MHV68 complement regulatory protein facilitates MHV68 replication in primary macrophages in a complement independent manner

Murine gammaherpesvirus-68 (MHV68) is genetically related to human Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus and provides a tractable model to study gammaherpesvirus-host interactions in vivo and in vitro. The MHV68-encoded v-RCA product inhibits murine complement activation and shares sequence homology with other virus and host regulators of complement activation. Here we show that v-RCA is required for efficient MHV68 replication in primary murine macrophages, but not in murine embryonic fibroblasts. v-RCA-deficient MHV68 mutant viruses display defects in viral DNA synthesis in infected macrophages. Importantly, attenuated growth of v-RCA mutant viruses is not rescued in macrophages lacking critical components of the complement system including C3, indicating that the macrophage-specific role of v-RCA in MHV68 replication is complement-independent. This contrasts with the situation in vivo in which attenuated neurovirulence of v-RCA mutant viruses is rescued in C3-deficient mice. This study shows a novel, complement independent cell-type-specific function of a gammaherpesvirus RCA protein.     

Discrepancy between training,competition and laboratory measures of maximum heart rate in NCAA division 2 distance runners

A percentage of either measured or predicted maximum heart rate is commonly used to prescribe and measure exercise intensity. However, maximum heart rate in athletes may be greater during competition or training than during laboratory exercise testing. Thus, the aim of the present investigation was to determine if endurance-trained runners train and compete at or above laboratory measures of ''maximum'' heart rate. Maximum heart rates were measured utilising a treadmill graded exercise test (GXT) in a laboratory setting using 10 female and 10 male National Collegiate Athletic Association (NCAA) division 2 cross-country and distance event track athletes. Maximum training and competition heart rates were measured during a high-intensity interval training day (TR HR) and during competition (COMP HR) at an NCAA meet. TR HR (207 ± 5.0 b·min^-1; means ± SEM) and COMP HR (206 ± 4 b·min^-1) were significantly (p < 0.05) higher than maximum heart rates obtained during the GXT (194 ± 2 b·min^-1). The heart rate at the ventilatory threshold measured in the laboratory occurred at 83.3 ± 2.5% of the heart rate at VO₂ max with no differences between the men and women. However, the heart rate at the ventilatory threshold measured in the laboratory was only 77% of the maximal COMP HR or TR HR. In order to optimize training-induced adaptation, training intensity for NCAA division 2 distance event runners should not be based on laboratory assessment of maximum heart rate, but instead on maximum heart rate obtained either during training or during competition.

Key points

• A percentage of maximum heart rate is commonly used to prescribe and measure exercise intensity. However, maximum heart rate may be greater during competition or training than during laboratory exercise testing.
• Heart rates during training and competition were significantly higher than maximum heart rates obtained during laboratory exercise testing.
• To optimize training-induced adaptation, training intensity for NCAA division 2 distance event runners should not be based on laboratory assessment of maximum heart rate, but instead on maximum heart rate measure obtained either during training or during competition.

Key words: Competition, heart rate, laboratory, performance, running, training     

Obesity Surgery in the Philippines: Experience in a Private Tertiary Care Hospital for Years 2002 to 2004

Background Information on experience in bariatric surgery in the Asia-Pacific region is minimal: hence the need for more reports from this area. Methods The procedures of bariatric surgery and outcome as part of a weight management program in a tertiary care private hospital in the Philippines is reported from years 2002 to 2004. 50 patients were included, of which 60% underwent laparoscopic adjustable gastric banding (LAGB) and 40% Roux-en- Y gastric bypass (RYGBP). Results There were more females than males (64% vs 36%) with the mean age 38 ± 13.1 years. Initial mean BMI was 46.2 kg/m2, which decreased to 27.0 kg/m² in 1 year. Initial mean weight was 126.7 ± 25.4 kg, of which the 1 year weight loss was 32.3 kg for the morbidly obese and 58.0 kg for the super obese. %EWL at 1 year was 30.2%. There was greater weight loss with RYGBP compared to LAGB at 1 year (43.5 kg vs 30.2 kg). There was no mortality, and early complications were: wound infection (2/50 or 4%), and 1/50 or 2% each for pneumonia, dehydration, gastritis, and leakage. Late complications were: band slippage (2/20 or 10%), stomal stenosis (1/20 or 5%), and ventral hernia (1/5 or 20%). Conclusion Bariatric surgery is safe with a low complication rate and the outcome was similar to the reported data from Asia and the western world.     

Metastatic Colorectal Cancer: Survival Comparison of Hepatic Resection Versus Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background

Liver resection has long been considered the standard of care for resectable colorectal hepatic metastases (HM). Patients with colorectal peritoneal surface disease (PSD) are now also being treated with aggressive therapy in the form of cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

A retrospective comparison of optimally-treated colorectal cancer patients with HM or PSD obtained from prospectively maintained databases (1991–2010).

Results

Liver resection was performed on 179 patients with HM, while 93 PSD patients received a complete cytoreduction followed by HIPEC. Patients differed in terms of age, performance status, site of primary cancer, T stage, and the use of perioperative chemotherapy. Five-year overall survival for HM patients was 36 %, with a median survival of 46 months, compared with 26 % and 34 months in patients with PSD (p = 0.024). When stratified by resection status, R0 HM (n = 170) and R0 PSD (n = 48) patients had similar median survival (49 vs. 41 months; p = 0.39). Median survival following R1 resection was also similar among HM (n = 9) and PSD (n = 45) patients (28 vs. 23 months; p = 0.68). Multivariate analysis identified distinctly different independent prognostic factors between HM and PSD patients. Major morbidity was 21 and 23 % (p = 0.88), while mortality was 3.9 versus 5.4 % (p = 0.55) in the HM and PSD patients, respectively.

Conclusion

Colorectal HM and PSD are distinct biologic diseases with different presentations and unique prognostic factors. However, long-term survival following CS/HIPEC is comparable to liver resection when stratified by completeness of resection. Furthermore, perioperative morbidity and mortality are similar.     

Antibody and cellular immune responses to microfilarial antigens in ferrets experimentally infected withBrugia malayi

Eleven of 15 ferrets experimentally infected withBrugia malayi became amicrofilaremic after a brief patency; only four ferrets remained patent after 6 months of infection and two of these ferrets developed a high, persistent microfilaremia. Blastogenic responses of peripheral blood lymphocytes to antigens of microfilariae (mf), assayed in vitro, demonstrated an antigen sensitivity at prepatent, patent and postpatent periods of infection. Lymphocytes from ferrets with high microfilaremia had elevated background responses in culture which were directly correlated with the number of circulating mf. This background response was attributed to antigenic stimulation by mf present in the lymphocyte cultures; addition of mf to cultures of lymphocytes from postpatent ferrets induced responses equivalent to those observed in microfilaremic ferrets. Lymphocyte responses to the mitogen, concanavalin A, did not differ significantly among microfilaremic, amicrofilaremic and uninfected ferrets. Antibody in IgG to antigens of mf measured by ELISA and by immunoblots from SDS-PAGE showed similar patterns of response in ferrets which became amicrofilaremic and in the few ferrets which remained microfilaremic. Prausnitz-Kustner tests demonstrated no consistent differences in titers to microfilarial antigens between patent and amicrofilaremic ferrets. The results suggest a high level of immune responsiveness to antigens of mf in infected ferrets with no evidence of immunosuppression associated with prolonged microfilaremia or of major changes in immune responses with development of amicrofilaremic infections.     

Outcome analysis of arthroscopic treatment of partial thickness rotator cuff tears

Background:

Partial thickness rotator cuff tears occupy an important position in the spectrum of rotator cuff disease. The development of a more comprehensive classification has been sought to address both the tear location and extent, which may influence clinical results. The purpose of this study is to classify partial thickness rotator cuff tears according to the arthroscopic findings and to evaluate the clinical outcomes after arthroscopic repair of partial thickness tears.

Materials and Methods:

One hundred and two patients had arthroscopic treatment of partial thickness rotator cuff tears. The inclusion criterion for the study was a partially torn supraspinatus tendon involving articular or bursal side, verified by direct arthroscopic visualization. Outcome analysis was exclusively applied to patients who underwent transtendon repair, using the shoulder index of American Shoulder and Elbow Society and the University of California Los Angeles (UCLA) rating system.

Results:

Partial thickness rotator cuff tears were divided into five groups according to arthroscopic findings. There was significant improvement after surgery in all parameters of clinical evaluation in the tears that warranted repair. Arthroscopic repair in situ (transtendon technique) may be the preferred option in unstable partial thickness tear.

Conclusion:

The proposed classification system may assist decision making in the treatment of partial thickness rotator cuff tears.     

Metabolism of androgens in various histological variants of bone tumors]

The role of androgens in human normal and neoplastic bone tissues is still unclear. The paper presents data on metabolism of androgens in homogenates of malignant (osteosarcoma, chondrosarcoma, Ewing and giant cell) and benign primary tumors from 46 male and female patients aged 14-58 years. Using two substrates (testosterone and 5 alpha-dihydrotestosterone) for the first time are shown activities of main enzymes of androgen metabolism in all tumor types. 5 alpha-reductase activity was similar in all tumors, 3 alpha-hydroxysteroid dehydrogenase activity was the highest while that of 17 beta-hydroxysteroid dehydrogenase was the lowest. Unknown metabolite(s) of 5 alpha-dehydrotestosterone was discovered which may be hydroxy-metabolites of 5 alpha-androstane-3 beta, 17 beta-diol. A principal scheme of androgen metabolism in human neoplastic tissue is proposed.