Protective Effect of Aqueous Extract of Lagenaria Siceraria (Molina) Against Maximal Electroshock (MES) -Induced Convulsions in Albino Rats.

Background The Lagenaria siceraria (Molina) belongs to family Cucurbitaceae, commonly known as bottle guard or calabash in English. All the parts of plant like root, fruit, leaves and flower has been evaluated for its various activities like antioxidant, antihelmintic, cognitive enhancer, anticancer, antianxiety, antidepressant, antihyperlipidemic, fibrinolytic cardio protective and hepatoprotective. Even though it is claimed to have antiepileptic action, no documentation is available. Objective To assess the anticonvulsant activity of aqueous extract of Lagenaria siceraria by Maximal Electroshock seizure induced seizure models on Albino rats. Method Albino rats were taken and divided into five groups, each consisting of five rats. One group was used as control (normal saline 10 ml/kg), one as standard (phenytoin), and three groups for the test drug (aqueous extract of Lagenaria siceraria (AELS) in the doses of 200, 400 and 800 mg/kg) treatment. In MES model, Maximal electrical shock of 150 mA was passed for 0.2 seconds through corneal electrodes after 30 minutes of giving the drugs and normal saline. Different stages of convulsions were noted down along with time spent by the animal in each phase of convulsions. Data were statistically analyzed by One way ANOVA followed by multiple Dunnett's test. Result The mean reduction in hind limb extension phase was 8.2±2.10 after 400 mg/kg of AELS which is highly significant (p<0.001) like phenytoin. AELS at 800 mg/kg exhibited a significant 17±2.64 (p<0.05) protection against tonic extensor phase. Conclusion Aqueous extract of Lagenaria siceraria has anticonvulsant activity.

Inlay osmotic pump tablets containing metformin and glipizide.

The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of an elevated blood glucose. A newly developed inlay osmotic pump tablet (IOPT) can deliver glipizide (GLZ) and metformin HCl (MET) gradually in controlled manner. The aim of present investigation was to prepare the IOPT that can deliver >75% of GLZ in 2 h, whereas MET released after 2 h and sustained up to 12 h. In the present work, HP-ß-CD was used to modify the solubility of GLZ before incorporating in the osmotic system and MET was spray-dried with HPMC A15C to modify its release profile, flow property, and compressibility. Various parameters mainly G(75%) (75% GLZ release), t(LMET) (lag time of MET release from device), Q(10 h) (percent of MET released within 10 h), and RSQ(ZERO) (R(2) of release data fitted to zero-order equation) were used to compare different formulations. The effects of different formulation variables, that is, osmagents, concentration of hydrophilic polymer, diameter of drug releasing orifice, and coating composition on the drug release profile were investigated. The release rate of GLZ could be effectively modified by the addition of sodium carbonate and sodium chloride, whereas the release rate of MET was adjusted by dual-coating system and by addition of hydrophilic polymer. The developed inlay osmotic system could be effective in the multidrug therapy of diabetes by delivering both drugs in a controlled manner.

Considerations for introduction of a rotavirus vaccine in Oman: rotavirus disease and economic burden.

Rotavirus is the most common cause of fatal childhood diarrhea worldwide. We provide the first estimates of the health care and economic burden of severe rotavirus disease in Oman. We conducted active, hospital-based surveillance of rotavirus disease at 11 regional public hospitals in Oman, using the guidelines suggested by the generic World Health Organization protocol. From July 2006 through June 2008, all children aged <5 years who were hospitalized for acute gastroenteritis were enrolled in the surveillance program, and their stool samples were tested for rotavirus using a commercially available enzyme immunoassay (ID EIA Rotavirus Test; Dako Diagnostics). Rotavirus was detected in samples from 1712 (49%) of 3470 children. These children were hospitalized for a median of 3 days for severe diarrhea. A marked seasonal peak was evident with a majority of the cases occurring from December through May. Of the rotavirus cases, 69% occurred in children aged 6-17 months. We identified a diverse strain pattern in Oman, with G2 (37%), G1 (38%), and G9 (11%) accounting for most of typeable strains. By our burden estimates, the Omani government spends an estimated US$791,817 and US$1.8 million annually to treat rotavirus-associated diarrhea in the outpatient and hospital settings, respectively. A rotavirus vaccination program might substantially reduce the burden of severe diarrhea among children in Oman.

Sensitizing acute myeloid leukemia cells to induced differentiation by inhibiting the RIP1/RIP3 pathway.

Tumor necrosis factor-α (TNF-α)-induced RIP1/RIP3 (receptor-interacting protein kinase 1/receptor-interacting protein kinase 3)-mediated necroptosis has been proposed as an alternative strategy for treating apoptosis-resistant leukemia. However, we found that most acute myeloid leukemia (AML) cells, especially M4 and M5 subtypes, produce TNF and show basal level activation of RIP1/RIP3/MLKL signaling, yet do not undergo necroptosis. TNF, through RIP1/RIP3 signaling, prevents degradation of SOCS1, a key negative regulator of interferon-γ (IFN-γ) signaling. Using both pharmacologic and genetic assays, we show here that inactivation of RIP1/RIP3 resulted in reduction of SOCS1 protein levels and partial differentiation of AML cells. AML cells with inactivated RIP1/RIP3 signaling show increased sensitivity to IFN-γ-induced differentiation. RIP1/RIP3 inactivation combined with IFN-γ treatment significantly attenuated the clonogenic capacity of both primary AML cells and AML cell lines. This combination treatment also compromised the leukemogenic ability of murine AML cells in vivo. Our studies suggest that inhibition of RIP1/RIP3-mediated necroptotic signaling might be a novel strategy for the treatment of AML when combined with other differentiation inducers.

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.

Long-term survival in tricuspid atresia.

A patient is described who, at the age of 39, was diagnosed by cardiac catheterization as having congenital tricuspid atresia. Now 57 years old, this patient has never had surgery to correct or change this abnormality. Her survival is the longest reported for a patient with tricuspid atresia without surgical intervention.

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.

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.

Interphenylene 7-oxabicyclo[2.2.1]heptane oxazoles. Highly potent, selective, and long-acting thromboxane A2 receptor antagonists.

A series of interphenylene 7-oxabicyclo[2.2.1]heptane oxazoles (2) were prepared and evaluated for their thromboxane (TxA2) antagonistic activity in vitro and duration of action in vivo. Examination of the carboxyl side chain indicated that the interphenylene ring substitution pattern and, to a lesser extent, chain length were important factors in determining TxA2 antagonistic potency. For the carboxyl side chain, ortho substitution, a single methylene spacer between the interphenylene and oxabicycloheptane rings, and a propionic acid side-chain length were determined to be optimal. With respect to the oxazole side chain a wide range of amide substituents with diverse structures and lipophilicities were compatible with potent antagonistic activity. Finally, an acidic functional group on the alpha-chain and a hydrogen bond acceptor on the 4-position of the oxazole ring were critical for potent activity. From the analogs prepared 42 (BMS-180,291: [(+)-1S-(1 alpha, 2 alpha, 3 alpha, 4 alpha)-2-[[3-[4-[(n- pentylamino)carbonyl]-2-oxazolyl]-7-oxabicyclo[2.2.1]hept-2- yl]methyl]benzenepropanoic acid) was found to be a potent, selective, and orally-active TxA2 antagonist with a long duration of action and has been selected as a candidate for clinical development. In human platelet-rich plasma, 42 inhibited arachidonic acid (800 microM) and U-46,-619 (10 microM) induced aggregation with I50 values of 7 and 21 nM, respectively. Radioligand binding studies of 42 with [3H]-SQ 29,548 showed a Kd value of 4.0 +/- 1.0 nM in human platelet membranes. Both in vitro and in vivo studies indicated 42 was devoid of direct agonistic activity. In vivo 42 (0.2 mg/kg, po) showed extended protection (T50 = 14.4 h) from U-46,619 (2 mg/kg, iv) induced death in mice, and a single oral dose of 42 (3 mg/kg) abolished U46,619-induced platelet aggregation ex vivo in African green monkeys for > 24 h.

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.

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.

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.

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.

Electrophoretic pattern of serum glycoproteins on polyacrylamide disc gel in patients with breast cancer.

Numerous investigators have identified, isolated and characterized serum glycoproteins that are claimed to be specifically associated with malignancy. We have carried out serum glycoprotein electrophoresis on polyacrylamide disc gel in 53 breast cancer patients, at diagnosis as well as during and after therapy. Follow-up samples were divided into complete responders (CR) (n = 138) and nonresponders (NR) (n = 44). Glycoprotein electrophoresis showed multiple bands for each sample which were categorized into four groups: albumin, alpha, beta and gamma. The results revealed a decreasing number of CR and increasing number of NR with elevated (as compared to pretreatment levels) albumin fraction glycoproteins. Gamma region glycoproteins showed the reverse pattern to that of albumin region glycoproteins. The alpha and beta region glycoproteins revealed an increasing number of CR having higher values with increase in follow-up duration. In comparison with their pretreatment values CR showed significantly increased (Paired "t" test) values of albumin, alpha and beta region glycoproteins (p < 0.01, p < 0.001 and p < 0.001, respectively) and decreased gamma region glycoproteins (p < 0.001). The albumin, alpha, beta and gamma region glycoprotein levels were comparable between NR and untreated cancer patients. The variations in albumin, alpha, beta and gamma region glycoproteins correlate with treatment response, which might be useful in the treatment monitoring, and prediction of recurrence in breast cancer patients.

Role of sialic acid and alkaline DNase in breast cancer.

Serum levels of sialic acid and alkaline DNase (ADA) were analysed in 495 blood samples collected from 170 breast cancer patients before and during/after anticancer treatment. Fifty-six healthy females were included in the study to define the cutoff values. The markers were analysed by highly sensitive spectrophotometric methods. Statistical evaluation of the data was done using Student's 't' test, paired 't' test and ROC curve analysis. The total sialic acid (TSA), lipid bound sialic acid (LSA) and ADA in sera of untreated breast cancer patients were significantly higher than in controls. ROC curve analysis revealed TSA and LSA to be useful markers for diagnosis of breast cancer. Serum levels of TSA and LSA were significantly decreased in complete responders as compared to their pretreatment values. The pretreatment ADA values showed much individual variation. However, responders showed higher levels of ADA than untreated patients. In nonresponders the values of the biomarkers were comparable with pretreatment levels. The study suggested that TSA and LSA can be helpful in the diagnosis of breast cancer. All three markers can be used for assessment of response to anticancer treatment in breast cancer patients.

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.

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.

Humoral immunological profile of workers exposed to asbestos in asbestos mines.

Humoral immunological profile including immunoglobulins IgG, IgA, IgM, C-reactive protein, rheumatoid factor, antinuclear antibodies and circulating immune complexes were studied in a representative sample of 36 workers suffering from asbestosis (group A), 35 workers who are exposed to asbestos but not having evidence of asbestosis (group B) and 28 control workers (group C). Mean IgG and IgA levels were found to be significantly higher in the two exposed groups than in the controls. Circulating immune complexes of IgG, IgA and IgM class were detected in a significant percentage of cases in exposed groups than in controls. In groups A and B, the percentage of positive ANF cases was much higher than in the controls. The results suggest that immunological changes are associated with exposure to asbestos and these may play an important role in the pathogenesis of the disease process.

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.

Legionnaires' disease.

The Legionella bacillus is a relatively common pulmonary pathogen that has been responsible for a number of outbreaks of respiratory illness this century. Not until 1976, however, after exciting epidemiologic and microbiologic investigation, was the organism isolated and identified. Legionnaires' disease does not have a characteristic radiographic appearance, but certain features may alert the clinician to its presence. It often rapidly progresses to a lobar pneumonia that may not respond immediately to treatment. The radiographic findings lag behind clinical improvement, and radiographic resolution is prolonged. Organ transplantation patients often present with ill-defined, rounded, pleura-based opacities that may simulate pulmonary infarction and can cavitate.