IL-12 and IL-23: master regulators of innate and adaptive immunity

Summary: Initiation of an effective immune response requires close interactions between innate and adaptive immunity. Recent advances in the field of cytokine biology have led to an increased understanding of how myeloid cell‐derived factors regulate the immune system to protect the host from infections and prevent tumor development. In this review, we focus on the function of interleukin (IL)‐23, a new member of the IL‐12 family of regulatory cytokines produced by activated macrophages and dendritic cells. We propose that IL‐12 and IL‐23 promote two distinct immunological pathways that have separate but complementary functions. IL‐12 is required for antimicrobial responses to intracellular pathogens, whereas IL‐23 is likely to be important for the recruitment and activation of a range of inflammatory cells that is required for the induction of chronic inflammation and granuloma formation. These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression.     

Parvalbumin neurons in the entorhinal cortex of subjects diagnosed with bipolar disorder or schizophrenia.

BACKGROUND: Growing evidence indicates that the entorhinal cortex (ECx) might be affected in schizophrenia (SZ) and bipolar disorder (BD). To test whether distinct interneuronal subpopulations might be altered, numbers of parvalbumin-immunoreactive (PVB-IR) neurons were measured in the ECx of BD and SZ subjects. These neurons play a pivotal role within ECx intrinsic circuits. METHODS: Numbers, numerical density, and soma size of PVB-IR neurons were measured in the ECx of normal control (n = 16), BD (n = 10), and SZ (n = 10) subjects. The volume of the ECx was measured in Nissl-stained sections. RESULTS: In BD, decreases of total numbers (p = .02) and numerical densities (p = .01) of PVB-IR neurons were detected in the ECx. Within distinct subregions, reductions were detected in the superficial layers of the lateral (p = .02), intermediate (p = .04), and caudal (p = .01) ECx. In SZ, total numbers and numerical densities were not altered. A reduction of soma size was present in the intermediate ECx (p = .01). Volume was unaffected in either disorder. CONCLUSIONS: In BD, a decrease of PVB-IR neurons may alter intrinsic inhibitory networks within the superficial layers of the ECx. The likely consequence is a disruption of integration and transfer of information from the cerebral cortex to the hippocampus.     

Anomalous flexor digitorum superficialis muscle belly presenting as a mass within the palm

Anomalies of the flexor digitorum superficialis muscle are extremely uncommon and usually present as a painful mass or pseudotumour within the palm. Diagnosis may be difficult because many other soft tissue tumours (lipomas, ganglions, giant cell tumours and hamartomas) may present similarly. Magnetic resonance imaging helps to define the extent and characteristics of this anomalous muscle belly and to distinguish it from a soft tissue sarcoma, whereas plain radiographs are of little value. Three types of flexor digitorum superficialis muscle anomalies have been described, and treatment consists of subtotal or total surgical debulking of the mass if symptoms persist or if the diagnosis is in question. Most patients have complete resolution and full recovery. To date, 20 cases have been reported in the literature, usually involving the right small finger. In the present paper, the case of an anomalous flexor digitorum superficialis muscle in a 17-year-old male patient’s left index finger is reported. Symptoms were relieved following surgical debulking and hand-based occupational therapy.     

Model of reentrant ventricular tachycardia based on infarct border zone geometry predicts reentrant circuit features as determined by activation mapping

BACKGROUND: Infarct border zone (IBZ) geometry likely affects inducibility and characteristics of postinfarction reentrant ventricular tachycardia, but the connection has not been established. OBJECTIVE: The purpose of this study was to determine characteristics of postinfarction ventricular tachycardia in the IBZ. METHODS: A geometric model describing the relationship between IBZ geometry and wavefront propagation in reentrant circuits was developed. Based on the formulation, slow conduction and block were expected to coincide with areas where IBZ thickness (T) is minimal and the local spatial gradient in thickness (DeltaT) is maximal, so that the degree of wavefront curvature rho proportional, variant DeltaT/T is maximal. Regions of fastest conduction velocity were predicted to coincide with areas of minimum DeltaT. In seven arrhythmogenic postinfarction canine heart experiments, tachycardia was induced by programmed stimulation, and activation maps were constructed from multichannel recordings. IBZ thickness was measured in excised hearts from histologic analysis or magnetic resonance imaging. Reentrant circuit properties were predicted from IBZ geometry and compared with ventricular activation maps after tachycardia induction. RESULTS: Mean IBZ thickness was 231 +/- 140 microm at the reentry isthmus and 1440 +/- 770 microm in the outer pathway (P <0.001). Mean curvature rho was 1.63 +/- 0.45 mm(-1) at functional block line locations, 0.71 +/- 0.18 mm(-1) at isthmus entrance-exit points, and 0.33 +/- 0.13 mm(-1) in the outer reentrant circuit pathway. The mean conduction velocity about the circuit during reentrant tachycardia was 0.32 +/- 0.04 mm/ms at entrance-exit points, 0.42 +/- 0.13 mm/ms for the entire outer pathway, and 0.64 +/- 0.16 mm/ms at outer pathway regions with minimum DeltaT. Model sensitivity and specificity to detect isthmus location was 75.0% and 97.2%. CONCLUSIONS: Reentrant circuit features as determined by activation mapping can be predicted on the basis of IBZ geometrical relationships.     

Cognitive Behavior Therapy for Psychotic Disorders: Current Issues and Future Developments

There is accumulating evidence, reviewed by Caudiano (this issue), that cognitive behavior therapy (CBT) is an effective adjunct treatment for schizophrenia. Schizophrenia treatment and research provides a range of challenges that are probably not present in other mental health problems. These include contextual issues, clinical issues, scientific and methodological issues, practical and pragmatic issues, public concern, and human rights issues. This paper discusses these issues with emphasis on the clinical and research challenges for the future.     

Positive predictive value of maximal posterior joint-line tenderness in diagnosing meniscal pathology: a pilot study

OBJECTIVE: The purpose of this prospective study was to determine the positive predictive value (PPV) of the point of maximal posterior joint line tenderness (JLT), as a clinical sign, to diagnose underlying meniscal tears. METHODS: We conducted a prospective study of patients requiring arthroscopic surgery, who consecutively presented to the University of Calgary's Sport Medicine Centre. The femurotibial joint line was palpated for the point of maximal tenderness. We recorded the data on the arthroscopy report. A second examiner (orthopedic sport medicine surgical fellow or sport medicine physician) performed the same protocol. An arthroscopist documented the site of pathology as detected by arthroscopy. RESULTS: We found a PPV of 60.0% and a negative predictive value of 62.5%, suggesting that maximal posterior JLT may be predictive of meniscal pathology. The sensitivity and specificity were 84.6% and 31.2%, respectively (p = 0.155), with Fisher's exact test. The kappa score assessed interobserver reliability and was good at 0.48. Patients with maximal posterior JLT but no meniscal pathology did have other confounding pathology and patients with no maximal posterior JLT who had meniscal pathology usually had confounding knee pathology. CONCLUSIONS: We found a PPV of 60.0% of maximal posterior JLT and meniscal pathology located at the same anatomical site on arthroscopic examination.