Understanding crossovers and potential ways to mitigate the problem: Lessons from influential trials on lumbar microdiscectomy.

BACKGROUND: Lumbar microdiscectomy is the most frequent surgical intervention used in the treatment of sciatica from herniated lumbar discs. Many discectomy trials have been plagued with an excessive number of crossovers that have rendered results inconclusive. METHODS: We review the design and results of influential lumbar microdiscectomy trials. We also discuss the various strategies that have been used to decrease the number of crossovers or to mitigate the effects of crossovers on analyses. RESULTS: Randomized trials on lumbar discectomy were affected by crossover rates of 8% to 42%. Various strategies that have been used to decrease that number or to mitigate the effects on results include: patient selection, blinding (placebo-controlled trials), an immediate access to surgery for the surgical group (but limited access to surgery for the conservative group), shortening the follow-up period necessary to reach the primary outcome measure, postponing crossovers to surgery after determination of the primary outcome, and modifying the primary outcome measure to include treatment failures. Crossovers should be anticipated and compensated for by increasing the number of participants. CONCLUSION: Non-adherence to randomly allocated management options can deprive trials of the statistical power needed to inform clinical care. Crossovers and ways to mitigate related problems should be anticipated at the time of trial design.

An analysis of ideal and actual time to surgery after traumatic spinal cord injury in Canada.

STUDY DESIGN: Retrospective analysis of a prospective registry and surgeon survey. OBJECTIVES: To identify surgeon opinion on ideal practice regarding the timing of decompression/stabilization for spinal cord injury and actual practice. Discrepancies in surgical timing and barriers to ideal timing of surgery were explored. SETTING: Canada. METHODS: Patients from the Rick Hansen Spinal Cord Registry (RHSCIR, 2004-2014) were reviewed to determine actual timing of surgical management. Following data collection, a survey was distributed to Canadian surgeons, asking for perceived to be the optimal and actual timings of surgery. Discrepancies between actual data and surgeon survey responses were then compared using χ2 tests and logistic regression. RESULTS: The majority of injury patterns identified in the registry were treated operatively. ASIA Impairment Scale (AIS) C/D injuries were treated surgically less frequently in the RHSCIR data and surgeon survey (odds ratio (OR)= 0.39 and 0.26). Significant disparities between what surgeons identified as ideal, actual current practice and RHSCIR data were demonstrated. A great majority of surgeons (93.0%) believed surgery under 24 h was ideal for cervical AIS A/B injuries and 91.0% for thoracic AIS A/B/C/D injuries. Definitive surgical management within 24 h was actually accomplished in 39.0% of cervical and 45.0% of thoracic cases. CONCLUSION: Ideal surgical timing for traumatic spinal cord injury (tSCI) within 24 h of injury was identified, but not accomplished. Discrepancies between the opinions on the optimal and actual timing of surgery in tSCI patients suggest the need for strategies for knowledge translation and reduction of administrative barriers to early surgery.

Vaginal prolapse in a pregnant Maine coon cat: a case report.

Vaginal prolapse is a condition characterised by excessive accumulation of mucosal oedema and protrusion of hyperplastic tissue through the vulva. It has been reported in ruminants and canines, but has not been characterised in felines. This report describes the history, clinical signs and treatment of a pregnant Maine coon cat with a Type III vaginal prolapse diagnosed approximately 54 days after the first day of mating. Prior to queening, the prolapse was reduced and retained using a vulvar cruciate suture. Due to the risk of dystocia and recurrence, a caesarean section with ovariohysterectomy was performed. Postoperatively, a stay suture was maintained in the vulva for 2 weeks, resulting in permanent reduction of the vaginal prolapse. To the authors' knowledge, this case represents the first report of the successful management of vaginal prolapse in a pregnant cat.

Vaginal microbiota of spayed dogs with or without recurrent urinary tract infections.

BACKGROUND: Limited information is available regarding the vaginal microbiota of normal spayed dogs and spayed dogs with recurrent UTIs. Vaginal lactic acid-producing bacteria (LAB) have been associated with decreased frequency of recurrent urinary tract infection in women and may have a protective role within the urinary tract of female dogs. HYPOTHESIS/OBJECTIVES: Spayed dogs with historical recurrent UTI will have decreased prevalence of LAB and increased prevalence of uropathogenic bacterial populations in the vaginal microbiota when compared with the vaginal microbiota of healthy, spayed dogs. ANIMALS: Twenty-one client-owned adult spayed female dogs with historical recurrent UTI and 23 healthy, spayed female dogs without a history of recurrent UTI. METHODS: Dogs were placed into a recurrent UTI group or control group in this prospective study. Bacterial populations were isolated and characterized from vaginal swabs obtained from each dog. RESULTS: The most common bacterial isolates obtained from the vaginal tract of all dogs were Escherichia coli (11/44) and S. pseudintermedius (13/44). E. coli was isolated from the vaginal tract of 8 of 21 (38%) dogs in the rUTI group and 3 of 23 (13%) dogs in the control group (P = .08). LAB were isolated from 7 of the 44 dogs. Two of these 7 dogs were in the rUTI group and 5 of the 7 dogs were in the control group. CONCLUSIONS AND CLINICAL IMPORTANCE: The vaginal microbiota of spayed female dogs with recurrent UTI was similar to the control population of normal, spayed female dogs.

The effect of an oral probiotic containing lactobacillus, bifidobacterium, and bacillus species on the vaginal microbiota of spayed female dogs.

BACKGROUND: Recurrent urinary tract infections (UTIs) are often difficult to treat. Vaginal colonization with lactic acid-producing bacteria (LAB) is associated with reduced frequency of recurrent UTIs in women. Oral probiotics might help increase the prevalence of vaginal LAB and decrease the frequency of recurrent UTIs in dogs. HYPOTHESIS: Administration of an oral probiotic supplement containing Lactobacillus, Bifidobacterium, and Bacillus species will increase the prevalence of LAB in the vagina of dogs. ANIMALS: Thirty-five healthy, spayed female dogs without history of recurrent UTIs. METHODS: Prospective, controlled study. Enrolled dogs received an oral probiotic supplement for 14 or 28 days. A vaginal tract culture was obtained from each dog before and after oral probiotic administration. Twenty-three dogs received the oral probiotic supplement daily for a period of 14 days and 12 dogs received the oral probiotic supplement daily for a period of 28 days. RESULTS: Lactic acid-producing bacteria were isolated from 7 of 35 dogs prior to probiotic administration. After the treatment course, 6 of 35 dogs had LAB isolated. Only one of these dogs had LAB (Enterococcus canintestini) isolated for the first time. Enterococcus canintestini was the most common LAB isolated from all dogs in this study, although it was not included in the probiotic supplement. CONCLUSIONS AND CLINICAL IMPORTANCE: Lactic acid-producing bacteria are not a common isolate from the vaginal vault of dogs. Administration of this oral probiotic supplement for a 2- or 4-week period did not increase the prevalence of vaginal LAB in dogs.

Uterine artery blood flow remains unchanged in pregnant mares in response to short-term administration of pentoxifylline.

The objective of this study was to use Doppler ultrasound technology to determine whether pentoxifylline administration increased uterine blood flow in normal pregnant pony mares. Thirteen pregnant pony mares between 18 and 190 d of gestation (mean ± SEM, 101 ± 55) were utilized for the study during two trial periods. In each trial, pentoxifylline (17 mg/kg by mouth every 12h, diluted in syrup) was administered to half of the mares for 3 d, while the other mares were treated with syrup only. Doppler measurements were obtained from the right and left uterine arteries from each mare for 2 d prior to treatment and throughout the treatment period. The mean Resistivity Index (RI), Pulsatility Index (PI), Uterine Artery Diameter (D), and Total Arterial Blood Flow (TABF) from each day were compared over time and between groups. Administration of pentoxifylline did not alter uterine blood flow parameters compared with controls (values for all treatment days combined were RI: 0.517 ± 0.014 vs 0.543 ± 0.016; PI: 0.876 ± 0.048 vs 0.927 ± 0.057; D: 0.388 ± 0.018 vs 0.379 ± 0.023 cm; and TABF: 35.26 ± 7.38 vs 30.73 ± 5.29 mL/min). Uterine blood flow increased over the course of the 5 d study, irrespective of treatment, and was higher in mares of greater gestational age than in early gestational mares (RI: r(2) = 0.35; PI: r(2) = 0.37; D: r(2) = 0.66; and TABF: r(2) = 0.67 - P < 0.00001). We concluded that any immediate benefits of pentoxifylline administration in the pregnant mare were not mediated through enhanced uterine artery blood flow.

B-mode and Doppler ultrasonography in pony mares with experimentally induced ascending placentitis.

REASONS FOR PERFORMING STUDY: Early, accurate diagnosis of ascending placentitis in mares remains a key challenge for successful treatment of the disease. Doppler ultrasonography has shown promise as a tool to diagnose pregnancy abnormalities and is becoming more available to equine clinicians. However, to date, no studies have prospectively compared this technique to standard B-mode measurement of the combined thickness of the uterus and placenta (CTUP). OBJECTIVES: The objective of the current study was to compare Doppler and B-mode ultrasonography for the detection of experimentally-induced ascending placentitis in mares. METHODS: Eleven healthy pony mares in late gestation were used in this study. Placentitis was induced in 6 mares between Days 280 and 295, while 5 mares served as negative controls. All mares were intensively monitored until delivery. Fetal heart rate, CTUP, uterine artery blood flow (resistance index, pulsatility index, arterial diameter and total arterial blood flow) and physical examination findings were recorded at each examination. Mares with an increased CTUP above published values were treated in accordance with published recommendations. Foals and fetal membranes were examined at birth. Ultrasonographic parameters were compared between groups using ANOVA. Foal viability and histological presence of placentitis were compared using a Fisher's exact test. RESULTS: The CTUP was increased above normal in 5 of 6 inoculated mares within 3 days after inoculation (P = 0.05). The sixth inoculated mare was excluded from subsequent data analysis. Uterine artery blood flow, physical examination findings and fetal heart rate were not different between groups. Gradual increases in CTUP, arterial diameter and total arterial blood flow were detected with increasing gestational age in the control mares (P = 0.02, P = 0.00001 and P = 0.00001, respectively). CONCLUSION: The CTUP, but not uterine blood flow, was different between groups (P = 0.00001). Recorded CTUP values for control pony mares were similar to previously published values for light breed horses.

Assessment of hepatic inflammation after spinal cord injury using intravital microscopy.

OBJECTIVES: The liver has been shown to play a particularly important role in the initiation and progression of the early systemic inflammatory response (SIR) to spinal cord injury (SCI). The purpose of this study was to determine the time course of leucocyte recruitment to the liver, and to determine the effect of injury severity on the magnitude of leucocyte recruitment and hepatic injury. METHODS: Rats were randomly assigned to one of the following groups: uninjured, sham-injured (laminectomy and no cord injury), cord compressed or cord transected. At 30 min and 90 min after SCI rats had the left lobe of their livers externalised and visualised using intravital video microscopy. RESULTS: Thirty minutes after injury the total number of leucocytes per post-sinusoidal venule was significantly increased after cord transection compared to that in uninjured and sham-injured rats (P<0.05). Of these leucocytes, significantly more were adherent to venule walls (P<0.05). At 90 min the total number of leucocytes per post-sinusoidal venule and the number of adherent and rolling leucocytes was significantly increased after cord transection and cord compression (P<0.05). DISCUSSION: This is the first study to use intravital microscopy to visualise systemic inflammation in the liver following SCI. We have demonstrated immediate leucocyte recruitment to the liver within 30 min after injury and have shown that systemic inflammation increases with time after injury and with severity of injury.

Treatment efficacy of trimethoprim sulfamethoxazole, pentoxifylline and altrenogest in experimentally induced equine placentitis.

The objective was to determine if long-term treatment with trimethoprim sulfamethoxazole (antimicrobial), pentoxifylline (anti-inflammatory/anti-cytokine) and altrenogest (synthetic progestin), would improve pregnancy outcome in mares with experimentally induced placentitis. Seventeen normal, pregnant pony mares were enrolled in the study at 280-295 d of pregnancy. Placentitis was induced in all mares by intra-cervical inoculation of Streptococcus equi subsp. zooepidemicus (10(7) CFU). Five mares served as infected, untreated control animals (Group UNTREAT). Twelve mares (Group TREAT) were infected and given trimethoprim sulfamethoxazole (30 mg/kg, PO, q 12h), pentoxifylline (8.5 mg/kg, PO, q 12h) and altrenogest (0.088 mg/kg, PO, q 24h) from the onset of clinical signs to delivery of a live foal or abortion. Blood samples were cultured from all foals at delivery and fetal stomach and thoracic contents were obtained for culture from dead fetuses. More mares in Group TREAT delivered viable foals (10/12; 83%; P < 0.05) than mares in Group UNTREAT (0/5; 0%). Ten of 12 foals (83%) in Group TREAT had negative blood cultures at birth. All foals in Group UNTREAT (5/5; 100%) had positive cultures from one or more samples (blood, stomach contents, and thoracic fluid). Bacteria were recovered from uterine culture samples in both groups. Streptococcus equi subsp. zooepidemicus was the predominant organism recovered from fetal/foal or mare culture samples. The authors inferred that administration of trimethoprim sulfamethoxazole, pentoxifylline and altrenogest may improve the viability of foals from mares with experimentally induced placentitis.

Use of co-registered high-resolution computed tomography scans before and after screw insertion as a novel technique for bone mineral density determination along screw trajectory.

INTRODUCTION: Bone mineral density (BMD) is an important factor in the examination of the performance of bone instrumentation both in and ex vivo, and until now, there has not existed a reliable technique for determining BMD at the precise location of such hardware. This paper describes such a technique, using cadaveric human sacra as a model. METHODS: Nine fresh-frozen sacra had solid and hollow titanium screws placed into the S1 pedicles from a posterior approach. High-resolution micro-computed tomography (CT) was performed on each specimen before and after screw placement. All images were reconstructed with an isotropic spatial resolution of 308 mum, reoriented, and the pre-screw and post-screw scans were registered and transformed using a six-degree rigid-body transformation matrix. Once registered, two points, corresponding to the center of the screw at the cortex and at the screw tip, were determined in each scan. These points were used to generate cylindrical regions of interest (ROI) with the same trajectory and dimensions as the screw. BMD measurements were obtained within each of the ROI in the pre-screw scan. To examine the effect of artefact on BMD measurements around the titanium screws, annular ROI of 1 mm thickness were created expanding from the surface of the screws, and BMD was measured within each in both the pre- and post-screw scans. RESULTS: The registration process was accurate to 190 mum, with a precision of 189 mum and error in BMD measurement of +/-2% in repeated scans. BMD values in the cylindrical ROI corresponding to screw trajectories were not statistically different from side to side of each specimen (p=0.23). Metal artefact created significant differences in BMD values (p=0.001) and followed an exponential decay curve as distance from the screws increased, approaching a low value of approximately 20 mg HA cm(-3), but not disappearing completely. SUMMARY: CT in the presence of metal creates artefact, making measured BMD values near implants unreliable. This technique is accurate for determination of BMD, non-destructive, and eliminates the problem of this metal artefact through the use of co-registered scans. This technique has applications both in vitro and in vivo.

Excessive calcium ingestion leading to milk-alkali syndrome.

This report describes the presentation and clinical course of a 40-year-old woman who had an emergency admission for eclampsia. During routine investigations, she was found to have profound hypercalcaemia, the cause of which was identified as milk-alkali syndrome, caused by self-medication with antacid tablets for dyspepsia. Treatment with aggressive rehydration, bisphosphonates and discontinuation of antacid tablets restored normocalcaemia. The patient made a full recovery with no long-term side-effects. Her male infant was safely delivered with no deleterious effects of exposure to high calcium concentrations in utero.

A clinical approach to managing the mare with placentitis.

Placental infections in the mare are a diagnostic and therapeutic challenge. The following article will review techniques for identifying placental infections, approaches for treating placentitis, and methods for managing these mares after foaling.

Outcome of plate fixation of olecranon fractures.

OBJECTIVES: To evaluate the functional outcome of plate fixation for displaced olecranon fractures, both simple and comminuted. DESIGN: Retrospective patient, chart, and radiographic review. SETTING: Academic teaching hospital. PATIENTS: Twenty-five patients who underwent plate fixation of displaced olecranon fractures by two surgeons were independently reviewed at an average follow-up of thirty-four months (range, 15-69 months). MAIN OUTCOME MEASUREMENTS: Physical capability was assessed by measuring range of motion and isometric elbow strength. Patient-rated outcomes were evaluated using the SF-36, DASH, Mayo Elbow Performance Index (MEPI), and visual analogue scales for patient satisfaction and pain. Radiographs were evaluated preoperatively, postoperatively, and at the time of final review. RESULTS: The average patient age was fifty-four years (range, 14-81 years). The Mayo classification of fractures was fourteen Type II and eleven Type III. An adequate reduction was maintained in all elbows until union. Physical capability measures indicated nonsignificant side-to-side differences in motion or strength, except for supination motion, which was reduced in the injured arm (p = 0.003). The MEPI-rated outcome was twenty-two excellent or good. Patient satisfaction was high (9.7/10), with a low pain rating (1/10). The mean DASH score was consistent with almost normal upper extremity function. The SF-36 showed no difference in physical health as compared with the average American population. Twenty percent of patients required plate removal because of prominence of the internal fixation. The outcome was not influenced by fracture pattern. CONCLUSION: Plate fixation is an effective treatment option for displaced olecranon fractures with a good functional outcome and a low incidence of complications.

Spinal epidural empyema in two dogs.

Extensive, diffuse, epidural spinal cord compression was visualized myelographically in two dogs presented for rapid development of nonambulatory tetraparesis and paraplegia, respectively. Purulent fluid containing bacterial organisms was aspirated percutaneously under fluoroscopic guidance from the epidural space of each dog. One dog responded poorly to aggressive medical therapy, which included installation of an epidural lavage and drainage system. Both dogs were euthanized due to the severe nature of their disorder and the poor prognosis. Spinal epidural empyema (i.e., abscess) is a rare condition in humans and has not been reported previously in the veterinary literature. Spinal epidural empyema should be considered as a differential diagnosis in dogs presenting with painful myelopathies, especially when accompanied by fever.

Use of internal controls to increase quantitative capabilities of the ribonuclease protection assay.

Through the use of two internal controls, we have developed an improved method of quantitating ribonuclease protection assay (RPA) results. A truncated sense RNA fragment and an antisense RNA fragment for the gene of interest were transcribed from PCR fragments containing T7 bacterial promoters. An 18S ribosomal RNA fragment was also used. When radiolabeled antisense and 18S probes, along with sense fragment and sample RNA, were hybridized, digested with RNase A/T1 and gel-electrophoresed, three distinct bands resulted. The antisense RNA fragment bound to the sense RNA fragment confirmed the integrity of the reaction. The antisense RNA fragment bound to endogenous mRNA measured the amount of specific gene expression in the sample. The 18S RNA fragment bound to endogenous mRNA determined the actual amount of sample added to the gel. Using the specific activities of the antisense and 18S transcripts, and scintillation counts of the protected fragments, we calculated the amounts of message and total RNA on the gel, determining picogram of message per microgram of total RNA. Final results were not based on assumed original amounts of RNA placed in the assay nor were they biased by lane-to-lane variations. Through the described adaptations, we have developed a well-controlled RPA that accurately and reproducibly quantifies gene expression.

Intravascular malignant T-cell lymphoma (malignant angioendotheliomatosis) in a cat.

A 7-year-old spayed female Siamese cat was presented with a 7-day history of ataxia, circling to the right, and involuntary micturition and defecation. Cerebrospinal fluid analysis showed increased protein content and relative eosinophilia. At necropsy, there was flattening of the cerebral cortical gyri of the right frontal and parietal lobes, and both kidneys had multiple wedge-shaped cortical indentations. Histologically, the cerebral cortex contained several extensive malacic foci, and the kidneys had multifocal parenchymal degeneration and atrophy. There was multifocal partial to complete thrombosis of renal interlobar arteries and of the right middle cerebral artery and meningeal branches; these thrombi contained large anaplastic round cells, which often invaded the arterial wall. Many smaller vessels within the kidneys and brain were occluded with clusters of similar cells, without thrombosis or vascular wall invasion. The neoplastic round cells had immunohistochemical staining properties of T lymphocytes.

Magnetic resonance imaging and computed tomography characteristics of intracranial intra-arachnoid cysts in 6 dogs.

Magnetic resonance imaging (MRI) and computed tomographic imaging (CT) characteristics of intracranial intra-arachnoid cysts in six dogs are described. Of the six dogs, three were less than one year of age and 4 were males. Five of the six dogs weighed less than 11 kg. Five cysts were located in the quadrigeminal cistern. On CT images, the intracranial intra-arachnoid cysts had sharply defined margins, contained fluid isodense to CSF and did not enhance following i.v. administration of contrast. On MRI images, the intracranial intra-arachnoid cysts were extra-axial, contained fluid isointense with CSF and did not enhance following i.v. contrast. While spinal arachnoid cysts of dogs have been reported in the literature, other than the six dogs contained in this report, intracranial intra-arachnoid cysts have not to our knowledge been described in animals. These six dogs have a similar age, sex, history, clinical signs, CT and MRI findings to those reported in people with intracranial intra-arachnoid cysts.