CT Angiography ASPECTS Predicts Outcome Much Better Than Noncontrast CT in Patients with Stroke Treated Endovascularly.

BACKGROUND AND PURPOSE: Noncontrast CT ASPECTS has been investigated as a predictor of outcome in patients with acute ischemic stroke. Our purpose was to investigate whether CTA source images are a better predictor of clinical and radiologic outcomes than NCCT ASPECTS in candidates for endovascular stroke therapy. MATERIALS AND METHODS: CT scans of patients (n = 124) were independently evaluated by 2 readers for baseline NCCT and CTA source image ASPECTS and for follow-up ASPECTS. An mRS of ≤2 at 3 months was considered a favorable outcome. Receiver operating characteristic curve analysis was used to assess the ability of NCCT and CTA source image ASPECTS to identify patients with favorable outcomes. A stepwise multiple regression analysis was performed to find independent predictors of outcome. RESULTS: Baseline CTA source image ASPECTS correlated better than NCCT ASPECTS with follow-up ASPECTS (r = 0.76 versus r = 0.51; P for comparison of the 2 coefficients < .001). Receiver operating characteristic curve analysis showed that baseline CTA source image ASPECTS compared with NCCT ASPECTS can better identify patients with favorable outcome (CTA source image area under the curve = 0.83; 95% CI, 0.76-0.91; NCCT area under the curve = 0.67; 95% CI, 0.58-0.77; P < .001). Finally, the stepwise regression analysis showed that lower age, good recanalization, lower time to recanalization, and good baseline CTA source image ASPECTS, not NCCT ASPECTS, were independent predictors of favorable outcome. CONCLUSIONS: CTA source image ASPECTS predicts outcome better than NCCT ASPECTS; this finding suggests CTA rather than NCCT as a main step in the decision-making process for patients with acute ischemic stroke.

PtI2(DACH), the iodido analogue of oxaliplatin as a candidate for colorectal cancer treatment: chemical and biological features.

Colorectal cancer (CRC) is a global health problem being the fourth most common cause of death due to cancer worldwide. Oxaliplatin plays a key role in current CRC treatment but shows serious drawbacks, such as a high systemic toxicity and the frequent insurgence of Pt resistance. In search of novel and more efficacious Pt-based drugs for CRC treatment, we synthesized and characterised PtI2(DACH), an oxaliplatin analogue. PtI2(DACH) was obtained through the replacement of bidentate oxalate with two iodides. PtI2(DACH) turned out to be more lipophilic than oxaliplatin, a fact that led to an enhancement of its cellular uptake. In contrast to oxaliplatin, PtI2(DACH) showed a scarce reactivity towards model proteins, while maintaining affinity for a standard DNA oligo. Notably, PtI2(DACH) induced cytotoxicities roughly comparable to those of oxaliplatin in three representative CRC cell lines. Moreover, it was able to trigger cell apoptosis, to an extent even better than cisplatin and oxaliplatin. Overall, a rather promising picture emerges for this novel Pt drug that merits, in our opinion, a deeper and more extensive preclinical evaluation.

Coronally Advanced Flap with Different Designs in the Treatment of Gingival Recession: A Comparative Controlled Randomized Clinical Trial.

The aim of this parallel double-blind randomized controlled clinical trial was to describe a modified approach using the coronally advanced flap (CAF) with triangular design and to compare its efficacy, in terms of root coverage and esthetics, with a trapezoidal type of CAF. A sample of 50 isolated Miller Class I and II gingival recessions with at least 1 mm of keratinized tissue apical to the defects were treated with CAF. Of these recessions, 25 were randomly treated with trapezoidal CAF (control group) while the other 25 (test group) were treated with a modified triangular CAF. The clinical and esthetic evaluations, made by the patient and an independent periodontist, were performed 3 months, 6 months, and 1 year after the surgery. No statistically significant difference was demonstrated between the two CAF groups in terms of recession reduction, complete root coverage, or 6-month and 1-year patient esthetic scores. Better 3-month patient esthetic evaluations and better periodontist root coverage, color match, and contiguity assessments were reported after triangular CAF. Trapezoidal CAF was associated with greater incidence of keloid formation. Single-type gingival recessions can be successfully covered with both types of CAF. The triangular CAF should be preferred for esthetically demanding patients.

The use of Animal-Assisted Therapy in adolescents with acute mental disorders: A randomized controlled study.

OBJECTIVES: The aim of this study was to compare the effects of Animal-Assisted Therapy (AAT) with a standard treatment protocol in children and adolescents admitted to the psychiatry hospital for acute mental disorders. We used a methodology involving high quality standards for AAT research. DESIGN: A pre-post experimental design with a randomized controlled trial (RCT) in 34 hospitalized patients (17 treatment, 17 control) was carried out. MAIN OUTCOME MEASURES: The study focused on improvement in clinical status including, global functioning measured by the Children Global Assessment Scale (C GAS), format of care and ordinary school attendance measured by a rating scale. RESULTS: Our results indicate a statistically significant improvement in global functioning, reduction in format of care and increased ordinary school attendance in the treatment group, but not in the control group. CONCLUSIONS: Our results verify that AAT can have significant positive effects on therapeutic progress and the recovery process.

Iatrogenic anemia (can it be prevented?).

'Iatrogenic anemia' is a condition of lowered hematocrit and hemoglobin count resulting from large or frequent removal of blood samples, usually for laboratory testing. It is frequently seen in patients who are already suffering from bone marrow depression, and thus may become a comorbidity. Because several different types of chemical agents may be required for test procedures, a large volume of blood could be removed for each set of testing, perhaps 50-60 mL. Often local and reference laboratories request larger samples than are really necessary to perform a given test and still have some left to perform any required repeat testing. My experience shows that a volume of about 3 mL of each type of sample should be sufficient for this purpose.

Phlebographic study does not show differences between patients with MS and control subjects.

BACKGROUND AND PURPOSE: Hypothetical correlation between chronic cerebrospinal venous insufficiency and MS has gained the attention of patients and the scientific community. Studies performed by echo-color Doppler ultrasonography have shown different results, and it is necessary to use more objective diagnostic techniques. The aim of our study was to evaluate the presence of stenoses affecting azygos veins and internal jugular veins by use of venography in patients with MS. MATERIALS AND METHODS: We recruited 2 groups of subjects who underwent venography: the study group included 29 patients with MS and the control group included 15 healthy volunteers. The ileo-lumbar plexus, the azygos, and the internal jugular veins were selectively catheterized. We considered any cross-sectional area reduction of the venous lumen >50% to be a significant stenosis. Furthermore, blood pressure was measured in the studied vessels at the stenotic internal jugular veins. RESULTS: Selective venography showed at least 1 significant venous stenosis in 84% of subjects examined, without significant difference between the study group and the control group. Positive venography chronic cerebrospinal venous insufficiency patterns were found in 50% of all subjects examined, without any significant difference between the 2 groups. The multivariate logistic regression analysis failed to assess any significant association between the presence of a positive venography and MS condition. The difference between the median blood pressure of stenotic and nonstenotic internal jugular veins was not statistically significant (P = .46). CONCLUSIONS: Our data exclude any direct correlation between chronic cerebrospinal venous insufficiency and MS because venous abnormalities were equally present in both groups.

Decompressive craniectomy may cause diagnostic challenges to assess brain death by computed tomography angiography.

According to Italian legislation to diagnose brain death (BD) after the initial documentation of the clinical signs, repetition of clinical testing and confirmation of the loss of bioelectrical activity of the brain (EEG) is required. However, when EEG is unreliable it is necessary to demonstrate cerebral circulatory arrest (CCA). Accepted imaging techniques to demonstrate CCA include: cerebral angiography, cerebral scintigraphy, transcranial Doppler (TCD) and computed tomography angiography (CTA). This latter technique, due to its large availability, low invasivity and easy and fast acquisition is widely used over the country. Nevertheless its diagnostic reliability is affected by some limitations in patients with decompressive craniectomy. Here we report two cases of brain injury with clinical signs of BD and at the same time, opacification of intracranial arteries on CTA and a pattern consistent with flow arrest on the corresponding insonable arteries on TCD. The discrepancy between CTA and TCD results points out a methodology limitation that could be overcome by updating Italian legislation according to other European Countries legislation.

Interaction of maternal separation on the UCh rat cerebellum.

Maternal care is the main source of signals and stimuli for proper development, growth, and production of adjustment responses to stressful factors. Adverse experiences in childhood are associated with a vulnerability to developing abusive ethanol ingestion via alterations of the response of the hypothalamic-pituitary-adrenal axis. Alcoholism causes global brain abnormalities, with the cerebellum being one of the most susceptible areas. We evaluated the effect of maternal separation on the cerebellum structure of male UCh rats. Adult male UChA (low 10% ethanol consumption) and UChB (high 10% ethanol consumption) rats were divided in to four experimental groups: (1) UChA, (2) UChA maternal separation (MS), (3) UChB, and (4) UChB MS. The MS occurred between the 4th and 14th days of age, for 240 min day(-1) . Euthanasia was performed at 120 days of age. An image analysis system was used to measure cerebellar cortical height and Purkinje cellular area and height in five rats from each group. The cerebellar sections were stained with antibodies against IGFR-I. MS did not alter the ethanol consumption of UChA and UChB rats. Corticosterone level was significantly higher in UChA MS and UChB MS rats than in UChA and UChB rats. The Purkinje cellular area and height were higher in UChA MS rats. IGFR-I expression was observed in the cortical glomerular area of UChA MS and UChB MS rats. MS altered the Purkinje cells in the cerebella of male UCh rats.

Patients with xeroderma pigmentosum complementation groups C, E and V do not have abnormal sunburn reactions.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair. It is divided into eight complementation groups: XP-A to XP-G (classical XP) and XP variant (XP-V). Severe and prolonged sunburn reactions on minimal sun exposure have been considered a cardinal feature of classical XP. However, it has recently become clear that not all patients have abnormal sunburn reactions. OBJECTIVES: To examine sunburn reactions in a cohort of patients with XP and correlate this to the complementation group. METHODS: Sixty patients with XP attending the U.K. National XP Service from 2010 to 2012 were studied. Their history of burning after minimal sun exposure was assessed using a newly developed sunburn severity score. The age at which the first skin cancer was histologically diagnosed in each patient, and the presence of any neurological abnormality, was also recorded. RESULTS: Sunburn severity scores were abnormally high in patients with XP-A, XP-D, XP-F and XP-G compared with non-XP controls. There was no significant difference in sunburn score of patients with XP-C, XP-E and XP-V compared with controls (P > 0·05). Patients with XP-C, XP-E and XP-V were more likely to have skin cancer diagnosed at an earlier age than those with severe sunburn on minimal sun exposure. In addition, patients with XP with severe sunburn had an increased frequency of neurological abnormalities. CONCLUSIONS: Not all patients with XP have a history of severe and prolonged sunburn on minimal sun exposure. The normal sunburn response of patients with XP-C, XP-E and XP-V may relate to the preservation of transcription-coupled DNA repair in these groups. Those with a history of severe sunburn on minimal sun exposure developed their first skin cancer at an older age compared with patients with XP-C, XP-E and XP-V, but they had an increased frequency of neurological abnormalities. Physicians need to be aware that about half of all patients with XP will present without a history of abnormal sunburn.

Endovascular management of acute stroke.

Ischemic stroke is the third leading cause of death and most common cause of permanent disability in industrialized nations. Eighty-five percent of strokes are ischemic in nature, with an associated mortality between 53% and 92%. The focus of treatment for acute stroke starts with prompt and accurate diagnosis of ischemic brain tissue at risk, followed by time sensitive delivery of therapy that effectively and safely restores flow to that vascular territory. Time-dependent reperfusion therapy is the only proven treatment for Acute Ischemic Stroke. In this paper, we review the clinical and imaging factors that are relevant to guide endovascular treatment decisions; the different approaches of stroke therapy and the devices used with the goal of obtaining the most rapid and complete recanalization possible, while minimizing vascular damage and hemorrhagic complications. It is paid particular attention to indications and outcomes of the different endovascular stroke therapy devices use, as defined in major clinical trials or current clinical practice. Anterior circulation strokes represent the primary focus of this review.

Glial cell line-derived neurotrophic factor promotes invasive behaviour in testicular seminoma cells.

The glial cell line-derived neurotrophic factor (GDNF) has multiple functions that promote cell survival, proliferation and migration in different cell types. The experimental over-expression of GDNF in mouse testis leads to infertility and promotes seminomatous germ cell tumours in older animals, which suggests that deregulation of the GDNF pathway may be implicated in germ cell carcinogenesis. GDNF activates downstream pathways upon binding to its specific co-receptor GDNF family receptor-a 1 (GFRA1). This complex then interacts with Ret and other co-receptors to activate several intracellular signalling cascades. To explore the involvement of the GDNF pathway in the onset and progression of testicular germ cell tumours, we analysed GFRA1 and Ret expression patterns in seminoma samples. We demonstrated, via immunohistochemistry, that GFRA1, but not Ret, is over-expressed in in situ carcinoma (CIS) and in intratubular and invasive seminoma cells compared with normal human germ cells. Functional analysis of the GDNF biological activity was performed on TCam-2 seminoma cell line. Reverse transcription-PCR (RT-PCR) and immunohistochemical analyses demonstrate that TCam-2 cells express both GFRA1 and Ret mRNA, but only GFRA1 was detected at the protein level. In TCam-2 cells, although GDNF is not mitogenic, it is able to induce migration, as demonstrated by a Boyden chamber assay, possibly through the Src and MEK pathways. Moreover, GDNF promotes invasive behaviour, an effect dependent on pericellular protease activity, possibly through the activity of matrix metalloproteinases. GFRA1 over-expression in CIS and seminoma cells, along with the functional analyses in TCam-2 cells, suggests an involvement of the GDNF pathway in the progression of testicular germ cell cancer.

Prevalence study of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: preliminary data.

PURPOSE: This study aimed to evaluate the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS). MATERIAL AND METHODS: From November 2009 to February 2010, 74 participants (40 MS patients and 34 healthy controls) were enrolled in a randomised singleblind prospective study. All participants underwent ultrasonography (US) to detect signs of CCSVI. RESULTS: CCSVI was detected in 55% of patients in the MS group and 35% in the control group; the difference was not statistically significant (p=0.089). CONCLUSIONS: In our experience, a slight difference exists in the prevalence of CCSVI between MS and healthy controls, but it is not as yet clear which parameters may be most significant. This preliminary study failed to show a statistically significant difference in the prevalence of CCSVI among patients affected by MS. It did, however, reveal a tendency that requires a larger number of patients to achieve statistically significant results.

Depression and anxiety in perinatal period: prevalence and risk factors in an Italian sample.

Accumulating evidence suggests that pregnancy does not protect women from mental illness. The aim of this study was to assess the prevalence, sociodemographic correlates, and the risks factors for perinatal depression and anxiety. Five hundred ninety women between 28th and the 32nd gestational weeks were recruited and submitted to a sociodemographic, obstetric, and psychological interview. The Edinburgh Postnatal Depression Scale (EPDS) and the state-trait anxiety inventory (STAI-Y) were also administered in antenatal period and 3 months postnatally. The Structured Clinical Interview for DSM-IV (SCID-I) was used to diagnose mood and anxiety disorders. Three months after delivery, EPDS was administered by telephone interview. Women with an EPDS score ≥10 were 129 in antenatal period (21.9%) and 78 in postnatal period (13.2%). During pregnancy 121 women (20.5%) were positive for STAI-Y state and 149 women (25.3%) for STAI-Y trait. The most important risk factors for antenatal depression are: foreign nationality, conflictual relationship with family and partner, and lifetime psychiatric disorders. The principal risk factors for postnatal depression are: psychiatric disorders during pregnancy and artificial reproductive techniques. Psychiatric disorders, during and preceding pregnancy, are the strongest risk factors for antenatal state and trait anxiety. Antenatal depressive and anxiety symptoms appear to be as common as postnatal symptoms. These results provide clinical direction suggesting that early identification and treatment of perinatal affective disorders is particularly relevant to avoid more serious consequences for mothers and child.

Coronaric stent-graft deployment in the treatment of carotid blowout.

"Carotid blowout syndrome" is defined as a hemorrhage caused by rupture of the carotid artery and its branches, and may be a severe complication of rhinopharyngeal carcinoma. This study aimed to highlight the usefulness and versatility of endovascular stent-graft placement as a rescue treatment in life-threatening carotid blowout syndrome. We describe the unconventional use of a 6 × 5 mm balloon-expandable coronaric covered stent in a patient with a diagnosis of spinocellular rhinopharyngeal carcinoma, followed by carotid blowout syndrome. Although long-term follow-up is needed to assess the eventuality of bleeding recurrence, the immediate clinical results were satisfactory.

The effect of hepatocyte growth factor on the initial stages of mouse follicle development.

Interactions between theca and granulosa cells of the follicle are critical for the coordination of ovarian follicle development. The cell-cell interactions are mediated through the local production and actions of a variety of factors. The current study is designed to investigate the expression of Hgf and its receptor, c-Met, in the mouse ovary during in vivo folliculogenesis. We found that Hgf and c-Met mRNAs were already expressed in 2-day-old ovaries, and that, while c-Met levels remained constant until 22-day-old, Hgf levels slightly but not significantly increased with age. The expression of Hgf mRNA in theca/interstitial cells was higher than in granulosa cells in 22-day-old ovaries. Immunohistochemistry analysis confirmed the expression pattern demonstrated by RT-PCR. We investigated the role of hepatocyte growth factor (HGF) at the beginning of mouse folliculogenesis and its possible interaction with kit ligand (KL). Interestingly, both KL and HGF were able to increase the expression of each other, creating a positive feedback loop. In the presence of HGF, we observed an increase of granulosa cell proliferation and an increase in the number of pre-antral and early antral follicles in ovary organ cultures. We also observed a significant increase in the diameters of follicles in individual follicle cultures. Moreover, HGF stimulated the expression of the FSH receptors, both in the whole ovary and in isolated pre-antral follicle cultures. Based on the data presented, we concluded that HGF exerts multiple levels of control over follicular cell functions, which collectively enable the progression of follicular development.

Trichothiodystrophy: from basic mechanisms to clinical implications.

Trichothiodystrophy (TTD) is an autosomal recessive disorder with symptoms affecting several tissues and organs. The most relevant features are hair abnormalities, physical and mental retardation, ichthyosis, signs of premature aging and cutaneous photosensitivity. The clinical spectrum of TTD varies widely from patients with only brittle, fragile hair to patients with the most severe neuroectodermal symptoms. To date, four genes have been identified as responsible for TTD: XPD, XPB, p8/TTDA, and TTDN1. Whereas the function of TTDN1 is still unknown, the former three genes encode subunits of TFIIH, the multiprotein complex involved in basal and activated transcription and in nucleotide excision repair (NER). Ongoing investigations on TTD are elucidating not only the pathogenesis of the disease, which appears to be mainly related to transcriptional impairment, but also the modalities of NER and transcription in human cells and how TFIIH operates in these two fundamental cellular processes.

Beta-chemokine receptor CCR5 in human spermatozoa and its relationship with seminal parameters.

BACKGROUND: Chemokine receptor CCR5, the main HIV-1 coreceptor, is present in the human spermatozoa. This study aimed to investigate (i) whether the percentage of CCR5-positive spermatozoa varies under conditions associated with changes in the membrane architecture, such as capacitation and fixation/permeabilization procedures; (ii) whether there is any relationship between individual variability in sperm CCR5 expression and semen parameters. METHODS AND RESULTS: In cytometric analysis, the percentage of CCR5-positive unfixed spermatozoa varied from approximately 10 to approximately 60%, and it significantly decreased after 5 h capacitation. The percentage of CCR5-positive spermatozoa was increased to more than 90% following fixation and permeabilization, suggesting the existence of large intracellular pools of the receptor. Immunocytochemistry showed positive staining in the anterior region of the sperm head. In ejaculates from male partner of 102 infertile couples, the CCR5 expression rate significantly correlated with sperm count, total sperm number and forward motility, but not with sperm morphology. In stepwise analysis, only forward motility entered into the model; however, this explained only approximately 8% of the variability in CCR5 expression. Interquartile analysis showed significant differences between the first and fourth quartiles of CCR5 expression for all semen parameters, except morphology. CONCLUSIONS: The percentage of CCR5-positive spermatozoa may vary under conditions associated with changes in membrane architecture and spermatozoa showed large intracellular pools of CCR5. A lower expression of CCR5 in asthenozoospermia seems to be suggested; however, it would only partially contribute to the inter-individual variability in the CCR5 expression. A genetic basis can be hypothesized to explain the variability.

Hand and ultrasonic instrumentation in combination with root-coverage surgery: a comparative controlled randomized clinical trial.

BACKGROUND: The role of vigorous root planing in the surgical treatment of gingival recession was recently questioned. The aim of the present randomized controlled split-mouth clinical study was to compare the effectiveness, in terms of root coverage, of hand and ultrasonic root instrumentation in combination with a coronally advanced flap for the treatment of isolated-type recession defects. METHODS: Eleven systemically and periodontally healthy subjects with bilateral recession defects (> or = 3 mm) of similar (< or = 1 mm) depth affecting contralateral teeth were enrolled in the study. Only Miller Class I gingival recession with no deep cervical abrasion or root caries/demineralization were included in the study. Control root exposures were treated with curets, whereas test roots were instrumented with ultrasonic piezoelectric devices. Randomization for test and control treatment was performed by a coin toss immediately prior to surgery. All recessions were treated with a coronally advanced flap surgical technique. The clinical reevaluation was made 6 months after surgery. RESULTS: The two approaches resulted in a high percentage of root coverage (95.4% in the control group and 84.2% in the test group) and complete root coverage (82% in the control group and 55% in the test teeth), with no statistically significant difference between them. Clinical attachment level gains were clinically significant in both groups (3.36 +/- 0.92 mm in the control group and 2.90 +/- 0.70 mm in the test group), with no statistically significant difference between them. The increase in keratinized tissue height was statistically significant in both groups (0.55 +/- 0.52 mm in the control group and 0.36 +/- 0.67 mm in the test group), with no difference between them. CONCLUSIONS: The present study failed to demonstrate any superiority, in terms of root-coverage results, for hand instruments over ultrasonic treatment of the root surface in combination with coronally advanced flap mucogingival surgery. Further studies of longer-term duration and larger sample size could help to establish the superiority of one form of root instrumentation in conjunction with root-coverage surgery.

Carotid artery stenting: findings based on 8 years' experience.

PURPOSE: Carotid artery stenting (CAS) may be an alternative to surgical endarterectomy not only in high-risk patients. Few data are available regarding the long-term clinical efficacy of CAS with the use of cerebral protection devices and the incidence of restenosis. Our experience demonstrates that if certain requirements are fulfilled, CAS can be considered a safe and effective treatment with high short-and long-term success rates. MATERIALS AND METHODS: In the past 8 years, we treated 1,003 patients (1,096 arteries) affected by internal carotid artery stenosis, 93 with bilateral stenosis. Of these, 567 (51.74%) were symptomatic and 529 (48.26%) asymptomatic lesions. The preprocedural evaluation was performed with Doppler ultrasound (US), magnetic resonance (MR) angiography/computed tomography (CT) angiography and a neurological evaluation. Antiplatelet therapy was administered before and after the procedure. RESULTS: Technical success was achieved in 1,092 cases (99.6%), and a cerebral protection device was successfully used in 1,019 procedures (92.9%). The 30-day transient ischaemic attack (TIA)/stroke/death rate was 2.16%: death (0.18%) major stroke (0.45%) and minor stroke/TIA (1.53%). During a follow-up up to 8 years, restenoses occurred in 39 cases (3.57%), of which 28 were post-CAS (2.57%) and 11 post-CAS performed for restenosis after carotid endarterectomy (1%). Only five symptomatic restenoses>80% were treated with a repeated endovascular procedure. CONCLUSIONS: A retrospective analysis of our experience suggests that CAS is a safe and effective procedure with better results than endarterectomy. In up to 8 years of follow-up, CAS seems to be effective in preventing stroke, with a low restenosis rate.