Epileptic seizure frequency and semiology in dogs with idiopathic epilepsy after initiation of imepitoin or phenobarbital monotherapy.

The aim of this study was to evaluate changes in epileptic seizures (ES) frequency and semiology in antiepileptic-medication (AEM)-naïve dogs with idiopathic epilepsy (DIE) after initiation of imepitoin (IMP) or phenobarbital (PB) monotherapy. In this observational prospective cohort study, inclusion criteria were as follows: diagnosis of idiopathic epilepsy (based on clinical, laboratory and magnetic resonance imaging investigations) in AEM-naïve dogs and presence of a detailed ES-diary. Exclusion criteria were: occurrence of cluster seizures (CS) or status epilepticus (SE) prior to treatment initiation and concurrent disease and/or treatments. Thirty-one DIE commenced IMP at 10-20mg/kg/12h and 30 dogs commenced PB at 2.50-3.30mg/kg/12h. AEM dosage was increased over time (up to IMP 30mg/kg/12h and PB 5.20mg/kg/12h). All dogs experienced generalised-tonic-clonic ES. In the IMP-group, pre-treatment median ES-frequency was 1.50ES/month (range, 1-4ES/month); post-treatment median ES-frequency was 0.95ES/m (range, 1ES/6m-3ES/m); n=21/31 (67.70%) dogs developed CS 1-18 months after initiation of treatment; n=7/31 (22.60%) dogs experienced unacceptable adverse events in the first month of treatment which required switching to an alternative AEM; and n=3/31(9.70%) dogs did not develop CS with a 3year follow-up. In the PB-group, pre-treatment median ES-frequency was 2.46ES/month (range, 1-7ES/month); post-treatment median ES-frequency was 0.36ES/month (range, 0ES/3years-1ES/month); n=11/30 (36.70%) dogs developed CS between 12-25 months after initiation of treatment. Nineteen of 30 (63.30%) dogs did not develop CS with a 3-year follow-up; three of these 19 dogs were ES free. In this study, AEM-naïve DIE receiving imepitoin-monotherapy developed CS significantly more frequently and earlier in the course of the disease, and developed aggression and required earlier discontinuation of monotherapy than AEM-naïve DIE receiving phenobarbital-monotherapy.

Recovery and characterization of nickel particles by chemical reduction method from wastes generated in electroless industry.

The discarded solutions by the chemical nickel industry have high amounts of nickel, this is why they are considered hazardous wastes for the health and the environment. On the other side, Ni particles can have potential applications in the developing of magnetorheological fluids currently being used to improve the performance of mechanical devices. The present study raises the treatment of a residual effluent from a chemical nickel industry by applying a chemical precipitation which uses sodium hypophosphite as a reducer, and varying the order of the reagents involved in the conditioning of the reaction with respect to the reducer. The recovered solids were studied using different material characterization techniques to recognize the chemical composition (X-Ray Fluorescence, Inductively Coupled Plasma Mass Spectrometry), crystallinity and morphology (X-Ray Diffraction, Scanning Electron Microscope), surface charge and size distribution (Dynamic Light Scattering). By the chemical reduction treatment it was possible to decrease the amount of nickel in the residual between 97.25% and 99.50%, obtaining Ni particles that were then tested to be used in magnetic fluids. To this purpose a suspension was prepared by mixing the Ni particles with silicone oil in a constant solid/liquid ratio, and the rheological behavior of this suspension was evaluated as a function of the magnetic field and the deformation applied, revealing an interesting magnetorheological behavior.

Clinical Features, Imaging Characteristics, and Long-term Outcome of Dogs with Cranial Meningocele or Meningoencephalocele.

BACKGROUND: The term meningoencephalocele (MEC) describes a herniation of cerebral tissue and meninges through a defect in the cranium, whereas a meningocele (MC) is a herniation of the meninges alone. HYPOTHESIS/OBJECTIVES: To describe the clinical features, magnetic resonance imaging (MRI) characteristics, and outcomes of dogs with cranial MC and MEC. ANIMALS: Twenty-two client-owned dogs diagnosed with cranial MC or MEC. METHODS: Multicentric retrospective descriptive study. Clinical records of 13 institutions were reviewed. Signalment, clinical history, neurologic findings and MRI characteristics as well as treatment and outcome were recorded and evaluated. RESULTS: Most affected dogs were presented at a young age (median, 6.5 months; range, 1 month - 8 years). The most common presenting complaints were seizures and behavioral abnormalities. Intranasal MEC was more common than parietal MC. Magnetic resonance imaging identified meningeal enhancement of the protruded tissue in 77% of the cases. Porencephaly was seen in all cases with parietal MC. Cerebrospinal fluid (CSF) analysis identified mild abnormalities in 4 of 11 cases. Surgery was not performed in any affected dog. Seventeen patients were treated medically, and seizures were adequately controlled with anti-epileptic drugs in 10 dogs. Dogs with intranasal MEC and mild neurologic signs had a fair prognosis with medical treatment. CONCLUSION AND CLINICAL IMPORTANCE: Although uncommon, MC and MEC should be considered as a differential diagnosis in young dogs presenting with seizures or alterations in behavior. Medical treatment is a valid option with a fair prognosis when the neurologic signs are mild.

Phenobarbital administration every eight hours: improvement of seizure management in idiopathic epileptic dogs with decreased phenobarbital elimination half-life.

Estimated prevalence of canine idiopathic epilepsy is 0.6 per cent in the first-opinion canine population in the UK. Phenobarbital monotherapy has been reported to reduce/eradicate seizure activity in 60-93 per cent of idiopathic epileptic dogs (IEDs). The objective of this study was to evaluate safety and efficacy of the administration of phenobarbital orally every eight hours in IEDs with phenobarbital elimination half-life less than 20 hours. Medical records of 10 IEDs in which steady state trough serum phenobarbital levels were within the reference range and phenobarbital elimination half-life had become less than 20 hours following prolonged administration every 12 hours were reviewed. Side effects and seizure frequency when phenobarbital was administered every 12 hours or 8 hours were compared. In all dogs the side effects of the antiepileptic medication treatment improved. When phenobarbital was administered every eight hours, 9/10 dogs experienced improvement in seizure frequency and 8/10 dogs maintained seizure freedom for a period three times longer than the longest interictal interval period previously recorded. Reduction in the severity and number of clusters of seizures was recorded in one of the remaining two dogs. The administration of phenobarbital orally every eight hours in IEDs with decreased phenobarbital elimination half-life appears safe and can improve seizure management. The results of this study were presented in abstract form (poster) for the 28th symposium of the European Society of Veterinary Neurology - European College of Veterinary Neurology (ESVN), September 18-19, 2015, Amsterdam, Netherlands.

Neurological signs and pre- and post-traction low-field MRI findings in Dobermanns with disc-associated cervical spondylomyelopathy.

OBJECTIVE: To investigate whether the presence of neurological signs and magnetic resonance imaging findings could predict the presence of a traction-responsive lesion in Dobermanns affected by disc-associated cervical spondylomyelopathy. METHODS: Retrospective review of neurological signs and low-field pre- and post-traction magnetic resonance imaging abnormalities of the cervical spine (abnormal vertebral body shape and vertebral tipping, intervertebral disc degeneration, protrusion and ligamentum flavum hypertrophy) in Dobermanns with disc-associated cervical spondylomyelopathy. The main outcome of interest was response to linear traction (dynamic versus static) at C6-C7 intervertebral disc space. The association between investigated variables and response to linear traction was assessed. RESULTS: The study included 25 dogs. No association was identified between neurological status grading and the presence of a static or traction-responsive lesion. Of the investigated magnetic resonance findings, C7-T1 intervertebral disc degeneration was significantly (P = 0 · 03) associated with the presence of a traction-responsive lesion at C6-C7 intervertebral disc space. CLINICAL SIGNIFICANCE: The presence of C7-T1 intervertebral disc degeneration might help in predicting the presence of traction-responsive C6-C7 intervertebral disc lesions.

Imaging diagnosis and minimally-invasive management of necrotizing fasciitis in a dog.

Necrotising fasciitis is a rapidly progressive, aggressive bacterial infection of the subcutis associated with significant morbidity and mortality in both man and domestic animals. To the best of our knowledge, this is the first veterinary report of magnetic resonance imaging findings in necrotising fasciitis, and the first reported case in a dog to be successfully treated with minimally invasive surgical intervention.

Nerve growth factor concentrations in the synovial fluid from healthy dogs and dogs with secondary osteoarthritis.

OBJECTIVE: To measure the concentrations of nerve growth factor (NGF) in the synovial fluid from normal dogs and dogs with osteoarthritis (OA) secondary to common joint disorders. METHODS: Nerve growth factor synovial concentrations were measured by ELISA assay in 50 dogs divided into three groups: 12 healthy, 16 affected by acute lameness within seven days before enrolment, and 22 with chronic lameness persisting by more than one month before enrolment and accompanied by radiological signs of OA. Both acute and chronic lameness were secondary to orthopaedic diseases involving the shoulder, elbow and stifle joints. Nerve growth factor synovial concentrations were compared between means for healthy and acute groups and between the three groups using an F-test. Significance level was set at p <0.05. RESULTS: Nerve growth factor was detected in all canine synovial fluid samples. However, the mean synovial NGF concentration of healthy dogs (3.65 ± 2.18 pg/ml) was not significantly different from the mean value in dogs with acute lameness (6.45 ± 2.45 pg/ml) (p = 0.79). Conversely, the mean synovial NGF concentration in dogs with chronic lameness (20.19 ± 17.51 pg/ml) was found to be significantly higher than that found in healthy dogs (p <0.01). CLINICAL SIGNIFICANCE: This study demonstrates for the first time the presence of NGF in canine synovial fluid and its increased concentrations in dogs with chronic lameness compared to healthy dogs and dogs with acute lameness. The association between chronic lameness and raised synovial concentrations may suggest an involvement of NGF in OA inflammation and chronic pain.

Optimising local therapy during oral surgery in patients with von Willebrand disease: effective results from a retrospective analysis of 63 cases.

Bleeding after dental extractions is very frequent in patients with von Willebrand disease (vWD) and in the past often necessitated transfusions with factor VIII/von Willebrand factor concentrates (vWFc). To evaluate the benefits of a standard local therapy on bleeding complications during oral surgery, 63 consecutive patients with vWD were analysed retrospectively. All types of vWD were included: type 1 (n=31), type 2 (n=22) and type 3 (n=10). All the patients had dental extractions or periodontal surgery at the same hospital by the same oral surgeons. All cases had been given tranexamic acid (TA) before and for 7 days after surgery. As additional local therapy fibrin glue (FG) was used during surgery in several patients. Additional systemic therapies were: desmopressin (DDAVP, 0.3 microg kg-1) and fVIII/vWF concentrates (vWFc, 40 U kg-1) given as a single dose before surgery. The 29 subjects (46%) treated locally did not bleed. Among the remaining cases, 24 (38%) were given DDAVP as additional systemic therapy and 6 (9.5%) received vWFc. There was bleeding after surgery in only two cases who had been given local FG (type 2 B) or systemic vWFc (type 3), but bleeding was stopped with an additional local application of FG. Our data suggest that a standard local therapy with TA and FG with DDAVP can prevent bleeding complications during oral surgery in the majority of patients (84%) with vWD and reduce the need for concentrates, with all their possible complications and high costs.

Locally advanced breast cancer treated with primary chemotherapy: comparison between magnetic resonance imaging and pathologic evaluation of residual disease.

AIMS AND BACKGROUND: We evaluated the response of locally advanced breast cancer to induction chemotherapy using MRI techniques. The size and vitality of any residual pathologic tissue was quantified by means of morphologic and dynamic analysis. A curve derived from the dynamic parameters shows the uptake intensity with respect to the time elapsed since administration, which is related to vascularization and therefore indirectly reflects the angiogenesis of malignant tissue. METHODS AND STUDY DESIGN: A group of 30 patients were examined with MRI for staging purposes before undergoing treatment and subsequently to assess the response to treatment. Alterations in size and dynamic parameters were closely monitored. RESULTS: The overall accuracy was 90%, the sensitivity 96%, the specificity 75%, the positive predictive value 92.5% and the negative predictive value 66%. Interestingly, analysis of the dynamic curves made it possible to obtain additional information regarding the angiogenetic activity of the residual tumor. CONCLUSIONS: Evaluation of the response to treatment by means of conventional imaging and clinical examination can be particularly difficult because of the fibrosis induced by cytotoxic drugs or the small volume of residual disease. The additional information supplied by MRI could therefore allow a more conservative surgical approach in selected cases of optimal response to treatment, as well as a much more accurate follow-up. Furthermore, the variation in dynamic parameters according to the vitality of residual disease could in the future become a useful tool for monitoring the effectiveness of anti-angiogenetic drugs.

Evaluation of the PFA-100 system in the diagnosis and therapeutic monitoring of patients with von Willebrand disease.

We have evaluated platelet function at high shear with the PFA-100 system in different subtypes of von Willebrand disease (vWD), before and after the intravenous infusions of desmopressin or a factor-VIII/von Willebrand factor (vWF) concentrate. Closure times with the PFA-100 system were determined for both the collagen/ADP and the collagen/epinephrine cartridges in 52 patients with vWD (9 type 1 "platelet normal", 5 type 1 "platelet-discordant", 8 type 1 "platelet-low", 6 type 2A, 9 type 2B, 6 type 2M Vicenza. 6 type 3 and 3 acquired vWD) and 40 controls. Measurements were repeated 1 and 4 h after the i.v. infusion of desmopressin (0.3 microg/Kg) in 26 patients with types 1, type 2M Vicenza or type 2A vWD, or of a factorVIII/vWF concentrate (Alphanate HT, 60 U/Kg) in 4 patients with type 3 vWD. At all time points, vWF plasma levels and the bleeding time (Symplate II) were also determined. Baseline closure times were longer in vWD patients than in controls with both the collagen/ADP and the collagen/ epinephrine cartridges. The sensitivity of the PFA-100 system (88% and 87% with the two cartridges) was higher than that of the bleeding time (65%). Treatment with desmopressin normalized the closure times in patients with type 1 "platelet-normal" or type 2M Vicenza vWD, had no significant effects in patients with type 1 "platelet-low", type 1 "platelet-discordant" or type 2A vWD. Infusion of a factorVIII/vWF concentrate in patients with type 3 vWD slightly shortened their prolonged closure times. In general, changes in PFA-100 were paralleled by shortenings of the bleeding times and increases in plasma vWF levels. The PFA-100 test reflects vWF-dependent platelet function under high shear stress and could be useful in the diagnosis and therapeutic monitoring of patients with vWD.

Treatment of acquired von Willebrand syndrome in patients with monoclonal gammopathy of uncertain significance: comparison of three different therapeutic approaches.

Patients with monoclonal gammopathies of uncertain significance (MGUS) may develop an acquired bleeding disorder similar to congenital von Willebrand disease, called acquired von Willebrand syndrome (AvWS). In these patients, measures to improve hemostasis are required to prevent or treat bleeding episodes. We diagnosed 10 patients with MGUS and AvWS: 8 had IgGkappa (3) or lambda (5) MGUS and 2 IgM-kappa MGUS. Three therapeutic approaches were compared in them: (1) desmopressin (DDAVP), (2) factor VIII/von Willebrand factor (FVIII/vWF) concentrate, and (3) high-dose (1 g/kg/d for 2 days) intravenous Ig (IVIg). In patients with IgG-MGUS, DDAVP and FVIII/vWF concentrate increased factor VIII and von Willebrand factor in plasma, but only transiently. IVIg determined a more sustained improvement of the laboratory abnormalities and prevented bleeding during surgery (short-term therapy). In addition to the standard 2-day infusion protocol, a long-term IVIg therapy was performed in 2 patients with IgG-MGUS: repeated (every 21 days) single infusions of IVIg did improve laboratory abnormalities and stopped chronic gastrointestinal bleeding. On the other hand, IVIg failed to correct laboratories abnormalities in patients with IgM-MGUS. These comparative data obtained in a relative large and homogeneous group of patients with AvWS and MGUS confirm that DDAVP and FVIII/vWF concentrates improve the bleeding time (BT) and FVIII/vWF measurements only transiently, whereas IVIg provides a sustained treatment of AvWS associated with IgG-MGUS, but not with IgM-MGUS.

[Locally advanced breast tumors. Role of magnetic resonance in the assessment of response to preoperative therapy and of neoplastic residue before the operation]. / Tumori della mammella localmente avanzati. Ruolo della Risonanza Magnetica nella valutazione della risposta alla terapia prechirurgica e del residuo neoplastico prima dell'intervento.

INTRODUCTION AND PURPOSE: Induction chemotherapy is the preoperative treatment for locally advanced breast carcinoma. The patients affected with this kind of tumor were previously considered inoperable. The sequential use of different cytotoxic drugs reduces the tumor mass effectively, thus allowing resection and improving patients prognosis. Tumor debulking is at times so significant that conservative treatment can even be considered. A reliable assessment of the response to drug therapy by conventional diagnostic procedures is usually hindered by chemotherapy-induced fibrosis. Magnetic resonance imaging (MRI) is a better tool for distinguishing fibrosis from still vascularized pathologic tissue and thus permits more accurate evaluation of tumor response to chemotherapy, namely tumor debulking and residual viability. MATERIAL AND METHODS: We selected 27 patients with breast cancer and submitted them to MRI both before and after chemotherapy. All examinations were performed with a high field system using 3D Flash sequences with optimized spatial and temporal resolution. RESULTS AND DISCUSSION: The morphologic and dynamic parameters of MRI were in agreement with pathologic findings. In case of persistent disease after chemotherapy, MRI demonstrated increased contrast agent uptake at restaging, with dynamic curves indicating early and intense uptake. In case of marked post-chemotherapy changes, the dynamic curves had a shorter and less steep trend. Finally, when no or very little (few microns) tumor tissue was left, MRI showed no uptake. CONCLUSIONS: Our initial experience indicates MRI as a valid too for monitoring chemotherapy response in breast cancer patients.

A type 2b von Willebrand disease mutation (Ile546-->Val) associated with an unusual phenotype.

Type 2B von Willebrand disease (vWD) is typically characterized by enhanced ristocetin-induced platelet aggregation (RIPA) caused by increased von Willebrand factor (vWF) affinity for platelets. Furthermore, absence of larger vWF multimers in plasma is characteristic of the originally described type IIB patients, now considered a subgroup of type 2B. We describe here three affected members of a family presenting with prolonged bleeding time, thrombocytopenia, markedly enhanced RIPA and spontaneous platelet aggregation, but normal plasma vWF antigen and ristocetin cofactor activity. Larger plasma vWF multimers, albeit decreased, were present in relatively greater proportion than in other type IIB patients. Genetic studies performed in two of these patients resulted in the identification of a previously unreported A-->G transition at nucleotide 4175 in the sequence of the pre-pro-vWF cDNA, corresponding to the substitution Ile546-->Val in the mature vWF subunit. This mutation appears to be responsible for an unusual type 2B phenotype, with greater enhancement of the vWF-platelet interaction than in typical cases but partial preservation of the larger vWF multimers in plasma.

Effects of moderate consumption of red wine on platelet aggregation and haemostatic variables in healthy volunteers.

OBJECTIVE: To evaluate the effect of moderate consumption of red wine on platelet aggregation and haemostatic variables, discriminating the effect of alcohol from that of non-alcoholic components. DESIGN: A randomised crossover study. SETTING: The Department of Food Science and Technology, University of Milan. SUBJECTS: Eleven healthy male volunteers who were moderate drinkers. INTERVENTIONS: For three periods of four weeks, subjects drank three different beverages [320 ml of red wine (providing 30 g/day of alcohol), 30 g/day of alcohol diluted in 320 ml of clear fruit juice or 320 ml of dealcoholised red wine] during the two main meals. Each treatment was preceded by a period of four weeks of complete withdrawal from any alcoholic beverage. At the end of each period platelet aggregation after collagen and ADP stimulus, and levels of fibrinogen, plasminogen, tissue-type plasminogen activator (t-PA) antigen and von Willebrand factor (vWF) were determined. RESULTS: Consumption for a period of four weeks of 30 g/day of alcohol either from red wine or alcohol resulted in similar decreases of collagen-induced platelet aggregation and fibrinogen levels. ADP-induced platelet aggregation, t-PA antigen, vWF and plasminogen levels were not affected by any treatment. No differences were detected when we compared platelet function and the other haemostatic variables at the end of red wine and dealcoholised treatments with findings at the end of alcohol treatment and abstinence. CONCLUSIONS: The well known positive effect of moderate consumption of red wine on haemostasis seems due to alcohol and not to the non-alcoholic fraction present in red wine.

End-stage renal failure from renal amyloidosis of the AA type associated with giant lymph node hyperplasia (Castleman's disease).

A case of end-stage renal failure caused by renal amyloidosis of the AA type is reported. No chronic disease responsible for the deposition of reactive amyloid was detected until giant lymph node hyperplasia of the angiofollicular type was identified in a mediastinal mass. Amyloid was found within the tumour mass and was characterized by immunochemistry with monoclonal antibodies to be of the AA type. Castleman's disease should be added to the list of chronic diseases endangering renal function by inducing the production and tissue deposition of secondary (AA) amyloid.

Orthotopic liver transplantation in a patient with severe hemophilia A: a life-saving treatment for the first Italian case.

Clinical cure of hemophilia A by orthotopic liver transplantation has been reported in 11 cases. We describe the first successful Italian case. A 27-year-old man had cirrhosis caused by previous infections with the hepatitis B, C and D viruses following life-long treatment with factor VIII concentrates made from large plasma pools. He was, however, seronegative for the human immunodeficiency virus. In the year before transplantation, life-threatening gastrointestinal bleeding due to severe esophageal varices required a large transfusion regimen (on average, 13 bags of red cell concentrates and 35,000 U of factor VIII/week). To perform orthotopic liver transplantation 8,000 U of factor VIII were given during surgery together with 10 bags of red cells and 11 of fresh-frozen plasma. Intraoperative bleeding was not different from that of non-hemophilic patients undergoing orthotopic liver transplantation. No additional factor VIII was used after transplantation and factor VIII levels in plasma were always above 50 U/dl, reaching the highest value of 184 U/dl on day 4 post transplantation. He was discharged from hospital 10 weeks after transplantation with factor VIII levels of 68 U/dl. All virological markers are currently negative, except anti-hepatitis C virus antibodies. In this patient orthotopic liver transplantation was a life-saving treatment for end-stage cirrhosis and a cure for hemophilia A.