A pilot study investigating the effect of pimobendan on the cardiac rhythm and selected echocardiographic parameters of healthy cats.

INTRODUCTION: The effects of pimobendan on the heart rhythm in cats are unknown. The purpose of this pilot study was to evaluate the effect of pimobendan on the cardiac rhythm and selected echocardiographic parameters of cats. ANIMALS, MATERIALS, AND METHODS: Six clinically healthy cats received each of four medication protocols for 15 days, with a washout period of at least one month between each protocol. The protocols were, pimobendan 0.5 mg/kg twice daily (high dosage group), pimobendan 0.25 mg/kg twice daily (standard dosage group), pimobendan 0.125 mg/kg twice daily (low dosage group), and Biofermin R, one tablet twice daily (placebo group). Twenty-four-hour ambulatory electrocardiogram recordings, blood pressure measurements, and echocardiographic examinations were performed after two weeks of each medication protocol. Electrocardiographic, echocardiographic, and blood pressure parameters were compared between the four groups. RESULTS: The total number of escape/idioventricular/idiojunctional complexes in the high dosage group was significantly higher compared with the placebo, low dosage, and standard dosage groups (p < 0.001). The blood pressure; total number of heart beats per day; and mean, minimum, and maximum heart rates were not significantly different between the groups. The longitudinal strain rate and calculated cardiac output were significantly increased in the high and standard dosage groups. CONCLUSIONS: The administration of pimobendan, especially at high doses, was associated with increased numbers of escape/idioventricular/idiojunctional complexes in some cats and echocardiographic parameters. Further studies are warranted to investigate both the mechanism underlying the observed changes and what, if any, clinical implications these changes might have in cats with heart disease.

POEMS syndrome with Guillan-Barre syndrome-like acute onset: a case report and review of neurological progression in 30 cases.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare cause of demyelinating neuropathy with monoclonal plasma cell proliferation, and POEMS neuropathy is usually chronically progressive. Herein, the authors report a 34-year-old woman with POEMS syndrome presenting as acute polyneuropathy. Within 2 weeks of disease onset, she became unable to walk with electrodiagnostic features of demyelination and was initially diagnosed as having Guillan-Barré syndrome. Other systemic features (oedema and skin changes) developed later, and an elevated serum level of vascular endothelial growth factor led to the diagnosis of POEMS syndrome. She received high-dose chemotherapy with autologous peripheral blood stem cell transplantation, resulting in good recovery. The authors also reviewed patterns and speed of progression of neuropathy in the 30 patients with POEMS syndrome; 22 (73%) of them were unable to walk independently with the median period of 9.5 months from POEMS onset (range 0.5-51 months). Whereas the speed of neuropathy progression varies considerably among patients, some POEMS patients can show acute or subacute polyneuropathy. The early diagnosis and treatment could result in rapid improvement as shown in the present patient.

Neuromuscular transmission is not impaired in axonal Guillain--Barré syndrome.

BACKGROUND: Previous studies have shown that anti-GQ1b antibodies induce massive neuromuscular blocking. If anti-GM1 and -GD1a antibodies have similar effects on the neuromuscular junction (NMJ) in human limb muscles, this may explain selective motor involvement in axonal Guillain--Barré syndrome (GBS). METHODS: Axonal-stimulating single-fibre electromyography was performed in the extensor digitorum communis muscle of 23 patients with GBS, including 13 with the axonal form whose sera had a high titre of serum IgG anti-GM1 or -GD1a antibodies. RESULTS: All patients with axonal or demyelinating GBS showed normal or near-normal jitter, and no blocking. CONCLUSION: In both axonal and demyelinating GBS, neuromuscular transmission is not impaired. Our results failed to support the hypothesis that anti-GM1 or -GD1a antibody affects the NMJ. In GBS, impulse transmission is presumably impaired in the motor nerve terminal axons proximal to the NMJ.

Prevalence of intestinal parasites and genotyping of Giardia intestinalis in pet shop puppies in east Japan.

The current study examined the prevalence of intestinal parasites and genotypes of Giardia intestinalis in puppies from nine pet shops in east Japan. Fresh fecal samples from 1794 puppies (≦3 months old) were collected on one occasion. Giardia spp. was examined for specific coproantigen using ELISA kit (SNAP®Giardia, IDEXX Laboratories, Inc., USA). Other intestinal parasites were detected microscopically using the formalin-ethyl acetate sedimentation technique. Genotyping was determined for the random 29 stool samples identified as Giardia spp. positive using PCR and direct sequencing of the glutamate dehydrogenase (gdh) gene. Overall prevalence of protozoan Giardia spp. and Cystoisospora spp. revealed 23.4% and 11.3%, respectively. Prevalence of ascarids, Strongyloides spp. and hookworms were recorded 1.8%, 1.1% and 0.1%, respectively. Protozoan Giardia spp. and Cystoisospora spp., thus, represent important pathogens among pet shop puppies. All genotyped G. intestinalis isolates were belonged to assemblage C or D, identified as dog-specific genotypes. Zoonotic assemblage A and B were not demonstrated. The result suggests that the risk of zoonotic transmission of G. intestinalis from pet shops puppies to humans may be quite low in Japan.

Physicochemical property changes of amino acid residues that accompany missense mutations in SCN1A affect epilepsy phenotype severity.

BACKGROUND: Several different missense mutations in the voltage-gated sodium channel subunit gene SCN1A have been identified in epileptic patients with benign phenotype and patients with severe phenotype. However, the reason why similar missense mutations in SCN1A result in different phenotypes has not yet been fully clarified. OBJECTIVE: To clarify the phenotype-genotype relationship in SCN1A, a meta-analysis was performed to quantitatively determine the effect of amino acid substitutions in SCN1A on epilepsy severity phenotype using physicochemical property indices of the amino acid, and to discuss in the context of the molecular evolution of the proteins. METHODS: PubMed was searched for articles and information was extracted on localisation and types of SCN1A missense mutations in patients with benign and severe epileptic syndromes; detailed information was also extracted. RESULTS: Meta-analysis quantitatively revealed that the physicochemical properties of several amino acids significantly affected epilepsy phenotype severity. It showed that missense mutations that decreased protein hydrophobicity were significantly associated with severe epilepsy phenotypes. It also showed that the phenotype severity of SCN1A missense mutations in the transmembrane domains of SCN1A (128/155; 82.6%) could be predicted with high sensitivity and positive predictive values using the physicochemical property changes, indicating the possibility of phenotype prediction for entirely new missense mutations using analytical methods. CONCLUSIONS: The results show that changes in the physicochemical properties of amino acids affected both the phenotype and clinical symptoms of patients with SCN1A missense mutations. This meta-analysis study provides new insights into SCN1A gene functions and a new strategy for genetic diagnosis, genetic counselling and epilepsy treatment.

Structural characterization of Tn916-like element in Streptococcus parauberis serotype II strains isolated from diseased Japanese flounder.

AIMS: To screen for the existence and determine the structure of Tn916-like element in Streptococcus parauberis serotype II strains isolated from cultured Japanese flounder in western Japan. METHODS AND RESULTS: In this study, the structure of Tn916-like element and the flanking regions were characterized by polymerase chain reaction (PCR) and inverse PCR, followed by cloning and sequencing. The Tn916-like element is 18 031 bp in length and composed of 22 ORFs. Southern blot hybridization analysis showed that the HincII-digested internal structures of Tn916-like elements yielded two patterns among S. parauberis serotype II strains. The flanking sequences were identical with the corresponding region of S. parauberis serotype I strain except for the addition of 6-bp coupling sequence (ATCATA) being adjacent to the upstream of the element. CONCLUSION: The Tn916-like element exhibited high homology (more than 99%) with Tn916 observed in other streptococci and enterococci and was integrated in the same site of chromosome for all of the tested S. parauberis serotype II strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The results indicate that the Tn916-like element encoding tet(M) gene is present in all of the tested S. parauberis serotype II strains, which are disseminated in the flounder-culturing areas in western Japan.

Anomalous electronic structure of ionic liquids determined by soft x-ray emission spectroscopy: contributions from the cations and anions to the occupied electronic structure.

Soft x-ray emission spectroscopy was used for elucidating the electronic structure of ionic liquids [C(4)mim](+)PF(6)(-) and [C(4)mim](+)OTf(-), where [C(4)mim](+) stands for methylbutylimidazolium cation and OTf(-) for the trifluoromethanesulfonate anion. Nonresonant spectra measured above N, O, and F 1s edges selectively probed the molecular orbitals (MOs) of the cation and anions. They give a clear evidence that the highest occupied molecular orbital of the [C(4)mim](+) cation contributes to the topmost occupied states of the ionic liquids [C(4)mim](+)PF(6)(-), while both cationic and anionic MOs contribute for the case of [C(4)mim](+)OTf(-). Resonant soft x-ray emission spectra at the N 1s edge of these ionic liquids revealed that the energy gap of [C(4)mim](+)PF(6)(-) is solely determined by the [C(4)mim](+) cation, in contrast to usual ionic crystals. The ionic liquids form a new class of the ionic materials from the viewpoint of the electronic structure.

Neurologic improvement after peripheral blood stem cell transplantation in POEMS syndrome.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare multisystem disorder associated with plasma cell dyscrasia. There is increasing evidence that high-dose chemotherapy with autologous peripheral blood stem cell transplantation (Auto-PBSCT) is an efficacious treatment. OBJECTIVE: To elucidate the extent and time course of neurologic improvement after Auto-PBSCT in patients with POEMS syndrome. METHODS: Clinical and electrophysiologic findings in nine patients were reviewed. The median follow-up period was 20 months (range, 8 to 49 months). Serum levels of vascular endothelial growth factor (VEGF) were measured by ELISA. RESULTS: Serum VEGF levels rapidly decreased a month after Auto-PBSCT. Within 3 months, neurologic improvement began, and all the patients showed substantial neurologic recovery during the next 3 months. Particularly, three initially chairbound patients regained ability to walk at 6 months. Nerve conduction studies showed significant increases in conduction velocities and amplitudes within 6 months of treatment. At the end of follow-up periods, neuropathy was still improving, and no patients had recurrence of symptoms. CONCLUSION: Autologous peripheral blood stem cell transplantation results in obvious neurologic improvement within 6 months, presumably by extensive axonal regeneration and remyelination. This therapy could be considered as a first line treatment for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome with younger onset even if they are tetraplegic.

Inhibition of angiogenic factor production from murine mast cells by an antiallergic agent (epinastine hydrochloride) in vitro.

Angiogenesis is an important event both in the development of allergic inflammatory responses and in the pathophysiology of tissue remodeling in allergic diseases. In the present study, therefore, we examined the influence of antihistamines on angiogenesis through the choice of epinastine hydrochloride (EP) and murine mast cells in vitro. Mast cells (5 x 10(5) cells/mL) presensitized with murine IgE specific for ovalbumin (OVA) were stimulated with 10 ng/mL OVA in the presence of various concentrations of EP for 4 hours. The levels of angiogenesis factors, keratinocyte-derived chemokine (KC), tumor necrosis factor-alpha (TNF), and vascular endothelial growth factor (VEGF) in culture supernatants, were examined by ELISA. We also examined mRNA expression for the angiogenesis factors by RT-PCR. EP significantly inhibited the production of KC, TNF, and VEGF induced by IgE-dependent mechanism at more than 25 ng/mL. Semiquantitative analysis using RT-PCR showed that EP also significantly reduced mRNA expressions for KC, TNF, and VEGF. These results strongly suggest that EP suppresses angiogenesis factor production through the inhibition of mRNA expression in mast cells and results in favorable modification of clinical conditions of allergic diseases.

Thalidomide reduces serum VEGF levels and improves peripheral neuropathy in POEMS syndrome.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome is a rare multi-system disorder associated with plasma-cell dyscrasia. Several case series and reports have suggested that high-dose chemotherapy with autologous peripheral blood stem-cell transplantation is efficacious treatment, but this transplantation is not indicated for elderly patients and patients with renal failure. OBJECTIVE: To investigate the effects of thalidomide treatment for POEMS syndrome. METHODS: Nine patients, who were not indicated for high-dose chemotherapy, were treated with thalidomide. Neurological disability scores, nerve conduction studies and serum levels of vascular endothelial growth factor (VEGF) were prospectively examined. VEGF levels were measured by an enzyme-linked immunosorbent assay. RESULTS: During follow-up periods of 8-23 months (mean, 15 months), all patients showed substantial clinical improvement (n = 6) or stabilisation of symptoms (n = 3). Serum VEGF levels decreased in all patients and were normalised in five patients. Nerve conduction velocities in the median nerve increased in seven patients. There were no serious adverse effects, including thalidomide neuropathy. CONCLUSION: Thalidomide treatment should be further studied as a treatment for POEMS syndrome, particularly for patients who are not indicated for transplantation therapy.

Evaluation of plasma C-terminal atrial natriuretic peptide in healthy cats and cats with heart disease.

BACKGROUND: The clinical implications of evaluating C-terminal atrial natriuretic peptide (ANP) concentration in cats are still controversial. HYPOTHESIS: The objective of this study was to investigate the relationship between plasma C-terminal ANP concentration and left atrial pressure (LAP) in healthy cats with volume overload (study 1), and to compare plasma C-terminal ANP in normal cats and cats with cardiomyopathy (study 2). ANIMALS: Five healthy adult cats were used in study 1, and clinically healthy cats (n=8) and cats with cardiomyopathy (n=14) were used in study 2. METHODS: In study 1, cats were anesthetized and given acetated Ringer's solution (100 mL/kg/h for 60 minute) via the cephalic vein. Hemodynamic measurements and blood samples, collected from the jugular vein, were performed at 10-min intervals. In study 2, blood samples from normal cats and cats with cardiomyopathy were collected from the cephalic vein. The plasma C-terminal ANP concentration was determined by radioimmunoassay for human alpha-ANP. RESULTS: In study 1, volume overload significantly increased the C-terminal ANP concentration and LAP from baseline. The C-terminal ANP concentration was strongly correlated with the mean LAP. In study 2, age, E wave velocity, and the ratios of the left atrium to aorta were significantly higher in the cats with cardiomyopathy compared with the normal cats. The C-terminal ANP concentration was significantly higher in the cats with cardiomyopathy compared with the normal cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that the measurement of plasma C-terminal ANP in cats may provide additional information for the diagnosis of heart disease.

RCA/IAEA third external dosimetry intercomparisons in East Asia region.

Several intercomparison exercises were organised by the International Atomic Energy Agency (IAEA) on the determination of operational quantities at the regional or interregional basis. In East Asia region, a third phase of the intercomparison finished in mid 2004. It was organised within the frame of the Regional Cooperation Agreement (RCA) as a follow-up to previous exercises carried out during 1990-1992 and 1995-1996. The results of this intercomparison for the determination of operational quantities were satisfactory for all Member States. The laboratories demonstrated a good performance in quantities tested. The purpose of this paper is to present the results of the RCA/IAEA intercomparison and the future of RCA activities in support of assessment of occupational exposure by organising intercomparison runs.

Aldose reductase inhibition alters nodal Na+ currents and nerve conduction in human diabetics.

BACKGROUND: In diabetic nerves, activation of the polyol pathway via an aldose reductase and the resulting impairment of the Na(+)-K(+) pump would lead to a decreased transaxonal Na+ gradient and thereby reduced nodal Na+ currents. OBJECTIVE: To investigate whether the aldose reductase inhibitor (ARI) epalrestat improves nodal Na+ currents and nerve conduction in human diabetic neuropathy. METHODS: The authors conducted a 6-month, open clinical trial with an ARI, epalrestat, in 30 patients with mild-to-moderate diabetic neuropathy. The latent addition technique and measurements of the strength-duration time constant were used to estimate nodal persistent Na+ currents in median motor axons. Excitability testing and extensive nerve conduction studies including F-wave analyses were performed before and 1 and 6 months after the initiation of treatment with oral epalrestat. RESULTS: Within a month of the start of treatment, there was a significant improvement in nerve conduction, particularly in conduction times across the carpal tunnel and F-wave latencies. The results of latent addition (p < 0.05) and strength-duration time constant (p = 0.06) suggested increased nodal persistent Na+ currents. At 6 months, nerve conduction continued to improve. CONCLUSIONS: Aldose reductase pathway inhibition could rapidly increase nodal Na+ currents and thereby improve the slowing of nerve conduction, presumably because of a restoration of the membranous Na+ gradient.