Scanning electron microscopy of aortic medial changes in aortic ascending dilatation

The study of cystic cavities and collagen fibers fragmentation is useful to for a better knowledge of pathogenesis and surgical therapy of medial ascending aortic degeneration. Thus, the aim of this study was to describe by scanning electron microscopy the surfaces and shape of the cysts, measure their area, and identify microcystic spaces related to this degenerative disease. Scanning electron microscopy analysis was performed in 16 out of 36 patients who underwent surgery for ascending aorta dilatation with associated aortic valve disease. The aortic medial wall showed a cribrose appearance at low magnification (×50-100) and the intima was effuse. At high magnification (×500-2000), small cavities (clefts) lined by normal or fragmented elastic fibers and large cavities (pseudocystes) with anfractuous borders lined by fragmented elastic fibers and smooth muscle cells were observed. Furthermore, in the outer media wall microvessels lined by endothelium were also observed. These changes were lacking or less pronounced in normal aorta. SEM allows one to better identify the pathological cavities and to differentiate them from microvessels. These pathological cavities are more numerous and larger in the convexity than in the concavity of the aorta in according to our previous morphological and morphometric findings in asymmetrical aorta dilatation.     

Clinical comparison of extended-release divalproex versus delayed-release divalproex: pooled data analyses from nine trials

Divalproex sodium is an effective anticonvulsant, antimanic, and migraine prophylaxis agent. Recently, a new extended-release (ER) formulation of divalproex sodium has become available, which allows for once-daily dosing and provides prolonged therapeutic serum levels. Using data pooled from nine open-label trials involving 321 epilepsy and psychiatry patients, we compared the efficacy and tolerability of divalproex ER with preceding treatment with the older delayed-release (DR) formulation, based on patient reports and analysis by McNemar's test for within-subject paired data. Divalproex ER was associated with superior tolerability with less frequent tremor, weight gain, and gastrointestinal complaints (all P<0.001), but not less hair loss. Divalproex ER also yielded improved seizure control and greater improvement of psychiatric symptoms, and was greatly preferred by patients over divalproex DR. Although the results of the current analyses must be considered highly tentative due to the open-label nature of the trials included, the findings do suggest broad clinical superiority of the new ER preparation.     

Classification of Farnsworth-Munsell 100-hue test results in the early treatment diabetic retinopathy study

PURPOSE: To classify and describe clinically meaningful classes of color vision defects using pretreatment Farnsworth-Munsell 100-hue results from the Early Treatment Diabetic Retinopathy Study (ETDRS) patients using standard statistical techniques. DESIGN: The ETDRS was a randomized trial investigating retinal photocoagulation and oral aspirin in diabetic retinopathy. METHODS: Farnsworth-Munsell (FM) 100-hue test was successfully administered before initiation of study treatment in each eye of 2701 of the 3711 ETDRS patients. Test results were converted into a Fourier series, classified by cluster analysis in the deferred-treatment group of eyes, and verified in the immediate-treatment group of eyes as separate samples. RESULTS: Cluster analysis uncovered thirteen distinct patterns. Pattern A (51% or 1366 of the eyes) showed unimpaired hue discrimination and was comprised of younger patients with no or little macular edema. Pattern B eyes (10% or 262) showed generalized impairment of hue discrimination with no main axis defect. Patterns C (C1, C2, C3), comprising 26% (or 698) of the eyes, showed increasing severity of the yellow-blue diabetic retinopathy defect, associated with increasing mean age and increasing macular edema severity. Patterns D (D1, D2), comprising 6% (or 164) of the eyes, were similar to the C patterns but showed a stronger yellow-blue defect. Patterns E (E1, E2, E3), or approximately 2% (or 38) of the eyes and predominantly male, exhibited the expected pattern for congenital protan defect. Patterns F, G, and H, approximately 6% (or 153) of the eyes, showed distinct patterns of one-sided axes. The nomenclature is arbitrary. CONCLUSIONS: Cluster analysis of FM 100-hue test results has found 13 patterns of impaired hue discrimination, helpful in understanding color vision defects in diabetes mellitus.     

Infusion of the substance P analogue, DiMe-C7, into the ventral tegmental area induces reinstatement of cocaine-seeking behaviour in rats

Rationale The mesocorticolimbic dopamine (DA) system is critically involved in mediating reinstatement of drug-seeking behaviour. Substance P (SP) is a neuropeptide that significantly interacts with the mesocorticolimbic system, therefore suggesting a possible role for the SP system in the mediation of relapse.Objectives This study examined the effects of injections of the SP analogue, DiMe-C7, into the ventral tegmental area (VTA) on reinstatement of cocaine-seeking behaviour, as well as on locomotor activity in rats. Additionally, this study examined whether these effects are DA-dependent.Methods Rats were trained to self-administer cocaine for 15 days followed by 15 days of extinction. Reinstatement of cocaine-seeking behaviour was then measured in response to bilateral intra-VTA microinjections of DiMe-C7 (0, 0.1, 0.5 and 2.5 g). In a separate group of rats, locomotor activity was measured in response to intra-VTA injections of DiMe-C7 (0, 0.5, 1.5 and 3 g). The effects of pre-treatment with DA receptor antagonists on DiMe-C7-induced reinstatement and locomotor activity were also examined. Animals were pre-treated with the D₁ and D₂ receptor antagonists, SCH23390 and haloperidol (0, 0.01 and 0.03 mg/kg, IP), respectively, prior to receiving intra-VTA injections of DiMe-C7 (0 and 2.5 g).Results Infusion of DiMe-C7 into the VTA increased locomotor activity and induced reinstatement of cocaine-seeking behaviour. Both SCH23390 and haloperidol blocked intra-VTA DiMe-C7-induced locomotor activation. In addition, SCH23390 attenuated DiMe-C7-induced reinstatement of cocaine-seeking behaviour, while haloperidol had no effect.Conclusions These results suggest that interactions between SP and the mesocorticolimbic DA system may play a role in mediating reinstatement of cocaine-seeking behaviour and that the involvement of these interactions in reinstatement are dependent upon D₁ receptor mechanisms.Canadian Institutes of Health Research grant to Franco J. Vaccarino.     

Mortality from cutaneous malignant melanoma in Europe. Has the epidemic levelled off?

Trends of mortality from cutaneous malignant melanoma (CMM) between 1960 and 1999 in several European countries and the European Union (EU) as a whole have been reviewed, using death certification data for skin cancer available from the World Health Organization. Separate analyses were performed for young (i.e., age 20-44 years) and middle-aged (i.e., age 45-64 years) adults, among whom around 80-90% of skin cancer deaths are attributable to CMM. After steady rises between 1960 and 1990, skin cancer rates among young adults have tended to decline since the mid-1990s in several European countries, with a fall of 14% in men and of 11% in women in the EU as a whole. In middle-aged adults, the trends were less favourable, although mortality started to level off since the mid-1990s. Thus, our data provide further evidence of an improvement of CMM mortality trends in recent years in several European countries. The particularly favourable trends in young people suggest that a further decline in mortality from CMM in Europe is likely to occur within the next few years.     

Cochlear implants in systemic autoimmune vasculitis syndromes

The concept that autoimmunity may damage the inner ear was introduced by McCabe in 1979. Audiovestibular symptoms may occur in isolation or may be mediated by vasculitis in patients affected by systemic autoimmune disorders. Sensorineural hearing loss (SNHL) is typical in Cogan's syndrome but occurs less frequently in Be?het's syndrome and in systemic necrotizing vasculitides. Patients affected by immune-mediated profound SNHL represent ideal candidates for cochlear implantation as these patients become deaf after years of hearing. The disease itself and the medication taken may, however, influence the prognosis of cochlear implantation in these patients. We retrospectively evaluated the pre- and intraoperative findings as well as the postoperative course and performance of a group of five patients affected by a systemic vasculitis syndrome who received a cochlear implant. Implantation was successful in all patients, no complications occurred and excellent postoperative speech perception was achieved. We conclude that cochlear implantation in patients affected by immune-mediated inner ear disorders is effective although the long-term results remain to be evaluated.     

Cisplatin may be a valid alternative approach in ovarian carcinoma with carboplatin hypersensitivity. Report of three cases

Platinum-based therapy is considered the standard treatment for patients with advanced ovarian cancer. Carboplatin has a more favorable toxicity profile than cisplatin; however, hypersensitivity reactions to carboplatin have been reported occasionally. We reviewed 112 cases of ovarian cancer treated with carboplatin at our institute to identify the hypersensitivity reactions to this chemotherapeutic agent. Hypersensitivity reactions were documented in nine cases (8%). No deaths occurred, but the reactions were judged severe in three of the 112 patients (2.6%). In our own experience with patients showing idiosyncrasy to carboplatin we observed successful resolution after retreatment with cisplatin. Since patients who relapse after initial treatment with carboplatin often respond to it a second time, it is important to continue this treatment.