Descriptive study of current therapeutic practices, clinical reproductive findings and incidence of pregnancy loss in intensively managed thoroughbred mares.

Therapeutic practices in equine reproductive medicine have dramatically evolved over the last 20 years but current usage is not described. The aims of this study were to provide a description of medication use and clinical findings of reproductive examinations alongside measures of reproductive efficiency in thoroughbreds. A prospective cohort study was conducted in the 2013 and 2014 breeding seasons. Mare and stallion details, information on veterinary interventions and findings of reproductive ultrasound scans were collected using questionnaires and entered into a custom-designed Microsoft Access database. Descriptive summary statistics were derived directly from the database and using Microsoft Excel. Information was collected from 2246 pregnancies in 1754 mares from 29 stud farms. Ovulatory induction agents were used in 91.8% of cases, oestrus induction agents in 38.4% and covering therapies in 62.7%. Intrauterine antimicrobials were used in 49.6% of mares. Single pregnancies accounted for 83.9% of pregnancies, twins for 15.3% and triplets for 0.7%. The overall incidence of pregnancy loss between days 15-42 was 6.4% (95% CI 5.4%, 7.4%) and 1.6% (95% CI 1.1%, 2.1%) between days 43-65. A further 1.3% of pregnancies were lost by October and 4.5% by birth (including stillbirths). Eighty-three percent of all pregnancies resulted in a live foal. In conclusion, there has been a considerable increase in the use of reproductive therapeutics over the last 12 years. Nonetheless, incidence of pregnancy loss and live foal percentages remain essentially unchanged. Risk factor studies are required to determine if the substantial increase in therapeutic usage is conferring positive benefits.

Sagittal distal limb kinematics inside the hoof capsule captured using high-speed fluoroscopy in walking and trotting horses.

Kinematic evaluation of the distal limb of the horse using standard methods is challenging, mainly due to the hoof capsule restricting visualisation, but the recent development of a high-speed fluoroscopy (HSF) system has allowed in vivo cineradiographic assessment of moving skeletal structures at high speeds. The application of this non-invasive method to the equine distal limb is used to describe 'internal' distal limb kinematics including intra-horse and inter-horse variability, and variability between walk and trot. Distal limb kinematic data were collected at walk and trot from six non-lame horses using HSF set over a force plate. The dorsal proximal interphalangeal joint (PIPJ) angle and the dorsal distal interphalangeal joint (DIPJ) angle were measured at toe-on and at 25%, 50% and 75% of stance. The PIPJ and DIPJ showed overall extension through stance. The mean ± SD range of motion (ROM) during stance of the PIPJ was 9.7 ± 2.7° (walk) and 8.7 ± 3.0° (trot) and of the DIPJ was 28.6 ± 4.6° (walk) and 26.5 ± 6.3° (trot) showing significant differences between gaits and changes through stance (P < 0.001). Inter- and intra- horse variations were also significant for both joint angles (P < 0.001). HSF allowed for kinematic assessment of the distal limb within the hoof capsule. The ROM of the PIPJ observed was similar to results published in the literature whilst the ROM for the DIPJ was less than values previously reported. Future studies will use HSF to estimate strain in the tendons and ligaments within the hoof capsule, which are a common site of lameness in the horse.

A serological survey of antibodies to Leptospira species in dogs in South Africa.

Leptospirosis, a disease more common in the tropics, can cause a life-threatening multisystemic syndrome in humans and animals. Immunity, whether natural or vaccine-induced, is serogroup-specific with the infecting serovars varying according to geographical locality. In South Africa, in spite of the fact that the bacterin vaccine for some Leptospira serovars is often used, there is no recent information on the incidence of canine leptospirosis as well as the infecting serovar/s. The aim of this study, which was undertaken on sera collected in 2008 and 2009 from both strays and owned dogs predominantly in the coastal regions of South Africa, was to determine the presence of leptospiral antibodies to 15 serovars known to infect dogs. Of the 530 samples tested, 25 tested positive to 7 different serovars with the microscopic agglutination test (MAT). Nine of the 25 samples tested positive to more than one serovar. The 2 serovars most frequently represented were Canicola, which reacted to 17 sera, and Pyrogenes, which reacted to 10 sera. Currently the only vaccines available in South Africa in different combinations contain serovars Canicola, Icterohaemorrhagiae, Pomona and Grippotyphosa. The results showed that the use of vaccines containing serovar Canicola is still justifiable in certain regions of the country. However, the presence of antibodies to serovar Pyrogenes in several dogs, pending a broader investigation, indicates that this serovar should also be included in the range of Leptospira vaccines for use in South Africa.

A case report on spontaneous return of levator function following postcataract blepharoptosis repair.

Blepharoptosis is a recognized complication of cataract extraction and other ocular procedures. A 6-month waiting period is recommended before repairing postcataract ptosis because most cases resolve during this time. We report the course of a patient who developed spontaneous recovery of eyelid function 11 months after cataract surgery. She had previously undergone successful ptosis repair 8 months after cataract extraction, but developed overcorrection 3 months later as her levator function returned to normal. We recommend at least a 1-year waiting period before repair of postcataract ptosis. If corrective surgery is undertaken earlier than 1 year due to visual obstruction or for aesthetic reasons, we suggest two guidelines. The levator should be plicated rather than resected and patients should be forewarned of the possibility for a revisionary procedure if spontaneous return of levator function occurs.

Urinary leukotriene E4 levels increase upon exposure to hypobaric hypoxia.

STUDY OBJECTIVE: To determine whether urinary leukotriene E4 (uLTE4) levels increase upon exposure to high altitude, and also to ascertain the relationship between uLTE4 levels and symptoms of acute mountain sickness (AMS). DESIGN: Prospective, unblinded, single-factor (altitude) experimental study. SETTINGS: US Army research laboratory facilities at sea level ([SL] 50 m), 1,830 m, and 4,300 m. PARTICIPANTS: Eight healthy male subjects ranging in age from 19 to 24 years. MEASUREMENTS: uLTE4 levels and symptoms of AMS were measured at just above SL (50 m), 3 1/2 days after being transported from SL to moderate altitude (MA) (1,830 m), and 1 1/2 days after ascent from 1,830 to 4,300 m (high altitude [HA]). Symptoms of AMS were assessed using standard indexes derived from the Environmental Symptoms Questionnaire weighted toward cerebral (AMS-C) and respiratory (AMS-R) manifestations. Oxygen saturation was measured noninvasively by pulse oximetry at SL and HA. RESULTS: The mean (+/-SEM) uLTE4 levels (pg/mg creatinine) were 67.9 (+/-13.2) at SL; 82.3 (+/-5.5) at MA; and 134.8 (+/-19.4) at HA (p < 0.05 comparing HA with SL and MA). CONCLUSIONS: We conclude that uLTE4 levels increase shortly after exposure to HA even after staging for 4 days at MA. Although this study does not clearly demonstrate a relationship between uLTE4 levels and symptoms of AMS, it supports the hypothesis that leukotrienes may be involved in the pathophysiologic state of AMS.

Eucapnic voluntary hyperventilation as a bronchoprovocation technique: development of a standarized dosing schedule in asthmatics.

A variety of dosing schedules have been reported for the hyperventilation method of broncho-provocation testing. To evaluate the effect of challenge technique on the bronchoconstrictive response, we had 16 subjects perform eucapnic voluntary hyperventilation (EVH) with dry, room temperature gas using four different dosing schedules. The hyperventilation challenge dosages included the following: (1) a target minute ventilation (VE) of 20 x FEV1 for 6 min; (2) a target VE of 15 x FEV1 for 12 min; (3) an interrupted challenge with a target VE of 30 x FEV1 for 2 min repeated 3 times; and (4) a target VE of 30 x FEV1 for 6 min. Challenges 2, 3, and 4 gave identical absolute ventilatory challenges (identical factor FEV1 x minutes) but at different VE dosages or time. Challenges 1 and 4 were of identical length, but different target VE. The mean postchallenge fall in FEV1 was 16.6 +/- 10.9%, 11.0 +/- 8.1%, 19.6 +/- 9.9%, and 26.7 +/- 11.3% for challenges 1, 2, 3, and 4, respectively. The response to an identical EVH challenge (FEV1 x 30 for 6 min) was reproducible when performed on separate days. We conclude that the challenge technique used for hyperventilation testing will have a significant impact on the bronchoconstrictive response and must be taken into account when interpreting study results. Tests may be quantitatively comparable over a narrow range of challenge time and VE. We recommend that a 6-min uninterrupted EVH challenge using dry, room temperature gas at a target VE of 30 x FEV1 be adopted as the "standard" challenge.

Interpretation of eucapnic voluntary hyperventilation in the diagnosis of asthma.

Eucapnic voluntary hyperventilation (EVH) of dry gas is a physiologic bronchoprovocation challenge useful in the diagnosis of asthma. To determine the best parameter and threshold for diagnosis and the proper timing of postchallenge measurements, we reviewed 120 challenges, comparing the decrement from baseline in FVC, FEV1, mean forced expiratory flow during the middle half of the FVC (FEF25-75%), and peak expiratory flow rate (PEFR) each at 0, 5, 10, and 20 min postchallenge. After adjustment to a standard minute ventilation of 30 times the baseline FEV1 for 6 min, the mean response by 90 mild asthmatics differed from 30 normal subjects in all four parameters (p < 0.0001). In asthmatics, maximum decline from baseline (mean +/- SEM) was as follows: FVC, 12.1 +/- 1.2%; FEV1, 19.7 +/- 1.7%; FEF 25-75%, 33.5 +/- 2.5%; and PEFR, 29.0 +/- 1.9%. Normal subjects had a maximum fall as follows: FVC, 2.9 +/- 0.7%; FEV1, 3.8 +/- 0.7%; FEF25-75%, 11.8 +/- 2.0%; and PEFR, 11.5 +/- 1.0%. Based on comparison of receiver operator characteristic curves, FEV1 was more accurate than FEF25-75% and equivalent to FVC and PEFR. A threshold of 10% change or greater in FEV1 had a specificity of 90%, with a sensitivity of 63.3%. A threshold of 15% or greater had a specificity of 100%, with a sensitivity of 53.3%. The FEV1 fell by 10% or more in 55 of 90 asthmatics at 5 or 10 min after hyperventilation. Measurements at 0 or 20 min added two additional positive responses. We conclude that in the proper clinical setting, subjects whose FEV1 declines by 10% or more at 5 or 10 min after EVH should be diagnosed as having asthma.

The refractory period after eucapnic voluntary hyperventilation challenge and its effect on challenge technique.

To evaluate whether there is a refractory period (RP) after hyperventilation challenge, we compared the bronchoconstrictive response to repetitive eucapnic voluntary hyperventilation challenge with dry, room temperature air (EVH). The serial challenges were identical with 11 known asthmatics hyperventilating for 6 min at a target minute ventilation of 30 times their FEV1 measured before either challenge. There was a significant difference between the mean postchallenge fall in FEV1 to the initial EVH challenge (27.4 +/- 9.8%) and the response to the second EVH challenge (16.1 +/- 5.9%) (p = 0.0001), indicating refractoriness. We then evaluated whether 6 min of uninterrupted EVH challenge gives a similar bronchospastic response to that which results from an equivalent (by total minute ventilation) interrupted challenge of 2 min of EVH repeated three times. The mean post-challenge fall in FEV1 in response to this interrupted challenge was 18.9 +/- 10.6%, which was significantly different from the 27.4% fall in response to 6 consecutive minutes of EVH (p = 0.036). This study demonstrates that there is a refractory period after repeated EVH challenges and this refractoriness affects the response to interrupted, or dosed, EVH challenge.

Production of brefeldin-A.

Fermentation conditions are described for the production of the antitumor antibiotic 7-(S)-brefeldin-A (brefeldin-A) in liquid culture by Eupenicillium brefeldianum, (B.Dodge) Stolk and Scott, ATCC 58665. An analytical hplc method was developed which allowed rapid quantitation of the compound during fermentation. A kilogram of brefeldin-A was isolated from a fermentation at the 6800-liter scale.

Refractory period during provocation with eucapnic hyperventilation and methacholine.

Eucapnic voluntary hyperventilation (EVH) and methacholine inhalation challenge (MIC) both cause bronchoconstriction in asthmatics. A refractory period, or time when the response to bronchoprovocation in a series of challenges is diminished, has been found after hyperventilation or exercise but not after MIC. We investigated whether EVH or MIC blunted the response to the other test. Sixteen asthmatics were studied on 2 d, taking both tests each day. They were randomized to either EVH or MIC first on Day 1, then the opposite order on Day 2, 6 to 14 d apart. After EVH as a first test, the mean decline in FEV1 from baseline was 18.66 +/- 4.76% (mean +/- SEM), but when EVH followed MIC, the response to EVH was reduced by 30%, to a decline in FEV1 of only 13.02 +/- 3.75% (p = 0.0026). During MIC, the mean provocation dose to cause 20% decrease in FEV1 (PD20) given as the initial challenge was 54.77 +/- 21.60 breath units, compared with 46.94 +/- 19.55 breath units when MIC followed EVH (p = 0.54). However, the subset of patients most sensitive to methacholine (PD20 < 0.1 breath unit) had changes suggestive of a refractory period after EVH, with a mean increase in the PD20 from 0.06 +/- 0.01 to 3.35 +/- 1.43 (p = 0.069). Our data show that MIC attenuates the response to subsequent challenge with EVH. Conversely, EVH may only affect subsequent MIC in those most sensitive to methacholine.

Eucapnic voluntary hyperventilation as a bronchoprovocation technique. Comparison with methacholine inhalation in asthmatics.

Methacholine inhalation challenge (MIC) is probably the most widely used and best standardized test for nonspecific bronchoprovocation challenge (BPC). There has been increasing interest in developing "physical" stimuli such as eucapnic voluntary hyperventilation (EVH) with dry gas to assess airway hyperreactivity (AHR), because of inherent problems with using a pharmacologic agent in epidemiologic surveys. To our knowledge, no studies exist that compare MIC with EVH in known asthmatics. We conducted a prospective, randomized, crossover trial with a group of subjects (n = 16) who met the American Thoracic Society definition of asthma with these objectives: (1) to compare the sensitivity of EVH with MIC; (2) to compare the quantitative response of one test with the response to the other challenge; and (3) to correlate the response of both tests with symptoms, serum IgE levels, and serum eosinophil counts. We found that (1) EVH was positive in 75 percent of cases and MIC was positive in 81 percent of cases; one subject reacted to EVH but not to MIC and vice-versa. (2) The quantitative response to one test correlated with the response to the other test (r = -0.60, p = 0.01). (3) There was a correlation between severity of asthma symptoms and the response to EVH (r = 0.62; p = 0.01), but not to MIC. (4) Response to MIC (log PD20), but not EVH, correlated with serum IgE level (r = -0.53, p = 0.04). We suggest that EVH may be used for the initial assessment of AHR in the evaluation of asthma. Eucapnic voluntary hyperventilation is a sensitive measure of AHR and it correlates well with symptoms. Furthermore, though these points were not addressed in our study, it is more physiologic than MIC, and it is easy and less expensive to perform.

Colonoscopically assisted intracorporeal laparoscopic wedge resection of a benign right colon lesion.

We present a case of colonoscopically assisted intracorporeal laparoscopic wedge resection of a benign right colon lesion. The operative technique is described and the rationale discussed with reference to current literature.

The effect of pyridostigmine on bronchial hyperreactivity.

We examined the effect of pyridostigmine (PY) at a dose of 30 mg orally three times a day on nonspecific bronchial hyperreactivity in ten normal nonsmokers (NNS), ten smokers (SM), and ten mild asthmatics (AS). We conducted a double-blind, placebo-controlled, crossover trial, randomly assigning subjects to receive either placebo (PL) or PY before undergoing bronchoprovocation challenge with eucapnic voluntary hyperventilation (EVH) using dry gas. Compliance with PY was confirmed by measuring red blood cell acetylcholinesterase (Achase) levels during both days of testing. While taking PL, the mean (+/- SEM) falls in FVC and FEV1 after the bronchoprovocation were as follows: NNS, 1.0 percent (+/- 0.6) FVC and 4.3 percent (+/- 1.0) FEV1; SM, 2.4 percent (+/- 1.1) FVC and 2.7 percent (+/- 1.3) FEV1; AS, 5.3 percent (+/- 2.3) FVC and 11.5 percent (+/- 2.8) FEV1. The mean decreases in FVC and FEV1 while taking PY were as follows: NNS, 1.8 percent (+/- 0.7) FVC and 4.3 percent (+/- 0.8) FEV1; SM, 3.8 percent (+/- 1.4) FVC and 5.2 percent (+/- 1.6) FEV1; AS, 4.4 percent (+/- 1.3) FVC and 11.8 percent (+/- 2.8) FEV1. Within each category, using a paired t test to compare the results on each day of testing, no statistically significant differences were noted. Pyridostigmine at the tested dose has no significant effect on nonspecific bronchial hyperreactivity in normal NNS, SM, or AS.

Right upper lobe pulmonary edema caused by acute mitral regurgitation. Diagnosis by transesophageal echocardiography.

Unilateral pulmonary edema is a distinctly unusual clinical entity, often misdiagnosed initially as one of the more common causes of focal lung disease. Predominantly lobar pulmonary edema is rarer still. We report a case of right upper lobe pulmonary edema caused by the acute onset of severe mitral regurgitation. In addition, we briefly review the other causes of unilateral pulmonary edema, focusing on the cases that have been reported in association with heart failure and valvular heart disease. The majority of cases of right upper lobe pulmonary edema have been associated with mitral regurgitation. In addition to confirming the presence of mitral regurgitation, transesophageal echocardiography proved useful in delineating the mechanism for edema formation. It detected differential gradients between the right and left pulmonary venous systems and documented the direction of the regurgitant flow.

Inadvertent loss of bronchoscopy instruments in the tracheobronchial tree.

Equipment malfunction is a rare complication of flexible fiberoptic bronchoscopy. We report an unusual example of equipment failure resulting in the inadvertent introduction of a foreign body (the tip of a cleaning brush) into the bronchial tree of a patient during FFB. In addition, we review several other cases in which problems have been caused by malfunction of accessory equipment. Careful inspection of all cleaning and biopsy utensils should reduce the chance of iatrogenically introducing a foreign body from the bronchoscope channel into the patient's airway. We suggest that biopsy forceps are the best retrieval instrument to use when the foreign body involved is a brush or a piece of wire.

Portal colopathy: prospective study of colonoscopy in patients with portal hypertension.

Twenty patients with portal hypertension related to a variety of causes prospectively underwent colonoscopy for hematochezia (n = 10), hemoccult positive stool and anemia (n = 9), or polyp found with screening flexible sigmoidoscopy (n = 2) (includes 1 patient with anemia/heme-positive stool). Twelve patients (60%) had previously undergone a course of sclerotherapy, and 10 (50%) had endoscopic evidence of congestive gastropathy. Colonoscopic findings included mucosal abnormalities resembling multiple vascular ectasias in 14 (70%), 4 of whom also had endoscopic features suggesting a mild, chronic colitis. Neither signs of chronic liver disease nor stigmata suggestive of more severe portal hypertension correlated with the colonoscopic findings. Two patients required heater probe therapy for actively oozing lesions resembling vascular ectasias and an additional two patients sclerotherapy for bleeding midrectal varices. Although likely an overestimate of the frequency, this study suggests that portal colopathy can occur in portal hypertension. Vascular ectasialike lesions in such settings may be associated with acute as well as chronic gastrointestinal bleeding and may require pharmacological, directed endoscopic, or portal decompressive therapy. Additional studies are required to determine not only the pathophysiology but also the true frequency of this entity.