Sensitivity of receptors for IgA on T560, a murine B lymphoma,to phorbol myristate acetate and to phosphatidylinositol-specific phospholipase C

A GALT-derived B lymphoma, T560, that bears IgAR is described. T560 is IgG2a kappa +, Ia+, B220+, J11d+, Thy-1-, CD3-, CD4-, CD5-, Mac 1-, Mac 2-, nonspecific esterase negative and binds bromelain-treated mouse RBC but not SRBC or ORBC. It presents antigen, secretes IL-1, IL-4 and IL-6 but not IL-2, IL-5 or TGF beta and appears to be related to the Lyt 1+(CD5) lineage of B cells though it lacks Lyt 1. T560 bears IgAR that, on the cell surface, are completely cross-inhibited by low concentrations of IgM and by high concentrations of IgG2a and IgG2b. They do not appear to represent a cell-surface form of galactosyl transferase. They are inducible by high concentrations of IgA, sensitive to trypsin and insensitive to neuraminidase. They are down-regulated by activation of PKC with PMA, but their recovery is not inhibited by cycloheximide, indicating that they are not degraded or shed. They may either lose their affinity for IgA or be internalized without degradation. Seventy percent of IgA receptor activity is lost when T560 is treated with PI-PLC; part of this loss of activity is due to activation of PKC and is inhibited by staurosporine, but approximately 30% of it is not protected by staurosporine indicating that some, or all, of the IgA receptor of T560 is connected to the cell membrane via a GPI linker. The T560 IgA receptor could be related to the poly-Ig or M cell receptor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Knowledge and attitudes towards cardiopulmonary resuscitation among university students in Riyadh, Saudi Arabia

OBJECTIVE: To assess the knowledge and attitudes towards cardiopulmonary resuscitation (CPR) among the students of King Saud University. METHODS: This study was a cross-sectional survey among King Saud University students, Riyadh, Kingdom of Saudi Arabia, which took place on December 17-20, 2006. The data was collected via self-administered questionnaires prepared in Arabic. The questionnaires were distributed to all 15 colleges of the University. RESULTS: Out of a study sample of 2250 students, 31% did not have prior CPR information. Of those with previous knowledge, 85% feel that it is inadequate. The most common sources of information were television and movies. The 12.7% of individuals encountered a situation that required the use of CPR. However, only 14% of them performed it. This was mostly due to lack of knowledge (48.2%). Eighty eight percent of students would like to learn how to perform CPR. Out of all King Saud University students, 45% believe that CPR training should be a graduation requirement. CONCLUSION: It was found that the overall attitude towards CPR was positive. However, the knowledge on the topic was insufficient. Thus, more focus should be placed on the improvement of CPR skills. In addition, more studies are needed to assess knowledge and attitudes towards CPR in the community.     

Lessepsian migration and tetrodotoxin poisoning due to Lagocephalus sceleratus in the eastern Mediterranean

Background

The Suez Canal permits migration of fish from the Indo-Pacific Ocean to the Mediterranean Sea. This phenomenon (Lessepsian migration) has enabled poisonous fish species to colonize the Mediterranean Sea.

Objective

To report clinical tetrodotoxin poisoning after consumption of the Lessepsian immigrant fish Lagocephalus sceleratus caught on the Israeli coast of the eastern Mediterranean.

Case series

Thirteen patients aged 26-70 years were admitted after consuming L. sceleratus. Signs of toxicity appeared within 1 h. The main manifestations included vomiting, diarrhea, headache, paraesthesias, slurred speech, muscle weakness, dyspnea, hypertension, tachycardia, respiratory arrest, seizures and coma. Treatment was supportive, including mechanical ventilation (two patients). Patients recovered within 4 days. All fish were identified as L. sceleratus, a species known to contain tetrodotoxin.

Discussion

The diagnosis of tetrodotoxin poisoning was suggested by typical clinical manifestations together with temporal proximity to consumption of tetrodotoxin-containing fish. To the best of our knowledge, this is the first case series of tetrodotoxin poisoning reported from the eastern Mediterranean and due to L. sceleratus. Man made disruption of the ecological balance has resulted in the spread of tetrodotoxin-containing fish from the Indo-Pacific region to the Mediterranean Sea. Increased awareness is required to identify tetrodotoxin poisoning in an atypical fauna.     

Vitamin D3 and Monomethyl Fumarate Enhance Natural Killer Cell Lysis of Dendritic Cells and Ameliorate the Clinical Score in Mice Suffering from Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a CD4⁺ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP_139–151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D₃ (vitamin D₃), or with monomethyl fumarate (MMF) was then examined. We observed that both vitamin D₃ and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK) cells from vitamin D₃-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells.     

Variations in the anatomy of the vertebral artery cervical loop segment - a potential predisposing factor for traumatic basal subarachnoid hemorrhage?

Fatal traumatic basal subarachnoid hemorrhage (TBSAH) is a characteristic forensic pathological entity, the investigation of which requires special techniques. In Liverpool, post-mortem room angiography is undertaken, followed by complete removal of the vertebral arteries and histological examination. It has been observed that the arterial anatomy can be highly variable, particularly the length and course of the loop segments located between the C2 vertebra and the dura. In a number of cases of TBSAH the loop segments of torn vessels have appeared relatively short. Having observed this phenomenon subjectively in our case work, a radiological study was undertaken with the aim of quantifying vertebral artery loop anatomy variation in a ‘normal’ population. Multiphase post-mortem computed tomography angiography (MPMCTA) scans of 98 subjects were reviewed and the lengths of the different portions of the loop segments (foramen magnum to the upper border of C1, between C1 and C2, and the bony foramina themselves) of each vertebral artery were measured using semi-automated vessel analysis software. The measurements obtained provide objective evidence of marked anatomical variation, with some loop segments more than twice the length of others. These results are important because a short vertebral artery loop segment might be a significant factor in predisposing an individual to TBSAH following a blow to the head or neck.     

Brain natriuretic peptide at discharge as a predictor of 6-month mortality in acute decompensated heart failure

Background

Brain natriuretic peptide (BNP) is well established in detecting acute decompensation of heart failure (ADHF). The role of BNP at discharge in predicting mortality is less established. Accumulating evidence suggests that inflammatory cytokines play an important role in the development of heart failure. We aimed to examine the contribution of BNP, interleukin 6, and procalcitonin to mortality in ADHF.

Methods

A cohort of 33 patients with ADHF was identified between March 2009 and June 2010 at Rambam Health Care Campus, Haifa, Israel. The cohort was followed up for all-cause mortality during 6 months after hospital discharge. Cox proportional hazard model was used to assess the association between BNP, interleukin-6 and procalcitonin and all-cause mortality.

Results

As compared to BNP at admission, BNP at discharge was more predictive for all-cause mortality. The area under the curve for BNP at admission and discharge was 0.810 (P = .004) and 0.864 (P = .001) respectively. Eleven patients (33.3%) patients who died during the follow-up period had higher BNP levels, median 2031.4 (IQR, 1173.4-2707.2), than those who survived; median 692.5 (IQR, 309.9-1159.9), (P = .001). On multivariate analysis, BNP remained an independent predictor for 6 month all-cause mortality HR 9.58 (95% CI, 2.0-45.89) for levels above the median compared to lower levels, (P = .005). Albumin, procalcitonin and interleukin 6 were not associated with all-cause mortality.

Conclusions

BNP at discharge is an independent predictor for all-cause mortality in patients with ADHF. Compared with BNP at admission, BNP at discharge has slightly higher predictive accuracy with regard to 6-month all-cause mortality.     

Adjunctive rifampin is crucial to optimizing daptomycin efficacy against rabbit prosthetic joint infection due to methicillin-resistant Staphylococcus aureus

Daptomycin is an attractive option for treating prosthetic joint infection, but the 6-mg/kg of body weight/day dose was linked to clinical failure and emergence of resistance. Using a methicillin-resistant Staphylococcus aureus (MRSA) knee prosthesis infection in rabbits, we studied the efficacies of high-dose daptomycin (22 mg/kg given intravenously [i.v.] once daily [o.d.]; equivalent to 8 mg/kg/day in humans) or vancomycin (60 mg/kg given intramuscularly [i.m.] twice daily [b.i.d.]), both either alone or with adjunctive rifampin (10 mg/kg i.m. b.i.d.). After partial knee replacement with a silicone implant, 10(7) MRSA CFU was injected into the knees. Treatment started 7 days postinoculation and lasted 7 days. Positive cultures were screened for the emergence of mutant strains, defined as having 3-fold-increased MICs. Although in vivo mean log(10) CFU/g of daptomycin-treated (4.23 ± 1.44; n = 12) or vancomycin-treated (4.63 ± 1.08; n = 12) crushed bone was significantly lower than that of controls (5.93 ± 1.15; n = 9) (P < 0.01), neither treatment sterilized bone (2/12 and 0/12 rabbits with sterile bone, respectively). Daptomycin mutant strains were found in 6/12, 3/12, and 2/9 daptomycin-treated, vancomycin-treated, and control rabbits, respectively; no resistant strains emerged (MIC was always <1 mg/liter). Adjunctive rifampin with daptomycin (1.47 ± 0.04 CFU/g of bone [detection threshold]; 11/11 sterile bones) or vancomycin (1.5 ± 0.12 CFU/g of bone; 6/8 sterile bones) was significantly more effective than monotherapy (P < 0.01) and prevented the emergence of daptomycin mutant strains. In this MRSA joint prosthesis infection model, combining rifampin with daptomycin was highly effective. Daptomycin mutant strains were isolated in vivo even without treatment, but adjunctive rifampin prevented this phenomenon, previously found after monotherapy in humans.