The cholinomimetic agent carbachol induces headache in healthy subjects

The parasympathetic nervous system is likely to be involved in migraine pathogenesis. We hypothesized that the cholinomimetic agonist carbachol would induce headache and vasodilation of cephalic and radial arteries. Carbachol (3 µg/kg) or placebo was randomly infused into 12 healthy subjects in a double-blind crossover study. Headache was scored on a verbal rating scale from 0–10. Velocity in the middle cerebral artery (V_MCA) and diameter of the superficial temporal artery (STA) and radial artery (RA) were recorded. Nine participants developed headache after carbachol compared with three after placebo. The area under the curve for headache was increased after carbachol compared with placebo both during infusion (0–30 min) ( P  = 0.042) and in the postinfusion period (30–90 min) ( P  = 0.027). Carbachol infusion caused a drop in V_MCA ( P  = 0.003) and an increase in STA diameter ( P  = 0.006), but no increase in the RA diameter ( P  = 0.200). In conclusion, the study demonstrated that carbachol caused headache and dilation of cephalic arteries in healthy subjects.     

Association between palmoplantar pustulosis and cigarette smoking in Brazil: a case–control study

Background  Palmoplantar pustulosis (PPP) discloses some differences compared to vulgar psoriasis (PV) in terms of age of onset, female predominance and low occurrence of psoriasis lesions elsewhere. Cigarette smoking has been associated to PPP in international studies; nevertheless, these studies were never performed among Brazilian.
Objectives  To compare prevalence of smoking among PPP, PV and other dermatologic patients (NPD).
Methods  Case–control study involving 25 PPP patients from a reference psoriasis centre. Two control groups were matched according to gender and age: 50 patients with PV and 50 NPD. Confounders were adjusted by conditional multiple logistic regression.
Results  Among cases, 84.0% were female and PPP age of disease onset (41.4 years) was greater than PV (34.5 years). Prevalence of ever smoking was higher among cases (92.0%) than PV (52.0%) and NPD (30.0%). Adjusted odds ratio of PPP ever smoking compared to PV and NPD was 9.5 and 36.2, respectively. All smokers reported the onset of their habit before the development of PPP.
Conclusions  There was significant association between PPP and smoking. However, the impact of giving it up in the clinical course of the disease remains to be established.     

Electroconvulsive seizure thresholds and kindling acquisition rates are altered in mouse models of human KCNQ2 and KCNQ3 mutations for benign familial neonatal convulsions

Purpose:   Benign familial neonatal convulsions (BFNC) is caused by mutations in the KCNQ2 and KCNQ3 genes, which encode subunits of the M-type potassium channel. The purpose of this study was to examine the effects of orthologous BFNC-causing mutations on seizure thresholds and the acquisition of corneal kindling in mice with heterozygous expression of the mutations.
Methods:   The effects of the Kcnq2 gene A306T mutation and the Kcnq3 gene G311V mutation were determined for minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizures. The rate of corneal kindling acquisition was also determined for Kcnq2 A306T and Kcnq3 G311V mice.
Results:   Seizure thresholds were significantly altered relative to wild-type animals in the minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizure models. Differences in seizure threshold were found to be dependent on the mutation expressed, the seizure testing paradigm, the genetic background strain, and the gender of the animal. Mutations in Kcnq 2 and Kcnq 3 were associated with an increased rate of corneal kindling. In the Kcnq2 A306T mice, an increased incidence of death occurred during and immediately following the conclusion of the kindling acquisition period.
Conclusions:   These results suggest that genetic alterations in the subunits that underlie the M-current and cause BFNC alter seizure susceptibility in a sex-, mouse strain-, and seizure-test dependent manner. Although the heterozygous mice do not appear to have spontaneous seizures, the increased seizure susceptibility and incidence of death during and after kindling suggests that these mutations lead to altered excitability in these animals.     

Surgical considerations for ‘intrinsic＇ brainstem gliomas： proposal of a modification in classification

BACKGROUND： Brainstem gliomas are highly heterogeneous tumors both in their clinical manifestation and in their pathology. Despite significant advances in the surgery for brainstem gliomas many aspects of this pathology are still unelear. OBJECTIVE： To evaluate the clinical, radiological and surgical outcome of 40 focal ＂intrinsic＂ brainstem gliomas and propose a surgical strategyoriented classification. MATERIALS AND METHODS： A total of 40 focal ‘intrinsie’ （＂expanding variety＂） tumors have been operated over a period of 8.5-years （January 1998-June 2007）. Our criteria included patients with （1） well-defined gadolinium enhancing tumor, （2） relatively long duration of symptoms （〉 six months） and （3） good neurological functional status and independent for all activities of davy living. The cutoff size of 2 cm was not rigidly adhered to. RESULTS： The ＂intrinsic＂ brainstem tumors were classified into three types： Expanding, diffuse infiltrative and pure ventral varieties.     

Foveomacular retinitis and associated optical coherence tomography findings.

A 45-year-old man presented with clinical manifestations of foveomacular retinitis, including visual symptoms and foveal lesions characteristic of solar retinopathy, but repeated questions failed to elicit a history of sun gazing. Cross-sectional retinal images produced by optical coherence tomography revealed localized loss of retinal pigment epithelium cells in both eyes. A different pattern of reflectivity at the level of the photoreceptor layer was observed between the right and left eye, reflecting asymmetry in tissue damage. This case is described to provide additional evidence that solar retinopathy and foveomacular retinitis are the same entity and may also have common optical coherence tomography findings.     

Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo

The goal of this study was to enhance gene delivery and tumor cell transfection in vivo by using a combination of ultrasonication with complex nanoparticles consisting of two types of nanoparticles: PEI/DNA β-gal plasmid with highly positive zeta-potential and air-filled poly (lactic-co-glycolic acid) (PLGA) particles (with negative zeta-potential) manufactured in our laboratory. The PLGA/PEI/DNA nanoparticles were a colloid with positive zeta-potential and injected i.v. in nude mice with DU145 human prostate tumors. We found that the combination of PLGA/PEI/DNA nanoparticles with ultrasonication substantially enhanced tumor cell transfection in vivo. The overexpression of β-gal gene was evaluated histochemically and by Western blot analysis. At least an 8-fold increase of the cell transfection efficacy was obtained in irradiated tumors compared to non-irradiated controls, while little to no cell death was produced by ultrasonication.     

Ocular Granulocytic Sarcoma in Childhood Acute Myelogenous Leukemia

We report two children of Greek origin with granulocytic sarcoma of the orbit and acute myelogenous leukemia. In the first case the orbital tumor was the initial manifestation of the disease, while the other occurred during hematological remission.