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Biomedical subjects

R K Gupta

Publications and source records attributed to R K Gupta.

At least 199 records · Page 11Linked to original sources
PubMed1998

Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine.

PURPOSE: The mechanisms that underlie the clinical efficacy of melanoma vaccines are not well understood. We hypothesized that the type and strength of the immune response generated by CancerVax (John Wayne Cancer Institute, Santa Monica, CA), a polyvalent melanoma cell vaccine (PMCV), might be correlated with its effect on overall survival (OS). PATIENTS AND METHODS: Seventy-seven patients began PMCV therapy after complete surgical resection of distant metastatic melanoma. During the first two treatments, PMCV was administered with bacille Calmette-Guerin (BCG). Blood was drawn at 0, 2, 4, 8, and 12 weeks to measure serum titers of immunoglobulin G (IgG) and IgM antibodies against a tumor-associated 90-kd glycoprotein antigen (TA90) expressed on most melanoma cells, including those of PMCV. Cellular immune response to PMCV was assessed by delayed-type hypersensitivity (DTH). General immune competence was assessed by skin tests to purified protein derivative (PPD), mumps, and candida. RESULTS: Median follow-up time was 31.5 months. Within the first 12 weeks of PMCV immunotherapy, there was a significant increase in the anti-TA90 IgM (P=.0001) and IgG titers (P=.0001), and in the DTH response to PMCV (P=.0001). Univariate analysis showed that high anti-TA90 IgM titer and strong PMCV-DTH were associated with improved survival (P=.051 and .0173, respectively), whereas elevated anti-TA90 IgG was correlated with decreased survival (P=.0119). Multivariate analysis considering clinical variables and PMCV immune responses identified anti-TA90 IgM, anti-TA90 IgG, and PMCV-DTH as significant independent variables influencing survival following PMCV immunotherapy (P=.0342, .0105, and .0082, respectively). These responses to PMCV were not correlated with immune responses to BCG and therefore were not a manifestation of general immune competence for responses to unrelated antigens. The median survival time and 5-year survival rate were more than 76 months and 75%, respectively, if both anti-TA90 IgM and PMCV-DTH responses were strong (> or = 800 and > or = 7 mm, respectively; n=29); 32 months and 36%, respectively, if only one response was strong (n=35); and 19 months and 8%, respectively, if neither was strong (n=13) (P < .0001). CONCLUSION: PMCV induces both humoral and cell-mediated immune responses to melanoma-associated tumor antigens, the type and strength of which appear to be directly related to its therapeutic efficacy.

Adult↗
PubMed1998

Biodegradable polymer microspheres as vaccine adjuvants and delivery systems.

Though vaccination has been the most cost-effective way of controlling infectious diseases, the logistics of delivering at least two to three doses of conventional vaccines for primary immunization to achieve protection are difficult and compliance is frequently inadequate, particularly in developing countries. In recent years biodegradable polymer microspheres have received much attention for the purposes of controlled release of antigens, (i) to reduce the number of doses needed for primary immunization to as few as a single dose and (ii) to target an antigen to microfold cells on mucosal surfaces after oral administration or to antigen-presenting cells after parenteral inoculations. A variety of vaccine antigens have been encapsulated in microspheres usually composed of poly (lactic/glycolic) acid (PLGA). Based on the size of the microspheres, molecular weight of polymer and ratio of lactic to glycolic acid in the polymer, the antigen may be targeted to various cells of the immune system or it may form a depot at the site of injection, allowing the slow release of the antigen for extended periods. Additionally, another adjuvant may be incorporated inside microspheres together with the antigen, further enhancing or modulating the immune response to the desired type. The major problems in developing controlled-release vaccines include instability of vaccine antigens during micro-encapsulation, storage and subsequent hydration. We encapsulated tetanus toxoid (TT) and Haemophilus influenzae type b capsular polysaccharide conjugated to TT (Hib-T) inside PLGA microspheres and evaluated the antibody levels in mice. A single injection of these micro-encapsulated vaccines elicited high antibody levels which persisted for several months. The antibody levels were similar or superior to those elicited by conventional formulations of AIPO4-adsorbed TT or soluble Hib-T conjugate vaccine.

Adjuvants, Immunologic↗
PubMed1998

PCPP as a parenteral adjuvant for diverse antigens.

The adjuvanticity of the phosphazene polymer, poly[di(carboxylatophenoxy) phosphazene] (PCPP) was examined with a diverse collection of immunogens. PCPP proved to be a potent adjuvant for trivalent influenza virus vaccine, tetanus toxoid, hepatitis B surface antigen, herpes simplex virus glycoprotein gD2 and the capsular polysaccharide, polyribosylribitolphosphate, from Haemophilus influenzae type b. Taken together these results clearly demonstrate the general utility of PCPP as an adjuvant. Furthermore, PCPP was a superior adjuvant at least with TT compared to similar negatively charged polyanions, polymethylacrylic acid and polyacrylic acid.

Acrylates↗
PubMed1998

Development of an animal model to assess the immunogenicity of single-dose tetanus and diphtheria vaccines based on controlled release from biodegradable polymer microspheres.

We have determined threshold doses of aluminium phosphate (AlPO4) adsorbed tetanus toxoid (TT) and diphtheria toxoid (DT) in mice and guinea pigs with a view to developing an animal model to assess the immunogenicity of controlled release vaccines. A dose was sought (threshold dose) which produces little antibody after primary injection and a moderate response after a booster injection, thus mimicking the adult human response to TT and DT vaccines adsorbed on to aluminium adjuvants. After the first injection, mice and guinea pigs showed a dose response for both tetanus toxin IgG antibodies and tetanus antitoxin over a wide range of doses of AlPO4-adsorbed TT (0.01 to 0.2 Lf). After the second and third injections, there was no clear dose response for doses between 0.05 and 0.2 Lf However, doses between 0.01 and 0.04 Lf still showed a dose response after the second injection. Dilution of AlPO4-adsorbed TT in saline just before injection did not alter immunogenicity after the first injection, but stronger booster responses were seen in mice to diluted versus undiluted vaccine after the second and third injections. The threshold dose of AlPO4-adsorbed TT for both mice and guinea pigs was 0.01 Lf given in 100 microliters. For AlPO4-adsorbed DT, three strains of mice (inbred, Balb/c and C57/B6, and outbred, CD-1) showed a dose response after the first injection for DT IgG antibodies and diphtheria antitoxin at 0.1 and 0.2 Lf doses. Outbred CD-1 mice showed a dose response after the second and third injections also, whereas inbred mice showed inconsistent dose responses after the second injection and none after the third injection. In contrast to AlPO4-adsorbed TT, mice injected with undiluted AlPO4-adsorbed DT elicited significantly higher antibodies than those injected with diluted formulations, particularly after the first injection. The threshold dose of AlPO4-adsorbed DT for mice was 0.1 Lf in a volume of 250 microliters. Lower doses did not produce consistent antibody responses in mice. We propose that a single dose of controlled release formulations at doses not greater than 1/10 of a single human dose when injected into mice and guinea pigs should produce an antibody response similar or higher than two to three threshold doses of AlPO4-adsorbed TT or DT.

Adjuvants, Immunologic↗
PubMed1998

Effect of skin abrasions on the efficacy of the repellent deet against Aedes aegypti.

Abrasion of repellent-treated human skin affected the efficacy of a sustained-release insect repellent containing N,N-diethyl-3-methylbenzamide (deet) against bites of Aedes aegypti. Skin treated with repellent when abraded up to 30 times showed significantly lower protection than unabraded skin against mosquito bites for 10 h. The mean value of the kinetic coefficient of friction during skin abrasion by clothing (battle dress uniform fabric) for repellent-treated skin (0.159 +/- 0.003) was significantly higher than untreated skin (0.122 +/- 0.005). Repellent-treated skin appeared stickier than the untreated skin. An increase in the number of skin abrasions by clothing resulted in a reduced duration of protection against mosquito bites.

Aedes↗
PubMed1997

A trial of two methods of taking cervical smears: the Aylesbury spatula plus cytology brush compared to the Cervex broom.

AIMS: To compare the adequacy of cervical smear taking, using the Aylesbury spatula plus cytology brush with the Cervex broom. METHODS: Two cervical smears were taken at the same visit, the women acting as their own controls. In Group 1 comprising 81 women, the first smear was taken using the Cervex broom. In Group 2 comprising 97 women, the first smear was taken using the Aylesbury spatula followed by the cytology brush. The tips of the samplers were sent to the laboratory in a cytology container with 30% ethyl alcohol in saline, for analysis of residual cells. RESULTS: It took experienced staff two or three smears before they were adept at taking an adequate Cervex broom sample as defined by the presence of endocervical cells. Both techniques were equally good at detecting significant abnormalities. When the Cervex broom was used first there were more smears with no blood present but when bleeding occurred there was no significant difference between the two groups. Both techniques were well accepted by the women. CONCLUSIONS: Although it is more expensive than the Aylesbury spatula and the cytology brush the Cervex broom has the advantage of allowing a simple one step procedure, thereby reducing the potential for air drying.

Female↗
PubMed1997

Short-term reduction in dietary intake of magnesium causes deficits in brain intracellular free Mg2+ and [H+]i but not high-energy phosphates as observed by in vivo 31P-NMR.

31P-NMR spectroscopic studies were performed in vivo on brains of rats fed 30-35% normal dietary Mg intake for 6 weeks. Within 2 weeks of the moderately restricted Mg diet serum Mg fell 50%, and brain intracellular free [Mg2+]i fell 15%; within 3 weeks of restricted diet, brain [Mg2+]i fell 40% and remained at this level for the additional 3 weeks. Intracellular pH (pH[i]) progressively rose in a reciprocal manner for 4 weeks. At no interval of time did brain phosphocreatine (PCr), [ATP], or inorganic phosphate change despite the fall in brain [Mg2+]i, brain pH(i) and serum Mg. The Mg-deficiency-induced cytosolic loss of protons (resulting in an alkaline cytosol) could be a compensatory mechanism to stabilize [PCr], [ATP] and [ADP] levels via creatine kinase, thus maintaining cytosolic phosphorylation potential. The rise in pH(i) associated with Mg-deficiency would also account for increased cerebral vascular muscle contractility under these conditions. Lastly, these studies indicate that brain [Mg2+]i may change without a concomitant change in cell [ATP], and that brain [Mg2+]i may be a useful marker for total body Mg2+ status.

Adenine Nucleotides↗
PubMed1997

Mg2+ modulates membrane lipids in vascular smooth muscle: a link to atherogenesis.

Epidemiological studies associate low dietary magnesium intake with an increased incidence of ischemic heart disease and sudden cardiac death. We have used proton-magnetic resonance (1H-NMR) techniques and Mg2+-selective electrodes to monitor changes in lipid extracts of aortic and cerebrovascular smooth muscle as extracellular ionized magnesium ion concentration ([Mg2+]o) is lowered. We have found that, within the pathophysiological range of Mg2+ concentrations, fatty acid chain length and double bond content are progressively reduced as [Mg2+]o is lowered. In contrast, the plasmalogen content is progressively increased. A concomitant decrease in fatty acid chain length and double bonds indicates oxidation of double bonds resulting in truncation of the fatty acids. A decrease in lipid oxidation in the presence of elevated Mg2+ could contribute to the apparent protective role of increased Mg2+ intake on vascular function in humans.

Animals↗
PubMed1997

Selective involvement of basal ganglia and occipital cortex in a patient with acute endosulfan poisoning.

We report a teenage girl with acute endosulfan poisoning who developed psychosis, generalized tonic-clonic seizures, myoclonic jerks, cortical blindness and limb rigidity. Serial magnetic resonance imaging (MRI) showed bilateral reversible lesions localized to caudate nucleus, putamen and occipital cortex; internal capsule and thalamus were spared. This selective involvement may have a bearing on mechanisms underlying endosulfan toxicity.

Adolescent↗
PubMed1997

Magnetic resonance imaging in juvenile asymmetric segmental spinal muscular atrophy.

Magnetic resonance imaging (MRI) of cervical spine was performed in 16 patients of juvenile asymmetric segmental spinal muscular atrophy (JASSMA) in neutral and flexed positions to look for abnormalities in the spinal cord and the surrounding structures. The study included 5 normal individuals and 5 disease-negative controls who had spinal cord atrophy due to amyotrophic lateral sclerosis. In normal and disease-negative controls, lower cervical spinal cord moved forward and got mildly flattened against the vertebral bodies during flexion. The subarachnoid space increased behind the cord with no significant forward movement of the posterior dura mater; epidural space was just visible. The patients of JASSMA showed spinal cord atrophy in a small vertical segment in front of cervical 4 to 7 vertebral bodies. In addition, 9 patients had high cord signal on T2 weighted images, mainly localized to anterior and lateral horns of the grey matter. In flexion, there was marked anterior displacement and anteroposterior flattening of lower cervical cord against the vertebral bodies; posterior dura mater also moved forward obliterating subarachnoid space in all the patients. A large posterior epidural space was visible which showed enhancement after gadolinium-DTPA administration. Twelve patients had prominent blood vessels in this epidural space. These findings suggest that MRI done in neck flexion may have diagnostic significance in JASSMA.

Adult↗
PubMed1997

MRI demonstration of Wallerian degeneration in various intracranial lesions and its clinical implications.

Dynamic signal intensity changes of Wallerian degeneration (WD) are well documented in cases of stroke. These changes have been staged I-IV, depending on time-specific signal intensity changes in corticospinal tract with magnetic resonance imaging (MRI). We performed both prospective and retrospective evaluation of various intracranial lesions to look for evidence of WD and to assess its prognostic implications. Eighteen patients of acute stroke were studied prospectively. Their functional disability was evaluated by using a modified Barthel index of activity of daily living (ADL) at presentation, at 1 month and at 4 months, and was correlated with presence or absence of WD on MRI. 10/18 patients showed signal intensity changes of WD on MRI and their mean ADL score changed from 9.1 at 1 month to 11.4 at 4 months duration suggestive of moderate to severe disability after 4 months of stroke. The rest of the eight patients, where MRI did not reveal signal intensity changes of WD, the mean ADL score improved from 10.37 at 1 month to 17.5 at 4 months, suggesting significant improvement in their clinical disability. 520 patients were studied retrospectively, out of whom 31 showed signal intensity changes of WD in various intracranial lesions, i.e. infarcts (14/220), intracranial haematoma (4/147), arterio-venous malformation (1/20), tumour (6/98), multiple sclerosis (5/20) and encephalitis (1/15). Presence of WD in these intracranial lesions correlated well with persistent clinical disability. This observation has immense prognostic value, particularly in relapsing and remitting disease like multiple sclerosis. We conclude that WD can be seen secondary to any CNS insult with MRI and its presence correlates well with persistent functional disability. It thus has prognostic value.

Adult↗
PubMed1997

Fine-needle aspiration cytodiagnosis of recurrent carcinoma of the breast in operative scars.

Recurrence of carcinoma in scars following surgical treatment of breast carcinoma is a frequent problem. An early diagnosis of recurrent lesions is essential to enable timely management. In this study, the role of fine-needle aspiration cytology (FNAC) in the diagnosis of scar lesions was evaluated in 156 women seen over a period of 12 1/2 yr. Ninety-eight of these on FNAC showed features of a recurrent carcinoma, and in six samples, the FNAC showed suspicious features. In all the six suspicious cases, a subsequent biopsy confirmed a recurrent breast carcinoma. The remaining 52 cases on repeated FNAC were diagnosed as benign, and this was confirmed on a subsequent biopsy. The sensitivity, specificity, and predictive value for cytologic findings were 94.2, 100, and 100%, respectively. It was concluded that FNAC clearly has a role as a first line of investigation for distinguishing between recurrent malignant and benign lesions in scars in women which have been surgically treated for a breast carcinoma.

Adolescent↗
PubMed1997

Cytodiagnosis of amelanotic metastatic malignant melanoma: an immunocytochemical study.

Malignant melanomas are known to present diverse patterns and this can result in considerable difficulties for an interpretation of malignancy type from cytohistologic material. Such difficulties are further compounded, if melanin pigment cannot be demonstrated by conventional histochemical stains; unfortunately many cases do exhibit this feature, especially in its metastases. This study was designed to review cases of amelanotic metastatic malignant melanomas in a variety of cytologic samples which were received from 40 patients with a known history of malignant melanoma. Cytomorphologically, the cases were classified as classical, carcinoma-like, spindle cell type, lymphoma-like, and undifferentiated type (Table I). While in 36 of the cases, the diagnosis of metastases from a melanoma was confirmed based on an immunopositivity to a variety of melanoma markers (Table III), in four of the cases, the immunostaining indicated metastases from another primary source, which was subsequently found. Based on our study, we are of the opinion that an immunologic characterization is useful to conclusively diagnose the majority of cases of metastatic amelanotic malignant melanomas. Furthermore, we feel that a reliance on a single melanoma marker is not justified, and a panel of antibodies should be used to distinguish a metastatic amelanotic malignant melanoma from other metastatic neoplasms.

Adolescent↗
PubMed1997

Cytodiagnosis of pure primary squamous-cell carcinoma of the breast by fine-needle aspiration cytology.

In this communication five cases of pure primary squamous-cell carcinoma of the breast are presented in which the diagnosis was made by fine-needle aspiration cytology. All patients were women. The aspiration cytodiagnosis was further confirmed by subsequent examination of cell blocks from the aspirated material and biopsy of the breast mass. The cytohistologic features in all cases were characterized by numerous malignant squamous cells with keratinizing cytoplasm, hyperchromatic dense nuclei, coarse chromatin, thickened nuclear membranes, keratin debris, and background necrosis. The identification of malignant squamous cells as predominant cells in aspirate samples from the breast is quite important and should be followed by a search for other sources of a primary tumor before a diagnosis of pure primary squamous-cell carcinoma of the breast is accepted. The value of immunocytochemical study despite immunopositivity for cytokeratin and epithelial membrane antigen (EMA) and immunonegativity for carcinoembryonic antigen (CEA) and B72.3 was considered to be somewhat uncertain.

Aged↗
PubMed1997

Fine-needle aspiration cytodiagnosis of Liesegang rings in women presenting with a mammographic opacity.

In this communication three women patients are described in which fine needle aspiration cytology was undertaken as a first line of noninvasive investigation to determine the cause of a mammographic opacity. The cytologic findings in the three cases showed features of apocrine cysts with numerous spherical ring-like structures resembling Liesegang rings of various sizes, with double-layer outer wall, striations, and an amorphous central nidus. Although similar structures have been described by us very rarely in breast cysts, their presence in a mammographic opacity was noted for the first time. Furthermore, in the three cases fine-needle aspiration cytology not only resulted in a specific diagnosis but also obviated the need for any invasive surgery apart from relieving patient anxiety and clinical concern by excluding a serious lesion.

Adult↗
PubMed1997

Duodenogastric reflux after choledochoduodenostomy.

Duodenogastric reflux (DGR) has been implicated in several disease processes. The present study was carried out to document the incidence and evaluate the clinical significance of DGR after choledochoduodenostomy (CDD). A total of 13 patients who had undergone cholecystectomy with a standard side-to-side CDD for choledocholithiasis or chronic pancreatitis were studied by symptom evaluation, scintigraphy, endoscopy, and gastric mucosal histology at least 6 months after surgery. The scintigraphic findings were then compared with those of 10 patients who had undergone cholecystectomy alone. Only two patients (15%) had mild dyspeptic symptoms. The incidence of DGR after CDD was 69% compared to 20% in the cholecystectomy alone group (P < 0.05). In the majority of patients the DGR was only mild to moderate and the severity correlated well with the degree of endoscopic gastritis, but not with the clinical symptoms or histological findings. These results indicate that while CDD is associated with a high incidence of DGR, its occurrence does not produce significant clinical symptoms.

Adult↗