TB Groups Research Articles

Risk factors for false-negative T-SPOT.TB assay results in patients with pulmonary and extra-pulmonary TB

To investigate the risk factors for false-negative T-SPOT.TB results in patients with pulmonary TB (PTB) and extra-pulmonary TB (EPTB). Patients with suspected TB who underwent valid T-SPOT.TB tests were prospectively enrolled at Beijing Chest Hospital between November 2012 and November 2013. Basic characters and clinical laboratory findings were compared between true-positive and false-negative T-SPOT.TB groups. Of 1928 suspected TB patients, 774 (530 PTB and 244 EPTB) microbiologically/histopathogenically-confirmed patients (636 culture-confirmed) were analyzed. Forty-six PTB patients (8.7%) and 32 EPTB patients (13.1%) had negative T-SPOT.TB results. Multivariate analysis showed that increased age [odds radio (OR) 2.26, 95% confidence interval (CI) 1.11-4.58], over-weight (BMI ≥ 25 kg/m(2), OR 2.43, 95% CI 1.05-5.63), and a longer period of illness before hospitalization (>6 months, OR 2.46, 95% CI 1.24-4.92) were independent risk factors for false-negative T-SPOT.TB results in PTB patients. In EPTB patients, increased age (OR 2.42, 95% CI 1.09-5.35) also showed an independent association with false-negative T-SPOT.TB results. Careful interpretation of negative T-SPOT.TB results is necessary in older patients with suspected PTB or EPTB, and in PTB patients who are over-weight or have had longer periods of illness before hospitalization.

Bone Regeneration by the Combined Use of Tetrapod-Shaped Calcium Phosphate Granules with Basic Fibroblast Growth Factor-Binding Ion Complex Gel in Canine Segmental Radial Defects

ABSTRACTThe effect of tetrapod-shaped alpha tricalcium phosphate granules (Tetrabones® [TB]) in combination with basic fibroblast growth factor (bFGF)-binding ion complex gel (f-IC gel) on bone defect repair was examined. Bilateral segmental defects 20-mm long were created in the radius of 5 dogs, stabilized with a plate and screws and implanted with 1 of the following: TB (TB group), TB and bFGF solution (TB/f group), and TB and f-IC gel (TB/f-IC group). Dogs were euthanized 4 weeks after surgery. Radiographs showed well-placed TB granules in the defects and equal osseous callus formation in all the groups. Histomorphometry revealed that the number of vessels and volume of new bone in the TB/f-IC group were significantly higher than those in the other groups. However, no significant differences in neovascularization and new bone formation were observed between the TB/f and TB groups. Furthermore, no significant difference in the lamellar bone volume or rate of mineral apposition was observed among groups. These results suggest that increased bone formation might have been because of the promotion of neovascularization by the f-IC gel. Therefore, the combinatorial method may provide a suitable scaffold for bone regeneration in large segmental long bone defects.

Topically administered bevacizumab had longer standing anti-angiogenic effect than subconjunctivally injected bevacizumab in rat corneal neovacularization.

To compare the effect of topically administered and subconjunctivally injected bevacizumab on experimental corneal neovascularization in rats for two weeks after treatment. Twenty-eight Sprague-Dawley rats were divided into four groups of 7 animals. Each corneal center of right eye was cauterized with silver/potassium nitrate for 8s. After corneal burning, bevacizumab (12.5mg/mL) was topically administered three times per day (TB group) for two weeks or subconjunctivally injected on days 2 and 4 after cauterization (0.02mL; SB group). As negative controls, rats received 0.9% saline topically three times per day (TS group) or subconjunctivally on days 2 and 4 (0.02mL; SS group). Digital photographs of the cornea were taken 1 and 2 weeks after treatment and analyzed to determine the area of cornea covered by neovascularization as the percentage of corneal neovascularization. One week after treatment, the percentage of corneal neovascularization was significantly lower in the TB and SB groups than in the TS and SS groups (all P<0.05). Two weeks after treatment, the percentage of corneal neovascularization was significantly lower in the TB group than in the TS group (P<0.05). In all groups, the percentage of neovascularization was decreasing as time passed (all P<0.05). Topically administered bevacizumab has longer standing anti-angiogenic effect than subconjunctivally injected bevacizumab in corneal neovascularization following chemical injury in rats.

Influence of the extent of aortic replacement on survival and quality of life in patients with aortic root replacement

Background: The influence of the extent of aortic replacement on the aortic root replacement is unclear. We investigated the clinical outcomes of the aortic root replacement in terms of the extent of aortic replacement and evaluated quality of life (QOL) after surgery. Methods: Thirty six patients were enrolled in this study. The mean age was 59.0 ± 13.1 years. The 36 patients were divided into three groups according the extent of aortic replacement: 21 patients with replacement of the ascending aorta (SB), 7 patients with hemi-arch replacement (HB), and 8 patients with total aortic arch replacement (TB). Postoperative health-related QOL was evaluated by SF-36 Version 2. Results: The hospital mortality in the 36 patients was 2.8%. The patient (TB) died from fungal infection of the prosthetic graft. Three late deaths (8.6%) were observed: cerebral hemorrhage in one (SB), pneumonia in one (SB), and unknown in one (HB). The 5-year survival was 94.1 ± 5.7% in the SB group, 100% in the HB and 87.5 ± 11.7% in the TB groups, respectively (p=0.84). One patient (4.8%) in the SB group had an aorta-related event 7 years after surgery. No patinets had aorta-related events in both the HB and the TB groups. There was no significant difference in postoperative health-related QOL among the three groups. Conclusions: Aortic root replacement at our hospital achieved excellent results. Neither long-term survival nor postoperative QOL differed significantly according to the extent of aortic root replacement. We plan to extend the present study by in cluding a larger number of subjects. ACTA MEDICA NAGASAKIENSIA 58: 49−56, 2013

Measurement of ESAT6-induced IFNγ responses adjunct with CXCL9 increases the rate of diagnosis of active tuberculosis in an endemic region

Due to difficulties in direct diagnosis of Mycobacterium tuberculosis infection where site-specific specimens are not available, indirect methods of testing for infection are required. M. tuberculosis early secreted antigen target-6 (ESAT6) induced IFN-γ responses are specific, but do not differentiate between latent and active TB. The use of adjunct biomarkers for TB diagnosis has been proposed, such as the chemokines: CXCL9, CXCL10 and CCL2.ESAT6-induced IFN-γ CXCL9, CXCL10 and CCL2 was measured in whole blood cell supernatants of patients with pulmonary tuberculosis (PTB, n=36) and extrapulmonary TB (ETB, n=31) and compared with healthy endemic controls (EC, n=33).ESAT6-induced IFN-γ responses were positive in 32% of TB cases as compared with 15% of EC cases (p=0.048). ESAT6-induced CXCL9 responses were positive in 42% of TB cases and 15% of EC cases (p=0.006). ESAT6-induced-CXCL10 and -CCL2 responses did not discriminate between TB and EC groups. Measurement of IFN-γ or CXCL9 together diagnosed TB (53%) cases and was significant as compared with EC (p=0.014) cases. IFN-γ and CXCL10 together did not increase the number of TB cases diagnosed.Within TB groups, ESAT6-IFN-γ/CXCL9-based detection increased to 53% in PTB (p=0.031) and 54% in ETB (p=0.021), with comparable diagnosis in less severe extrapulmonary TB (L-ETB, 55%) and severe disseminated extrapulmonary TB (D-ETB, 50%). Given that 47% of TB cases remained undetected, this study shown that ESAT6-induced IFNγ and CXCL9 can support diagnosis, but must be supported by clinical correlation and other relevant investigations.

Risk and outcome of multidrug-resistant tuberculosis: vitamin D receptor polymorphisms and serum 25(OH)D

All India Institute of Medical Sciences and Rajan Babu Institute of Pulmonary Medicine and Tuberculosis, New Delhi, India. To investigate the association of vitamin D receptor (VDR) polymorphisms and serum 25(OH)D with susceptibility to, and response to treatment of, multidrug-resistant tuberculosis (MDR-TB) in comparison with drug-susceptible pulmonary TB (DS-PTB) and healthy controls. Cross-sectional study. A total of 897 participants from northern India were consecutively enrolled into three groups (MDR-TB 354, DS-PTB 338, controls 205). Genotypic and allelic frequencies of FokI, BsmI and TaqI VDR polymorphisms, and serum 25(OH)D, calcium and intact parathyroid hormone were measured in all participants. In those with active TB, disease severity, time to sputum smear and culture conversion were correlated with VDR genotype and biochemical parameters. FokI Ff genotype and TaqI t allele correlated positively with MDR-TB; Ff genotype and f allele of FokI frequency were higher in both TB groups. BsmI Bb genotype correlated inversely with MDR-TB. Serum 25(OH)D concentrations were significantly lowest in MDR-TB, correlating inversely with time to sputum smear conversion. VDR gene polymorphisms and hypovitaminosis D may predispose to MDR-TB. Lower serum 25(OH)D may increase time to MDR-TB sputum smear negativity.

Rebonding of unused brackets with different orthodontic adhesives

OBJECTIVE: To compare in vitro shear bond strength (SBS) of different orthodontic adhesives in bonding and repeatedly rebonding metal brackets, and to evaluate the bond failure site with the adhesive remnant index (ARI). METHODS: Specimens consisted of 90 extracted human first premolars, randomly divided into three groups (n=30). The adhesives Alpha Plast (AP), ConciseTM (CO) and TransbondTM XT (TB) were used in each group. Three SBS tests were performed, i.e., one at T0 (initial) and the other two at T1 and T2 (first and second rebondings, respectively), observing a 24-hour interval. The tests were performed in a Shimadzu AG-I (10kN) SBS testing machine, at a speed of 0.5 mm/min. RESULTS: SBS data were subjected to ANOVA, Tukey's test and Bonferroni test (p<0.05). For the ARI, the Kruskal Wallis test was performed, followed by the Dunn test. The results revealed that at T0 groups AP and CO showed SBS values that were near, but above TB values; and at T1 and T2, the highest SBS values were observed for the AP group, followed by the CO and TB groups. CONCLUSION: Statistically significant differences were found in SBS between groups AP, CO and TB during bonding and repeated rebondings of unused metal brackets, with group AP achieving the highest SBS value. Regarding ARI, adhesive AP exhibited bond failure at the enamel-adhesive interface, with a higher enamel fracture frequency.

The comparison of intraarticular morphine–bupivacaine and tramadol–bupivacaine in postoperative analgesia after arthroscopic anterior cruciate ligament reconstruction

To compare intraarticular morphine-bupivacaine and tramadol-bupivacaine as postoperative analgesics in patients undergoing arthroscopic anterior cruciate ligament (ACL) reconstruction. A randomized, double blind, controlled trial study of 60 ASA I-II patients undergoing arthroscopic ACL reconstruction was performed under general anesthesia. Patients were randomly allocated into three groups. The MB group (n = 20) received 10 mg morphine and 0.5% bupivacaine; the TB group (n = 20) received 100 mg tramadol and 0.5% bupivacaine; and the control group (n = 20) received isotonic saline intraarticularly in a total volume of 20 ml after the operation. Postoperative pain was assessed with visual analogue scale (VAS) at 0, 30, 60, 90 min and 2, 4, 6, 12, 24 h being at rest. Analgesic duration as defined was the time of first request for analgesics, the first 24 h analgesic consumption, time to unassisted ambulation, discharge time and incidence of side effects were also evaluated. The VAS scores at 30, 60, 90 min and 2, 4, 12, 24 h were significantly less in the MB and TB groups in comparison with the control group (P < 0.05); VAS scores also decreased significantly in the MB group compared to the TB group at 2, 4 and 24 h (P < 0.05). Analgesic duration was longer and analgesic consumption was substantially less in the MB group (P < 0.05). Moreover, unassisted ambulation time and discharge time were significantly shorter in the MB group than the TB and control groups (P < 0.05). Side effects were similar among the groups. Intraarticular morphine-bupivacaine provides effective pain relief, longer analgesic duration, less analgesic requirement, shorter unassisted ambulation and discharge time were compared with intraarticular tramadol-bupivacaine after ACL reconstruction arthroscopy. I.

Virulence Factors and Anti Fungal Sensitivity Pattern of Candida Sp. Isolated from HIV and TB Patients

The study comprised of 60 Candida spp., 50 isolates from HIV and TB positive individuals (immunocompromised) and 10 isolates from non-HIV and -TB patients (immunocompetent). Among the 60 Candidal isolates, 83.3% were identified as C. albicans, 11.6% as C. glabrata and rest 5% as C. krusei. There is no study in production pattern of extracellular enzymes of Candida spp. isolated from HIV and TB patients in comparison with non-HIV and -TB patients in India. The comparison of phospholipase activities showed that there was a significant difference between the groups at (P=0.001). The non-HIV and -TB groups of C. glabrata and C. krusei did not show detectable phospholipase activity when compared to the HIV and TB groups. The mean difference in the phospholipase activities of these two groups was significant (P=<0.001). Candida spp. of both the groups do not possess the ability to hydrolyze gelatin. All the strains possessed the ability to show alpha haemolysis. Even though it had shown alpha haemolysis, the significant difference in haemolytic activity was observed only in C. albicans (P=<0.001). None of the isolates from the two groups possessed the ability to hydrolyze gelatin. In the resistance profile of Candida spp., C. albicans of HIV and TB groups had shown resistance to fluconazole, Itraconazole, ketaconazole, nystatin but showed 100% sensitivity towards amphotericin-B. The isolates of C. krusei and C. glabrata showed no resistance to any of the drugs tested. In the case of, non-HIV and -TB patients the resistance pattern was low.

Relationship between Toll-Like Receptor 8 Gene Polymorphisms and Pediatric Pulmonary Tuberculosis

Objectives:Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population.Methods:The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects.Results:We did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p&gt; 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98,p= 0.007).Conclusions:Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control.

Relationship between toll-like receptor 8 gene polymorphisms and pediatric pulmonary tuberculosis.

Objectives: Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population. Methods: The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects. Results: We did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p > 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98, p = 0.007). Conclusions: Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control.

High Numbers of Interferon-.GAMMA.-Producing T Cells and Low Titers of Anti-Tuberculous Glycolipid Antibody in Individuals with Latent Tuberculosis

Latent tuberculosis infection (LTBI) is defined as an infection with Mycobacterium tuberculosis (MTB) without clinical, bacteriological, or radiological findings, and its early diagnosis is essential for eradication of tuberculosis. To identify LTBI, we measured the numbers of interferon-gamma producing T cells, based on the ELISPOT assay, and the antibody titers in the sera to tuberculous glycolipid antigen (TBGL-Ab). Seventeen culture-confirmed TB patients, 13 controls from TB endemic areas (EC) and 13 controls from TB non-endemic areas (NEC) were enrolled. Peripheral blood mononuclear cells (2.5 x 10(5) per well) were cultured on plates precoated with antibody against interferon-gamma. ELISPOT response was defined as positive when the MTB-specific antigen-containing wells showed at least 6 spots and twice numbers of spots than negative control wells. ELISPOT responses were positive in 15 (88%), 8 (62%) and 4 (31%) subjects of TB, EC and NEC groups, respectively. The ELISPOT data differ between TB and NEC groups (p < 0.01) but not between TB and EC groups. In contrast, TBGL-Ab titers were elevated (> 2.0 U/ml) in 12 TB patients (71%), but only in one subject (8%) each from EC and NEC groups. These results indicate the high prevalence of LTBI in EC. In conclusion, LTBI is associated with positive ELISPOT assay and the low titer of TBGL-Ab, while positive results both in ELISPOT and TBGL-Ab assays indicate active TB. The low titer of TBGL-Ab is a helpful marker to identify LTBI in ELISPOT-positive individuals in TB endemic areas.

Gonadal alterations in male eelpout ( Zoarces viviparus) exposed to ethinylestradiol and trenbolone separately or in combination

To evaluate the interaction between 17β-trenbolone (TB) and 17α-ethinylestradiol (EE2) in relevant environmental concentrations, male eelpout Zoarces viviparus were exposed in a flow-through seawater-system for 21 days to 5 ng l −1 EE2, 5 ng l −1 or 20 ng l −1 TB or to combinations of both compounds. The effects on hepatosomatic index (HSI), gonadosomatic index (GSI) and gonadal histology were studied. No significant effects on HSI were observed in any treatment; in contrast, decreased GSI was observed in males exposed to EE2 alone or in combination with TB compared to controls ( p < 0.05). The histology revealed that the males were in the beginning of spermatogenesis. Males from the control group and some from the TB groups showed tubules with cysts containing spermatogonia, spermatocytes and spermatids; however, some testes of males exposed to TB showed slight to moderate interstitial fibrosis. Nevertheless, the most severely affected were males exposed to EE2 showing marked interstitial fibrosis, necrosis of germinal cells and reduced number of spermatocytes and spermatogonia in the cyst. Likewise, increased tubule number and proportionally decreased tubule diameter were observed in the testis of all EE2 exposed groups ( p < 0.05). Finally, a similar tubule number was observed in males exposed to EE2 + 20 ng l −1 TB compared to control ( p > 0.05). This study shows that EE2 dramatically disrupts the spermatogenesis and low doses of 17β-trenbolone are unable to effectively counteract the morphological effects of EE2.

Immunoreactivity of five antigens of Mycobacterium tuberculosis in patients attending a public health care facility in an area with high endemicity for TB

The objective of this study was to evaluate people attending a primary health clinic in Rio de Janeiro, Brazil for immunoreactivity to five Mycobacterium tuberculosis antigens, as these antigens are markers of immune response and factors associated with active TB. The serum antibody titers of different categories of patients (defined by microbiological and radiological characteristics and by response to therapy on follow-up) to 38 kDa, 16 kDa, MPT64, ESAT-6 and MT10.3 antigens were determined blind with ELISA. Positive tests to each antigen were defined with ROC analysis. OR were calculated for factors associated with humoral response in patients with active TB. A total of 201 patients underwent serological testing. Patients with confirmed active TB responded more frequently to MPT64 (44%), 16 kDa (37.7%) and 38 kDa (36.1%). ESAT-6 and MT10.3 were also able to distinguish people in TB groups from controls. TB infected subjects responded less frequently to ESAT-6 and MT10.3 (3.7% and 11%, respectively). Sensitivity and specificity to all antigens combined were 58.4% and 60.7%, respectively. Reactivity to 38 kDa and to MPT64 was more likely among alcohol users OR 2.61 (95%CI;1.05-6.94) and OR 3.27 (95%CI;1.33-8.15), respectively. 16 kDa antigen elicited a more protective response among smokers, OR 0.29 (95%CI; 0.10-0.83). It was concluded that reactivity to all antigens tested represented markers of active disease. ESAT-6 and MT10.3 could not be identified as markers of TB infection in this community. Sensitivity was higher to all antigens combined, but at a cost of lower specificity. Interestingly, among factors associated with positive immunoreactivity, alcohol use and smoking seem to polarize the humoral response in different directions. This finding deserves further investigation.

Consumption of three supplements with identical micronutrient content in pregnant Mexican women

The objective of this analysis was to compare consumption of three nutritional supplements with identical micronutrient content for pregnant women. Communities (18 per supplement) were randomly assigned to receive a fortified beverage (FB, 54 g of milk‐based powder dissolved in a glass of water), tablets (TB, 1 tablet) or Sprinkles (SK, 1 g dissolved in food). Pregnant women, beneficiaries of the Oportunidades program were recruited before 25 wk pregnancy. Supplements were delivered daily (6 mo) then weekly during pregnancy until 3 m postpartum (pp). Compliance and consumed amount (0, 1 for TB; 0, ¼, ½, ¾, 1 of portion served for FB and SK) was recorded. Appropriate statistical analyses for cluster randomized trials were used. 715 women were recruited (FB n=233; TB n=238; SK n=244). Supplement was consumed for 180±39 days and there was no difference in the mean proportion of days offered that any supplement was consumed between groups (91.0%). The mean proportion of days that the complete dose was consumed was significant lower in the FB group (86.4%) than the TB (91.1%) or SK (90.8%) groups. The proportion of days offered that any supplement was consumed was significantly higher pp than during pregnancy in the FB (+3.6%) and TB (+2.9%) groups, but there was no difference in the SK group (+1.2%). Despite the controlled nature of this study, consumption of the entire dose was lower among women consuming the FB.The Oportunidades program financed this study and holds the rites to the data presented.

Effects of tuna bone and herbal extract on bone metabolism in ovariectomized rats

This study was conducted to examine the effects of herb extract addition on bone metabolism of ovariectomized (OVX) rats fed a diet with tuna bone as a source of calcium. The experimental groups were sham–control (CaCO 3 [CC]), OVX-CC (OVX-control), OVX–CC + herb extract, OVX–tuna bone powder (TB), OVX–tuna bone powder + herb extract, OVX–citrated tuna bone powder (CTB), and OVX–citrated tuna bone powder + herb extract (CTBH). The herb extract included Rehmanniae radix and Angelicae gigantis radix, following the prescribed theories of Oriental herb medicine. In the OVX-CTBH group, the level of fecal (33.6%) and urinary calcium excretion (45.8%) greatly decreased compared with the TB groups. Osteocalcin concentrations were significantly lower in the OVX-CC group and higher in the OVX-CTB group. The deoxypyridinoline value was significantly influenced by ovariectomy. It was elevated in all OVX groups compared with the sham group, and it was reduced by 12.8% in rats supplemented with the herb extract. The bone density value per 100-g body weight was lowest in the TB group, and it was higher in the tuna bone powder + herb extract, CTB, and CTBH groups. We concluded that TB can be a good calcium source, and it was effective in maintaining skeletal metabolism of OVX rats when it was fed in the form of citrated or herb extract–supplemented diets.

PET-based mapping of lymph node spread in lung cancer (NSCLC)

7187 Background: The aim of this study was to investigate the pattern of mediastinal nodal involvement in NSCLC in relation to primary tumour location using PET imaging. Methods: A database of 800 patients scanned for suspected lung cancer was studied. The locations of the primary tumour and of any nodal metastases were noted. Nodes were considered positive if the uptake was significantly raised relative to the surrounding region. The study was intended to generate hypotheses for potential areas of research. Results: UZ = upper zone, MZ = mid-zone, LZ = lower zone, IH = ipsilateral hilar, SC = subcarinal, TB = tracheobronchial, PT = paratracheal, CH = contralateral hilar, AP/SM = Aortopulmonary /Superior Mediastinal, N+ = node positive. In IHN positive patients 14%, 6% and 23% respectively of UZ, MZ and LZ tumours showed increased activity in the SCN, 11%, 6% and 5% in the TBN and 17%, 7% and 14% in the CHN. In IHN negative patients the corresponding figures were 18%, 27% and 70% for SCN, 14%, 18% and 0% for TBN and 21%, 18% and 10% for CHN. Increased activity was seen in the TBN and SCN of 24 and 55 patients respectively, only 5 of these in the same patients. Conclusions: Hypotheses consistent with these results are: 1. IHN involvement is similar regardless of primary tumour location. 2. SC nodal involvement is more common with LZ tumours. 3. TB nodal involvement is more common with UZ tumours. 4. The CH nodes are more commonly involved than other nodal areas more frequently sampled or treated in routine clinical practice. This could mean that some NSCLC patients are significantly undertreated. 5. The TB and SC node groups might represent 2nd station nodes of distinct lymphatic pathways from IH nodes. These results give valuable information for further research into patterns of nodal spread in NSCLC aimed at improving radiotherapy and surgical planning. No significant financial relationships to disclose.

Growth performance, muscle structure and flesh quality in out-of-season Atlantic salmon ( Salmo salar) smolts reared under two different photoperiod regimes

This experiment on farmed Atlantic salmon ( Salmo salar L.) was designed to investigate the effect of postsmolt photoperiodic regime on growth performance, muscle cellularity, and flesh quality in out-of-season produced smolts. The offspring from three pairs of half-sibling crosses were studied to provide information on the genetic variability of treatment effects. In both treatments, parr were initially held on 10-h light/14-h dark for 6 weeks from the 27 September until the 8 November 2000, and then transferred to continuous light. All fish were transferred from fresh to salt water on the 12 January. In treatment A (TA), smolts were transferred from continuous light to ambient short days (23 January 2001), whereas in treatment B, (TB) smolts were continued on 24-h light until natural day length approached the seasonal maximum (1 June 2001). Fish were reared in outdoor saltwater tanks and transferred to 5×5×5 m sea cages at the Feed Trial Unit, Loch Duich, Scotland on the 21 April 2001. In the 6–9 months following smoltification, the growth performance of 835 fish held on continuous light (TB) was superior to that of 715 fish returned to short days (TA). Thereafter, in five out of the six families, growth performance was higher in TA than TB groups, such that the average bodyweight of families was no different between treatments over the production cycle. Bodyweight, however, showed significant family effects and a significant treatment×family interaction. The cellularity of the fast myotomal muscle was determined in a subset of fish sampled 2 weeks after the lights were switched-off in the TB groups (14 June 2001) and when a commercial harvest weight was achieved (5 September 2002). In June 2001, the average bodyweight was 80% higher, and the number of muscle fibres per myotomal cross-section was 43.5% greater in TB than TA groups. Muscle fibre recruitment was subsequently higher in the TA than TB groups such that the maximum fibre number (5.88×10 5) was similar between treatments. However, the density of fast muscle fibres (fibres mm −2 muscle cross-sectional area) remained 7.5% higher for TB (82.1±1.3, n=46) than TA (76.4±1.1, n=53) groups (mean±S.E.; P<0.05). Firmness was assessed in fillets 3 days postmortem using an instrumental texture method (TA-Hdi Texture Analyser, Stable Microsystems). The total work done to shear tissue samples (mJ) was 8.3% higher in TB (432±11, n=46) than TA (399±7, n=53) groups (mean±S.E.; P<0.05). At the family level, there was a significant correlation between the total shear work (Sw) and muscle fibre density (Fd), explaining 49% of the total variation. Individual growth ( α) rate was investigated using a statistical model. For the relatively modest growth rates achieved in the trial, there was no significant correlation between α and either Sw or Fd. The concentration of muscle lipid was 9.1% higher in the TA (14.7% dry mass) than TB groups (13.3% dry mass). Muscle astaxanthin concentration was independent of treatment but showed significant differences between families. It was concluded that continuous light treatment immediately following seawater transfer produced small but significant effects on muscle growth over the production cycle resulting in a higher fibre density and a firmer flesh. The magnitude of such effects is likely to be critically dependent on the timing of the harvest.

ADVANCED GLYCATION END PRODUCT LEVELS IN EYE LENSES, AORTA, AND TAIL TENDON IN TRANSPLANTED DIABETIC INBRED LEWIS RATS1

Pancreatic islet transplantation in diabetes, by restoring euglycemia, should in time correct the abnormal accumulation of advanced glycation end products (AGEs) over target tissues, thus delaying the development of late diabetic complications. Homologous islet transplantation was performed in inbred Lewis rats 15 days (TA), 4 months (TB), and 8 months (TC) after streptozotocin diabetes. Group TA was studied for 12 months and groups TB and TC were studied for 4 months after transplantation. Normal (N) and diabetic (D) rats formed the control groups. Metabolic control in the transplant (T) groups was evaluated by oral glucose tolerance test. Blood glucose, glycated hemoglobin, and body weight were determined in all groups. AGE levels were determined by spectrofluorometry in eye lens proteins and by ELISA in aortic and tail tendon collagen. T groups showed normal oral glucose tolerance tests and metabolic parameters. The latter were altered in all D groups (P<0.005 to P<0.0001 versus N and T groups). AGEs were increased in the D groups (P<0.05 to P<0.001) versus the N groups. AGEs in the TA and TB groups were not different from those of the N groups but were significantly reduced (P<0.05 to P<0.001) when compared with those of the D groups. In the TC group, eye lens AGEs were significantly elevated (P<0.001) or significantly reduced (P<0.01) when compared with those of the N or D groups, respectively. Aortic collagen AGEs were elevated (P<0.01) by comparison with those of the N groups and not statistically different from those of the D groups. Tail tendon collagen AGE levels lay between those of the N and D groups, without reaching a statistical significance. These results indicate that primary and early secondary (groups TA and TB) but not late secondary (group TC) islet transplantations are capable of blocking or reducing an abnormal accumulation of AGEs, thus confirming the importance of preventive transplantation therapies.

Antituberculosis treatment: increasing evidence for drug effects on innate cellular immunity.

Over the past several years we have gathered increasing evidence suggestive of direct effects of one or more of the currently used antituberculosis (TB) drugs on various immune parameters in patients with pulmonary TB. Throughout the studies, the standard regimen for treatment of tuberculosis consisted of rifampin, isoniazid, pyrazinamide, and ethambutol given for 2 months during the intensive phase of treatment followed by isoniazid and rifampin given for 4 months. The mean duration of anti-TB treatment at the time of blood collection from patients did not differ significantly between the TB and human immunodeficiency virus-infected TB (HIV/TB) groups in any of the studies. Some of the effects on neutrophil function and receptor expression were contrary to what one might expect given that the resolution of active TB would be associated with recovery of function and normalization of receptor expression. Most of this evidence is inferred from crosssectional studies conducted on TB patients, with only some support from longitudinal data. The primary objective in all of these studies was not the evaluation of the role of anti-TB treatment, and findings reported with respect to drug treatment were incidental to the hypothesis being tested in each individual study. Nonetheless, the findings highlight some important issues that deserve consideration.