Pressure pain sensitivity mapping of the temporalis muscle revealed bilateral pressure hyperalgesia in patients with strictly unilateral migraine

Previous studies on pressure pain sensitivity in patients with migraine have shown conflicting results. There is emerging evidence suggesting that pain sensitivity is not uniformly distributed over the muscles, indicating the existence of topographical changes in pressure pain sensitivity. The aim of this study was to calculate topographical pressure pain sensitivity maps of the temporalis muscle in a blind design in patients with strictly unilateral migraine compared with controls. For this purpose, an electronic pressure algometer was used to measure pressure pain thresholds (PPT) over nine points of the temporalis muscle: three points in the anterior, medial and posterior parts, respectively. Pressure pain sensitivity maps of both sides (dominant or non-dominant; symptomatic or non-symptomatic) were calculated. The analysis of variance showed significant differences in PPT values between both groups ( F  = 279.2; P  < 0.001) and points ( F  = 4.033; P  < 0.001). Patients showed lower PPT at all nine points than healthy controls ( P  < 0.001). We also found lower PPT in the centre of the muscle compared with the posterior part of the muscle within both groups ( P  < 0.01). Interaction between group and points ( F  = 1.9; P  < 0.05) was also found. Within the migraine group, PPT levels were decreased bilaterally from the posterior to the anterior column of the temporalis muscle (Student–Newman–Keuls analysis; P  < 0.05), with the most sensitive in the anterior part of the muscle. For controls, PPT did not follow such anatomical distribution, the most sensitive point being the centre of the mid-muscle belly. This study showed bilateral sensitization to pressure in unilateral migraine, suggesting the involvement of central components.     

Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets

CD1d-restricted invariant NKT (iNKT) cells are immunoregulatory cells whose loss exacerbates diabetes in nonobese diabetic (NOD) female mice. Here, we show that the relative numbers of iNKT cells from the pancreatic islets of NOD mice decrease at the time of conversion from peri-insulitis to invasive insulitis and diabetes. Conversely, NOD male mice who have a low incidence of diabetes showed an increased frequency of iNKT cells. Moreover, administration of alpha-galactosylceramide, a potent activating ligand presented by CD1d, ameliorated the development of diabetes in NOD female mice and resulted in the accumulation of iNKT cells and myeloid dendritic cells (DC) in pancreatic lymph nodes (PLN), but not in inguinal lymph nodes. Strikingly, injection of NOD female mice with myeloid DC isolated from the PLN, but not those from the inguinal lymph nodes, completely prevented diabetes. Thus, the immunoregulatory role of iNKT cells is manifested by the recruitment of tolerogenic myeloid DC to the PLN and the inhibition of ongoing autoimmune inflammation.     

The utility of therapeutic plasma exchange for amphotericin B overdose

Medication error is a preventable cause of morbidity and death in the inpatient population. We describe a patient with an antifungal overdose treated with therapeutic plasma exchange (TPE). The patient was diagnosed with cryptococcal meningitis and received an acute overdose of amphotericin B deoxycholate instead of the prescribed liposomal amphotericin B. Consequently, the patient developed clinical symptoms including tremors, hypertension, visual hallucinations, vertigo, fever, and acute renal failure. A series of four TPEs was emergently initiated, resulting in complete resolution of most symptoms.     

Radiographically negative avascular necrosis: detection with MR imaging

To correlate the morphologic appearance on magnetic resonance (MR) images of radiographically negative avascular necrosis (AVN) of the femoral head with that on computed tomographic (CT) and radionuclide scans, the radiographic and clinical records of 24 patients were reviewed retrospectively. In 18 patients the MR signal intensity features were monitored by means of serial imaging. All MR studies included T1-weighted (short repetition time [TR], short echo delay time [TE] ) imaging and T2-weighted imaging (long TR, long TE). Thirty-one hips were determined with MR to be involved by AVN; 27 were staged on the basis of signal intensity characteristics within the low-intensity rim. Core decompression was performed on 18 hips. Afterward, progression of disease occurred in only one hip. Fourteen of the 16 asymptomatic patients (88%) had early-stage focal lesions. CT scans were obtained in 15 patients and radionuclide scans in 21. Ten hips at radionuclide imaging and five at CT appeared normal when MR results were distinctly abnormal. MR can depict early radiographically negative AVN in asymptomatic individuals. At this early stage, the lesions in this series appear to be nonprogressive after treatment.     

Glycoprotein IV-independent adhesion of sickle red blood cells to immobilized thrombospondin under flow conditions

The abnormal adherence of red blood cells (RBC to the blood vessel wall is believed to contribute to the vascular occlusion observed in patients with sickle call anemia. The cell adhesion receptors GPIV (CD36) and integrin alpha 4 beta 1 (CD49d/CD29) were previously identified on circulating sickle reticulocytes, and shown to mediate sickle RBC adhesion to the endothelium. The presence of damaged endothelium in these patients suggests that exposed extracellular matrix proteins could provide a potential substrate for sickle RBC adhesion. To determine whether RBC adhesion receptors could mediate adhesion to extracellular matrix proteins, we tested their ability to adhere to a variety of immobilized, purified proteins under flow conditions. Neither sickle nor normal RBC adhered to fibronectin, vitronectin, fibrinogen, or collagen. In contrast, we observed substantial adhesion of sickle but not normal RBC to thrombospondin (TSP). The adhesion was not inhibited with known antagonists of the GPIV-TSP interaction, nor by inhibitors of several other known binding domains in TSP. Moreover, the adhesion was resistant to inhibition by soluble TSP, suggesting that immobilization of TSP exposes an adhesive site that is cryptic on TSP in solution. However, the glycosaminoglycans, chondroitin sulfate A, and dextran sulfate were potent inhibitors of this adhesion. These results suggest that a mechanism distinct from GPIV is responsible for sickle RBC adhesion to immobilized TSP under flow conditions.     

PI 3-kinase activation in BCR/abl-transformed hematopoietic cells does not require interaction of p85 SH2 domains with p210 BCR/abl

BCR/abl is a chimeric oncogene implicated in the pathogenesis of human chronic myelogenous leukemia. Expression of the BCR/abl gene induces hematologic malignancies in transgenic mice and transformation of interleukin-3-dependent hematopoietic cells. The mechanism of BCR/abl- mediated transformation of hematopoietic cells is poorly understood and involves activation of at least two signaling pathways, p21ras and PI 3- kinase. Here we report that PI 3,4-P2 and PI 3,4,5-P3, the enzymatic products of PI 3-kinase, accumulate in metabolically labeled transformed hematopoietic cells, in contrast to our previous report on the lack of accumulation of PI 3-kinase products in nontransformed NIH 3T3 fibroblasts that express p210 BCR/abl. Transformed cells also have increased PI 3-kinase activity in total cell extracts and membrane fractions. Activation of PI 3-kinase occurs by occupancy of SH2 domains of PI 3-kinase regulatory subunit, p85, by phosphorylated YXXM motifs. Therefore, we investigated whether BCR/abl binds to p85 and whether this binding is mediated by interaction of p85 SH2 domains with YXXM motif of BCR/abl. Association of p210 BCR/abl with p85 in immune complexes and with p85 SH2 domains was evident in hematopoietic cells that express the wt p210 BCR/abl. However, the binding of BCR/abl to p85 SH2 domains was abolished in cells expressing mutant, temperature- sensitive (ts) p210 BCR/abl in which the tyrosine in the YXXM motif of p210 BCR/abl was replaced by histidine. Despite lack of direct interaction with p85 SH2 domains, expression of ts p210 BCR/abl resulted in rapid, time-dependent activation of total and membrane- associated PI 3-kinase and increased PI 3-kinase activity in anti-P-tyr and anti-abl immunoprecipitates. These data suggest that BCR/abl- induced activation of PI 3-kinase in hematopoietic cells does not require binding of p85 SH2 domains to BCR/abl gene product and involves interaction with other tyrosine phosphorylated intermediate proteins.     

Case Report: Gastrointestinal tuberculosis simulating Crohn's disease

A male Caucasian presented with abdominal pain and a right iliac fossa mass. There were no risk factors for Mycobacterium tuberculosis infection. He was investigated by upper and lower gastrointestinal endoscopy, chest and small bowel radiology. The latter showed stricturing of the third and fourth parts of the duodenum, mid-jejunum and terminal ileum. Biopsies were non-specific and he was thought to have Crohn's disease. Subsequent treatment with corticosteroids resulted in improved well being and weight gain; however, the patient demonstrated disease progression with the development of complex fistulae and Escherichia coli septicaemia. At surgery the patient was found to have an ileal inflammatory mass with fistulae to the sigmoid colon. The terminal ileum, fistulae and a segment of colon were resected. Treatment with anti-tuberculous drugs ensued and the patient is now asymptomatic after 15 months of follow-up. This case serves to highlight the difficulty in making the diagnosis of gastrointestinal tuberculosis, a disease that may mimic Crohn's disease, and the need for caution in the use of corticosteroids in any disease in which tuberculosis enters into the differential diagnosis. The role of surgery in making the diagnosis and managing the complications, in conjunction with anti-tuberculous drugs, and the prospect of cure are exemplified by this case.