar prevalence of complex lesions. Surgical mortality was low, and long‐term functional outcome was gratifying.     

Hereditary hemolytic disorders among the Ashram school children in Mayurbhanj district of Orissa

Hemoglobinopathy and allied hemolytic disorders are important genetic and public health problems in Orissa. These cause high degree of hemolytic anemia, morbidity and mortality in the vulnerable populations. A total of 465 Ashram School children aged 6-15 years belonging to Bathudi, Bhumiz, Kolha and Santal tribes in six localities of Mayurbhanj district of Orissa were screened for hemoglobinopathy, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, ABO and Rhesus blood groups serology and any other hereditary condition. The sickle cell trait (Hb AS) was detected in Santal (1.0%), Bathudi (1.0%) and Bhumiz (0.9%) tribals. No case of homozygous sickle cell disease was detected among the tribes of Mayurbhanj district. The beta-thalassemia trait was detected in Santal (8.0%), Kolha (2.0%), Bhumiz (1.7%) and other tribal (3.8%) students. Sickle cell hemoglobinopathy and beta-thalassemia are prevalent in this district among the tribes, but the frequency is very low. The prevalence of G-6-PD deficiency is considerably high (7.7-9.8%) among the tribes of Mayurbhanj district in Orissa. Out of total 43 G-6-PD deficient subjects, there were 32 males, 9 heterozygote females and 2 homozygous females. This shows that the antimalarial drugs should be administered with caution as these cause hemolytic anemia, sometimes fatal also. The distribution of ABO and Rhesus blood groups shows the preponderance of B blood group (33.8%) over O (29.6%) and 2.1% cases of Rhesus negativity were detected among the Bathudi tribe. This pattern is consistent with the characteristic features of tribal populations in India.