Interleukin-17 family and IL-17 receptors.

Interleukin-17 (IL-17) is a pro-inflammatory cytokine secreted by activated T-cells. Recently discovered related molecules are forming a family of cytokines, the IL-17 family. The prototype member of the family has been designated IL-17A. Due to recent advances in the human genome sequencing and proteomics five additional members have been identified and cloned: IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. The cognate receptors for the IL-17 family identified thus far are: IL-17R, IL-17RH1, IL-17RL (receptor like), IL-17RD and IL-17RE. However, the ligand specificities of many of these receptors have not been established. The IL-17 signaling system is operative in disparate tissues such as articular cartilage, bone, meniscus, brain, hematopoietic tissue, kidney, lung, skin and intestine. Thus, the evolving IL-17 family of ligands and receptors may play an important role in the homeostasis of tissues in health and disease beyond the immune system. This survey reviews the biological actions of IL-17 signaling in cancers, musculoskeletal tissues, the immune system and other tissues.

Short-segment pedicle instrumentation. Biomechanical analysis of supplemental hook fixation.

STUDY DESIGN: This biomechanical study of fractures in cadaver vertebrae used specially designed pedicle screws to determine screw strains during loading of two different fixation constructs. OBJECTIVES: The authors determined the relative benefit of adding offset sublaminar hooks to standard pedicle screw constructs to reduce screw bending moments and prevent fixation failure and sagittal collapse. SUMMARY OF BACKGROUND DATA: Clinical studies have demonstrated a high incidence of early screw failure in short-segment pedicle instrumentation constructs used to treat unstable burst fractures. Strategies to prevent early construct failure include longer constructs, anterior strut graft reconstruction, and use of offset sublaminar hooks at the ends of standard short-segment pedicle instrumentation constructs. METHODS: Human cadaver spines with an L1 burst fracture were instrumented with a standard short-segment pedicle instrumentation construct using specially instrumented pedicle screws. Mechanical testing was carried out in flexion, extension, side bending, and torsion, and stiffness and screw bending moments were recorded. Offset hooks were applied initially, then removed and testing repeated. Stiffness data were compared to intact and postfracture results, and between augmented and standard constructs. RESULTS: Addition of offset laminar hooks, supralaminar at T11 and infralaminar at L2, to standard short-segment pedicle instrumentation constructs increased stiffness in flexion by 268%, in extension by 223%, in side bending by 161%, and in torsion by 155% (all were significant except torsion). Sublaminar hooks also reduced pedicle screw bending moments to roughly 50% of standard in both flexion and extension (P < 0.05). CONCLUSIONS: Supplemental offset hooks significantly increase construct stiffness without sacrificing principles of short-segment pedicle instrumentation, and absorb some part of the construct strain, thereby reducing pedicle screw bending moments and the likelihood of postyield deformation and clinical failure.

Lumbar pedicle screw salvage: pullout testing of three different pedicle screw designs.

Although research has determined pedicle screw pullout strengths for normal and osteoporotic bone, this study provides the first biomechanical analysis of pedicle screw salvage. Ten fresh frozen human lumbar spines were separated into individual vertebrae; 6.0 x 40 mm pedicle screws were placed in each pedicle; and an axial pullout test was performed to establish control values. Ultimate load, initial stiffness, work, and displacement data were calculated. Each vertebra was reinstrumented with one 7.0 x 40 mm variable screw placement (VSP) screw side by side with either a 7.0 mm Cotrel Dubousset sacral screw (CD) or a 7.0 mm Compact Cotrel Dubousset pedicle screw (CCD). Pullout tests were repeated and compared to control data for individual screws and for each VSP/CD or VSP/CCD pair. Vertebrae were then reinstrumented with 8.0 mm VSP and CD screws and paired pullouts repeated. Statistical analysis was carried out using a paired T test. Analysis of intravertebral and intergroup variation of controls was carried out using a Paired Two Sample T test. The 7.0 mm CCD screws restored pullout strength to 62% of control pullouts; 7.0 mm CD screws, to 85%; 7.0 mm VSP screws, to 99%; 8.0 mm CD screws, to 109%; and 8.0 mm VSP screws, to 148% of control pullouts. The 7.0 mm VSP salvage screws exceeded CD screws in ultimate load by 22.5% (p < .03) and CCD screws by 33.5% (p < .05). The 8.0 mm salvage screws significantly increased pullout relative to both controls and all 7.0 mm salvage screws, with 8.0 mm VSP exceeding 8.0 mm CD by 34% (p < .03). Initial stiffness was also significantly greater in VSP than CD screws. Although applied in a smaller number of vertebrae, 8.0 mm screws sufficiently outperformed smaller screws to provide statistically significant differences. The 7.0 mm VSP salvage screws restored pullout to control levels, roughly equivalent to outcomes previously obtained with unpressurized polymethylmethacrylate (PMMA).

Sub-axial cervical dissociation. Anatomic and biomechanical principles of stabilization.

Four fresh human cadaver spines were analyzed during and after disruptive hyperflexion and hyperextension to characterize the pathoanatomy of three-column cervical dissociation. In both flexion and extension, the posterior longitudinal ligament and facet capsules provided the greatest resistance to disruption. At low loading rates, all structures failed through the soft tissues. Three-column disruption caused by either pure flexion or extension resulted in marked elongation of the neural axis, inconsistent with cord survival. Biomechanical studies were carried out in seven additional fresh frozen human cadaver specimens to determine the most rigid method of internally stabilizing three-column cervical dissociations. Specimens were tested in compressive flexion and distractive extension to evaluate stability of anterior, posterior, and combined fixation constructs. Specimens were tested intact, after partial two-column disruption, and after complete three-column dissociation. Posterior wiring provided significantly better flexural stability in two- rather than three-column disruptions. Posterior wiring reduced posterior displacement in two-column partial disruptions to 25% of control. In three-column dissociations, posterior wiring only reduced posterior displacement to 50% of control. In extension, posterior wiring was ineffective in preventing displacement. Anterior plating, used alone, tolerated only 37% of the maximum flexion moment before early failure. On the other hand, combined anterior plating and posterior Roger's wiring reduced posterior displacement in flexion to 20% of control, while reducing anterior displacement in extension to 50% of control. This improvement over the other constructs was statistically significant. In highly unstable cervical injuries, Morscher anterior cervical plates and modified Roger's posterior wire fixation provide a safe, rigid construct that protects neural function while allowing early and aggressive mobilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of eicosanoids in abortion and its prevention by treatment with flunixin meglumine in cows during the first trimester of pregnancy.

Intravenous infusion of E. coli endotoxin at a rate of 4.16 ng/kg/min over 6 hr (total dose 1.5 micrograms/kg) in 5 cows in the first trimester of gestation induced abortion between 60 and 72 hr in three cows. Plasma PGF2 alpha levels in the aborting cows increased significantly to 289% of the zero time control (ZTC) at 1 hr and remained elevated for 9 hr. The PGF2 alpha level remained unaffected in the non-aborting cows except at 2 hr. The plasma TxB2 levels were increased by 6 to 18 fold for 6 hr in both the aborting and non-aborting cows relative to their ZTC controls. The 6-keto-PGF1 alpha levels were significantly increased to 2 to 3 fold only in the aborting cows. Plasma cortisol levels were increased maximally to 1,500% of ZTC at 5 hr in the aborting cows. Thereafter, the levels gradually declined but remained significantly elevated for 24 hr. The increases in the cortisol levels in the non-aborting cows were only 280% of ZTC at 5 hr and returned to ZTC value by 12 hr. Plasma progesterone levels in the aborting cows remained unaffected until 12 hr followed by a progressive decline through 18 hr to extremely low levels at 3, 4, and 5 days. Endotoxin-infusion caused hyperglycemia in both aborting and non-aborting cows and lactic acidemia in the aborting cows. Treatment with two doses of flunixin meglumine (FM, 1.1 mg/kg), an inhibitor of cyclooxygenase, 1 hr prior to endotoxin infusion and then 13 hr later, completely prevented the endotoxin-induced abortion and increases in the plasma PGF2 alpha, TxB2 and 6-keto-PGF1 alpha concentrations. The PGE level remained unaffected. Although FM treatment failed to abolish endotoxin-induced increases in the plasma cortisol and lactic acid levels, it effectively prevented marked decreases in the progesterone and increases in the glucose concentrations. It was concluded that the use of FM offers therapeutic promise in preventing bovine abortion caused by endotoxin resulting from bacterial infection during the 1st trimester of gestation.

Myoclonic seizures following chlorambucil overdose.

A 3 1/2-year-old child developed myoclonic seizures following a chlorambucil overdose. Serial electroencephalograms showed paroxysmal discharges that continued several days beyond clinical seizure activity. The use of the electroencephalogram when chlorambucil toxicity is suspected is discussed.

Mailed versus telephoned appointment reminders to reduce broken appointments in a hospital outpatient department.

This study compared mail, telephone, and control strategies to reduce the rate of broken appointments in a pediatric outpatient department. Based on 1,039 randomly assigned appointments, the mail strategy had a broken appointment rate of 29.1 per cent, the telephone strategy of 25.3 per cent, and the control of 44.2 per cent. Both strategies were significantly effective, but the difference between them was not significant. Patients without telephones had a higher rate of broken appointments than patients with telephones. Mailed reminders are the more cost-effective intervention.