PubMed Health⌕ Search

Biomedical subjects

M M Patel

Publications and source records attributed to M M Patel.

At least 19 recordsLinked to original sources
PubMed2006

Physicochemical characterization and evaluation of buccal adhesive patches containing propranolol hydrochloride.

Buccal adhesive patches containing 20 mg of propranolol hydrochloride were prepared using solvent casting method. Chitosan was used as a natural bioadhesive polymer. Patches were prepared at different ratios of PVP K-30 and evaluated for various physicochemical characteristics such as weight variation, drug content uniformity, folding endurance, surface pH, ex-vivo mucoadhesive strength, ex-vivo residence time, in vitro drug release and in vitro buccal permeation study. Patches exhibited sustained release over a period of 7 hours. The mechanism of drug release was found to be Non-Fickian diffusion. Addition of PVP K-30 generally enhanced the releasing rate. The ex-vivo mucoadhesive strength was performed using sheep buccal mucosa on modified physical balance. Optimized patches (batch F4) showed satisfactory bioadhesive strength (9.6 degrees 2.0 gram) and ex vivo residence time (272 degrees 0.25 minutes). Swelling index was proportional to PVP K-30. The surface pH of all batches was within satisfactory limit (7.0+/-1.5) and hence patches would not cause irritation in the buccal cavity. Good correlation was observed between in vitro drug release and in vitro drug permeation with correlation coefficient of 0.9364. Stability of optimized patches was performed in natural human saliva showed that both drug and dosage forms were stable in human saliva.

Adhesiveness↗
PubMed2004

Impaired glucose-stimulated insulin secretion, enhanced intraperitoneal insulin tolerance, and increased beta-cell mass in mice lacking the p110gamma isoform of phosphoinositide 3-kinase.

Phosphoinositide 3-kinase (PI3 kinase) has been implicated in G protein-coupled receptor regulation of pancreatic beta-cell growth and glucose-stimulated insulin secretion. The G protein-activated p110gamma isoform of PI3 kinase was detected in insulinoma cells, mouse islets, and human islets. In 7- to 10-wk-old mice, knockout of p110gamma reduced the plasma insulin response to ip glucose injection and impaired first and second phase glucose-stimulated insulin secretion from pancreata perfused ex vivo. The p110gamma -/- mice responded to preinjection with the glucagon-like peptide-1 receptor agonist exendin 4, such that plasma glucose and insulin responses to ip glucose injection were not different from wild types. Mice lacking p110gamma were not diabetic and were only slightly glucose intolerant (ip glucose injection) compared with wild types, in part due to enhanced responsiveness to insulin as determined by an ip insulin tolerance test. Despite severely reduced insulin secretion in these animals, the p110gamma -/- mice had greater pancreatic insulin content, and an increased beta-cell mass due to beta-cell hypertrophy. These surprising results suggest that the G protein-coupled p110gamma isoform of PI3 kinase is not central to the development or maintenance of sufficient beta-cell mass but positively regulates glucose-stimulated insulin secretion.

Animals↗
PubMed2003

Comparison of a microtiter plate system to Southern blot for detection of human herpesvirus 8 DNA amplified from blood and saliva.

The recent discovery of human herpesvirus 8 (HHV-8) as the etiologic agent of Kaposi's sarcoma (KS) has led to the interest in the development of PCR for this virus that is accurate, rapid, and convenient. We developed a sensitive PCR assay for HHV-8 with microtiter plate detection of amplimers. DNA was purified from white blood cells and saliva from HIV-infected men with and without Kaposi's sarcoma and one-step PCR was undertaken with primer sets specific for the N-terminal region of the glycoprotein B gene and open reading frame (orf) 26 of HHV-8. PCR was performed on 40 clinical specimens, followed by Southern blot and microtiter plate detection of amplimers. Results from the two methods of detection were nearly identical. Sensitivity for both methods based on serial dilution of a known standard was five to ten copies of HHV-8 per 400 ng of cellular DNA. In conclusion, microtiter plate detection of HHV-8 PCR amplimers is as sensitive and specific as Southern blot with much faster turnaround time at comparable cost, and utilizes common laboratory equipment.

Base Sequence↗
PubMed2003

Development of modified release diltiazem HCl tablets using composite index to identify optimal formulation.

This article reports the preparation of tartaric acid treated ispaghula husk powder for the development of modified release tablets of diltiazem HCl by adopting direct compression technique and a 32 full factorial design. The modified ispaghula husk powder showed superior swelling and gelling as compared to untreated powder. Addition of compaction augmenting agent such as dicalcium phosphate was found to be essential for obtaining tablets with adequate crushing strength. In order to improve the crushing strength of diltiazem HCl tablets, to modulate drug release pattern, and to obtain similarity of dissolution profiles in distilled water and simulated gastric fluid (pH 1.2), modified guar gum was used along with modified ispaghula husk powder and tartaric acid. A novel composite index, which considers a positive or a negative deviation from an ideal value, was calculated considering percentage drug release in 60, 300, and 540 min as dependent variables for the selection of a most appropriate batch. Polynomial equation and contour plots are presented. The concept of similarity factor (f2) was used to prove similarity of dissolution in water and simulated gastric fluid (pH 1.2).

Compressive Strength↗
PubMed2002

Serum glutathione-S-transferase and glutathione reductase activity in head and neck cancer patients.

Glutathione, an antioxidant plays an important role in phase-II detoxification of carcinogens. The levels of reduced glutathione are maintained by glutathione-depleting as well as replenishing enzymes such as glutathione-s-transferase (GST) and glutathione reductase (GR), respectively. Pre and post treatment changes in GST and GR activities in head and neck cancer patients were analysed. Serum GST and GR were analysed from untreated head and neck cancer patients (PT) (n=146), controls with habit of tobacco (VHT) (n=25) as well as without (no) habit of tobacco (NHT) (n=25) and patients with oral precancerous conditions (OPC) (n=50). The cancer patients were followed-up after initiation of anticancer therapy. Follow-up blood samples were collected. Serum GST and GR activities were estimated by highly sensitive and specific spectrophotometric methods. Untreated cancer patients showed elevated mean serum GST and GR activities as compared to NHT. Patients with OPC had declined mean GST activity as compared to WHT and untreated cancer patients. Paired t-test revealed that complete responders (CR) showed significantly elevated GST levels and declined GR activities (p < 0.001) as compared to those in PT. No correlation was found between stage of the disease and GST, GR activity. Paired t-test showed significant decreased in GR activity in nonresponders (NR) treated with radiotherapy (p=0.01). The study suggested that analysis of glutathione and glutathione-depleting enzymes can be helpful for treatment monitoring of head and neck cancer patients.

Adult↗
PubMed2001

Quantitative, fluorogenic probe PCR assay for detection of human herpesvirus 8 DNA in clinical specimens.

A quantitative, fluorescence-based PCR assay (TaqMan-based system) was developed for detection of human herpesvirus 8 (HHV-8) DNA in clinical specimens. Primers and probes chosen from each of five 10-kb segments from the unique region of the HHV-8 genome were evaluated for sensitivity with dilution series of DNA extracted from a cell line (BCBL-1) that harbors HHV-8 DNA. Although several of the primer-probe sets performed similarly with BCBL-1 DNA that had been diluted in water, their performance differed when target DNA was diluted in a constant background of uninfected cell DNA, an environment more relevant to their intended use. The two best primer-probe combinations were specific for HHV-8 relative to the other known human herpesviruses and herpesvirus saimiri, a closely related gammaherpesvirus of nonhuman primates. PCRs included an enzymatic digestion step to eliminate PCR carryover and an exogenous internal positive control that enabled discrimination of false-negative from true-negative reactions. The new assays were compared to conventional PCR assays for clinical specimens (saliva, rectal brushings, rectal swab specimens, peripheral blood lymphocytes, semen, and urine) from human immunodeficiency virus-positive patients with or without Kaposi's sarcoma. In all instances, the new assays agreed with each other and with the conventional PCR system. In addition, the quantitative results obtained with the new assays were in good agreement both for duplicate reactions in the same assay and between assays.

AIDS-Related Opportunistic Infections↗
PubMed2000

Alveolar dead space as a predictor of severity of pulmonary embolism.

OBJECTIVE: To determine whether the alveolar dead space volume (V(D)alv), expressed as a percentage of the alveolar tidal volume (V(D)alv/V(T)alv), can predict the degree of vascular occlusion caused by pulmonary embolism (PE). METHODS: Fifty-three subjects with suspected PE were prospectively studied. Pulmonary embolism was diagnosed in 33 by high-probability ventilation/perfusion (V/Q) scan (n = 19) or by pulmonary arteriography (PAG, n = 14). Pulmonary embolism was excluded by PAG in 20 subjects. The V(D)alv/V(T)alv was determined from volumetric capnography and arterial blood gas analysis, which permits measurement of the physiologic dead space, V(D)phys (mL) = [(PaCO2 - PeCO2)/PaCO2]. tidal volume. Airway dead space (V(D)aw) was subtracted to yield the alveolar dead space [(V(D)phys - V(D)aw) = V(D)alv (mL)]; the percentage of alveolar volume occupied by alveolar dead space per breath = V(D)alv/V(T)alv x 100%. Percentage perfusion defect was determined from V/Q scans by a radiologist blinded to other data. Regression analysis was performed to show correlation between V(D)alv/V(T)alv and defect on V/Q scan or systolic pulmonary arterial pressure (SPAP). RESULTS: For subjects with PE, the mean perfusion defect on lung scan was 38 +/- 22%; the mean V(D)alv = 208 +/- 115 mL, V(T)alv = 452 +/- 251 mL, and V(D)alv/V(T)alv = 43 +/- 18%. Regression of V(D)alv/V(T)alv vs perfusion defect yielded r2 = 0.41. Regression of V(D)alv/V(T)alv vs pulmonary artery pressures yielded r2 = 0.59. For subjects without PE, V(D)alv/V(T)alv = 27 +/- 14% and V(D)alv = 89 +/- 66 mL. CONCLUSIONS: The V(D)alv/V(T)alv correlates with the lung perfusion defect and the pulmonary artery pressures in subjects with PE. These findings show the potential for V(D)alv/V(T)alv to quantify the embolic burden of PE.

Adult↗
PubMed1999

Assessment of glutathione-S-transferase and glutathione reductase in patients with squamous-cell carcinoma of buccal mucosa.

Serum and tumor cytosolic levels of glutathione-S-transferase (GST) and glutathione-reductase (GR) activity were determined spectrophotometrically. The levels were correlated with clinicopathological criteria and a tobacco-associated protein band (T band) found in serum. The results showed significantly decreased mean serum GST levels (p < 0.02) in cancer patients as compared with controls. However, mean serum GR levels were significantly higher in patients than in controls (p < 0.01). T-band-positive patients showed low GST and low GR activity as compared with T-band-negative patients. Tumor cytosolic-enzyme levels of GST and GR activity were significantly higher (p < 0.0003 and p < 0.0001, respectively) than in corresponding adjacent noncancerous mucosa. Tumour cytosolic GST and GR activity showed significant association with clinicopathologic criteria, e.g., stage, histologic grade and nodal involvement. T-band-negative patients showed significantly higher levels of GST (p < 0.0001) than did T-band-positive patients. Low levels of cytosolic GST may be associated with increased susceptibility towards carcinogen-induced damage. The results suggest that the presence of T band in the sera may be associated with a high-risk phenotype due to decreased detoxification ability.

Adult↗
PubMed1999

Evaluation of glycoprotein constituents in head and neck cancer patients undergoing radiotherapy.

BACKGROUND: Alterations in serum levels of several glycoprotein constituents are reported to be useful for treatment monitoring of cancer patients. The purpose of this study was to determine efficacy of sialic acid and seromucoid fraction as treatment monitors for head and neck (H&N) cancer patients undergoing radiotherapy (RT). METHODS: Serum levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), and seromucoid fraction (measured as Mucoid protein [MP] and hexose) were studied in age matched controls and in patients with H&N cancer at diagnosis and during/after completion of RT. The markers were estimated by spectrophotometric methods. RESULTS: Serum levels of sialic acid forms and seromucoid fraction were significantly elevated (p<.001) in untreated H&N cancer patients (n = 32) as compared with controls (n = 50). The marker levels were significantly declined (p<.001) in H&N cancer patients who responded to RT as compared with their levels at diagnosis, whereas the levels were persistently elevated in nonresponders. CONCLUSION: Evaluation of sialic acid forms and seromucoid fraction could be used for monitoring the treatment of H&N cancer patients undergoing RT.

Adult↗
PubMed1999

Evaluation of telomerase activation in head and neck cancer.

During replication of the linear chromosomes, telomeres, i.e. the ends of the chromosomes, are not replicated completely by the conventional DNA polymerases. Therefore, normal somatic cells senesce after certain number of cell divisions. Telomerase is a special reverse transcriptase used by most eukaryotes to achieve immortalization. Telomerase activity has been determined in a variety of cancers. However, there are few reports on telomerase activity in head and neck cancer. The etiology of the disease in India is completely different from Western countries. Tobacco consumption is more prevalent in India and the mode of tobacco consumption (e.g. chewing, snuffing, bidi smoking, reverse smoking) is also different. The present study determined telomerase activity in 32 malignant tumour samples of head and neck cancer patients, 11 samples from patients with precancerous/benign lesions and 30 samples of adjacent normal tissues. Telomerase was found to be activated in 80% of the patients with head and neck cancer, 100% of the patients with precancerous/benign lesions and 74% of the adjacent normal tissues. According to the theory of field cancerization, carcinogenic insults (e.g. tobacco) may result into multiple malignant foci. This fact may explain the reason for high telomerase positivity in adjacent normal as well as precancerous/benign tissues. Telomerase activation and the clinical or histopathological characteristics of the head and neck cancer patients were observed to be independent features. This is a preliminary report which has generated a greater interest for in-depth elucidation of the role of telomerase and telomeres in head and neck carcinogenesis in India.

Adult↗
PubMed1999

Neural network analysis of the volumetric capnogram to detect pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) produces ventilation/perfusion mismatch that may be manifested in various variables of the volume-based capnogram (VBC). We hypothesized that a neural network (NN) system could detect changes in VBC variables that reflect the presence of a PE. METHODS: A commercial VBC system was used to record multiple respiratory variables from consecutive expiratory breaths. Data from 12 subjects (n = 6 PE+ and n = 6 PE-) were used as input to a fully connected back-propagating NN for model development. The derived model was tested in a prospective, observational study at an urban teaching hospital. Volumetric capnograms were then collected on 53 test subjects: 30 subjects with PE confirmed by pulmonary angiography or diagnostic scintillation lung scan, and 23 subjects without PE based on pulmonary angiography. The derived NN model was applied to VBC data from the test population. RESULTS: Seventeen VBC variables were used by the derived NN model to generate a numeric probability of PE. When the derived NN model was applied to VBC data from the 53 test subjects, PE was detected with a sensitivity of 100% (95% CI = 89% to 100%) and a specificity of 48% (95% CI = 27% to 69%). The likelihood ratio positive [LR(+)] for the VBC-NN test was 1.82 and the LR (-) was 0.1. CONCLUSION: This study demonstrates the feasibility of developing a rapid, noninvasive breath test for diagnosing PE using volumetric capnography and NN analysis.

Angiography↗
PubMed1998

Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome.

PURPOSE: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities. METHODS AND MATERIALS: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55-70 Gy), 144 with preoperative radiation therapy (20-40 Gy), and 86 with postoperative irradiation (50-60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. RESULTS: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20-25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35-40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04-0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone. CONCLUSION: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1-T2 carcinoma of the tonsillar fossa. In patients with T3-T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.

Analysis of Variance↗
PubMed1998

Seromucoid fraction: a useful biomarker for patients with breast cancer.

Seromucoid fraction was measured in terms of mucoid proteins (MP) and hexose content from sera of 1) 47 healthy women, 2) 48 women who had benign breast diseases, 3) 151 untreated patients with breast cancer, and 4) 245 follow-up samples collected from the same breast cancer patients. Mucoid proteins and hexose levels were found to be significantly elevated in untreated patients with breast cancer when compared with the healthy participants (p < 0.001) and patients who had benign breast diseases (p < 0.02 and p < 0.05, respectively). Receiver operating characteristic (ROC) curve analysis revealed potential diagnostic application of both markers for breast cancer. A good correlation was observed between favorable treatment response and decline in serum-marker levels. The markers in patients who did not respond to anticancer therapy remained stable or increased during follow-up. These data indicate that seromucoid fraction can be an useful biochemical marker for breast cancer patients.

Adolescent↗
PubMed1998

Preliminary investigations in matrix-based tablet formulations of diltiazem hydrochloride containing succinic acid-treated methylcellulose.

The feasibility of using succinic acid-treated methylcellulose in matrix-based tablets of diltiazem hydrochloride was investigated in this study. A 2(3) factorial design was employed to investigate the effect of ratio of methylcellulose to succinic acid, amount of ethyl alcohol, and drying time on the percentage drug dissolved in 300 min. The tablets were prepared by wet granulation technique. The ratio of methylcellulose to succinic acid was found to significantly influence the swelling and gelling characteristics of the polymer. Carbonyl peak was found in the infrared (IR) spectra of the samples modified using succinic acid, suggesting the presence of an ester group. The results of an ANOVA test revealed that the significance of the ratio of methylcellulose to succinic acid and drying time was greater in magnitude than that of amount of alcohol in controlling the drug release in 300 min. The results of F-test revealed that the zero-order model fits well to the in vitro dissolution data. The characteristics of methylcellulose can be changed by reacting it with succinic acid and the resultant product can be used as a hydrophilic matrixing agent.

Calcium Channel Blockers↗
PubMed1996

Development of highly potent inhibitors of Ras farnesyltransferase possessing cellular and in vivo activity.

Analogs of CVFM (a known nonsubstrate farnesyltransferase (FT) inhibitor derived from a CA1A2X sequence where C is cysteine, A is an aliphatic residue, and X is any residue) were prepared where phenylalanine was replaced by (Z)-dehydrophenylalanine, 2-aminoindan-2-carboxylate, 1,2,3,4-tetrahydroisoquinoline-3-carboxylate (Tic), and indoline-2-carboxylate. The greatest improvement in FT inhibitory potency was observed for the Tic derivative (IC50 = 1 nM); however, this compound was ineffective in blocking oncogenic Ras-induced transformation of NIH-3T3 fibroblast cells. A compound was prepared in which both the Cys-Val methyleneamine isostere and the Tic replacement were incorporated. This derivative inhibited FT with an IC50 of 0.6 nM and inhibited anchorage-independent growth of stably transformed NIH-3T3 fibroblast cells by 50% at 5 microM. Replacing the A1 side chain of this derivative with a tert-butyl group and replacing the X position with glutamine led to a derivative with an IC50 of 2.8 nM and an EC50 of 0.19 microM, a 26-fold improvement over (S*,R*)-N-[[2-[N-(2-amino-3-mercaptopropyl)-L-valyl]-1,2,3,4- tetrahydro-3-isoquinolinyl]carbonyl]-L-methionine. This derivative, (S*,R*)-N-[[2-[N-(2-amino-3-mercaptopropyl)-L-tert-leucyl]-1,2,3,4 - tetrahydro-3-isoquinolinyl]-carbonyl]-L-glutamine, was evaluated in vivo along with (S*,R*)-N-[[2-[N-(2-amino-3- mercaptopropyl)-L-tert-leucyl]-1,2,3,4-tetrahydro-3- isoquinolinyl]carbonyl]-L-methionine methyl ester for antitumor activity in an athymic mouse model implanted ip with H-ras-transformed rat-1 tumor cells. When administered by injection twice a day at 45 mg/kg for 11 consecutive days, both compounds showed prolonged survival time (T/C = 142-145%), thus demonstrating efficacy against ras oncogene-containing tumors in vivo.

3T3 Cells↗