The cannabinoid agonist DALN positively modulates L-type voltage-dependent calcium-channels in N18TG2 neuroblastoma cells

The present study demonstrates a novel stimulatory effect of a cannabinoid agonist on calcium channels. DALN (1 nM) potentiated 45Ca(2+)-uptake by N18TG2 neuroblastoma cells, an effect that was abolished by the specific CB1 receptor antagonist SR141716A. The stimulation of 45Ca(2+)-uptake by DALN was resistant to pertussis toxin (PTX), suggesting that Gi/Go GTP-binding proteins did not mediate this effect. Furthermore, PTX unmasked a stimulatory effect of a high concentration of DALN (1 microM), which by itself failed to stimulate calcium uptake in naive cells. The stimulatory effect of DALN on calcium entry to the cells was blocked by nicardipine but not by omega-conotoxin GVIA, indicating the entry of calcium through L-type voltage-dependent calcium channels. Blocking cAMP-dependent protein kinase (PKA) by H-89 completely eliminated the elevation in calcium uptake, while blocking protein kinase C (PKC) by chelerythrine and calphostine-C only partially attenuated the stimulation. Blocking calmodulin by W-7 revealed a similar partial inhibition of the stimulatory effect of DALN. Hence, we suggest a cannabinoid-specific, PTX-insensitive, stimulatory effect on L-type voltage-dependent calcium channels, which is mediated by PKA and modulated by PKC and calmodulin.     

Paediatric Behçet disease manifested as recurrent myositis: from an incomplete to a full-blown form

A 12-year-old boy presented with a limp and findings suggesting localised myositis of his right calf and a working diagnosis of Behçet disease was made. During 3 years of follow-up, he had another three episodes of calf myositis, all responsive to corticosteroids within days. Conclusion A case of recurrent localised myositis as a main manifestation of Behçet disease is reported. The evolution of incomplete Behçet disease, which is common in children, to the full blown form, with the emphasis on muscle involvement and the importance of early diagnosis of Behçet disease, is discussed.     

Management of intrinsic gliomas of the tectal plate in children. A ten-year review

The natural history, management, and long-term outcome for patients with benign, intrinsic tectal plate gliomas remain controversial in spite of their propensity to cause late-onset hydrocephalus. A 10-year retrospective review has identified 11 consecutive children with tectal plate lesions. Headache, vomiting, a decline in school performance, tremor, and complex partial seizures were common presenting symptoms. All patients presented with signs and symptoms of hydrocephalus. Magnetic resonance (MR) imaging delineated an intra-axial mass lesion of the midbrain primarily localized to the tectal plate which uniformly was hyperintense on T2-weighted imaging and had a more variable appearance on T1-weighted imaging and rare enhancement with gadolinium. No patient underwent surgical resection, chemotherapy, or radiotherapy. Three of 11 patients (27%) showed evidence of progression in size or a new focus of enhancement on MR imaging, which was clinically asymptomatic. In this series, no patient with a tectal plate lesion less than 1.5 cm in maximal diameter and without gadolinium enhancement showed any evidence of clinical or radiological progression. Although intrinsic tectal lesions in children are clinically indolent and the initial management consists of CSF diversion, these lesions may eventually progress and still warrant long-term follow-up with serial MR imaging.     

Injectable fluid silicone therapy. Human morbidity and mortality.

Four patients who had received silicone injections had the following complications: migration, hepatic disease manifested as granulomatous hepatitis (previously undescribed, to our knowledge), hypopigmentation, and death. Silicone should now be considered as a possible cause of hepatic granulomas in an appropriate host.     

Association between alopecia and response to chemotherapy in patients with Hodgkin lymphoma

Alopecia and bone marrow suppression are prominent effects of doxorubicin-containing chemotherapy. The aim of the study was to validate our preliminary clinical observation that the lack of alopecia in Hodgkin lymphoma patients may predict poor response to chemotherapy and low rate of bone marrow suppression. Sixty-six patients with Hodgkin lymphoma were reviewed. They were treated between 1991 and 2001 with at least 4 courses of doxorubicin-containing chemotherapy (MOPP/ABV or ABVD) in 2 university-affiliated hematology departments. Thirty-four patients exhibited complete or near complete alopecia, and 32 retained their hair or had only minimal hair loss. The 2 groups were compared by response to treatment and episodes of bone marrow suppression. Alopecia was associated with a high rate of remission (OR 8.48, 95% CI 2.77-25.95), episodes of neutropenia (OR 3.55, 95% CI 1.28-9.84), leukopenia (OR 1.83, 95% CI 0.68-4.92), delays in scheduled treatments (OR 1.61, 95% CI 0.607-4.30), or number of courses with dose reduction (OR 1.63, 95% CI 0.56-4.74). Significantly more patients with alopecia had at least 1 of these parameters (88% versus 62%, P=0.015; OR 4.50, 95% CI 1.27-15.94). In conclusion, in patients with Hodgkin lymphoma treated with doxorubicin-containing chemotherapy, the absence of alopecia may predict poor response to treatment along with fewer episodes of bone marrow suppression. The absence of alopecia in such patients should alert clinicians to the possibility of treatment failure.     

No-touch aorta off-pump coronary surgery: the effect on stroke

OBJECTIVE: Studies examining the neuroprotective effects of off-pump coronary artery bypass grafting have shown inconsistent results. Most studies, however, have not differentiated between clampless and clamp off-pump techniques. The aim of this study was to evaluate the effect of avoiding aortic manipulation on major neurologic outcomes after off-pump coronary artery bypass grafting. METHODS: A total of 700 consecutive patients undergoing multiple-vessel off-pump coronary artery bypass grafting between 2000 and 2003 were included. The 429 patients undergoing aortic no-touch technique were compared with 271 patients in whom partial aortic clamps were applied. The aorta was screened by manual palpation, and epiaortic ultrasonography was used selectively. RESULTS: The frequency of detected atherosclerotic aortic disease was higher in the no-touch group (17.4% vs 5.1%, P < .0001). No-touch revascularization was achieved with arterial conduits, arranged in T-graft or in situ configurations (50%). The respective graft/patient ratios were 2.5 +/- 0.6 and 2.6 +/- 0.6 in the side-clamp and no-touch groups ( P = .009); however, revascularization of the posterolateral myocardial territory was comparable (87% vs 90%, difference not significant). The incidence of stroke (0.2% vs 2.2%, P = .01) was significantly lower in the no-touch group (1/429). Logistic regression identified partial aortic clamping as the only independent predictor of stroke (odds ratio 28.5, confidence interval 0.22-333, P = .009), increasing this risk 28-fold. Peripheral vascular disease ( P = .068), diabetes ( P = .072), and history of stroke ( P = .074) trended toward stroke. CONCLUSIONS: Avoiding partial aortic clamping during off-pump coronary artery bypass grafting provides superior neurologic outcome. The results are reproducible and irrespective of the severity of aortic disease or the method of aortic screening. This technique is recommended whenever technically feasible.