(68)Ga-DOTANOC PET/CT detection of multiple extracranial localizations in a patient with anaplastic meningioma.

We report herein a case of a 65-year-old male with intracranial recurrence of atypical meningioma initially treated with a combination of surgical resection and gamma knife radiotherapy. Afterwards, he underwent a (68)Ga-DOTANOC PET/CT scan in order to evaluate the feasibility of peptide receptor radionuclide therapy (PRRT). The scan identified multiple pulmonary, pleural and lymph node localizations. Histological diagnosis was consistent with intracranial atypical meningioma with diffuse metastatic spread. In our case, we have shown that meningioma with extracranial locations may present high uptake of somatostatin receptor analogues. Among other radionuclides, we believe that (68)Ga-DOTANOC PET/CT may be particularly useful for staging, detection of recurrence, evaluation of disease extension and alternative therapeutic approaches.

Diabetic mastopathy: case report.

UNLABELLED: Diabetic mastopathy is a rare fibro-inflammatory breast disease, which occurs in premenopausal women affected by longstanding type I insulin-dependent diabetes. It is a benign disease and it is often misunderstood for its clinical and radiological features that may mimic a breast cancer. The diagnosis of diabetic mastopathy is based on histological examination and it is characterized by lymphocytic lobulitis with glandular atrophy and perivascular lymphocytic infiltration. The patients do not need to undergo surgery but it is necessary to plan an adequate clinical and radiological monitoring program. KEY WORDS: Diabetic mastopathy, Diagnostic and therapeutic features.

Clostridium difficile-related pancolitis in lung-transplanted patients with cystic fibrosis.

C. difficile (C. d.) is the main cause of antibiotic-associated diarrhea and colitis. It is shown in literature a high asymptomatic carriage rate of C. d. in patients with cystic fibrosis (CF), though C. d.-related colitis is an uncommon complication in these patients, despite the use of multiple high-dose antibiotic regimes and the frequency of hospital admissions. Lung transplantation with the associated immunosuppression and aggressive antibiotic therapy may increase the risk of the clinical manifestation of C. d. In this paper, we describe three cases of severe C. d. colitis in patients with CF following lung transplantation and illustrate our experience in the diagnosis and management of these patients.

Heat stress disorders and headache: a case of new daily persistent headache secondary to heat stroke.

Headache is considered as a common symptom of heat stress disorders (HSD), but no forms of secondary headache from heat exposure are reported in the International Classification of Headache Disorders-2 Edition (ICHD-II). Heat-stroke (HS) is the HSD most severe condition, it may be divided into two forms: classic (due to a long period environmental heat exposure) and exertional (a severe condition caused by strenuous physical exercises in heat environmental conditions). Here we report the case of a patient who developed a headache clinical picture fulfilling the diagnostic criteria for new daily persistent headache (NDPH), after an exertional HS, and discuss about possible pathophysiological mechanisms and classification aspects of headache induced by heat conditions.

Evaluation and proposal for optimalization of neurophysiological tests in migraine: part 1--electrophysiological tests.

Neurophysiological testing has become a valuable tool for investigating brain excitability and nociceptive systems in headache disorders. Previous reviews have suggested that most neurophysiological tests have limited value for headache diagnosis, but a vast potential for exploring the pathophysiology of headaches, the central effects of certain pharmacological treatments and phenotype-genotype correlations. Many protocols, however, lack standardization. This meta-analytical review of neurophysiological methods in migraine was initiated by a task force within the EUROHEAD project (EU Strep LSHM-CT-2004-5044837-Workpackage 9). Most of the neurophysiological approaches that have been used in headache patients are reviewed, i.e. evoked potentials, nociception-specific blink reflex, single-fibre electromyography, neuroimaging methods (functional MRI, PET, and voxel-based morphometry) and the nitroglycerin attack-provoking test. For each of them, we summarize the results, analyse the methodological limitations and propose recommendations for improved methodology and standardization of research protocols. The first part is devoted to electrophysiological methods, the second to neuroimaging techniques and the NTG test.

Interictal abnormalities of gamma band activity in visual evoked responses in migraine: an indication of thalamocortical dysrhythmia?

Between attacks, migraineurs lack habituation in standard visual evoked potentials (VEPs). Visual stimuli also evoke high-frequency oscillations in the gamma band range (GBOs, 20-35 Hz) assumed to be generated both at subcortical (early GBOs) and cortical levels (late GBOs). The consecutive peaks of GBOs were analysed regarding amplitude and habituation in six successive blocks of 100 averaged pattern reversal (PR)-VEPs in healthy volunteers and interictally in migraine with (MA) or without aura patients. Amplitude of the two early GBO components in the first PR-VEP block was significantly increased in MA patients. There was a significant habituation deficit of the late GBO peaks in migraineurs. The increased amplitude of early GBOs could be related to the increased interictal visual discomfort reported by patients. We hypothesize that the hypofunctioning serotonergic pathways may cause, in line with the thalamocortical dysrhythmia theory, a functional disconnection of the thalamus leading to decreased intracortical lateral inhibition, which can induce dishabituation.

Sertoli cell tumor: a rare case in an elderly patient.

Sertoli-Leydig cell tumors constitute < 1% of ovarian tumors, mostly in young women with virilization; however, not all present endocrine manifestations. A 72-year-old female presented with an abdominal mass and no signs of virilization. Total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy and selective pelvic lymphadenectomy was performed. The pathologic diagnosis was poorly-differentiated sex cord-stromal tumor with Sertoli cells. No adjuvant chemotherapy or radiation was administered. At 12-month follow-up the patient showed no evidence of disease.

A novel ATP1A2 mutation in a family with FHM type II.

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura with an autosomal dominant pattern of inheritance. Six FHM families underwent extensive clinical and genetic investigation. The authors identified a novel ATP1A2 mutation (E700K) in three patients from one family. In the patients, attacks were triggered by several factors including minor head trauma. In one subject a 3-day coma developed after a cerebral angiography. Overall, the phenotype of the patients closely resembles that of previously reported cases of FHM type II. The E700K variant might be regarded as the cause of the disease in this family, but this was not tested functionally.

Familial basilar migraine associated with a new mutation in the ATP1A2 gene.

Basilar migraine (BM), familial hemiplegic migraine (FHM), and sporadic hemiplegic migraine (SHM) are phenotypically similar subtypes of migraine with aura, differentiated only by motor symptoms, which are absent in BM. Mutations in CACNA1A and ATP1A2 have been found in FHM. The authors detected a novel mutation in the ATP1A2 gene (R548H) in members of a family with BM, suggesting that BM and FHM may be allelic disorders.

Human subtelomere structure and variation.

Work towards completion of the human reference genome sequence has revealed a great deal of complexity and plasticity in human subtelomeric regions. The highly variable subtelomeric repeat regions are filled with recently shuffled genomic segments, many of which contain sequences matching transcripts and transcript fragments; the rapid duplication and combinatorial evolution of these regions has generated an extremely diverse set of subtelomeric alleles in the human species, the complexity and potential significance of which is only beginning to be understood. This review summarizes recent progress in analyzing human subtelomeric sequence assemblies and large-scale variation in human subtelomere regions.

On the importance of anandamide structural features for its interactions with DPPC bilayers: effects on PLA2 activity.

The acylethanolamide anandamide (AEA) occurs in a variety of mammalian tissues and, as a result of its action on cannabinoid receptors, exhibits several cannabimimetic activities. Moreover, some of its effects are mediated through interaction with an ion channel-type vanilloid receptor. However, the chemical features of AEA suggest that some of its biological effects could be related to physical interactions with the lipidic part of the membrane. The present work studies the effect of AEA-induced structural modifications of the dipalmitoylphosphatidylcholine (DPPC) bilayer on phospholipase A2 (PLA2) activity, which is strictly dependent on lipid bilayer features. This study, performed by 2-dimethylamino-(6-lauroyl)-naphthalene fluorescence, demonstrates that the effect of AEA on PLA2 activity is concentration-dependent. In fact, at low AEA/DPPC molar ratios (from R = 0.001 to R = 0.04), there is an increase of the enzymatic activity, which is completely inhibited for R = 0.1. X-ray diffraction data indicate that the AEA affects DPPC membrane structural properties in a concentration-dependent manner. Because the biphasic effect of increasing AEA concentrations on PLA2 activity is related to the induced modifications of membrane bilayer structural properties, we suggest that AEA-phospholipid interactions may be important to produce, at least in part, some of the similarly biphasic responses of some physiological activities to increasing concentrations of AEA.

[Renal transplantation in the North Italy Transplant program (NITp): Organ allocation and results]. / Il trapianto renale nel Nord Italia Transplant program (NITp): assegnazione degli organi e risultati.

Renal transplantation is an effective therapeutic tool for patients with end-stage renal diseases (ESRDs). Data reported in this article summarize the results obtained from 30 years' activity in the North Italy Transplant program (NITp), the first transplant organization in Italy that implemented a donor procurement and organ transplantation network. In the NITp kidney allocation is governed by a computerized algorithm, NITK3, put in place in 1997, aimed at ensuring equity, transparency and traceability during the stages of the allocation decision-making process. The NITp working group has recognized the NITK3 criteria and they are periodically reviewed following the results of the analysis of patients' transplantation odds. The results obtained with the use of the NITK3 algorithm have been very satisfactory: after 6 yrs, a significantly higher percentage of patients at immunological risk (sensitized or waiting for re-transplant), of patients waiting for >3 yrs and of patients with 0-1 HLA A,B,DR mismatches have been transplanted. Moreover, a higher percentage of kidneys were used locally (in a hospital within the procurement area), and this is known to stimulate donor procurement. Finally, we performed a preliminary statistical analysis of transplants carried out from 1998-2002 in 5/16 centers of the NITp area, demonstrating the quality of the NITp program in terms of patient and graft survival, and that donor and recipient age are the variables significantly impacting on transplant results.

Adenosarcoma of the ovary. A case report.

Adenosarcoma of the ovary is a rare condition. We report a case of a 32-year-old patient that has been treated in our Department. The diagnosis of ovarian adenosarcoma was carried out after laparoscopy with removal of an ovarian endometriotic cyst. Laparoscopic homolateral ovariectomy was then performed and conservative treatment was decided on considering the young age, low stage and low grade of the disease. Second-look laparoscopy, clinical evaluation and ultrasound were performed for four years of follow-up. No recurrence has been detected. Conservative treatment should be proposed in fertile age with low-grade ovarian adenosarcoma, but a strict follow-up is always necessary.

Efficacy of an acidic vaginal gel on vaginal pH and interleukin-6 levels in low-risk pregnant women: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Increased interleukin-6 (IL-6) levels and a vaginal pH of > 4.7 are associated with obstetric complications such as preterm delivery and low birth weight. Topical treatments, able to maintain a physiological vaginal pH, could help in the prevention of vaginal infections. STUDY AIM: In a randomized, double-blind, placebo-controlled trial, we evaluated the effects of an acidic buffering vaginal gel (Miphil) on vaginal pH and IL-6 levels in pregnant women. PATIENTS AND METHODS: Seventy low-risk women pregnant with a singleton (second trimester) were enrolled in the trial. Thirty-five were randomized to the acidic gel, 2.5 g every 3 days for 12 weeks, and 35 to the corresponding placebo. Vaginal pH and vaginal IL-6 level were measured at baseline and after 12 weeks. Women were then followed until delivery. The main outcome measures were vaginal pH, vaginal pH normalization (pH < 4.5) and vaginal IL-6 levels. RESULTS: Vaginal pH at baseline was 4.6 +/- 0.4 and 4.4 +/- 0.3 in the acidic gel and the placebo group, respectively. At baseline, a total of 40% (14/35) and 22% (8/35) of women in each group, respectively, had a vaginal pH of > or = 4.7. At week 12, the vaginal pH was 4.3 +/- 0.3 in the acidic gel group and 4.3 +/- 0.3 in the placebo group (NS). The acidic gel normalized the vaginal pH in ten out of 14 women (p = 0.04) in comparison with only one out of eight women in the placebo group (NS). The acidic gel induced a significant (p < 0.02) reduction of vaginal IL-6 from 12.0 +/- 7 to 8.9 +/- 5 pg/l (-36%). In the placebo group, IL-6 increased from 9.0 +/- 5 to 13.5 +/- 6.8 pg/l (+50%) (p = 0.05). Birth weight was 2978 +/- 700 g in the placebo group and 3241 +/- 477 g in the acidic gel group (p = 0.06). CONCLUSIONS: The use of the acidic gel in low-risk pregnant women is able to maintain a physiological vaginal ecosystem and prevents the increases of vaginal pH and vaginal IL-6. Prospective and controlled trials are warranted to evaluate whether this acidic gel can reduce obstetric complications linked to vaginal inflammation during pregnancy.

Lack of habituation causes high intensity dependence of auditory evoked cortical potentials in migraine.

Migraineurs are characterized interictally by lack of habituation, or even potentiation, of cortical evoked potentials during repetitive stimulation and by a strong intensity dependence of auditory evoked potentials (IDAP). To determine whether these two features of sensory processing are interrelated, we have studied them simultaneously on the same recordings of auditory evoked potentials (AEPs). AEPs were obtained at four different stimulation intensities in 14 patients suffering from migraine without aura (MO) and 14 healthy volunteers (HV). For each intensity, 120 trials were averaged off-line globally and over four sequential blocks of 30 trials. IDAP was expressed by the amplitude/stimulus intensity function (ASF slope) for global and block averages. Habituation was calculated as the percentage amplitude variation between the first and fourth blocks for each stimulus intensity. The IDAP slope for global averages was higher in MO (1.05 +/- 0.27 microV/10 dB) than in HV (0.64 +/- 0.45 microV/10 dB) (P = 0.008), but IDAP slopes for block averages were greater in MO only at the fourth block (P = 0.048). First block amplitudes tended to be lower in MO, except at 80 dB. There was a potentiation of AEP amplitudes at every stimulus intensity in MO, contrasting with habituation in HV. IDAP slopes were negatively correlated with mean habituation percentages in pooled data from patients and controls (r = -0.610; P = 0.0006). This study confirms that IDAP is higher in migraineurs than in healthy controls. It also shows that the AEP habituation is replaced by potentiation at all stimulus intensities. The negative correlation found between IDAP and habituation suggests that the latter is able to have a strong influence on the former and perhaps even lead to it. In migraine, the habituation deficit amplifies the IDAP and may thus be the causal functional abnormality. We propose that it is due to a decreased pre-activation level of sensory cortices, a hypothesis also supported in this study by the lower amplitude of first AEP blocks in patients.

Idiopathic infertility: susceptibility of spermatozoa to in-vitro capacitation, in the presence and the absence of palmitylethanolamide (a homologue of anandamide), is strongly correlated with membrane polarity studied by Laurdan fluorescence.

Capacitation is a widely investigated process, which induces sperm plasma membrane changes resulting in its increased affinity for the zona pellucida. The fluorescent probe Laurdan, localized only within the plasma membrane of spermatozoa, is particularly useful to evaluate bilayer polarity in this part of the cell. According to a previous study, sperm membranes from oligozoospermic and some normozoospermic subjects (defined according to World Health Organization criteria), are characterized by low polarity (high Laurdan exGP(340)), while the spermatozoa from the remaining normozoospermic men show a larger polarity (low exGP(340)). In this paper, Laurdan was used to study membrane changes occurring during in-vitro capacitation, on sperm membranes from oligozoospermic and normozoospermic subjects. Results indicated that cells with high exGP(340) show a different susceptibility to Ca(2+)-induced capacitation in vitro, as compared with cells with low exGP(340). Palmitylethanolamide, physiologically present in human reproductive tracts, affects the time-course of in-vitro capacitation, increasing the rate of this process only in the cells with a lower membrane polarity.

Electrophysiological studies in migraine: a comprehensive review of their interest and limitations.

Electrophysiological methods may help to unravel some of the pathophysiological mechanisms of migraine. Lack of habituation is the principal and most reproducible interictal abnormality in sensory processing in migraineurs. It is found in evoked potential (EP) studies for every stimulation modality including nociceptive stimuli, and it is likely to be responsible for the increased intensity dependence of EP. We have hypothesized that deficient EP habituation in migraine could be due to a reduced preactivation level of sensory cortices because of hypofunctioning subcortico-cortical aminergic pathways. This is not in keeping with simple hyperexcitability of the cortex, which has been suggested by some, but not all, studies of transcranial magnetic stimulation (TMS). A recent study of the effects of repetitive TMS on visual EP strongly supports the hypothesis that migraine is characterized by interictal cortical hypoexcitability. With regard to pain mechanisms in migraine, electrophysiological studies of trigeminal pathways using nociceptive blink and corneal reflexes have confirmed that sensitization of central trigeminal nociceptors occurs during migraine attacks.