A Placebo-Controlled, Prospective, Randomized Clinical Trial of Polyethylene Glycol and Methylprednisolone Sodium Succinate in Dogs with Intervertebral Disk Herniation.

BACKGROUND: Acute intervertebral disk herniation (IVDH) is a common cause of spinal cord injury in dogs and currently there is no proven medical treatment to counter secondary injury effects. Use of methylprednisolone sodium succinate (MPSS) or polyethylene glycol (PEG) as neuroprotectants is advocated but controversial because neither treatment has been tested in placebo-controlled, randomized, blinded trials in dogs. HYPOTHESIS: Polyethylene glycol will improve the outcome of severe spinal cord injury caused by IVDH compared to MPSS or placebo. ANIMALS: Client-owned dogs with acute onset of thoracolumbar IVDH causing paralysis and loss of nociception for <24 hours. METHODS: Dogs were randomized to receive MPSS, PEG, or placebo; drugs appeared identical and group allocation was masked. Drug administration was initiated once the diagnosis of IVDH was confirmed and all dogs underwent hemilaminectomy. Neurologic function was assessed 2, 4, 8, and 12 weeks postoperatively using an open field gait score (OFS) as the primary outcome measure. Outcomes were compared by the Wilcoxon rank sum test. RESULTS: Sixty-three dogs were recruited and 47.6% recovered ambulation. 17.5% developed progressive myelomalacia but there was no association with group. There was no difference in OFS among groups. Although full study power was not reached, conditional power analyses indicated the futility of continued case recruitment. CONCLUSIONS: This clinical trial did not show a benefit of either MPSS or PEG in the treatment of acute, severe thoracolumbar IVDH when used as adjunctive medical treatment administered to dogs presenting within 24 hours of onset of paralysis.

Chiari-like malformation and syringomyelia in American Brussels Griffon dogs.

BACKGROUND: Although Chiari-like malformation (CM) and syringomyelia (SM) have been described in many small breed dogs, the prevalence and clinical manifestations of this complex have not been documented in a large cohort of American Brussels Griffon (ABG) dogs. OBJECTIVES: To characterize the clinical and magnetic resonance imaging (MRI) features of CM and SM in the ABG breed. ANIMALS: Eighty-four American Kennel Club registered ABG dogs were recruited. METHODS: Prospective study. Complete histories and neurologic examinations were obtained before MRI. Images were blindly reviewed and calculations were made by using OsiriX. All analyses were performed by Student's t-test, Spearman's correlation, ANOVA, and chi-square test where appropriate. RESULTS: Chiari-like malformation and SM were present in 65% and 52% of dogs, respectively. Twenty-eight percent of dogs had neurologic deficits and 20% had neck pain. Mean central canal (CC) transverse height was 2.5 mm with a mean length of 3.6 cervical vertebrae. Neurologic deficits were significantly associated with a larger syrinx (P = .04, P = .08) and syrinx size increased with age (P = .027). SM was associated with a smaller craniocervical junction (CCJ) height (P = .04) and larger ventricles (P = .0001; P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Syringomyelia and CM are prevalent in American Brussels Griffon dogs. Syrinx size is associated with neurologic deficits, CM, larger ventricles, a smaller craniocervical junction height, neurologic deficits, and cerebellar herniation. Fifty-two percent of dogs with a SM were clinically normal.

Magnetic resonance imaging enhancement of intervertebral disc disease in 30 dogs following chemical fat saturation.

OBJECTIVE: To describe the patterns of enhancement of extradural intervertebral disc on chemically fat saturated gadolinium-enhanced magnetic resonance images and to investigate the clinical and pathological associations with enhancement. METHODS: Medical records and magnetic resonance images were reviewed from 30 dogs with histopathologically confirmed disc disease and enhancement on a T1-weighted postcontrast fat saturated sequence. RESULTS: Median duration of neurological signs was 4 days and the most common grade of severity was II, seen in 46·6% of dogs. Homogeneous, heterogeneous and peripheral patterns of disc enhancement were described, with peripheral enhancement most commonly identified (57% of dogs). There were no clinical or pathological differences between the dogs with each of the patterns. The mean signal intensity of a region of interest within the extruded disc material and contrast-to-noise ratio of the disc material were significantly higher on postcontrast T1-weighted fat saturated images (P=<0·0001 each). CLINICAL SIGNIFICANCE: The use of fat saturated gadolinium-enhanced magnetic resonance imaging can detect enhancement of extradural disc material. Patterns of enhancement are not associated with the clinical presentation or pathological features.

Serum leptin in disabled and non-disabled children in an Indian slum population.

OBJECTIVE: To assess the concentration of serum leptin in a population of malnourished children and to compare the leptin levels of disabled and non-disabled children in this population. DESIGN: Case-control study. SUBJECTS: Eighty-one children, comprising 41 children with mixed disabilities and 40 non-disabled controls, were selected from 425 children involved in a case-control study assessing the nutritional status of children with disabilities in an Indian slum population. METHODS: Leptin was measured in the serum samples and was compared with anthropometry (weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ), weight-for-height Z-scores (WHZ), body mass index (BMI), mid-upper-arm circumference (MUAC), sub-scapular skinfold thickness and triceps skinfold thickness) and serum acute phase proteins. RESULTS: The children were very malnourished with WAZ=-2.07 (s.d. 1.15), HAZ=-2.15 (s.d. 1.85) and WHZ=-1.07 (s.d. 0.83). Leptin was extremely low in both the disabled (1.44 ng/ml; 95% confidence interval, CI, 1.23-1.69) and the non-disabled (1.19 ng/ml; 95% CI 1.04-1.35) children. There were no differences between the disabled and non-disabled groups as a whole but 15 children with neurological disabilities had significantly higher (P<0.05) serum leptin (1.65 ng/ml; 95% CI 1.29-2.06) than the non-disabled children. Girls (1.55 ng/ml; 95% CI 1.29-1.87) had significantly higher concentrations of leptin than boys (1.11 ng/ml; 95% CI 1.02-1.22; P=0.002). Leptin did not correlate with any biochemical or anthropometric measures. CONCLUSIONS: In this population, where malnutrition was common, serum leptin levels were very low and did not correlate with anthropometry. SPONSORSHIP: UK Department for International Development; Virgin Airways through the Great Ormond Street Hospital Trustees.

Why general practitioners do not implement evidence: qualitative study.

OBJECTIVES: To explore the reasons why general practitioners do not always implement best evidence. DESIGN: Qualitative study using Balint-style groups. SETTING: Primary care. PARTICIPANTS: 19 general practitioners. MAIN OUTCOME MEASURES: Identifiable themes that indicate barriers to implementation. RESULTS: Six main themes were identified that affected the implementation process: the personal and professional experiences of the general practitioners; the patient-doctor relationship; a perceived tension between primary and secondary care; general practitioners' feelings about their patients and the evidence; and logistical problems. Doctors are aware that their choice of words with patients can affect patients' decisions and whether evidence is implemented. CONCLUSIONS: General practitioner participants seem to act as a conduit within the consultation and regard clinical evidence as a square peg to fit in the round hole of the patient's life. The process of implementation is complex, fluid, and adaptive.

Nucleoside analogues as highly potent and selective inhibitors of herpes simplex virus thymidine kinase.

A series of carboxamide derivatives of 5'-amino-2',5'-dideoxy-5-ethyluridine has been prepared as inhibitors of HSV-TK (herpes simplex virus thymidine kinase). The most potent compounds were derived from xanthene, thioxanthene and dihydroanthracene carboxylic acids. The lead compounds show subnanomolar IC(50) values against HSV TKs.

The design, synthesis and properties of highly potent and selective inhibitors of herpes simplex virus types 1 and 2 thymidine kinase.

The rational design and synthesis of nucleotide analogues as inhibitors of herpes simplex virus (HSV) thymidine kinase is described. Starting from thymidine, product analogues which included phosphates, phosphonates, sulphonates, sulphonamides and carboxamides were prepared. The carboxamide series showed good structure-activity relationships and afforded a lead structure which inhibited the HSV-2 enzyme in the low micromolar range. Replacing the 5-methyl group in thymidine by ethyl enhanced the potency of the lead structure 10-fold. Further optimization of the carboxamide moiety afforded inhibitors active in the sub-nanomolar range and finally the introduction of a 2'-beta-fluoro substituent improved the potency a further twofold. The low water solubility of the most potent inhibitor was overcome by conversion to the 3'-valyl ester, which had good oral bioavailability and showed activity by the oral route in murine models of infection.

Predictors of bleach use among current African-American injecting drug users: a community study.

One hundred seventeen African-American current injecting drug users were interviewed in a closely matched pair of census tract communities in Dallas, Texas. A brief street intercept interview was administered that included an eligibility screener and questions on sexual behaviors with main or other partners and on injection drug paraphernalia bleaching behavior. Multiple regressions were conducted to determine significant predictors of frequency and duration of cleaning needles with bleach using different models (risk, attitude, exposure, and full). The variables measuring risk behaviors were age, frequency of sharing, exchanging sex for money, and sexual partner's use of injecting drugs. The predictors for the attitude model included normative, attitudinal, and self-efficacy items. The exposure to HIV information variables included seeing/hearing information; talking to someone about HIV, condoms, cleaning needles; and antibody testing for HIV. The full model combined predictors from each of the other models. Overall, bleach use is best explained in terms of specific attitudes rather than risk behaviors or information about HIV.

Elbow synovectomy in rheumatoid arthritis. Long-term results.

Fifty-seven elbows in 46 rheumatoid arthritis patients were followed from one to 20 years, with an average follow-up period of 86 months, and were treated with synovectomy and radial head resection. A silicone radial head prosthesis was inserted in 13 elbows. Surgery was performed through a lateral incision. Long-term follow-up study showed 77% of the elbows to fall in the excellent and improved categories. A trend toward better results was seen if the surgery was done at an earlier stage of the disease. The radial head prosthesis did not influence the results of synovectomy.