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Biomedical subjects

A K Gupta

Publications and source records attributed to A K Gupta.

At least 253 records · Page 14Linked to original sources
PubMed2000

RAS-Mediated radiation resistance is not linked to MAP kinase activation in two bladder carcinoma cell lines.

The expression of activated RAS oncogenes has been shown to increase radioresistance in a number of cell lines. The pathways by which RAS leads to radioresistance, however, are unknown. RAS activates several signal transduction pathways, with the RAF-MAP2K-MAP kinase pathway perhaps the best studied. MAP kinase has also been shown to be activated by radiation through this pathway. Given the important role of MAP kinase in multiple signaling events, we asked if radioresistance induced by RAS was mediated through the activation of MAPK. Cells of two human bladder carcinoma cell lines were used, one with a mutated oncogenic HRAS (T24) and other with a wild-type HRAS (RT4). The surviving fraction after exposure to 2 Gy of radiation (SF2) for the T24 cell lines was found to be 0.62, whereas that for RT4 cells was 0.40. Treatment with the farnesyl transferase inhibitor (FTI) L744,832, which inhibits RAS processing and activity, decreased the SF2 of T24 cells to 0.29, whereas the SF2 of RT4 cells remained unchanged after FTI treatment, thus demonstrating the importance of RAS activation to the radiosensitivity of cells with mutated RAS. MAP kinase activation was found to be constitutive and dependent on RAS in T24 cells, while it was inducible by radiation and was independent of RAS in RT4 cells. Treatment of both cell lines with the MAP2K inhibitor PD98059 inhibited MAPK activation; however, inhibiting MAPK activation had no effect on radiation survival of T24 or RT4 cells. These data indicate that MAPK activation does not contribute to RAS-induced radioresistance in this system.

Cell Survival↗
PubMed2000

A risk-benefit assessment of the newer oral antifungal agents used to treat onychomycosis.

The newer antifungal agents itraconazole, terbinafine and fluconazole have become available to treat onychomycosis over the last 10 years. During this time period these agents have superseded griseofulvin as the agent of choice for onychomycosis. Unlike griseofulvin, the new agents have a broad spectrum of action that includes dermatophytes, Candida species and nondermatophyte moulds. Each of the 3 oral antifungal agents, terbinafine, itraconazole and fluconazole, is effective against dermatophytes with relatively fewer data being available for the treatment of Candida species and nondermatophyte moulds. Itraconazole is effective against Candida onychomycosis. Terbinafine may be more effective against C. parapsilosis compared with C. albicans; furthermore with Candida species a higher dose of terbinafine or a longer duration of therapy may be required compared with the regimen for dermatophytes. The least amount of experience in treating onychomycosis is with fluconazole. Griseofulvin is not effective against Candida species or the nondermatophyte moulds. The main use of griseo-fulvin currently is to treat tinea capitis. Ketoconazole may be used by some to treat tinea versicolor with the dosage regimens being short and requiring the use of only a few doses. The preferred regimens for the 3 oral antimycotic agents are as follows: itraconazole - pulse therapy with the drug being administered for 1 week with 3 weeks off treatment between successive pulses; terbinafine - continuous once daily therapy; and fluconazole - once weekly treatment. The regimen for the treatment of dermatophyte onychomycosis is: itraconazole - 200mg twice daily for I week per month x 3 pulses; terbinafine - 250 mg/day for 12 weeks; or, fluconazole - 150 mg/wk until the abnormal-appearing nail plate has grown out, typically over a period of 9 to 18 months. For the 3 oral antifungal agents the more common adverse reactions pertain to the following systems, gastrointestinal (for example, nausea, gastrointestinal distress, diarrhoea, abdominal pain), cutaneous eruption, and CNS (for example, headache and malaise). Each of the new antifungal agents is more cost-effective than griseofulvin for the treatment of onychomycosis and is associated with high compliance, in part because of the shorter duration of therapy. The newer antifungal agents are generally well tolerated with drug interactions that are usually predictable.

Administration, Oral↗
PubMed2000

Onychomycosis in the elderly.

Onychomycosis is found more frequently in the elderly, and in more males than females. Onychomycosis of the toes is usually caused by dermatophytes, most commonly Trichophyton rubrum and T. mentagrophytes. The most common clinical presentations are distal and lateral subungual onychomycosis (which usually affects the great/first toe) and white superficial onychomycosis (which generally involves the third/fourth toes). Only about 50% of all abnormal-appearing nails are due to onychomycosis. In the remainder, trauma to the nail, psoriasis and conditions such as lichen planus should be considered in the differential diagnosis. Therefore, the clinical impression of onychomycosis should be confirmed by mycological examination, whenever possible. The management of onychomycosis may include no therapy, palliative treatment with mechanical or chemical debridement, topical antifungal therapy, oral antifungal agents or a combination of treatment modalities. In the US, the only new oral agents approved for treatment of onychomycosis are terbinafine and itraconazole. Fluconazole is approved for onychomycosis in some other countries. Ciclopirox nail lacquer has recently been approved in the US for the treatment of onychomycosis. In some other countries topical agents such as amorolfine are also used. Griseofulvin and ketoconazole are no longer preferred for the treatment of onychomycosis. The new oral antifungal agents are effective and well tolerated in the elderly. Patient selection should be based on the history (including systems review and medication record), examination and baseline monitoring, if indicated. Laboratory monitoring during therapy for onychomycosis varies among physicians. A combination of removal of the diseased nail plate or local measures and oral antifungal therapy may be optimal in certain instances, e.g. when lateral onychomycosis or dermatophytoma are present. For dermatophyte toe onychomycosis the recommended duration of therapy with terbinafine is 250 mg/day for 12 weeks. For itraconazole (pulse) the regimen is 200 mg twice daily for 1 week on, 3 weeks off, repeated for 3 consecutive pulses and with fluconazole the regimen is 150 to 300 mg once weekly given for a usual range of 6 to 12 months or until the nail plate has grown out. In some instances, if extra therapy is required, one suggestion is that 4 weeks of terbinafine or an extra pulse of itraconazole are given between months 6 and 9 from the start of therapy. Once cure has been achieved, it is important to counsel patients on the strategies of reducing recurrence of disease.

Age Factors↗
PubMed2000

CT of recurrent retroperitoneal sarcomas.

OBJECTIVE: We reviewed the medical records and CT scans of 33 patients with recurrent retroperitoneal sarcomas to determine the patterns of recurrent disease. MATERIALS AND METHODS: We reviewed the medical records and CT examinations obtained at the time the recurrence was diagnosed and tabulated data for all patients. Data for patients with high-grade malignancies were compared with those of patients with low-grade malignancies to determine whether there were differences in the interval between initial tumor resection and recurrence. We also compared CT appearances to determine patterns of recurrent disease. RESULTS: Twenty-five of 33 recurrences were detected within 2 years of initial surgery. Only 16 patients had symptoms, and when present, most symptoms were nonspecific. In 28 (85%) patients, recurrent tumor was in the abdomen at the time of diagnosis. In nine patients, the largest detectable abdominal tumor was less than 5 cm in diameter. Interval to recurrence was similar for patients with low- and high-grade tumors. Although the CT appearance was similar for both grades, distant metastases were identified only in patients with high-grade malignancies. CONCLUSION: Primary retroperitoneal malignancies frequently recur within 2 years of initial surgical resection. For asymptomatic patients, diagnosis is typically made during routine follow-up CT. Most patients have abdominal recurrences that may be small when first detected.

Adult↗
PubMed2000

Sonography and CT of pancreatoblastoma in children.

OBJECTIVE: We reveal the sonography and CT findings of three children with pancreatoblastoma. CONCLUSION: Pancreatoblastomas are invasive tumors that encase adjacent vessels and infiltrate surrounding organs. Original and atypical findings include metastases to the omentum and lymph nodes of the neck and direct extension of the tumor to the portal vein and its branches.

Child↗
PubMed2000

Clinical cerebral microdialysis: a methodological study.

OBJECT: Clinical microdialysis enables monitoring of the cerebral extracellular chemistry of neurosurgical patients. Introduction of the technique into different hospitals' neurosurgical units has resulted in variations in the method of application. There are several variables to be considered, including length of the catheter membrane, type of perfusion fluid, flow rate of perfusion fluid, and on-line compared with delayed analysis of samples. The objects of this study were as follows: 1) to determine the effects of varying catheter characteristics on substance concentration; 2) to determine the relative recovery and true extracellular concentration by varying the flow rate and extrapolating to zero flow; and 3) to compare substance concentration obtained using a bedside enzyme analyzer with that of off-line high-performance liquid chromatography (HPLC). METHODS: A specially designed bolt was used to conduct two adjacent microdialysis catheters into the frontal cortex of patients with head injury or poor-grade subarachnoid hemorrhage who were receiving ventilation. One reference catheter (10-mm membrane, perfused with Ringer's solution at 0.3 microl/minute) was constant for all studies. The other catheter was varied in terms of membrane length (10 mm or 30 mm), perfusion fluid (Ringer's solution or normal saline), and flow rate (0.1-1.5 microl/minute). The effect of freezing the samples on substance concentration was established by on-line analysis and then repeated analysis after storage at -70 degrees C for 3 months. Samples assayed with the bedside enzyme analyzer were reassessed using HPLC for the determination of glutamate concentrations. CONCLUSIONS: Two adjacent microdialysis catheters that were identical in membrane length, perfusion fluid, and flow rate showed equivalent results. Variations in perfusion fluid and freezing and thawing of samples did not result in differences in substance concentration. Catheter length had a significant impact on substance recovery. Variations in flow rate enabled the relative recovery to be calculated using a modification of the extrapolation-to-zero-flow method. The recovery was approximately 70% at 0.3 microl/minute and 30% at 1 microl/minute (10-mm membrane) for all analytes. Glutamate results obtained with the enzyme analyzer showed good correlation with those from HPLC.

Adult↗
PubMed2000

Biochemical changes related to hypoxia during cerebral aneurysm surgery: combined microdialysis and tissue oxygen monitoring: case report.

OBJECTIVE AND IMPORTANCE: The objective of this study was to monitor brain metabolism on-line during aneurysm surgery, by combining the use of a multiparameter (brain tissue oxygen, brain carbon dioxide, pH, and temperature) sensor with microdialysis (extracellular glucose, lactate, pyruvate, and glutamate). The case illustrates the potential value of these techniques by demonstrating the effects of adverse physiological events on brain metabolism and the ability to assist in both intraoperative and postoperative decision-making. CLINICAL PRESENTATION: A 41-year-old woman presented with a World Federation of Neurological Surgeons Grade I subarachnoid hemorrhage. Angiography revealed a basilar artery aneurysm that was not amenable to coiling, so the aneurysm was clipped. Before the craniotomy was performed, a multiparameter sensor and a microdialysis catheter were inserted to monitor brain metabolism. INTERVENTION: During the operation, the brain oxygen level decreased, in relation to biochemical changes, including the reduction of extracellular glucose and pyruvate and the elevation of lactate and glutamate. These changes were reversible. However, when the craniotomy was closed, a second decrease in brain oxygen occurred in association with brain swelling, which immediately prompted a postoperative computed tomographic scan. The scan demonstrated acute hydrocephalus, requiring external ventricular drainage. The patient made a full recovery. CONCLUSION: The monitoring techniques influenced clinical decision-making in the treatment of this patient. On-line measurement of brain tissue gases and extracellular chemistry has the potential to assist in the perioperative and postoperative management of patients undergoing complex cerebrovascular surgery and to establish the effects of intervention on brain homeostasis.

Adult↗
PubMed2000

Psychological findings in benign paroxysmal positional vertigo and psychogenic vertigo.

OBJECTIVE: A prospective study conducted at the Post Graduate Institute of Medical Education and Research, Chandigarh, India, to study the psychological factors in cases of benign paroxysmal positional vertigo (BPPV) and to compare them with patients with psychogenic vertigo. METHODS: In the present study, 75 subjects each (25-45 years) with BPPV and psychogenic vertigo were compared with an equal number of age- and sex-matched normal controls using the psychological and audiovestibular test batteries. RESULTS: The psychological variables tested, namely, loneliness, depression, anxiety components, introversion, and social desirability, were found to be statistically significant (p < .01) for the three groups (i.e., BPPV, psychogenic, and control). There was no significant difference among the three groups on the audiovestibular measures. CONCLUSION: Psychological factors play an important role in patients with BPPV. The provoking activities result in precipitation of an acute attack and the patients experience heightened emotionality because of the incapacitating feeling of severe vertigo.

Acute Disease↗
PubMed2000

Olanzapine is effective in the management of some self-induced dermatoses: three case reports.

Self-inflicted dermatoses are often difficult to treat. We present three patients with excoriated acne, self-induced skin ulcers, and trichotillomania, respectively, whose symptoms responded favorably to a 2- to 4-week course of the atypical antipsychotic olanazpine at a dosage of 2.5 to 5.0 mg daily. In two of three patients, the efficacy of the olanzapine was most likely related to an attenuation of dissociative symptoms that were associated with the self-induced skin ulcers and trichotillomania.

Acne Vulgaris↗
PubMed2000

Herpes zoster in the medically healthy child and covert severe child abuse.

Herpes zoster is associated with depressed cell-mediated immunity and occurs rarely in the medically healthy nonimmunocompromised child. We report 4 cases of childhood-onset herpes zoster in the absence of a medical disorder. All 4 patients reported experiencing severe, chronic child abuse when the herpes zoster first appeared. It is possible that the severe chronic psychologic stress resulting from the abuse depressed the patients' cell-mediated immune status and thereby predisposed them to herpes zoster. Our findings suggest that the clinician's suspicion should be heightened for the possibility of covert child abuse and secondary stress when managing an otherwise apparently healthy child with herpes zoster.

Adolescent↗
PubMed2000

Ciclopirox nail lacquer topical solution 8%.

Ciclopirox nail lacquer 8% (Penlac, Aventis Pharma) was approved by the US FDA in December 1999, as a component of a comprehensive management program, for use in immunocompetent patients who have mild to moderate onychomycosis of the fingers and toes without lunula involvement due to Trichophyton rubrum. The comprehensive management program includes removal of the unattached, infected nails as frequently as once per month, by a health care professional who has special competence in the diagnosis and treatment of nail disorders, including minor nail procedures. The nail lacquer is not approved in Canada.

Administration, Topical↗
PubMed2000

Imaging in epilepsy.

Epilepsy is a common problem in the paediatric age group. Imaging plays a vital role in identifying the seizure focus. Cross-sectional imaging modalities like CT and MRI have had a major impact on the management of seizure disorders. MRI, because of its high contrast resolution and multiplanar capability is the ideal imaging modality but its use is restricted due to high cost. Computed tomography is cheaper and is the first, and often, the only modality used, especially in the underprivileged areas of the world. In the tropical countries inflammatory granuloma are a common cause of epilepsy and CT is adequate to detect these lesions. Other causes include congenital abnormalities, neoplastic and vascular causes.

Astrocytoma↗
PubMed2000

Surgery in tuberculosis.

Tuberculosis in children involves many organs and systems including lymphatics, lungs, CNS, GIT and genitourinary. Although the mainstay of treatment is medical, surgery has a definite role under specific circumstances. It is important to differentiate atypical mycobacterial infection wherein surgery is the primary modality of treatment. The lung is most commonly involved in tuberculosis and besides bronchoscopy, thoracic procedures range from tube thoracostomy to decortication and lung resection. Neurotuberculosis constitutes almost half the cases of extrapulmonary tuberculosis and tuberculous meningitis (TBM) is the commonest type of CNS involvement. Hydrocephalus is a late complication of TBM and shunt surgery is indicated when signs and symptoms of raised intracranial pressure persist despite adequate medical therapy. Abdominal tuberculosis could be peritoneal or gastrointestinal. Either form can complicate the other and each can present in acute, subacute or chronic form. Surgical therapy is reserved for complications like strictures, fistulae and GI bleed. Genitourinary tuberculosis constitutes 15-20% of all extrapulmonary disease and epididymitis is the most common manifestation in the males. Surgery is generally reserved for management of complications such as ureteral strictures, perinephric abscesses and nonfunctioning kidneys.

Child↗
PubMed2000

Relevance of direct agglutination test in seroepidemiological survey of Kala-azar in epidemic foci of Bihar.

The performance of direct agglutination test (DAT) was evaluated under field conditions in three endemic districts of Bihar. In three villages of these districts, 197 households were surveyed with a population of 1167 individuals. Out of 1167 individuals, 603 were clinically examined for VL and blood samples of each examined individual were collected for DAT. The proportion of DAT positivity in both males (32.33%) and females (32.94%) was statistically not significant (p > 0.05). The proportion of DAT positivity in all age groups was observed to be similar (p > 0.05). The GMRT was observed highest in active VL cases. Out of 20 DAT positive individuals having fever, 5 were examined parasitologically (bone marrow aspiration) and in three cases positivity was observed. This showed the relevance of DAT in early diagnosis of visceral leishmaniasis and usefulness of DAT in field conditions.

Adolescent↗
PubMed2000

Loss of virus specific epitopes on JE virus 'E' glycoprotein by acetone treatment.

BACKGROUND & OBJECTIVES: Some Japanese encephalitis (JE) virus strains have been placed in group II based on the loss of reactivity against Hs (H = HI positive; s = JE virus specific) group of monoclonal antibodies (MAbs) in haemagglutination-inhibition (HI) test employing sucrose acetone (SA) extracted antigens. Also acetone-fixation of cells infected with some of the virus strains results in the loss of immunofluorescence (IF) against virus specific MAbs. The present study was undertaken to elucidate the effect of acetone on virus specific haemagglutination (HA) epitopes expressed on 'E' glycoprotein of group II strains of JE virus. METHODS: Porcine kidney (PS) cells were infected with JE virus strains (2 group I Indian strains, 5 group II strains and one neutralization-escape variant of 733913 group I strain). HI and complement fixation (CF) tests were carried out employing both polyethylene glycol (PEG) precipitated and SA extracted antigens of JE virus. RESULTS: Employing PEG precipitated antigens, Indian strain G9473 showed titres ranging from 1:40 to 1:160 against all the four virus specific HsMAbs and strain 641686 (1:160) with one of the four MAbs (Hs-1) by HI test whereas their SA extracted antigens did not react at all. In contrast, CF was positive employing both SA and PEG antigens in the presence of all four HsMAbs. The reactivity shown by PEG antigens in the HI test was confirmed by blocking the HA activity with the respective MAb. SA antigens, though negative in the HI test, were positive by the blocking assay. Interestingly, some of the non-HI MAbs which were negative against SA antigens, showed positive HI reaction with PEG antigens. Also, additional epitopes on Japanese (Yoken), Sri Lankan (691004) and two Indian (755468 and 641686) JE virus strains were detected either by blocking HA or surface IF. INTERPRETATION & CONCLUSIONS: It seems that the acetone treatment might result in HA property of the antigen which is no longer inhibited by an antibody in the HI test. The characterization of such labile and conformation-dependent epitopes is currently been undertaken to elucidate their role either in protection or immunopathogenesis of JE.

Acetone↗