Edemas of the face and lymphoscintigraphic examination.

Facial edemas not secondary to surgery and/or radiotherapy for head and neck cancer are relatively uncommon. Our aim is to report a retrospective analysis of the lymphoscintigraphic and SPECT-CT investigations obtained in patients with such facial edema. Retrospective review of exams (planar imagings in all and with SPECT-CT in 5) obtained after the subcutaneous injection of 99mTc HSA Nanosized colloids between the eyebrows in five men and seven women. Four main lymphatic pathways were identified on sequential planar imagings: para-nasal left and right and supra- ocular left and right. For eleven patients, the absence of visualization of lymphatic drainage and/or their delayed appearance correlated well with the localisation of the edematous areas. In two patients with post-traumatic and post- surgical edemas, SPECT-CT showed one deep left sided cervical lymph node (LN) in front of the first cervical vertebra. This lymphoscintigraphic approach represents a simple and valuable way to assess the lymphatic drainage pathways of the face and to establish the diagnosis of facial lymphedema.

Supermicrosurgical Lymphaticovenular Anastomosis for a Breast Lymphedema Secondary to vascularized Axillary Lymph Node Flap Transfer.

Breast lymphedema (BLE) can occur after breast cancer treatments, but there have been no cases of BLE secondary to lymph node transfer (LNT) using an axillary lymph node (ALN). We report the first case of LNT-related BLE successfully treated with supermicrosurgical lymphaticovenular anastomosis (LVA). A 50-year-old female presented with left BLE after LNT harvesting from the left axilla for the treatment of secondary lower extremity lymphedema in another hospital. Although the left breast did not seem edematous, the patient suffered from sensation of tension and frequent episodes of left breast cellulitis. Since conservative treatments were not effective, LVA was performed at the lateral thoracic region. A 0.5 mm lymphatic vessel was found and anastomosed to a nearby 0.35 mm vein in an intima-to-intima coaptation manner. After the LVA, the patient experienced no sensation of tension or further cellulitis attacks. Although rarely encountered, BLE can occur after axillary LNT, and LVA may be a useful therapeutic option.

Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke.

AIM: Constitutive genetic deletion of the adaptor protein p66(Shc) was shown to protect from ischaemia/reperfusion injury. Here, we aimed at understanding the molecular mechanisms underlying this effect in stroke and studied p66(Shc) gene regulation in human ischaemic stroke. METHODS AND RESULTS: Ischaemia/reperfusion brain injury was induced by performing a transient middle cerebral artery occlusion surgery on wild-type mice. After the ischaemic episode and upon reperfusion, small interfering RNA targeting p66(Shc) was injected intravenously. We observed that post-ischaemic p66(Shc) knockdown preserved blood-brain barrier integrity that resulted in improved stroke outcome, as identified by smaller lesion volumes, decreased neurological deficits, and increased survival. Experiments on primary human brain microvascular endothelial cells demonstrated that silencing of the adaptor protein p66(Shc) preserves claudin-5 protein levels during hypoxia/reoxygenation by reducing nicotinamide adenine dinucleotide phosphate oxidase activity and reactive oxygen species production. Further, we found that in peripheral blood monocytes of acute ischaemic stroke patients p66(Shc) gene expression is transiently increased and that this increase correlates with short-term neurological outcome. CONCLUSION: Post-ischaemic silencing of p66(Shc) upon reperfusion improves stroke outcome in mice while the expression of p66(Shc) gene correlates with short-term outcome in patients with ischaemic stroke.

Analysis of genes, pathways and networks involved in disease severity and age at onset in primary-progressive multiple sclerosis.

BACKGROUND: The role of genetic factors in influencing the clinical expression of multiple sclerosis (MS) is unclear. OBJECTIVE: The objective of this paper is to identify genes, pathways and networks implicated in age at onset (AAO) and severity, measured using the Multiple Sclerosis Severity Score (MSSS), of primary-progressive MS (PPMS). METHODS: We conducted a genome-wide association study (GWAS) of 470 PPMS patients of Italian origin:. Allelic association of 296,589 SNPs with AAO and MSSS was calculated. Pathway and network analyses were also conducted using different tools. RESULTS: No single association signal exceeded genome-wide significance in AAO and MSSS analyses. Nominally associated genes to AAO and MSSS were enriched in both traits for 10 pathways, including: "oxidative phosphorylation" (FDRAAO=9*10(-4); FDRMSSS=3.0*10(-2)), "citrate (TCA) cycle" (FDRAAO=1.6*10(-2); FDRMSSS=3.2*10(-3)), and "B cell receptor signaling" (FDRAAO=3.1*10(-2); FDRMSSS=2.2*10(-3)). In addition, an enrichment of "chemokine signaling pathway" (FDR=9*10(-4)) for AAO and of "leukocyte transendothelial migration" (FDR=2.4*10(-3)) for MSSS trait was observed, among others. Network analysis revealed that p53 and CREB1 were central hubs for AAO and MSSS traits, respectively. CONCLUSIONS: Despite the fact that no major effect signals emerged in the present GWAS, our data suggest that genetic variants acting in the context of oxidative stress and immune dysfunction could modulate the onset and severity of PPMS.

Stroke care in young patients.

The aims of this study were (i) to evaluate the clinical features of a consecutive series of young patients with ischemic stroke and (ii) to assess the changes in the clinical management of these patients over the study period. All consecutive cases of young adults aged 16 to 44 years, with ischemic stroke, that were admitted between 2000 and 2005 in 10 Italian hospitals were included. We retrospectively identified 324 patients. One or more vascular risk factors were present in 71.5% of the patients. With respect to the diagnostic process, an increase in the frequency of cerebral noninvasive angiographic studies and a decrease in the use of digital subtraction angiography were observed (P < 0.001 and P = 0.03, resp.). Undetermined causes decreased over 5-year period of study (P < 0.001). The diagnosis of cardioembolism increased. Thrombolysis was performed for 7.7% of the patients. PFO closure (8%) was the most frequently employed surgical procedure. In conclusion, the clinical care that is given to young patients with ischemic stroke changed over the study period. In particular, we detected an evolution in the diagnostic process and a reduction in the number of undetermined cases.

Differential features of carotid and vertebral artery dissections: the CADISP study.

OBJECTIVE: To examine whether risk factor profile, baseline features, and outcome of cervical artery dissection (CEAD) differ according to the dissection site. METHODS: We analyzed 982 consecutive patients with CEAD included in the Cervical Artery Dissection and Ischemic Stroke Patients observational study (n = 619 with internal carotid artery dissection [ICAD], n = 327 with vertebral artery dissection [VAD], n = 36 with ICAD and VAD). RESULTS: Patients with ICAD were older (p < 0.0001), more often men (p = 0.006), more frequently had a recent infection (odds ratio [OR] = 1.59 [95% confidence interval (CI) 1.09-2.31]), and tended to report less often a minor neck trauma in the previous month (OR = 0.75 [0.56-1.007]) compared to patients with VAD. Clinically, patients with ICAD more often presented with headache at admission (OR = 1.36 [1.01-1.84]) but less frequently complained of cervical pain (OR = 0.36 [0.27-0.48]) or had cerebral ischemia (OR = 0.32 [0.21-0.49]) than patients with VAD. Among patients with CEAD who sustained an ischemic stroke, the NIH Stroke Scale (NIHSS) score at admission was higher in patients with ICAD than patients with VAD (OR = 1.17 [1.12-1.22]). Aneurysmal dilatation was more common (OR = 1.80 [1.13-2.87]) and bilateral dissection less frequent (OR = 0.63 [0.42-0.95]) in patients with ICAD. Multiple concomitant dissections tended to cluster on the same artery type rather than involving both a vertebral and carotid artery. Patients with ICAD had a less favorable 3-month functional outcome (modified Rankin Scale score >2, OR = 3.99 [2.32-6.88]), but this was no longer significant after adjusting for baseline NIHSS score. CONCLUSION: In the largest published series of patients with CEAD, we observed significant differences between VAD and ICAD in terms of risk factors, baseline features, and functional outcome.

IL28B polymorphisms are not associated with the response to interferon-ß in multiple sclerosis.

Recent studies have revealed an association between interleukin 28B (IL28B) and response to IFN-alpha treatment in hepatitis C patients. Here we investigated the influence of IL28B polymorphisms in the response to interferon-beta (IFNß) in multiple sclerosis (MS) patients. We genotyped two SNPs of the IL28B gene (rs8099917 and rs12979860) in 588 MS patients classified into responders (n=281) and non-responders (n=307) to IFNß. Combined analysis of the study cohorts showed no significant associations between SNPs rs8099917 and rs12979860 and the response to treatment. These findings do not support a role of IL28B polymorphisms in the response to IFNß in MS patients.

Surgical treatment of patent omphalomesenteric duct presenting as faecal umbilical discharge.

A newborn infant with patent omphalomesenteric duct (POMD), who presented faecal umbilical discharge, was treated with a semicircular periumbilical incision up to the abdominal cavity. The omphalomesenteric duct was followed up to the junction with the small intestine and there resected. The abdominal wall was closed without resection of the umbilicus.

Effect of melatonin on hypoglycemia and metoclopramide-stimulated arginine vasopressin secretion in normal men.

The present study was performed in order to establish whether melatonin (MEL) plays a role in the regulation of arginine vasopressin secretion (AVP) in normal human subjects. For this purpose, the effects of an oral administration of 6 or 12 mg MEL on basal and metoclopramide (MCP)- or hypoglycemia-stimulated AVP secretion was tested in 18 normal men. MCP was given at a dose of 20 mg as an intravenous (i.v.) bolus; hypoglycemia was induced with an i.v. bolus injection of 0.15 IU/kg body weight of insulin. In addition, in view of the well-known inhibitory effect of MEL on the growth hormone (GH) response to hypoglycemia, GH levels were measured during the insulin tolerance test (ITT), as an independent index of MEL activity. MEL did not produce any change in AVP secretory patterns in basal conditions or during the MCP test. In contrast, the mean peak AVP response to hypoglycemia was 2.33 times higher than baseline in the control ITT, whereas it was only 1.77 times higher than baseline in the ITT plus MEL tests. Also, the GH response to hypoglycemia was significantly lower in the presence than in the absence of MEL. For both AVP and GH, the inhibitory effect of MEL during ITT was similar, when either 6 or 12 mg MEL was given. These data indicate an involvement of MEL in the control of the AVP response to hypoglycemia, but not of basal and MCP-induced AVP secretion. In addition, the similar effects of MEL on GH and AVP secretions during ITT suggest that similar neuroendocrine mechanisms underlie these hormonal responses to hypoglycemia.

Effect of propionyl-L-carnitine on the mechanics of right and left papillary muscles from volume-overloaded rat hearts.

Propionyl-L-carnitine (PLC) was shown to improve global cardiac function in pressure overload hypertrophy by acting directly on muscle mechanics. We investigated whether PLC can effectively ameliorate papillary muscle mechanics in a volume overload (VO) model. We induced VO by constructing an aortocaval anastomosis in adult Wistar rats. Three experimental groups were studied: sham-operated controls and untreated and PLC-treated VO animals. Isometric function of right and left papillary muscle was studied 16-18 weeks later. PLC was administered in the drinking water at the dose of 180 mg/kg for the last 2 weeks before experiment. One-way analysis of variance (ANOVA) showed that in right papillary muscles from the untreated VO group the time course of the isometric contraction was significantly prolonged [time-to-peak tension (TPT, ms +/- SEM) from 126 +/- 4.9 to 156 +/- 7.1; time from peak tension to 30% relaxation (TRel) from 133 +/- 11.9 to 196 +/- 13.9; n = 11 and 8, respectively], and peak rates of contraction and relaxation normalized over developed tension were significantly decreased in comparison with sham [from (s-1 +/- SEM) 12.9 +/- 0.5 to 10.8 +/- 0.6, and from 7.2 +/- 0.6 to 5.2 +/- 0.4, respectively]. These parameters in the PLC VO group did not differ from sham (TPT, 140 +/- 5.7; TRel, 158 +/- 14.4; +dF/df/DT, 12.2 +/- 0.6; -dF/df/DT, 6.5 +/- 0.5; n = 8). Function of left papillary muscle was not modified by either VO or PLC treatment. Total carnitine levels in either ventricle free walls were unchanged by VO. PLC significantly increased total carnitine content of left ventricle free wall (from 5.4 +/- 0.28 to 7.0 +/- 0.50). The contraction changes observed in the right papillary muscle are likely to depend on the pressure overload occurring in the right chamber; moreover, they are unrelated to tissue carnitine depletion. PLC improved the altered right papillary muscle mechanics without exerting any apparent effect on the functionally normal left papillary muscle. PLC activity is independent of carnitine stores, but may presumably be ascribed to its anaplerotic properties.

Propionyl-L-carnitine prevents myocardial mechanical alterations due to pressure overload in rats.

This study investigated if propionyl-L-carnitine (PLC) treatment can directly affect cardiac mechanics, secondary to increase in myocardial carnitine content, in rats with aortic constriction and sham-operated controls. After weaning, rats were fed one of the following diets for 8 wk: 1) a low-carnitine diet (containing 2 nmol/g carnitine); 2) the same diet supplemented with PLC (710 mumol/kg body wt); 3) L-carnitine (LC; 118 mumol/kg body wt, given in tap water; or 4) a standard diet (containing 56 nmol/g carnitine). A 4-wk constriction of the abdominal aorta caused left ventricular hypertrophy associated with significantly prolonged timing parameters and reduced rate of tension decay in papillary muscles. In group 2, however, PLC treatment prevented hypertrophy-induced changes in these parameters and the reduction in unloaded shortening velocity in skinned trabeculae. Finally, PLC treatment maintained the relative proportion of myosin heavy chain isoforms in left ventricular wall of animals subjected to aortic constriction. Both PLC and LC completely prevented carnitine depletion due to hypertrophy and to dietary restriction. Because LC did not modify papillary muscle contractile function, these results demonstrate that PLC affects hypertrophy-induced changes in muscle mechanics and ventricular wall composition independently of tissue carnitine levels.

Different effects of delta-sleep-inducing peptide on arginine-vasopressin and ACTH secretion in normal men.

UNLABELLED: Delta-sleep-inducing peptide (DSIP) is a well-known inhibitor of pituitary ACTH secretion. In order to evaluate the possible influence of DSIP on basal arginine-vasopressin (AVP) secretion and/or on the AVP-response to osmotic and pressure/volumetric stimuli, DSIP (25 nmol/kg) was infused in 10 min to 8 normal men (23-34 years old) just before a 2-hour infusion of normal saline (NaCl 0.9%; DSIP test) or hypertonic saline (0.51 M NaCl; osmotic test) or before an orthostatic test (standing upright and maintaining an orthostatic position for 20 min). In different occasions, a 10-min infusion of normal saline (placebo) was given instead of DSIP. In an additional 7 subjects, DSIP or placebo was given 60 min before hypertonic saline or the orthostatic test. The results obtained after the administration of DSIP at time 0 and at -60 min were similar. RESULTS: The administration of DSIP or normal saline alone did not change the concentrations of circulating AVP. A slight physiological decline in ACTH levels was observed during saline infusion, whereas a significant decrease in ACTH levels was induced by DSIP administration. Osmotic stimulation of AVP secretion by hypertonic NaCl induced a significant increase in plasma AVP concentrations which was not modified by DSIP administration. The ACTH secretory patterns during hypertonic NaCl and hypertonic NaCl plus DSIP were similar to those observed during normal saline and normal saline plus DSIP, respectively. The orthostatic test provided similar plasma AVP increments, regardless of the previous treatment with DSIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of potentiation of cholinergic tone by pyridostigmine on the GH response to GHRH in elderly men.

The plasma GH response to GHRH (100 micrograms i.v.) was evaluated either alone or after pretreatment with pyridostigmine (120 mg orally 1 h prior to GHRH) in 9 younger men (age range: 22-39 years) and in 9 healthy elderly men (age range: 63-77 years). On a different occasion, subjects were tested with pyridostigmine alone. Basal concentrations of glucose, cortisol, androgens, estrogens, thyroid hormones and GH were similar in all subjects, whereas insulin-like growth factor was lower in elderly men. The GH response to GHRH was significantly lower in the older (mean peak was 6 times higher than baseline) than in the younger group (mean peak was 11.3 times higher than baseline). The pretreatment with pyridostigmine induced a striking increase in the GH response to GHRH in the younger subjects (mean peak was 26 times higher than baseline), whereas it produced only a slight increase in the GHRH-induced GH response in elderly men (mean peak was 8.7 times higher than baseline). When pyridostigmine was given alone, plasma GH levels rose significantly in both groups; however, the pyridostigmine-stimulated GH response was significantly higher in younger (mean peak was 6 times higher than baseline) than in older subjects (mean peak was 2.5 times higher than baseline). These data indicate that the cholinergic stimulatory regulation of GH release is reduced in elderly subjects. Since acetylcholine inhibits hypothalamic somatostatin release, the reduced cholinergic tone in elderly subjects may result in an increased somatostatinergic tone.

Effects of intravenous endothelin on hemodynamics and cardiac contractility in conscious Milan normotensive rats.

The effects of endothelin-1 (ET-1) on hemodynamics and cardiac contractility were compared with the responses to angiotensin I (AI) and phenylephrine (PE) in Milan normotensive rats. Intravenous (i.v.) injection of ET-1 (0.8 nmol/kg) initially decreased mean blood pressure (MBP), total peripheral resistance (TPR), and dP/dt (-28 +/- 2, -34.8 +/- 3.7, and -9.4 +/- 1.3%, p less than 0.01, respectively), and increased heart rate (HR), cardiac output (CO), and the velocity of myocardial anterior wall shortening (dL/dt) (11.8 +/- 2.1, 10.4 +/- 2.9, and 28.3 +/- 8.3% p less than 0.05, respectively). These effects were followed by a sustained increase in MBP and TPR and a decrease in CO. As compared with AI (0.25 nmol/kg) and PE (35 nmol/kg), which produced a similar degree of increase in TPR, the reduction in CO induced by ET-1 was more prominent (-25 +/- 2 by ET-1 vs. -14 +/- 2 by AI and -14 +/- 3% by PE, p less than 0.05, respectively). Moreover, ET-1 induced a significant decrease in dP/dt, shortening fraction (SF), and dL/dt (-6.1 +/- 1.6, -35.0 +/- 3.8, and -38.6 +/- 5.5%, p less than 0.01, respectively), whereas these indexes of left ventricle performance were not affected by either AI or PE. Furthermore, the reduction in SF induced by ET-1 was mainly due to the decrease in myocardial diastolic segment length, suggesting reduction in diastolic filling volume.(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary myxedema in an adult. Notes on a case]. / Mixedema primitivo dell'adulto. Osservazioni su un caso.

In the case of adult primary myxedema reported the diagnostic suspicion aroused by objective examination was confirmed by assaying the hypophysial-thyroid hormones (blood T4 and T3 below normal levels) and by the behaviour of certain muscle enzymes (CPK, LDH, GOT) that bore witness to diffuse muscle and bone damage (hypothyroid "myopathy"). The presence of antithyroid antibodies, though in small amounts suggested earlier and unnoticed thyroiditis as a possible aetiopathogenic explanation. The clinical and metabolic picture undoubtedly benefited from treatment with L-Thyroxine.

[In vitro chemo-antibiotic sensitivity of gram-negative bacteria from various biological materials. Comparison between aztreonam and other agents]. / Chemioantibiotico sensibilità "in vitro" di batteri gram-negativi provenienti da diverso materiale biologico. Confronto tra aztreonam ed altri agenti.

527 Gram negative bacterial strains isolated from different biological substances were studied by chemo-antibiotic sensitivity. The examination was carried out by the agar diffusion test (Kirby-Bauer). A very good sensitivity to aztreonam (E. coli, Serratia spp., Klebsiella spp., Proteus spp.), to amikacin (Pseudomonas spp., Enterobacter spp., Citrobacter spp.) and to norfloxacin (Citrobacter spp.) was found. Even when it was not the best, aztreonam was the second (Citrobacter spp.) or the third choice (Pseudomonas spp.), always near to the drug of first choice.