Immunomodulatory Activity of A Novel Nucleoside, 7-thia-8-oxoguanosine: I. Activation of Natural Killer Cells in Mice

We reported recently that a novel immunomodulator, 7-thia-8-oxoguanosine (7T80G)² inhibited formation of pulmonary melanoma metastases (1), prevented against viral infection in mice (2) and potentiated the efficacy of a weakly immunogenic leukemia vaccine (3). Since certain tumor metastases and virus infected cells are targets to natural killer cells (NK cells), we now investigated whether 7T80G is capable of activating NK cells in mice using NK cell sensitive YAC-1 and B16 and NK cell insensitive P815 targets. CBA/CaJ spleen cells incubated in vitro with 7T80G at concentrations ranging from 0.005 to 0.5 mM responded with increased NK cell activity (32-62 %) compared to controls (4-8%) to YAC-1 targets. Similar levels of augmentation in NK cell activity were observed when 40-168 mg/kg of 7T80G was administered in vivo. In addition to the spleen, 7T80G activated NK cells in the bone marrow (BM), the lungs, the liver, and in peritoneal exudate cells (PE). Although 7T80G elicited activation of NK cells was observed as early as three hours after treatment, the maximal activity was observed after 24 h in the spleen; 12 h in the BM; 48 h in the lungs, and 72 h in PE. Administration of the drug by s.c, i.v., and i.p. routes all induced activition of NK cells in spleen, BM and PE. 7T80G was found to activate NK cells in seven inbred and an outbred mouse strain, suggesting that the induced cytotoxicity against allogeneic and syngeneic tumor cells is not strain specific as well as independent of MHC restriction. C3H/He, CBA/CaJ and BDF/1 displayed higher levels of increased NK cell activity, whereas AKR mice were low responders. Low concentrations of IL-2 (0.25-5 U/ml) that induce little or no NK cell activity, when used in combination with 7T80G, elicited significant enhancement of NK cell cytotoxicity. In contrast, IFN and 7T80G showed no such synergism.     

How Important is the Tunnel Position in Outcomes Post-ACL Reconstruction: A 3D CT-Based Study

BackgroundDrilling the femoral and tibial tunnels at their anatomical locations are critical for good outcomes and involve seeing the footprints well. We intended to compare two techniques of drilling the tunnels and the patient-reported outcomes and knee stability of patients undergoing single bundle ACL reconstruction using 3D CT to evaluate if the tunnels were anatomical or not.Materials and MethodsSixty single bundle ACL reconstructions were analyzed, 30 each with Technique A and B. Pre-operative and after a minimum 27 month follow-up Lysholm, IKDC, Tegner score, hop test, and Lachman test were noted. 3D CT was done to classify femoral tunnels positions as being well placed, slightly or grossly misplaced and tibial tunnels as optimal or suboptimal and compared.ResultsSixty ACL reconstructions had full follow-up with a mean follow-up of 34 months. There was no significant difference between tunnel positions between the two techniques. Well-placed femoral tunnel had better Lysholm score (62.2 ± 16.2 v/s 48.5 ± 17.2, p 0.002) and IKDC score (62.5 ± 14.3 v/s 52.7 ± 15.1, p 0.012).). Those who had their surgeries within 3 months of their injury had better hop test (4.4 ± 0.9 v/s 3.9 ± 1, p 0.034) and IKDC scores (62.5 ± 15.8 v/s 33.2 ± 13.8, p 0.026) as compared to those that had surgery done after 3 monthsConclusionTibial tunnel positions were optimal in most cases and did not differ between the two techniques. Well-placed femoral tunnels and surgeries done within 3 months of the injury produced best results.     

A prospective randomized comparison of type of nephrostomy drainage following percutaneous nephrostolithotomy: large bore versus small bore versus tubeless

PURPOSE: We compared postoperative outcomes among tubeless, conventional large bore nephrostomy drainage and small bore nephrostomy drainage following percutaneous nephrostolithotomy (PCNL) in a prospective randomized fashion. MATERIALS AND METHODS: Between January and June 2001, 30 patients undergoing PCNL were randomized to receive conventional large bore (20Fr) nephrostomy drainage (group 1, 10 patients), small bore (9Fr) nephrostomy drainage (group 2, 10 patients) or no nephrostomy drainage (group 3, 10 patients). Inclusion criteria included a single subcostal tract, uncomplicated procedure, normal preoperative renal function and complete stone clearance. Factors compared among the 3 groups were postoperative analgesia requirement, urinary extravasation, duration of hematuria, duration of urinary leak, decrease in hematocrit and hospital stay. RESULTS: The postoperative analgesic requirement was significantly higher in group 1 (217 mg) compared to groups 2 (140 mg, p <0.05) and 3 (87.5 mg, p <0.0001). Patients in group 3 had a significantly shorter duration (4.8 hours) of urinary leak through the percutaneous renal tract compared to patients in groups 1 (21.4 hours, p <0.05) and 2 (13.2 hours, p <0.05). Hospital stay was significantly shorter in group 3 (3.4 days) compared to groups 1 (4.4 days, p <0.05) and 2 (4.3 days, p <0.05). All 3 groups were similar in terms of operative time, duration of hematuria and decrease in hematocrit. Postoperative ultrasound did not reveal significant urinary extravasation in any case. CONCLUSIONS: Tubeless PCNL is associated with the least postoperative pain, urinary leakage and hospital stay. Small bore nephrostomy drainage may be a reasonable option in patients in whom the incidence of stent dysuria is likely to be higher.     

Factor XIII deficiency: a rare cause of repeated abortions

Factor XIII deficiency is a rare cause of early abortion. The obstetrical outcome of four pregnancies in two women with factor XIII deficiency is reported. Both women were treated with substitution therapy using locally-prepared cryoprecipitate. The outcome in these two women demonstrated the need for substitution therapy in early pregnancy leading to an increased chance of obstetrical success.     

Serum nitrate levels as an index of endothelial function in pre-eclamsia and normal pregnancy

The study was conducted in St. John's Medical College Hospital and Department of Physiology, with the aim of studying the serum nitrate levels in pre-eclampsia and normal pregnancy. The total number of subjects studied in various groups were 159, control (n = 55), first trimester (n = 13), second trimester normal (n = 42), second trimester pre-eclampsia/PET (n = 5), third trimester normal (n = 32), third trimester pre-eclampsia/PET (n = 12). The serum nitrate was measured by one step enzymatic assay using Nitrate reductase from Aspergillus species. The nitrate levels in the third trimester pre-eclamptic group was found to be significant lower (P = 0.02), as compared to normal subjects, however the renal functions were normal in all the subjects.     

The relationship between maternal physical activity during pregnancy and birth weight

INTRODUCTION: Earlier studies in India have demonstrated an inverse relationship between physical activity and birth weight in rural women who had high levels of physical activity related to agricultural and domestic activities. There are no data on urban Indian women from a wide range of socio-economic backgrounds with varying levels of physical activity. This study assessed the role of different domains of physical activity during pregnancy and its relation to birth weight. METHODS: Data on maternal anthropometry and maternal physical activity level were collected at the 1st trimester (baseline), the 2nd trimester and the 3rd trimester of pregnancy. Birth weight for 546 live born babies was measured immediately after delivery. RESULTS: The time spent in sedentary activities (median "cut-off" of 165 min/d) was significantly associated with maternal body weight in the first trimester of pregnancy (51.2 kg vs. 54.1 kg, p < 0.001). Women in the highest tertile of physical activity level in the 1st trimester were 1.58 times (95% CI: 1.02-2.44) more likely of having a baby in the lowest tertile of birth weight with reference to the first tertile. This significant association continued after adjustment for maternal weight and energy intake. CONCLUSION: The present study shows that physical activity in the first trimester is associated with low birth weight in Indian babies.     

Published methodological quality of randomized controlled trials does not reflect the actual quality assessed in protocols

ObjectivesTo assess whether the reported methodological quality of randomized controlled trials (RCTs) reflects the actual methodological quality and to evaluate the association of effect size (ES) and sample size with methodological quality.Study Design and SettingSystematic review. This is a retrospective analysis of all consecutive phase III RCTs published by eight National Cancer Institute Cooperative Groups up to 2006. Data were extracted from protocols (actual quality) and publications (reported quality) for each study.ResultsFour hundred twenty-nine RCTs met the inclusion criteria. Overall reporting of methodological quality was poor and did not reflect the actual high methodological quality of RCTs. The results showed no association between sample size and actual methodological quality of a trial. Poor reporting of allocation concealment and blinding exaggerated the ES by 6% (ratio of hazard ratio [RHR]: 0.94; 95% confidence interval [CI]: 0.88, 0.99) and 24% (RHR: 1.24; 95% CI: 1.05, 1.43), respectively. However, actual quality assessment showed no association between ES and methodological quality.ConclusionThe largest study to date shows that poor quality of reporting does not reflect the actual high methodological quality. Assessment of the impact of quality on the ES based on reported quality can produce misleading results.     

Autoantibodies to zona pellucida in tubectomized women

The study was conducted to detect autoantibodies to zona pellucida by indirect immunofluorescence technique. A total of 60 human sera was examined, which included 15 tubectomized, 15 pregnant, 15 nonpregnant fertile women, and 15 fertile men. In the unabsorbed sera, anti-zona activity was observed in 53.3% of the tubectomized women and in 40.0% of the nonpregnant fertile women, 20.0% of the pregnant women and 26.7% of the fertile men. All the positive sera were then absorbed with porcine red blood cells and retested to exclude the false positive reaction due to nonspecific serum components. After absorption, immunological response was retained in 26.7% of the tubectomized women and lost in all the other women and men. The positive sera were further absorbed with zona-coated eggs and were retested. Fluorescence was lost in all the positive sera. This observation demonstrates the presence of antibodies, specific to zona antigens, in tubectomized women. To date, however, antibodies to zona antigen have not been demonstrated in the tubectomized women. Presence of anti-zona activity in tubectomized women may be an autoimmune response, possibly due to absorption and degradation of the ova into the peritoneal cavity or in the reproductive tract and the subsequent exposure of the degradation products to the immune system.