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Biomedical subjects

V Kaushal

Publications and source records attributed to V Kaushal.

At least 19 recordsLinked to original sources

Pansinusitis due to Sporothrix schenckii.

Summary A case of mucocutaneous sporotrichosis presenting as mycotic pansinusitis with polyposis with intracranial and intraorbital extension in a patient from Punjab, India is described. The patient had nasal discharge, sneezing and nasal obstruction for 12 years, had undergone repeated surgeries (for endoscopic clearance) but had recurrence. Computerized tomography (CT) and magnetic resonance imaging (MRI) findings revealed pansinusitis. A definitive diagnosis of sporotrichosis was established by culture of Sporothrix schenckii, verification of its dimorphic character and a positive pathogenicity test. The patient was successfully treated with potassium iodide and itraconazole.

Adult↗

Thalidomide protects endothelial cells from doxorubicin-induced apoptosis but alters cell morphology.

Antiangiogenesis agents are now being used in clinical trials to reduce the risk of recurrence of cancer. Several of these agents, however, are associated with thrombosis, especially when used in combination with chemotherapy. Antiangiogenesis and thrombosis are both endothelial-related activities, and we therefore evaluated one presumed antiangiogenesis agent (thalidomide) on intact cultured endothelial cells, and on cultured endothelial cells injured by preincubation with doxorubicin. We evaluated cell viability, caspase-3 activation, morphology of cells using light microscopy, and protease activated receptor-1 (PAR-l) expression. In our experiments, doxorubicin induced a dose- and incubation time-dependent and caspase-3-mediated apoptosis of endothelial cells. Thalidomide alone caused no changes in intact endothelial cells in terms of morphology, cell viability or activation of caspase-3. In contrast, when thalidomide was added to doxorubicin-injured endothelial cells, there was protection from cell death, increase in viability of endothelial cells, induction of differentiation and formation of neotubules. Doxorubicin reduced the expression of thrombin receptor, PAR-1, as evaluated by immunostaining and flow cytometry. Thalidomide did not alter PAR-1 expression in untreated cells but restored its expression reduced by doxorubicin. These findings suggest that thalidomide may be procoagulant, not by enhancing doxorubicin-mediated endothelial cell injury, but by altering the expression of PAR-1 on injured endothelium and resulting in endothelial dysfunction, which may explain hypercoagulability in patients treated with chemotherapy followed by thalidomide.

Angiogenesis Inhibitors↗

Prospective study of circulating angiogenic markers in prostate-specific antigen (PSA)-stable and PSA-progressive hormone-sensitive advanced prostate cancer.

OBJECTIVES: To prospectively describe and compare circulating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in two groups of advanced prostate cancer patients undergoing androgen deprivation. The first patient group (n = 21) consisted of patients with stable serum prostate-specific antigen (PSA) and the second group (n = 20) consisted of patients with a rising serum PSA during androgen deprivation. METHODS: Patients with diabetes or active heart disease or those receiving anticoagulants were excluded. Circulating VEGF and bFGF were measured in platelet-poor plasma. bFGF was also measured in urine. Platelet factor 4 protein (PF4) assays were performed to evaluate platelet activity in platelet-poor plasma samples. Commercially available enzyme-linked immunosorbent assay kits were used for all assays, and all tests were performed in duplicate. RESULTS: The median age of this study population was 75 years (range 58 to 85). Median plasma VEGF measured in the PSA-stable group was 801.5 pg/mL and in the PSA-rising group was 655.5 pg/mL (P = 0.464). Circulating bFGF was undetectable in plasma, but 4 patients in the PSA-stable group had measurable urine levels. Platelet-poor plasma PF4 assays in all patients were less than 3 IU/mL (normal range 0 to 10). CONCLUSIONS: Our pilot study suggests elevated plasma VEGF levels in advanced prostate cancer do not increase during failure of androgen deprivation therapy. Most of the advanced cancer patients in this study expressed plasma VEGF. This suggests its potential role as a surrogate marker for response assessment during antiangiogenic therapy in this stage.

Aged↗

Giant cell reparative granuloma of the base of the skull presenting as a parapharyngeal mass.

Giant cell reparative granuloma is an infrequent non-tumoral lesion affecting the maxillary and mandibular bones and only rarely, the cranial bones. We report a case of giant cell reparative granuloma of the base of the skull in a 12-year-old female who presented with a parapharyngeal mass. Computerized Tomography (CT) showed the intracranial extension and destruction of surrounding bones.

Bone Diseases↗

Teratomas in infancy and childhood.

A 10-year-experience with 42 cases of teratomas in paediatric age group is presented. The commonest type of teratoma was sacrococcygeal followed by ovarian and retroperitoneal teratomas. An analysis of clinical profile, malignant potential, management, prognostic factors and follow up is discussed with review of literature.

Age of Onset↗

Pancreatoblastoma.

Pancreatoblastoma is an extremely rare pancreatic tumor in childhood, comprising 0.5% of pancreatic non endocrine tumors. Just over 50 cases have been reported in the literature till 1997. A 10 year-old male child presented with mass abdomen of 9 months duration. USG and CT abdomen showed a large mixed density lobulated mass in abdomen anterior to, and displacing down the portal vein and splenic veins. Exploratory laparotomy revealed a large mass, arising from body and tail of pancreas, not infiltrating the adjacent structures. Complete excision of the mass along with removal of body and tail of pancreas was done. The histopathological examination revealed pancreatoblastoma. He is well without any evidence of disease 6 months after the operation. To the best of our knowledge this is the first case of pancreatoblastoma with a large size (25 x 20 x 15 cm,) weight 2.5 kg, which was localized and where complete excision was possible. The largest size reported in the literature reviews has been around 15 cm. The literature review confirms that an aggressive surgical attack on resectable pancreatoblastoma may often be curative. The role of adjuvant chemotherapy or radiotherapy is still under discussion due to small number of patients treated as yet.

Biopsy, Needle↗

Hepatotoxicity in rat induced by partially purified toxins from Eupatorium adenophorum (Ageratina adenophora).

A group of rats were administered a methanolic extract of Eupatorium adenophorum (Ageratina adenophora) oven-dried (60 degrees C) leaf powder and a partially purified fraction from the methanolic extract. Administration of the methanolic extract and the partially purified fraction elicited a significant increase in total and conjugated bilirubin, alkaline phosphatase, 5'-nucleotidase and transaminases. Histopathology of the livers from these animals revealed dilated bile ducts and proliferative changes. Hepatocytes around the bile ducts showed necrotic changes. Biochemical and histopathological changes resembled those observed in response to administration of whole leaf powder. The hepatotoxin present in E. adenophorum leaves can be extracted with methanol and partially purified further using the procedure described.

Alkaline Phosphatase↗

Biochemical alterations in the blood plasma of rats associated with hepatotoxicity induced by Eupatorium adenophorum.

Eupatorium adenophorum (Crofton weed), a native of Central America. has appeared as a major weed in several areas in different parts of the world. Horses that eat this plant are poisoned on prolonged exposure. Toxicity due to consumption of this plant by other grazing animals is not clear. Administration of freeze-dried leaf powder to mice results in hepatotoxicity. Earlier attempts to produce toxicity in rats using the leaves of this plant were not successful. In the present study, administration of oven-dried E. adenophorum leaves collected at the flowering stage elicited hepatotoxicity in rats. The affected animals had a marked increase in the concentration of plasma bilirubin and in the activities of 5'-nucleotidase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase. There were no significant differences in plasma creatinine, urea or total protein values in the affected animals compared to controls. The livers of the affected animals had focal areas of necrosis throughout the parenchyma and hepatocytes showed megalocytosis. The bile ducts were dilated and the epithelium showed degenerative to necrotic changes. The alterations in bilirubin, enzymes and histopathological changes imply cholestasis and liver injury.

5'-Nucleotidase↗

Role and regulation of activation of caspases in cisplatin-induced injury to renal tubular epithelial cells.

BACKGROUND: Cellular and molecular mechanisms responsible for cisplatin-induced nephrotoxicity to renal tubular epithelial cells are not well understood. Although caspases play a critical role in the execution of the cell death pathway, their specific role in toxic injury to renal tubular epithelial cells has not been elucidated previously. METHODS: The role of caspases in cisplatin-induced injury was determined using caspase inhibitors and p35 transfected LLC-PK1 cells. The Akt/PKB phosphorylation pathway was studied for the regulation of caspase activation in these cells. RESULTS: The activation of initiator caspases-8, -9 and -2, and executioner caspase-3 began after eight hours of cisplatin treatment, thereafter markedly increased in a time (8 to 24 hours) and dose-dependent manner (0 to 200 micromol/L). Proinflammatory caspase-1 did not show cisplatin-induced activation. Inhibition of caspase-3 by over expressing cowpox virus p35 protein or alternatively by the peptide inhibitor DEVD-CHO provided marked protection against cell death and partial protection against DNA damage. We then examined the role of the Akt/PKB phosphorylation pathway in regulation of cisplatin-induced caspase activation. There was a marked induction of Akt/PKB phosphorylation in a time (0 to 8 hours) and dose-dependent (0 to 200 micromol/L) manner during the course of cisplatin injury. Cisplatin-induced Akt/PKB activation was associated with Bad phosphorylation, suggesting induction of a cell survival signal mediated by the Bcl-2 family member, Bad. Wortmannin or LY294002, two structurally dissimilar inhibitors of phosphatidylinositol 3'-kinase (PI-3 kinase), abolished both cisplatin-induced Akt phosphorylation and Bad phosphorylation, and promoted cisplatin-induced early and accelerated activation of caspase-3 and caspase-9, but not of caspase-8 and caspase-1, indicating that inhibition of the Akt/PKB phosphorylation pathway enhances the mitochondrial-dependent activation of caspases. The impact of enhanced activation of caspases by wortmannin or LY294002 was reflected on accelerated cisplatin-induced cell death. CONCLUSIONS: These studies demonstrate differential activation and role of caspases in cisplatin injury, and provide the first evidence of cisplatin-induced induction of the Akt/PKB phosphorylation pathway, inhibition of which enhances activation of caspase-3 and caspase-9.

Animals↗

Clinical evaluation of human placental extract (placentrex) in radiation-induced oral mucositis.

To evaluate human placental extract in the treatment of radiation mucositis involving the oral/oropharyngeal region, a prospective randomized study was carried out in 120 patients with squamous cell carcinoma of the head and neck from August 1997 to March 1999. The study was conducted in patients receiving radical external radiation therapy, planned for = > 60 Gy/30 F/6 weeks, who developed grade 2 radiation mucositis (patchy mucositis) during radiation treatment. The patients were randomized in two groups of 60 patients each to receive either placentrex treatment (placentrex group) or conventional treatment (control group). Placentrex treatment was given as Inj Placentrex 2 ml by deep intramuscular injection 5 days a week for 15 injections. Conventional treatment given in the control group was disprin gargles and betamethasone oral drops. A subjective decrease in pain was observed in 48/60 (80%) of patients in the placentrex group compared with 22/60 (36.7%) in the control group. The progression to grade 3 radiation mucositis was 24/60 (40%) in the placentrex group compared with 52/60 (86.7%) in the control group. The subjective improvement in difficulty in swallowing was seen in 56/60 (93%) of patients in the placentrex group compared with 9/60 (15%) of patients in the control group. Only one patient in the placentrex group compared with three in the control group required interruption of radiation therapy because of severe radiation reactions. Human placental extract appears to be effective in the management of radiation-induced oral/oropharyngeal mucositis and especially in controlling subjective symptoms.

Abnormalities, Radiation-Induced↗

Risk of seizures and neurocysticercosis in household family contacts of children with single enhancing lesions.

A small, single enhancing lesion (SEL) is often noted upon computed tomography (CT) in children and young adults with recent focal or generalized seizures. A high frequency of seizures has been reported in family members of persons with SEL. We studied the prevalence of seizures and cysticercus electro-immuno-transfer blot (EITB) based seropositivity among family members, specifically household family contacts of pediatric subjects with a SEL. An attempt was also made to determine the etiology of seizures in household family contacts using magnetic resonance imaging (MRI). Information regarding seizure semiology, personal and food habits and detailed family pedigrees was obtained from 20 consecutive pediatric subjects with a SEL and 51 of their household family contacts. EITB sero-assays and stool examinations were performed on all participating subjects. MRIs were done on all EITB positive household family contacts. A family history of seizures was obtained in six index children (30%) (five household first-degree relatives and two distant relatives). Seventeen index children (85%) and 14 family contacts (27%) were EITB positive. A tendency towards clustering of EITB positive cases within individual families was observed. Stool examinations did not reveal Taenia species ova in any of EITB positive subjects. Neuroimaging studies revealed abnormalities consistent with active or inactive neurocysticercosis in all five household family contacts with history of seizures. Four of these five subjects were EITB positive and one was EITB negative. We concluded that children with SEL and seizures may have a family history of seizures. There is a high seropositivity rate in household family contacts of pediatric subjects with solitary cysticercus granulomas (SCGs). EITB based seropositivity in household family contacts with seizures, strongly predicts a cysticercal etiology for seizures. It may be worthwhile to screen household family contacts of children with SEL for taeniasis-cysticercosis.

Cerebral Cortex↗

Comparison of two radiation dose schedules in post mastectomy carcinoma of the breast.

In 108 histopathologically proved breast cancer patients, after surgical treatment with modified radical mastectomy, two radiation dose schedules have been compared. Radiation therapy was given on a 60Co teletherapy machine using gent pair technique for chest wall irradiation and direct fields for lymphatic drainage areas. The patients were randomly divided into two groups (Group A and Group B). 54 patients were given external radiotherapy 40 Gy/17 F/3.2 weeks and remaining 54 patients were given 45 Gy/20 F/4 weeks. Results of treatment in Group A versus Group B were as follows; chest wall failure 5/50(10%) versus 3/54 (5.6%), axillary lymphnods failure 3/50(6%) versus 4/54(7%), distant metastasis 16/50(32%) versus 15/54(28%). Radiation reactions were almost similar in both the groups. Skin reactions were most common radiation effects [45/50 (90%) in Group A and 43/54 (79.6% in Group B]. Thus no statistically significant difference in local control and efficacy of these two radiation dose schedules was observed in postmastectomy carcinoma of the breast.

Adult↗

Cysticercus immunoblot assay in patients with single, small enhancing lesions and multilesional neurocysticercosis.

A single, small (< 20 mm), ring or disc shaped contrast enhancing lesion located at the cortical-subcortical junction with minimal or no surrounding edema on computed tomography is the commonest mode of presentation of neurocysticercosis in the Indian subcontinent. Serum samples of 37 patients with these single, small enhancing lesions (SSEL's) and five patients with typical multilesional parenchymal neurocysticercosis were tested by the electro-immunoblot transfer (EITB) assay and the enzyme linked immunosorbent assay (ELISA). EITB was positive in 18 patients (48.64%) and ELISA was positive in 21 patients (56.76%) with SSEL's. On the other hand EITB was positive in all five patients (100%) and ELISA was positive in four patients (80%) with multilesional neurocysticercosis. The low sensitivity of the EITB in the SSEL's is probably linked to an insufficient immune stimulation provided by a single cysticercus cyst.

Humans↗

Incidence of dengue fever in relation to climatic factors in Ludhiana, Punjab.

An outbreak of dengue fever occurred in Ludhiana in 1996 and 1997. A total of 505 patients who attended the hospital attached to Dayanand Medical College, Ludhiana were clinically diagnosed to have dengue fever. Of these, 460 cases were noticed between October and December 1996 while during 1997 only 45 dengue fever cases were observed. Serological examination using dengue IgG and IgM blot was performed with single serum samples of 189 patients. Of these, 129 serum samples were detected positive for anti dengue antibodies. Twenty eight patients died in the dengue epidemic, 12 of whom suffered from dengue haemorrhagic fever (DHF) and six with dengue shock syndrome (DSS). Male patients outnumbered the female patients. Seasonal and cyclic pattern of the disease incidence was observed.

Adolescent↗

Comparative role of three-dimensional radiotherapy planning and inhomogeneity corrections in carcinoma of the tongue.

The authors have assessed the role of computerized three-dimensional (3-D) and traditional (TD) radiotherapy planning and inhomogeneity corrections in improving target volume coverage and normal tissue sparing in carcinoma of the tongue. Coverage of target volumes in 3-D versus TD plans revealed the following. Volume receiving 95% of dose, clinical target volume (CTV): 1-68% versus 0-24%; gross tumour volume-lymph nodes (GTV-l): 0-80% versus 0-20%; gross tumour volume-primary tumour (GTV-II): 0-65% versus 0-26%. Dose to 95% of target volume CTV 77-92% versus 76-87%; GTV-I: 81-90% versus 61-88%; GTV-II: 82-93% versus 68-87%. Minimum dose to 5% of target volume, CTV: 77-93% versus 74-81%; GTV-I: 81-90% versus 61-88%; GTV-II: 76-93% versus 68-87%. Minimum dose to a volume of no less than 5% of the target volume, CTV: 93-98% versus 88-96%; GTV-I: 87-100% versus 88-97%; GTV-II: 86-98% versus 88-96%. A new parameter (inhomogeneity difference) was devised to study target volume dose homogeneity and was found to be very useful. Dose to two-thirds of the parotid glands in 3-D versus TD plans showed a mean of 46 versus 65% for right parotid glands and 44 versus 56% for left parotid glands in all patients. Better tumour dose homogeneity, increased mean tumour dose, avoidance of geographic misses and better parotid sparing was achieved in 3-D plans as compared to TD plans. We could not demonstrate any role for inhomogeneity corrections using currently available computerized dose algorithms.

Carcinoma, Squamous Cell↗