Mutations of CD40 ligand in two patients with hyper-IgM syndrome

Two patients with the X-linked form of the hyper-IgM syndrome have been studied. Both patients present: 1. Mutations in the CD40L gene (a nonsense point mutation that introduces a termination codon at the extracellular domain of the protein, and a deletion that eliminates exon 4 as consequence of an abnormal splicing). 2. Lack of CD40L expression on the lymphocyte surface after stimulation with ionomycin and PMA. 3. Altered lymphocytic proliferation in response to anti-CD3. 4. Hyper IgM, low IgG and IgA levels and neutropenia. One of the patients shows, in addition, low Natural Killer cell numbers and severe herpetic infections, which distinguishes this case from the common hyper-IgM syndrome phenotype. Finally, a hyper-IgM stable phenotype has been immortalized by Herpes virus Saimiri for the first time.     

Polymorphonuclear activation in leprosy. I. Spontaneous and endotoxin-stimulated reduction of nitroblue tetrazolium: effects of serum and plasma on endotoxin-induced activation.

Spontaneous nitroblue tetrazolium (NBT) reduction was evaluated in neutrophils from patients with the different types and forms of leprosy, and compared with reduction obtained form cells from normal controls. Leucocytes from the same subjects were stimulated in vitro by endotoxin, and the rise in percentage of cells reducing NBT was determined. Patients of all groups, with the exception of those with reactional lepromatous leprosy (RLL) had an essentially normal proportion of reducing cells. Neutrophils were normally activated by endotoxin. This indicates that while Mycobacterium leprae does not by itself stimulate leucocytes from leprosy patients, there is no overall anergy of neutrophils in lepromatous or other forms of leprosy. In RLL the proportion of reducing cells was significantly raised. Stimulation with endotoxin was able further to enhance this proportion, but not above levels reached by stimulation of normal cells. Neutrophil activation could not be reproduced by mixing serum from highly activated RLL patients with normal leucocytes. An inhibitory effect of serum and plasma over in vitro endotoxin activation of neutrophils was found.     

Validation of Musculoskeletal Ultrasound in the Assessment of Experimental Gout Synovitis

The objective of this study was to validate musculoskeletal ultrasound (US) in a rabbit model of acute gout. Acute gout was induced by intra-articular injection of monosodium urate (MSU) crystals in 10 rabbits; the 3 controls received vehicle. Rabbit knees were assessed by B-mode and power Doppler (PD) US 24 and 72?h after injections. After 72?h, all rabbits were euthanized. US discriminated between the MSU-injected and control groups with respect to the different inflammatory findings at both at 24 and 72?h and for MSU crystal-related findings after 24?h of injection. US synovial thickening, intra-synovial power Doppler signal and global joint distension significantly correlated with the synovial global histopathological score (r?=?0.47, p?=?0.0188), tissue vascularization measured by CD31 immunohistochemical-positive staining (r?=?0.46, p?=?0.0172) and tissue levels of interleukin-1β (r?=?0.53, p?=?0.0078), respectively. US is a valid method for assessment of synovial inflammation in experimental gouty arthritis in rabbits.     

CC chemokine ligand 20 partially controls adhesion of naive B cells to activated endothelial cells under shear stress

Chemokines are thought to control lymphocyte recruitment to the inflamed endothelium. To dissect chemokine-mediated adhesion, binding of ex vivo isolated splenocytes to tumor necrosis factor (TNF)-activated endothelial cells was analyzed under shear stress. We observed specific adhesion of naive follicular B cells, which could be blocked by pertussis toxin. This indicated a G protein-mediated binding and pointed at a contribution of chemokine receptors to B-cell adhesion. Analysis of chemokines expressed by TNF-activated endothelial cells showed that CC chemokine ligand 2 (CCL2), CCL17, and CCL20 were up-regulated. Only on follicular B cells was the cognate receptor for CCL20, CC chemokine receptor 6 (CCR6), expressed strongly, and a functional transmigration assay with CCR6-negative B cells demonstrated conclusively the sole signaling of CCL20 through CCR6. Desensitization of CCR6 on naive B cells with CCL20 resulted in receptor down-regulation and reduced B-cell adhesion. We conclude that CCL20 plays a vital role in B-cell adhesion to the inflamed endothelium.     

Long-term follow-up of hemodynamic responders to pharmacological therapy after variceal bleeding

Although it is assumed that hemodynamic responders to pharmacological therapy after a variceal hemorrhage are adequately protected from rebleeding, there is no evidence that either this response or its protective effect extend beyond the usual 2-year follow-up featured in available studies. We aimed to assess the maintenance of hemodynamic response and its impact on outcomes in a large cohort of hemodynamic responders during a long follow-up. One hundred three patients with cirrhosis admitted with acute variceal bleeding between 2001 and 2010 were prospectively evaluated. The hepatic venous pressure gradient (HVPG) was determined 5 days after the bleeding and repeated 5-7 days after maximal tolerated doses of nadolol and nitrates. Hemodynamic responders (HVPG ≤ 12 mm Hg or ≥ 20% decrease from baseline) were maintained on drugs and followed up with annual HVPG measurements. Forty-eight patients (47%) were hemodynamic responders. The median follow-up was 48 months (range, 2-108 months). Long-term HVPG evaluations could not be performed in eight patients (four deaths, two rebleedings, two follow-ups <1 year). Among the remaining 40 patients, hemodynamic response was maintained in 26 (65%) and lost in 14 (35%). There were no baseline differences between the two subgroups. However, 100% of alcoholic patients who remained abstinent maintained long-term response, compared with 36% of nonabstinent alcoholics and 50% of patients with viral cirrhosis. Patients with loss of hemodynamic response rebled more during follow-up and showed a higher incidence of death or liver transplantation. Conclusions: After variceal bleeding, long-term maintenance of hemodynamic response to drug therapy is mainly restricted to patients with alcoholic cirrhosis who remain abstinent. The loss of this long-term response carries worse clinical outcomes.     

Lesion mimicking perianal abscess in an immunocompromised patient: Report of a case

INTRODUCTION

Ischiorrectal tumoral masses mimicking perianal abscess and abscess from uncommon microbiological origins have previously been reported.

PRESENTATION OF CASE

Unusual perianal abscess arising from an hematoma in an elderly woman with myelodysplastic syndrome: the patient presented on the emergency with gluteal pain and fever after intramuscular injection of analgesic drug. Physical examination revealed subcutaneous thickening on gluteus and perianal region, without skin changes. Magnetic resonance reported an heterogeneous mass sized 5 cm × 12 cm × 20 cm from gluteus maximus to ischioanal fat under levator ani muscle, through sciatic notch. Debridement of an staphylococceal infected hematoma through a single left lateral gluteus incision, and primary closure was performed. Proctologic examination was normal, so any perianal incision was done. The site infection progressed, so the patient required new surgery with wet cure. The patient contracted nosocomial pneumonia and died due to sepsis.

DISCUSSION

Hematological diseases can yield infectious and bleeding disorders. Intramuscular injections often cause haematomas that can lead to pyomyositis. Pyomyositis requires early debridement and continue cure.

CONCLUSION

Intramuscular administration of drugs should be avoided in patients with thrombocytopenia. Gluteal region is connected to perianal area through the sciatic notch. Usually perianal abscess in immunocompromised patients arise from proctologic origin, but other causes may be taken into account.