Periodic paralysis in quarter horses: a sodium channel mutation disseminated by selective breeding.

We recently reported on a linkage study within a Quarter Horse lineage segregating hyperkalaemic periodic paralysis (HYPP), an autosomal dominant condition showing potassium-induced attacks of skeletal muscle paralysis. HYPP co-segregated with the equine adult skeletal muscle sodium channel alpha subunit gene, the same gene that causes human HYPP. We now describe the Phe to Leu mutation in transmembrane domain IVS3 which courses the horse disease. This represents the first application of molecular genetics to an important horse disease, and the data will provide an opportunity for control or eradication of this condition.

Retrospective evaluation of crib-biting and windsucking behaviours and owner-perceived behavioural traits as risk factors for colic in horses.

REASONS FOR PERFORMING STUDY: Although crib-biting (cribbing)/windsucking has previously been associated with 2 types of colic, additional research into the possible role of other behaviours on incidence of colic by type and severity has not been undertaken. OBJECTIVES: To investigate: a relationship between cribbing/windsucking and colic; a relationship between cribbing/windsucking and different types of colic, both medical and surgical; and whether horses displaying specific behaviour traits were more likely to have had colic. METHODS: A matched case-control retrospective study was conducted evaluating horses with various surgical and medical colic diagnoses, admitted to a referral hospital over a 3 year period. Computerised records and a validated internet questionnaire were used to obtain information on owner-perceived behavioural traits and repetitive behaviours. RESULTS: Cribbing/windsucking was significantly associated with colic but was unassociated with one category or severity of colic over another. No other repetitive behaviour was associated with colic. Age (≥20 years) was significantly associated with colic. An anxious temperament was not associated with risk of colic. CONCLUSION: Animals at higher risk for colic may be identified based on history of cribbing/windsucking behaviour, but this behaviour was unassociated with increased risk for a particular category or severity of colic. Horses characterised as being more anxious were not at increased risk for colic. POTENTIAL RELEVANCE: There is a need to elucidate a causal relationship between cribbing/windsucking and gastrointestinal function as development of more effective and humane strategies to treat cribbing/windsucking behaviour may help to improve equine welfare and reduce the risk of colic.

Effect of antihypertensive therapy on calcium transport by cardiac sarcoplasmic reticulum of SHRs.

Cardiac hypertrophy develops during the course of blood pressure elevation in spontaneously hypertensive rats (SHRs) and is associated with defective calcium transport by cardiac sarcoplasmic reticulum (SR). AT 20 weeks of age, calcium uptake is reduced in SHRs (42 +/- 1.3 vs 64 +/- 1.6 nmol X mg-1 X min-1 in age-matched normotensive Wistar-Kyoto rats, P less than 0.01), while Ca2+ ATPase activity is enhanced (44 +/- 1.1 vs 35 +/- 0.7 nmol X mg-1 X min-1 in WKYs, P = 0.02); this results in low stoichiometry between calcium uptake and ATP hydrolysis in SHRs. The steady-state levels of the phosphoprotein intermediate [EP] of the transport ATPase are higher in normotensive rats (0.97 +/- 0.1 vs 0.67 +/- 0.08 nmol X mg-1 in SHRs, P less than 0.01) but the Ca2+- and ATP-dependency are similar in the two groups. In order to study the relative roles of hypertension and cardiac hypertrophy in the depression of SHR function, 20-week old SHRs and normotensive rats were treated for 10 weeks with either hydralazine (100 mg X litre-1) or alpha-methyldopa (8 g X litre-1). Both therapeutic regimens resulted in near normalisation of blood pressure of SHRs (hydralazine: 18.1 +/- 0.5 kPa [136 +/- 4 mmHg]; alpha-methyldopa 17.6 +/- kPa [132 +/- 3 mmHg]). Regression of cardiac hypertrophy, however, was seen only in the alpha-methyldopa-treated group, as judged by changes in left ventricular weight, RNA/DNA ratio, and hydroxyproline content. Furthermore, improvement in calcium transport capacity by the SHR, as reflected in higher calcium uptake and stoichiometric ratio between uptake and ATP hydrolysis, was found after alpha-methyldopa, but not hydralazine treatment. These results indicate that reversal of cardiac hypertrophy is required for improvement in calcium transport by cardiac SR after antihypertensive therapy of SHRs.

Effects of chronic heart failure on microvascular oxygen exchange dynamics in muscles of contrasting fiber type.

UNLABELLED: In rat spinotrapezius muscle, chronic heart failure (CHF) speeds microvascular O2 pressure (pO2; index of O2 delivery-to-O2 uptake) dynamics across the rest-contractions transition [Cardiovasc. Res. 56 (2002) 479]. Due to the mosaic nature of this muscle, the effect of CHF on microvascular pO2 dynamics in different fiber types remains unclear. OBJECTIVE: Based upon derangements of endothelial function and blood flow responses, we hypothesized that CHF would speed microvascular pO2 dynamics (reduced O2 delivery-to-O2 uptake ratio) in type I muscle (soleus, approximately 84% type I), but not in type II muscle (peroneal, approximately 86% type II [J. Appl. Physiol. 80 (1996) 261]). METHODS: Using phosphorescence quenching, microvascular pO2 was measured at rest and across the rest-contractions transition (1 Hz) in soleus and peroneal of non-infarcted control (control; n=7), and Sprague-Dawley rats with moderate (moderate; elevated left ventricular end-diastolic pressure (LVEDP) 10 +/- 2 mm Hg; n=10) and severe (severe; LVEDP 28 +/- 4 mm Hg; n=5) CHF. RESULTS: The microvascular pO2 mean response time (time delay+time constant) was progressively speeded with increasing severity of CHF in soleus (control, 38.7 +/- 2.0; moderate, 29.1 +/- 1.5; severe, 22.5 +/- 3.9 s; P< or =0.05), but not in peroneal (control=moderate=severe). CONCLUSION: As type I fibers are recruited predominately for moderate intensity exercise, the more rapid lowering of soleus microvascular pO2 in CHF would reduce the blood-muscle O2 driving gradient, exacerbate phosphocreatine and glycogen breakdown, and provide a mechanism for slowed O2 uptake kinetics and premature fatigue in CHF.

Septic sialoadenitis in equids: a retrospective study of 18 cases (1998-2010).

REASON FOR PERFORMING STUDY: Septic sialoadenitis, although uncommonly reported in equids, is a significant cause of pain, inappetence, dysphagia and discomfort. There are currently few reported cases possibly as a result of its infrequent occurrence. OBJECTIVES: To review cases presenting with sialoadenitis and describe the presenting complaints, results of diagnostic tests, treatment and outcome. STUDY DESIGN: Retrospective case series. METHODS: Records were reviewed for equids presenting to the UC Davis William R. Pritchard Veterinary Medical Teaching Hospital between 1998 and 2010 for salivary gland swelling. Equids were included if a diagnosis of septic sialoadenitis was made based on a combination of oral examination and/or ultrasonographic findings and/or microbial culture. Data collected included age, breed, presenting complaints, diagnostic results, treatment and outcome. RESULTS: Eighteen equids were diagnosed with septic sialoadenitis affecting the parotid gland (11) or the mandibular salivary gland (7). Ultrasound was useful to differentiate whether the mandibular or parotid salivary gland was involved. Affected equids ranged in age from 4 to 30 years (mean 17.7 years). Fourteen of 15 (93.3%) equids that underwent a complete oral examination had dental or other oral abnormalities. Six of 18 cases had evidence of sialolithiasis. Culture of the infected salivary gland or secretions was performed in 9 equids and all yielded growth of Fusobacterium sp. along with other aerobic and anaerobic bacteria. Infection resolved in 15/18 cases (83.3%) and 2/18 (11.1%) were subjected to euthanasia. CONCLUSIONS: Dental disease and sialolith formation may play important roles in the development of septic sialoadenitis in equids. Anaerobic infection should be assumed in all cases and affected horses should be treated for this until culture and sensitivity results are available. Prognosis is favourable (83.3%) with appropriate treatment.

Minimum inhibitory concentrations of equine Corynebacterium pseudotuberculosis isolates (1996-2012).

BACKGROUND: Few studies report the minimum inhibitory concentrations for antimicrobials against equine Corynebacterium pseudotuberculosis isolates. HYPOTHESIS/OBJECTIVES: To evaluate trends in the in vitro activities of 20 antimicrobials against equine Corynebacterium pseudotuberculosis isolates from 1996 to 2012 and to determine if a relationship exists between the minimum inhibitory concentration (MIC) and location of the abscess. ANIMALS: Corynebacterium pseudotuberculosis isolates from 196 horses with naturally occurring disease. METHODS: Retrospective and cross-sectional design. Medical records were reviewed to obtain clinical and MIC data. Minimum inhibitory concentrations were determined by the microdilution technique. The MIC results over 3 periods were compared (1996-2001, 2002-2006, 2007-2012). RESULTS: The MIC90 values for clinically relevant antimicrobials were as follows: chloramphenicol ≤ 4 µg/mL, enrofloxacin ≤ 0.25 µg/mL, gentamicin ≤ 1 µg/mL, penicillin =0.25 µg/mL, rifampin ≤ 1 µg/mL, tetracycline ≤ 2 µg/mL, trimethoprim-sulfamethoxazole (TMS) ≤ 0.5 µg/mL, ceftiofur =2 µg/mL, and doxycycline ≤ 2 µg/mL. There were no significant changes in MIC results over the study period. There was no relationship between MIC patterns and abscess location. CONCLUSIONS AND CLINICAL IMPORTANCE: The MIC50 and MIC90 values of antimicrobials evaluated in this study for equine isolates of C. pseudotuberculosis did not vary over time. Abscess location was not associated with different MIC patterns in cultured isolates. Several commonly used antimicrobials are active in vitro against C. pseudotuberculosis in vitro.

Unexpected deaths in depressed medical inpatients treated with fluoxetine.

BACKGROUND: Depression in the medically ill is underdiagnosed and undertreated. Fluoxetine would appear promising in this population because of its efficacy and benign side effect profile, but it has not been systematically studied in the medically ill. METHOD: The authors report the cases of three seriously medically ill patients, seen in psychiatric consultation while patients on a general medical service, who were treated with fluoxetine for depression. Each was an elderly white female with pulmonary disease and atrial arrhythmias, including atrial fibrillation, and each was prescribed diuretics, nitrates, and other cardiac and/or pulmonary agents. RESULTS: Each patient died within 10 days of beginning fluoxetine treatment, from unexplained causes. CONCLUSIONS: The authors hypothesize that direct cardiac effects mediated by fluoxetine, or other factors, may have been contributory. The effects of fluoxetine on electrolytes, fluoxetine's possible effects on drug levels, and serotonin's effect on the pulmonary system are examined. Other antidepressant agents should be considered in this particular population until further data are available.

Treatment of panic disorder and agoraphobia with clonazepam.

Clonazepam, a high-potency benzodiazepine marketed for the treatment of minor motor epilepsy, was used to treat 50 patients with panic disorder (N = 22) or agoraphobia with panic attacks (N = 28). Of the 50 patients, 41 had previously been poorly responsive to standard pharmacologic therapies. At a mean dose of only 1.9 (+/- 1.0) mg/day, 39 patients (78%) responded. No serious adverse effects were encountered. This study, although retrospective and uncontrolled, suggests that clonazepam, like alprazolam, may be effective in blocking panic attacks. A possible common mechanism for the two drugs as high-potency benzodiazepines is discussed.

Double-blind, placebo-controlled comparison of clonazepam and alprazolam for panic disorder.

To test the reported antipanic efficacy of clonazepam, the authors randomized 72 subjects with panic disorder to 6 weeks of treatment with either alprazolam, clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial effect of both active treatments, but not placebo treatment, on the frequency of panic attacks, overall phobia ratings, and the extent of disability. Comparison of the two active treatments revealed no significant differences and no consistent tendency for one agent to be favored over another, although power to detect small differences was limited. Sedation and ataxia were the most common side effects reported, but these effects were mild and transient and did not interfere with treatment outcome. The results of this double-blind, placebo-controlled trial are consistent with previous reports of clonazepam's antipanic efficacy.

Sleep in Pierre Robin syndrome.

Eight patients (aged 8 to 22 years) with the Pierre Robin syndrome underwent sleep studies. Seven demonstrated significant although minor degrees of increased sleep disturbances and apneas, and less time spent in the rapid-eye-movement (REM) stage of sleep. One patient who had previously undergone mandibular corrective surgery had major sleep abnormalities (central apnea index of 81.7 although an obstructive sleep apnea index of only 1.9). The patients had small mandibles, as demonstrated by lateral cephalometric roentgenography, and mildly increased right ventricular diastolic dimensions, as shown by M-mode echocardiography. Snoring was present in all of these patients and in 13 of 22 patients questioned from our Pierre Robin clinic. We conclude that minor abnormalities in sleep, mandibular size, and right ventricular size persist well into adolescence in the majority of patients with Pierre Robin syndrome. These appear to be clinically insignificant; however, a small percentage of such patients may continue to have major sleep disturbances.

Histamine challenge test in children using forced oscillation to measure total respiratory resistance.

This study analyzed the relationship between total respiratory resistance (Rrs) measured by forced oscillation technique and FEV1 during histamine provocation test in 31 children between seven and 17 years of age. Rrs was measured at frequencies between 6 (R6) and 26 Hz (R26). (R6-R26)/R26 was used as an index of frequency dependency of Rrs. A positive histamine test was defined as PC20 less than 8 mg/ml. Seventeen subjects had a positive test, and all of these had increases from baseline of R6 greater than 50 percent and (R6-R26)/R26 greater than 0.45. Of the 14 subjects whose PC20 was greater than 8 mg/ml, only two had changes in R6 and (R6-R26)/R26 of this magnitude. These two subjects had changes in FEV1 of 16 and 18 percent. There was a strong linear relationship between the changes in FEV1 and both R6 and (R6-R26)/R26 from baseline to the final value at the end of the test (r = 0.87 and 0.91 respectively). In conclusion, this study demonstrated that the evaluation of airway reactivity by histamine challenge may be done by forced oscillation technique. It is easy to administer and may allow testing of children unable to perform spirometry.

Effects of acute and chronic exercise on vasoconstrictor responsiveness of rat abdominal aorta.

Reductions in blood pressure that are associated with exercise training have been hypothesized to be the result of a sustained postexertional vascular alteration following single bouts of exercise. The purpose of this study was to determine whether a decrease in vascular sensitivity to vasoconstrictor agonists occurs after a single bout of exercise and whether this vascular alteration is sustained through various periods of exercise training. Vascular responses of abdominal aortic rings to norepinephrine (NE; 10(-9)-10(-4) M) were determined in vitro. Aortas were isolated from sedentary rats immediately after rats performed a single bout of treadmill exercise (30 m/min for 1 h); 24 h after the last exercise bout in rats exercised for 1 day; and 1, 2, 4, and 10 wk of training at 30 m/min, 60 min, 5 days/wk. Sensitivity to NE was only diminished after 10 wk of training. This diminished vascular sensitivity to NE was abolished with the removal of the endothelial cell layer. Furthermore, there were no reductions in developed tension or vascular sensitivity to the vasoconstrictor agonists KCl (10-100 mM), phenylephrine (10(-8)-10(-4) M), and arginine vasopressin (10(-9)-10(-5) M) in vessels either with or without the endothelial layer after a single bout of exercise. These data indicate that a single bout of exercise does not diminish aortic responsiveness to vasoconstrictor agonists and thus is not responsible for the diminished contractile responsiveness that occurs between 4 and 10 wk of moderate-intensity exercise training in rats. This vascular adaptation to exercise training appears to be mediated through an endothelium-dependent mechanism.

Sporotrichoid leishmaniasis.

American leishmaniasis that is acquired in Panama may appear clinically as a sporotrichoid eruption. When leisons reminiscent of sporotrichosis are encountered, a careful history of the patient's travels should be made, as well as a search for the organism of leischmaniasis in tissue smears, histopathological sections, and cultured media. We report the case of an American soldier stationed in Panama who had developed an ulcer on the dorsum of his right wrist, and nodules on his right forearm that were arranged in a linear pattern. The initial clinical impression was that of sporotrichosis, but on careful study of the patient's history, and after other appropriate investigations were made, it was discovered that the patient had leishmaniasis.

Inferior vena cava stenosis in scimitar syndrome: a case report.

The scimitar syndrome, first described by Chassinat in 1836, consists aessentially of an anomalous pulmonary vein draining whole or part of the right lung into the inferior vena cava. Associated anomalies are frequent, such as hypoplasia of the right lung, dextrocardia, malformations of the right pulmonary artery and bronchial tree, and abnormal arterial supply of the right lung (the so-called sequestration). This article describes a scimitar syndrome associated with stenosis of the inferior vena cava, whose initial diagnosis was made by two-dimensional echocardiographic Doppler color flow mapping. To our knowledge this is the first description of such an unusual association.

Noninvasive determination of respiratory mechanics during mechanical ventilation of neonates: a review of current and future techniques.

Study of the mechanical properties of the respiratory system is needed to help provide a better understanding of the pathogenesis of diseases causing respiratory failure. The nature of neonatal intensive care requires that any technique for monitoring respiratory mechanics be simple, noninvasive, and allow continued free access to the neonate. The peak airway pressure developed during volume cycled ventilation reflects the mechanical properties of the respiratory system but cannot distinguish between changes in the flow-resistive or elastic properties. Similarly, dynamic compliance combines both the flow-resistive and elastic components of the respiratory system in a single number and flow-volume loops also reflect both elements. Extracting a single time-constant from the expiratory limb of the latter assumes a single-compartment model for the respiratory system and, as such, does not provide sufficient information to describe frequency dependence of resistance and compliance. Furthermore, flow-volume loops are markedly distorted by the presence of an endotracheal tube, which must be corrected for, before calculating values of resistance and compliance. To provide the information to understand better the physiologic processes and adaptive mechanisms in diseased states causing acute respiratory failure, it is necessary to use a method that is based on a more detailed and realistic model of the respiratory system. Two such techniques that appear to warrant further investigation in ventilated infants are the interrupter technique and the forced-oscillation technique.

Comparative molecular characterization of Corynebacterium pseudotuberculosis of different origin.

Ribotyping and susceptibility to 17 antimicrobial agents were used to compare 37 isolates of Corynebacterium pseudotuberculosis (28 from horses, 1 from cattle, 3 from sheep and 5 from goats) derived from various types of lesions, and different geographic locations. According to the presence of nitrate reductase, all but one isolate from horses reduced nitrate (nitrate-positive), whereas all isolates from sheep and goats were unable to reduce nitrate (nitrate-negative). The ribotype of the nitrate-negative isolate from a horse with ulcerative lymphangitis was identical to all the other isolates from horses, and different than the ribotype of nitrate-negative isolates from sheep and goats. Ribotyping with one of the restriction endonucleases, Apa 1, revealed differences between, but not within, the two biotypes. However, ribotyping with Pst 1 endonuclease revealed one variant within the equine biotype and one variant within the ovine biotype. The minimum inhibitory concentration (MIC; microgram/ml) of antimicrobial agents against isolates from nitrate-negative and nitrate-positive groups was very similar, with the exception of isolates from sheep and goats which had a higher MIC for amikacin than isolates from horses and cattle.

What is new since the last (1999) Canadian Asthma Consensus Guidelines?

The objective of the present document is to review the impact of new information on the recommendations made in the last (1999) Canadian Asthma Consensus Guidelines. It includes relevant published studies and observations or comments regarding what are considered to be the main issues in asthma management in children and adults in office, emergency department, hospital and clinical settings. Asthma is still insufficiently controlled in a large number of patients, and practice guidelines need to be integrated better with current care. This report re-emphasises the need for the following: objective measures of airflow obstruction to confirm the diagnosis of asthma suggested by the clinical evaluation; identification of contributing factors; and the establishment of a treatment plan to rapidly obtain and maintain optimal asthma control according to specific criteria. Recent publications support the essential role of asthma education and environmental control in asthma management. They further support the role of inhaled corticosteroids as the mainstay of anti-inflammatory therapy of asthma, and of both long acting beta2-agonists and leukotriene antagonists as effective means to improve asthma control when inhaled corticosteroids are insufficient. New developments, such as combination therapy, and recent major trials, such as the Children's Asthma Management Project (CAMP) study, are discussed.

Sleep apnea following a pharyngeal flap: a feared complication.

Pharyngeal flaps are often used to correct velopharyngeal insufficiency. They produce a permanent partial obstruction of the velopharyngeal space. Respiratory obstruction and obstructive sleep apnea have been reported following this surgery. We undertook a study to find out the incidence of sleep apnea associated with pharyngeal flap surgery. Forty-one children (aged 2 to 22 years) admitted for a pharyngeal flap underwent a polysomnographic recording prior to their surgery. One child with Steinert's disease showed some episodes of obstructive apnea, and the surgery was canceled. Forty children underwent pharyngeal flap surgery, and polysomnography with continuous arterial saturation was repeated following surgery. Postoperative polysomnograms were normal in 26 patients (65 percent) and abnormal in 14 patients (35 percent). Among the 14 abnormal patients, we found 6 with obstructive apneas, 6 with central apneas, and 2 with both central and obstructive apneas. Ten of the 14 abnormal patients were restudied in the following months. Eight children had normal recordings, while 2 had central apneas. The 4 patients who declined a follow-up recording had no clinical symptoms of respiratory difficulty when sleeping. Of the 2 children with abnormal recordings on long-term follow-up, 1 is asymptomatic, while the second has persistent snoring, nocturnal awakening, sweating, and daytime lethargy. A section of his flap has been recommended. Independent analysis of arterial oxygen saturation revealed that the percentage of time with a saturation of less than 90 percent identifies patients with clinically significant apneas. Our data show that significant sleep apneas following pharyngeal flaps may not be as frequent or permanent as previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunological response to long-term transport stress in mature horses and effects of adaptogenic dietary supplementation as an immunomodulator.

REASONS FOR PERFORMING STUDY: Little information exists on the immunological effects of transport or the use of supplements to minimise transport stress. OBJECTIVES: To establish baseline ranges and evaluate immunophenotypic and functional changes associated with transport and a nutritional 'adaptogen' supplement. METHODS: Horses received either supplement (n = 10) or placebos (n = 9) during the 30 day study. After 28 days in stalls, 12 horses (6 supplement; 6 placebo) were transported for 24 h, then unloaded and recovered. Venous blood samples were collected on Days 1, 14 and 28 to establish baselines, and on Days 28, 29 and 30 to examine changes during transport and recovery. RESULTS: Transport prompted elevations (P<0.05) in cortisol concentration, neutrophil count and white blood cell counts, while lymphocyte subpopulation counts (CD3+, CD4+, CD8+, CD21+) decreased (P<0.05). Normal phenotypic lymphocyte profiles returned within 24 h of recovery. Supplement effects on immunophenotype (CD21+ and CD8+) were observed in stabled horses (P<0.05), but not in transported horses. CONCLUSIONS: These results provide insights into the immunological mechanisms associated with long-term transport. POTENTIAL RELEVANCE: The existence of a small window of immunological uncertainty follows long-term transportation, enhancing the potential risk of infectious disease in susceptible individuals.

A clinical trial of probiotic administration for prevention of Salmonella shedding in the postoperative period in horses with colic.

The purpose of this study was to evaluate the effects of probiotic administration on the prevalence of fecal shedding of Salmonella, the prevalence of postoperative diarrhea, the length of antimicrobial therapy, and the length of the hospitalization stay during the postoperative period in horses with colic. Two commercially available probiotics for horses were used in a double-blind prospective study of 200 horses undergoing surgery for colic. Probiotic or placebo was administered PO once a day for 7 days postoperatively, and fecal cultures for Salmonella were obtained daily for 10 days. After selection of 186 patients completing the treatment protocol, the results indicated that the commercial probiotic formulations had no effect on Salmonella shedding, prevalence of diarrhea, length of antimicrobial therapy, or length of hospitalization (P > .05). Twenty percent of the horses yielded 1 or more positive fecal cultures for Salmonella; of these horses, 74% were classified as asymptomatic shedders. Twenty-six percent of all horses had fluid diarrhea postoperatively, with only 12% of these horses having positive fecal cultures for Salmonella. The most common isolate was Salmonella krefeld (24 of 39 isolates). Among the different gastrointestinal disorders, horses with feed and sand impactions appeared to be more prone to shed Salmonella.