Flunarizine in migraine prophylaxis: efficacy and tolerability of 5 mg and 10 mg dose levels

The use of flunarizine, a drug which has proven its efficacy in migraine, is often associated with important side effects. The aim of this paper has been to check their incidence at different dose levels (5 mg vs 10 mg). Our data confirm the occurrence of important side effects (in particular weight gain); on the other hand, they emphasize the dose-dependency of the side effects.     

Hypochromic Reticulated Streaks in Incontinentia Pigmenti: An Immunohistochemical and Ultrastructural Study

A 25-year-old woman who recently gave birth to a baby affected by classic lesions of incontinentia pigmenti (IP), had hypochromic, atrophic, and reticulated streaks on both lower limbs. Her personal history was unremarkable for IP, and physical examination revealed no other cutaneous signs of the disease. Immunohistochemical and electron microscopic studies were performed on biopsies obtained from both normal and hypochromic skin of the leg. Hypochromic skin showed epidermal atrophy and lack of adnexae, without significant melanocyte abnormality. As demonstrated by this patient, hypochromic reticulated streaks can represent the only cutaneous marker of IP in adulthood. Careful search for such skin lesions in the mother of a child with IP is essential in order to ascertain whether there is a risk of its occurrence in future offspring.     

A family with autosomal dominant mutilating neuropathy not linked to either Charcot-Marie-Tooth disease type 2B (CMT2B) or hereditary sensory neuropathy type I (HSN I) loci.

Sensory loss and ulcero-mutilating features have been observed in hereditary sensory neuropathy type I and in hereditary motor and sensory neuropathy type IIB, also referred as Charcot-Marie-Tooth disease type 2B. To date two loci associated with ulcero-mutilating neuropathy have been described: CMT2B at 3q13-q22 and HSN I at 9q22.1-q22.3. We performed linkage analysis with chromosomal markers representing the hereditary sensory neuropathy type I and Charcot-Marie-Tooth disease type 2B loci on an Italian family with a severe distal sensory loss leading to an ulcero-mutilating peripheral neuropathy. Negative likelihood-of-odds scores excluded any evidence of linkage to both chromosome 3q13 and chromosome 9q22 markers, confirming the genetic heterogeneity of this clinical entity and the presence of a third locus responsible for ulcero-mutilating neuropathies.     

BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial

Vitamin D receptor (VDR) gene polymorphisms could be considered one of the factors influencing the efficacy of the anti-osteoporotic treatments. In this multicenter, prospective, randomized and controlled trial we evaluated whether BsmI vitamin D receptor (VDR) genotypes influence the efficacy of antiresorptive treatment regimes (administered alone or in combination) in postmenopausal osteoporotic women. Using restriction endonuclease, we identified the BsmI VDR polymorphism in 1,100 postmenopausal women with osteoporosis. The women were randomized, taking account of genotype, into five treatment groups: (1) alendronate (Aln, 10 mg/day) plus raloxifene (Rlx, 60 mg/day); (2) Aln plus hormone replacement therapy (HRT, 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate); (3) Aln alone; (4) HRT alone; and (5) Rlx alone. Lumbar-spine bone mineral density (BMD) and bone turnover markers were measured at study entry and after 1 year of treatment. Using the general linear model (GLM) repeated-measures procedure, the means of BMD and bone turnover markers significantly differed from baseline after a period of treatment. In particular, the mean change from baseline for BMD was –0.034 (95% confidence interval [CI]: –0.037 to –0.031, P <0.001); for serum osteocalcin (OC) it was 1.369 (95% CI: 1.289 to 1.448, P <0.001); and for urinary deoxypyridinoline (DPD) it was 1.322 (95% CI: 1.242 to 1.401, P <0.001), indicating a considerable variation before and after treatment of these indicators. In all three cases these effects appeared significantly influenced by treatments, genotypes, and the treatments*genotypes interaction term (P <0.001 each, except for the BMD and genotype effect with P =0.02), and not by the investigational centers involved in the study. In conclusion, in postmenopausal osteoporotic women, BsmI VDR genotypes influence the efficacy of antiresorptive drugs particularly when used in combination.     

Grammar improvement following deep brain stimulation of the subthalamic and the pedunculopontine nuclei in advanced Parkinson's disease: A pilot study

Combined deep brain stimulation of the subthalamic (STN) and pedunculopontine (PPN) nuclei has been recently proposed as surgical treatment of advanced Parkinson's disease. STN stimulation alone has been shown to provide selective improvement of the grammatical aspect of language. We studied five advanced Parkinson's disease patients who underwent combined deep brain stimulation (STN + PPN). Overall cognitive profile did not change. On the contrary, an interesting trend towards reduction of ungrammatical errors (particularly substitution of free and inflectional morphemes) was found when stimulating the STN, and also the PPN, when the STN was switched off. These findings replicate previous observations on the STN, and provide the rationale for further investigation of the role of the PPN in processing linguistic grammar.     

Drugs of anaesthesia and cancer

Anaesthesia represents one of the most important medical advances in history, and, nowadays, can widely be considered safe, thanks to the discovery of new drugs and the adoption of modern technologies. Nevertheless, anaesthetic practices still represent cause for concern regarding the consequences they produce. Various anaesthetics are frequently used without knowing their effects on specific diseases: despite having been reported that invasion or metastasis of cancer cells easily occurs during surgical procedures, numerous anaesthetics are used for cancer resection even if their effect on the behaviour of cancer cells is unclear.Guidelines for a proper use of anaesthetics in cancer surgery are not available, therefore, the aim of the present review is to survey available up-to-date information on the effects of the most used drugs in anaesthesia (volatile and intravenous anaesthetics, nitrous oxide, opioids, local anaesthetics and neuromuscular blocking drugs) in correlation to cancer. This kind of knowledge could be a basic valuable support to improve anaesthesia performance and patient safety.     

Can the reversible regional wall motion abnormalities on stress gated Tc-99m sestamibi SPECT predict a future cardiac event?

BACKGROUND: Myocardial stunning has recently been demonstrated by use of stress gated technetium 99m sestamibi single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy. However, its prognostic value is less well determined. The aim of this study was to investigate the prognostic value of reversible regional wall motion abnormalities (RWMAs). METHODS AND RESULTS: We studied 303 consecutive subjects with known or suspected coronary artery disease who underwent 2-day stress-rest gated Tc-99m sestamibi SPECT and were followed up for 19 +/- 16 months. Clinical and test-derived variables were evaluated to predict cardiac death, nonfatal myocardial infarction (MI), unstable angina, and early or late coronary revascularization. Reversible RWMAs were identified in 102 patients. On Cox analysis, the presence, site, degree, and extent of reversible RWMAs did not identify an adverse outcome, except in patients without prior MI. After adjustment for prescan data, the strongest predictors of hard events and all cardiac events were poststress RWMAs and the amount of ischemia. The addition of poststress RWMAs to the combined model of prescan and perfusion data yielded incremental prognostic value. CONCLUSION: Poststress RWMAs and ischemia by perfusion were the most powerful predictive parameters of cardiac events. However, myocardial stunning should always be considered, particularly in patients without prior MI and in the referral of patients for early revascularization.     

Suggestive association between the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia.

G-proteins are composed of alpha, beta and gamma subunits. Once activated, these subunits play a major role in the conversion of external receptor activation into intracellular signals. The functional C825T polymorphism of the beta3 subunit gene (GNB3) has recently been shown to modulate antidepressant response, with the T-allele conferring an increased signaling and being associated with favorable antidepressant response. We hypothesized that this polymorphism may be associated with response to antipsychotics in a population of 145 chronic schizophrenic patients deriving from two study-samples and being mainly treated with clozapine for up to 6 months. Overall, the C/C genotype was significantly associated with relative clinical improvement as measured by Brief Psychiatric Rating Scale (BPRS) change scores after 6 and 12 weeks (p<0.01 and p=0.03, respectively), with estimated effect sizes ranging from 4.8 to 7%. Our results further suggest that this effect is only attributable to Caucasians when compared to African-Americans. Moreover, our findings point to the role of intracellular mechanisms in antipsychotic response.     

Dedifferentiated chordoma of the thoracic spine with rhabdomyosarcomatous differentiation. Report of a case and review of the literature

A case of spinal thoracic chordoma involving the T9 vertebra in a 70-year-old male patient, destroying the vertebral body and invading the vertebral canal with compression of the spinal cord, is presented. The patient was referred to our neurosurgical unit with a history of an irradiated metastatic adenocarcinoma to the thoracic vertebra, a diagnosis that was rendered 3 years earlier at another hospital on presentation. This misdiagnosis was likely due to the absolute rarity of thoracic vertebral chordomas (2%-3% of all chordomas), the higher frequency of metastatic deposits to the vertebrae from visceral cancers in the elderly, the limited amount of biopsy material available for histologic examination, and the epithelial phenotype of the tumor (keratin/EMA positive). The patient underwent second palliative surgery with subtotal piecemeal removal of the tumor bringing relief of the neurologic symptoms. The bulk of the tumor was represented by a high-grade pleomorphic sarcoma with adjacent areas of atypical chordoma. Small foci of conventional chordoma were also found. The previous histologic slides were also reviewed, which were consistent with the areas of atypical chordoma. Small targeted tissue fragments from areas of (atypical) chordoma and from sarcomatous areas were recovered for electron microscopy. The fine features of chordoma and focal rhabdomyoblastic differentiation were found with the latter retrospectively supported by immunohistochemical detection of striated muscle markers. A final diagnosis of dedifferentiated chordoma with rhabdomyoblastic differentiation was finally established. Rhabdomyoblastic metaplasia is a novelty in dedifferentiated chordoma. The patient died after 5 months. Autopsy was not requested.