Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses

Hepatic fibrosis represents the generalized response of the liver to injury and is characterized by excessive deposition of extracellular matrix. The cellular basis of this process is complex and involves interplay of many factors, of which cytokines are prominent. We have identified divergent fibrosing responses to injury among mouse strains and taken advantage of these differences to examine and contrast T helper (Th)-derived cytokines during fibrogenesis. Liver injury was induced with carbon tetrachloride, fibrosis was quantitated, and Th1/Th2 cytokine mRNAs measured. Liver injury in BALB/c mice resulted in severe fibrosis, whereas C57BL/6 mice developed comparatively minimal fibrosis. Fibrogenesis was significantly modified in T and B cell-deficient BALB/c and C57BL/6 severe combined immunodeficient (SCID) mice compared with wild-type counterparts, suggesting a role of Th subsets. Fibrogenic BALB/c mice exhibited a Th2 response during the wounding response, whereas C57BL/6 mice displayed a Th1 response, suggesting that hepatic fibrosis is influenced by different T helper subsets. Moreover, mice lacking interferon γ, which default to the Th2 cytokine pathway, exhibited more pronounced fibrotic lesions than did wild-type animals. Finally, shifting of the Th2 response toward a Th1 response by treatment with neutralizing anti-interleukin 4 or with interferon γ itself ameliorated fibrosis in BALB/c mice. These data support a role for immune modulation of hepatic fibrosis and suggest that Th cytokine subsets can modulate the fibrotic response to injury.     

Glyceraldehyde-3-phosphate dehydrogenase: Nuclear translocation participates in neuronal and nonneuronal cell death

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein levels increase in particulate fractions in association with cell death in HEK293 cells, S49 cells, primary thymocytes, PC12 cells, and primary cerebral cortical neuronal cultures. Subcellular fractionation and immunocytochemistry reveal that this increase primarily reflects nuclear translocation. Nuclear GAPDH is tightly bound, resisting extraction by DNase or salt treatment. Treating primary thymocytes, PC12 cells, and primary cortical neurons with antisense but not sense oligonucleotides to GAPDH prevents cell death. Because cell-death-associated nuclear translocation of GAPDH and antisense protection occur in multiple neuronal and nonneuronal systems, we propose that GAPDH is a general mediator of cell death and uses nuclear translocation as a signaling mechanism.     

Seminal papers in spinal surgery

Evidence based medicine should underpin the practice of all orthopaedic surgeons. Spinal pathology should be considered in the differential diagnosis for pain in every upper and lower limbs region and an understanding of spinal anatomy and physiology is vital in the management of the trauma patient.We present ten key articles, which have been selected for their impact within the field. They encompass trauma, degenerative, inflammatory, deformity and emergency spinal disorders. The articles range from level I randomized control trials to level V expert opinion. An understanding of their methodology and key findings should be part of the core knowledge encompassing spinal surgery and will, in particular, be of benefit for those preparing for final professional examinations.     

The effects of soft-start vs continuous-light polymerization on microleakage in Class II resin composite restorations

PURPOSE: Despite the different light sources and polymerization techniques developed to eliminate it, microleakage of resin composite still remains a problem. This in vitro study was designed to compare the effects of exponential mode soft-start polymerization with those of standard and high-intensity continuous light polymerization on microleakage in Class II resin composite restorations. MATERIALS AND METHODS: Standardized Class II cavities (4 mm wide, 4 mm long, 5 to 6 mm high, 2 mm deep) were prepared in 50 extracted human molars. Specimens were divided into 5 groups (n = 10) and restored using the same hybrid resin composite (Z250), but separately polymerized by one of five different methods: group 1: continuous halogen light polymerization for 40 s; group 2: continuous high-intensity halogen light polymerization for 10 s; group 3: exponential mode soft-start halogen light polymerization for a total of 40 s; group 4: continuous LED light polymerization for 40 s; Group 5: exponential mode soft-start LED light polymerization for a total of 40 s. All specimens were thermocycled for 1000 cycles at 5 degrees C to 55 degrees C and then placed in 0.5% basic fuchsin dye for 24 h. Specimens were then rinsed, embedded in resin and sectioned longitudinally. Dye penetration at occlusal and cervical margins was rated using a scale of 0 to 4. Data was analyzed using Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: Significantly lower marginal leakage was recorded with exponential mode soft-start polymerization when compared to continuous light polymerization. No significant differences in microleakage were observed between LED and halogen light polymerization. CONCLUSION: Within the limits of this in vitro study, the use of the soft-start exponential mode of LED and/or halogen light units in the polymerization of hybrid composite was found to produce significantly lower microleakage at both occlusal and cervical margins when compared to continuous light polymerization methods.     

Neonatal necrotizing enterocolitis

PURPOSE: A retrospective, 12-year review of neonatal necrotizing enterocolitis was undertaken at a county hospital, with emphasis on presentation signs and symptoms. METHODS: Eighty-two patients with presence of intramural air were included in the study. The following signs and symptoms were studied: evidence of respiratory distress, use of umbilical catheters, white blood cell count and temperature at presentation, time interval from birth to diagnosis and time interval from diagnosis to operative intervention, presence of intramural air, air in biliary tree or free air, changes in abdominal girth, and presence of occult or gross blood in stools. Comparison was done among infants who had surgical or medical treatment, premature and full-term infants, and infants who had neonatal necrotizing enterocolitis less than or more than 20 days after birth. RESULTS: Eleven patients had a fatal outcome, with an overall survival of 87 percent. Sixty-four patients were treated medically and 18 had operative treatment. Mortality of the surgically treated group was 44 percent. Neonates who had surgical intervention had a left shift of the white blood cell count more commonly present, and all had documented abdominal distention. There were 62 premature and 20 full-term neonates in the group. Full-term neonates developed neonatal necrotizing enterocolitis earlier after birth (5.3 days compared with 15.3 days in the premature neonate group). Full-term neonates had a better prognosis in our series. Presentation of symptoms more than 20 days after birth did not change outcome. CONCLUSION: Our results reflect the experience of a community-based hospital. Clinical acumen remains the cornerstone of diagnosis and management.     

Risk factors for the development of acute lung injury in patients with infectious pneumonia

ABSTRACT: INTRODUCTION: Although pneumonia has been identified as the single most common risk factor for acute lung injury (ALI), we have a limited knowledge as to why ALI develops in some patients with pneumonia and not in others. The objective of this study was to determine frequency, risk factors, and outcome of ALI in patients with infectious pneumonia. METHODS: A retrospective cohort study of adult patients with microbiologically positive pneumonia, hospitalized at two Mayo Clinic Rochester hospitals between January 1, 2005, and December 31, 2007. In a subsequent nested case-control analysis, we evaluated the differences in prehospital and intrahospital exposures between patients with and without ALI/acute respiratory distress syndrome (ARDS) matched by specific pathogen, isolation site, gender, and closest age in a 1:1 manner. RESULTS: The study included 596 patients; 365 (61.2%) were men. The median age was 65 (IQR, 53 to 75) years. In total, 171 patients (28.7%) were diagnosed with ALI. The occurrence of ALI was less frequent in bacterial (n = 99 of 412, 24%) compared with viral (n = 19 of 55, 35%), fungal (n = 39 of 95, 41%), and mixed isolates pneumonias (n = 14 of 34, 41%; P = 0.002). After adjusting for baseline severity of illness and comorbidities, patients in whom ALI developed had a markedly increased risk of hospital death (ORadj 9.7; 95% CI, 6.0 to 15.9). In a nested case-control study, presence of shock (OR, 8.9; 95% CI, 2.8 to 45.9), inappropriate initial antimicrobial treatment (OR, 3.2; 95% CI, 1.3 to 8.5), and transfusions (OR, 4.8; 95% CI, 1.5 to 19.6) independently predicted ALI development. CONCLUSIONS: The development of ALI among patients hospitalized with infectious pneumonia varied among pulmonary pathogens and was associated with increased mortality. Inappropriate initial antimicrobial treatment and transfusion predict the development of ALI independent of pathogen.     

Effect of LED curing modes on the microleakage of a pit and fissure sealant

PURPOSE: To evaluate in vitro the curing effect of a very high intensity light-emitting diode (LED) unit and a conventional LED unit (including "soft-start" modes) on the microleakage of a pit and fissure sealant. METHODS: 120 intact caries-free human molars were randomly divided into six groups (n=20), sealed with Fissurit-F and polymerized using either a conventional halogen unit (Optilux) (Control group) in standard mode (40 seconds @ 600 mW/cm2); a very high intensity LED unit (Mini LED) in fast (10 seconds @ 1,100 mW/cm2) or soft-start mode (pulse mode: ten 1-second flashes @ 1,100 mW/cm2; exponential mode: exponential increase from 0 to 1,100 mW/cm2 within 10 seconds followed by 10 seconds @1,100 mW/cm2); or a conventional LED unit (Elipar Freelight) in standard (40 seconds @ 400 mW/cm2) or exponential mode (exponential increase from 0 to 400mW/cm2 within 12 seconds followed by 28 seconds @ 400 mW/cm2). Restored specimens were stored in distilled water at 37 degrees C for 24 hours. Specimens were then immersed in a 0.5% fuchsin dye solution for 24 hours, with half of the specimens from each group subjected to thermocycling (5/55 degrees C; x 1000) prior to dye immersion. After removal from the dye solution, specimens were sectioned and the degree of dye penetration scored. Data was statistically analyzed using the Kruskal-Wallis H test and the Mann-Whitney U-test (P< 0.05). RESULTS: There was no statistically significant difference in microleakage of pit and fissure sealant polymerized using various curing techniques. Thermocycling regimens had no effect on either LED- or halogen-cured specimens.     

The foot in systemic disease: management of the patient with rheumatoid arthritis or diabetes mellitus

The foot is commonly affected in systemic diseases such as rheumatoid arthritis and diabetes mellitus. Treating patients who suffer with foot pathology secondary to systemic diseases requires a multidisciplinary approach, following the principles outlined within this review. There is little high level evidence in this field, such as prospective controlled clinical trials, hence much of what we know and practise is based upon the expert opinion of key individuals in specialist centres, to whom we owe a great debt.