Intra-operative neurophysiological mapping to identify distorted functional anatomy of the 4th ventricle in a 5-month-old infant.

BACKGROUND: Neurophysiological brainstem mapping techniques facilitate the intra-operative localisation of cranial nerve nuclei amidst distorted anatomy. Neurophysiological recording in young infants can be limited due to immature myelination and synaptogenesis, as well as an increased sensitivity to anaesthetic agents. CASE REPORT: A 5-month-old boy was diagnosed with a cystic brainstem lesion located dorsally within the pons and upper medulla. An open surgical biopsy was undertaken via a posterior fossa craniotomy, revealing a grossly distorted fourth ventricular floor. Intra-operative neurophysiological mapping produced oculomotor, facial, glossopharyngeal and vagal muscle responses allowing a deviated functional midline to be identified. Direct stimulation was used to identify an area in the floor of the fourth ventricle eliciting no cranial nerve responses and allow safe entry into the tumour cavity and biopsy. Transcranial motor evoked responses (TcMEPs), short-latency somatosensory evoked potentials (SSEPs) and brainstem auditory evoked potentials (BAEPs) were all successfully recorded throughout the procedure, despite the use of halogenated gaseous anaesthesia. CONCLUSIONS: We describe the use of brainstem mapping techniques for identification of a distorted midline on the floor of the 4th ventricle in an infant, with reproducible recordings of intra-operative TcMEPs, SSEPs and BAEPs.

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model.

BACKGROUND: The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood-brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). MATERIALS AND METHODS: The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. RESULTS: Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P<0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. CONCLUSION: CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic.

An analysis of survey data by size of the breeding herd for the reproductive management practices of North American sow farms.

A survey was performed to assess whether reproductive management differed among small-sized (Sm, <500 sows), medium-sized (M, 501 to 2,000 sows), and large-sized (Lg, 2,001 to 8,000 sows) farms (n=113). Farms with 501 to 4000 sows/barn were most frequent with sows kept in stalls on 90% of farms. More Lg farms (P<0.05) functioned as breed to wean and more Sm and M as farrow to finish. More Sm and Lg farms weaned at >21 d, whereas M farms were more likely to wean at 18 to 21 d (P<0.05). More Lg farms had farrowing rates above 89% than Sm and M farms (P<0.05), and culling rates above 40% were more frequent on M and Lg farms than on S. On M and Lg farms, sows were bred in larger batches, using lower person to sow ratios, and with more people required than on Sm farms (P<0.05). More (P<0.05) M and Lg farms spent time moving sows and on records, but hours devoted to estrous detection, breeding, and other tasks did not differ among farms (P>0.10). More M and Lg farms used more boars for estrus detection, rotated boars, and controlled boar movement than Sm farms (P<0.05). Farm size also influenced semen sourcing, number of doses received, and frequency of semen delivery (P<0.05). More M and Lg farms performed AI in the presence of a boar, left the AI rod in after AI, checked for returns, and diagnosed pregnancy than Sm farms (P<0.05). Start of boar exposure after weaning began on 69% of farms within 2 d, occurring most often in the AM, but with exposure times varying from 1 to 5 min/sow. Semen was thermally protected for 50% of farms receiving shipments, and semen storage was consistent among farms. For AI, service occurred within minutes to hours after detection of estrus on 61% of farms. During AI, procedures such as back-pressure were required, whereas techniques such as hands-free AI were prohibited on most farms. Sow movement was allowed only once at 4 wk after breeding on 50% of farms, and pregnancy diagnosis occurred at 3 to 5 wk on 78% of farms. Most sows were allowed ≥1 chance for breeding after conception failure before culling. Incidence of fail to farrow was <5% and litter size was 10 to 13 pigs on >82% of farms. Summer infertility was observed on 69% of farms with estrus and pregnancy failures the leading causes. Over 70% of farms reported a technician effect on fertility. These results suggest that reproductive management of farms in key areas related to weaning, breeding, gestation, and labor use could be a source of variation in reproductive performance.

An update on North American boar stud practices.

This survey included 44 boar studs from Canada and the USA with a total of approximately 10,000 boars. Studs with 51-500 boars accounted for 84% of respondents. More than 90% of boars were housed in stalls. Evaporative and mechanical cooling systems predominated and boars were typically fed based on body condition. The predominant age of boars was 1-2 years with annual culling rates between 20 and 70%. The primary reasons for culling included genetic improvement, semen quality and feet and leg issues. Collection occurred commonly on Mondays and Thursdays and boars were rested 3-7 days between collections. The average sperm produced per boar per week was 51-150 billions and resulted in 21-40 doses per boar per week. Most studs collected boars using double gloves and disposable cups or liners and used pre-warmed containers. Ejaculate pooling was practiced by >60% of studs. Evaluation of semen for motility was performed with 0-5min of warming in extender with viewing at 100-400x magnification. Concentration estimation occurred by photometer and CASA for 88% of studs. Ejaculate discard occurred for reasons of poor motility, abnormal sperm and bacteria. Most studs retained extended samples for 3-7 days for quality control. Discard rates were most common between 1 and 10% and were related to individual boar and season. Doses of semen contained 2-4 billion sperms, with final sperm numbers adjusted for fertile sperm and packaged as doses in tubes and bags with 60-100mL.

Frontoethmoidal meningoencephalocoele repair in Cambodia: outcomes and cost comparisons.

In Cambodia, spina bifida is rare, but frontoethmoidal meningoencephalocoeles (MECs) are common. Mean life expectancy for patients with congenital MECs may be <20 years, but the complex treatment required has not been available in the country until recently. During visits by combined neurosurgical/craniofacial teams from both Germany and France, a method of repair has been developed that is suitable for the local conditions, affordable and has allowed Cambodian surgeons to learn how to successfully treat MECs. The surgical technique and initial results with 30 patients have been described in a previous publication. This paper presents the outcomes of 128 cases and illustrates that it is cost-effective for these patients to be treated in Cambodia.

Characterization and differential nuclear localization of Nopp140 and a novel Nopp140-like protein in trypanosomes.

Trypanosomatids possess two homologues of Nopp140: a canonical Nopp140 and a Nopp140-like protein (TbNoLP) in which a GAR domain replaces the C-terminal SRP40 domain. Both are phosphorylated and coimmunoprecipitate with RNA polymerase I. Each paralogue has a distinct subnuclear localization, and depletion of TbNoLP produces an enlarged nucleolus in which TbNopp140-containing regions disperse. The restricted occurrence pattern of NoLP proteins reflects an intriguing convergence in evolution, suggestive of a function in nucleoplasmic small nucleolar ribonucleoprotein shuttling.

Effects of lactation length and an exogenous progesterone and estradiol-17beta regimen during embryo attachment on endogenous steroid concentrations and embryo survival in sows.

The hypotheses that short lactation lengths increase embryo mortality by altering endogenous post-weaning steroid concentrations, and that an exogenous steroid regimen during embryo attachment might increase embryo survival were tested using 36 s parity sows assigned randomly to a 2 x 2 factorial. Sows were subjected to either a short lactation (SL, 13.0 days, n = 25) or a long lactation (LL, 31.5 days, n = 11), artificially inseminated at first estrus and treated daily with 2 ml i.m. of either 25 mg progesterone (P4) and 1.25 pg estradiol-17beta (E2) (steroid treatment, ST, n = 17) or the vehicle alone (control treatment, CT, n = 17) on Days 14-20 post-insemination. Blood samples were collected by jugular venipuncture from weaning to 24 days post-insemination on alternate days. Sows subjected to the SL compared to the LL tended to have a longer weaning-to-estrus interval (WEI) (5.3 versus 4.6 days; P < 0. 10), but did not have a significantly reduced conception rate (CR) (71 versus 90%; P > 0.10). The SL and LL sows had a similar ovulation rate (19.9 versus 21.3 corpora lutea, CL; P > 0.05), but SL sows had fewer viable embryos than LL sows (11.5 versus 15.3; P < 0.05) when reproductive tracts were recovered 28-32 days post-insemination. In addition, even after correction for the difference in number of embryos between groups, viable embryos from the SL versus the LL group weighed less (1.63 versus 1.79 g; P < 0.05), had a decreased amnion volume (1.02 versus 1.22 ml; P < 0.05) and apparently produced less estrogens since estrone sulfate concentration was decreased at 24 days post-insemination in SL versus LL sows (4.3 versus 6.3 ng/ml; P < 0.05). Embryo survival (percentage of CL represented by a viable embryo) however, was not different between SL and LL sows (60 versus 74%; P > 0.05) and no differences in post-weaning P4 or E2 concentrations were apparent. Sows that received the ST only tended to have increased P4 concentrations at 16 days post-insemination compared to CT sows and neither the number of viable embryos, nor embryo survival, was increased in ST versus CT sows (14.7 versus 12.2; P > 0.05 and 66 versus 68%; P > 0.05, respectively). These data suggest that short lactations do not increase embryo mortality by inducing aberrant endogenous post-weaning P4 or E2 concentrations. It is unclear whether or not small, repeated doses of exogenous P4 and E2 during attachment can increase embryo survival.

State of the art in artificial insemination of pigs in the United States.

Currently, the United States ranks second in pork production worldwide. In 1999 the breeding herd consisted of approximately 6.2 million breeding females with an annual production of 100 million market animals having an average market live weight of 118.6 kg. The objective of this paper is to briefly describe the current US swine artificial insemination (AI) industry and to profile semen production and insemination practices that are currently in use.

A spontaneously arising porcine model of bullous pemphigoid.

Bullous pemphigoid (BP) is an IgG-mediated autoimmune blistering disease targeting the hemidesmosomal proteins bullous pemphigoid antigens 1 and 2. Currently, there is no active animal model in which to dissect the immunopathogenic mechanism. We noticed that cutaneous blistering arose spontaneously in 12 adult Yucatan minipigs. Skin lesions consisted of turgid, isolated or clustered vesicles that occasionally evolved from erythematous and pruritic patches. Histopathological examination revealed subepidermal vesicles rich in intact and degranulated eosinophils. Antigen mapping and transmission electron microscopy confirmed that dermoepidermal separation took place in the lamina lucida of the epidermal basement membrane zone. Direct immunofluorescence revealed the presence of IgG deposited linearly at the dermoepidermal junction in seven of nine skin specimens examined. Indirect immunofluorescence testing confirmed the presence, in the serum from eight of eight affected pigs, of circulating basement membrane-specific IgG autoantibodies (titers 1 : 50 to 1 : 250). Using uncleaved and salt-split lip substrates, the autoantibodies were shown to target antigens situated not only at the basal, but also at the lateral and apical aspects of stratum basale keratinocytes. Immunoelectron microscopy confirmed that circulating IgG autoantibodies recognized hemidesmosomal antigen(s). ELISA, immunoblotting and immunoadsorption demonstrated that five of eight serum samples exhibited high immunoreactivity against BPAG2-NC16A peptides. This novel porcine acquired blistering dermatosis could be proposed as a valuable model to conduct immunomechanistic studies on the natural progression of BP, correlation of autoreactive T cells or autoantibodies with disease activity, and the role of eosinophils in the blistering process, as these diseases cannot be modeled easily in human patients or in murine passive transfer models.

Failure of vitamin A to increase litter size in sows receiving injections at various stages of gestation.

To determine the effectiveness of a single injection of vitamin A to increase litter size, 1,375 sows were assigned randomly to 11 treatment groups (125 sows per treatment). Treatments included injection of 1 x 10(6) IU of vitamin A dissolved in corn oil at weaning or on d 0, 2, 6, 10, 13, 19, 30, 70, or 110 after breeding. Sows in the control group were injected with corn oil on corresponding days. A total of 396 sows were removed from the study following treatment or treatment assignment. Therefore, farrowing data were collected for 979 sows. Injection of vitamin A did not influence (P > . 10) total litter size, live litter size, litter weight, pig weight, number of runts, or number of mummies. Mean live litter size was 10.1 +/- .1 for all sows that farrowed in the experiment. Parity group affected total litter size, live litter size, live litter weight, and number stillborn (P < .01) but not pig weight, number of runts, number of mummies, or gestation length (P > . 10). In this study, a single injection of vitamin A at any time from weaning to farrowing did not increase litter size in sows.

Hormonal and behavioral correlates of emotional states in sexually trained boars.

Physiological and behavioral traits of sexually mature boars were compared between episodes of copulation and sexual frustration in order to determine reliable indicators of the differences in emotional states. Ten boars, approximately 6 mo of age, were trained to mount a stationary artificial sow (ArtSow) and to ejaculate when digital pressure was applied to the extended penis. This method of semen collection is the typical procedure of the industry. All 10 boars used in this study were fully trained to this procedure before the onset of the study. Each boar was subjected to trials in which one of the following two treatments was applied. In the control (CTRL) treatment, boars were treated the same as during their training (i.e., allowed to complete ejaculation). In the frustration (FRUS) treatment, boars were allowed to mount the ArtSow, but because no manual pressure was applied to the extended penis, ejaculation never occurred. Blood was collected via indwelling catheters before onset of the trial, during exposure to the ArtSow, and after returning to their home pen. Concentrations of testosterone, cortisol, and beta-endorphin were quantified. Behavior of the boars was recorded during exposure to the ArtSow and for 30 min after return to their home pen. Relative to preexposure levels, serum cortisol increased (P<.05) during CTRL exposure and after exposure to both treatments (CTRL; P<.04 and FRUS; P<.06). Serum testosterone did not change during and after either treatment. Serum concentrations of beta-endorphin did not change during or after CTRL trials, but serum beta-endorphin was greater (P<.05) during FRUS than during CTRL trials. Behavioral analysis revealed that boars spent less time lying down and more time moving about their home pen (P<.05) after a FRUS than after a CTRL trial. In summary, serum cortisol did not allow us to distinguish between the excitement of copulation and the negative affect associated with sexual frustration, whereas increases in serum beta-endorphin and motor activity seemed to be indicators of the negative emotional state of sexual frustration in trained boars.

Surgical correction of severe vaginal introital stenosis in female baboons (Papio sp.) infected with simian agent 8.

Simian agent 8 (SA8) is a neurotropic, endemic alphaherpesvirus in Papio sp. Lesions associated with simian agent 8 infections usually involve the genitalia of sexually mature baboons. In females, secondary bacterial infections may lead to scarring of the vulva and perineum, with resulting vaginal obstruction. Affected baboons are poor breeders and often develop urinary tract infections due to retention of urine in the vagina. Reconstructive vaginal surgery was performed on seven baboons with vaginal obstruction. Four weeks before surgery, 50 mg of Depo-Provera was administered intramuscularly to each animal to arrest the estrous cycle, reduce swelling, and allow adequate surgical exposure of the vagina. Ventral and circular incisions were made around the constricted vagina. The peripheral skin was excised to break down the underlying connective tissue, allowing access to the vaginal mucosa. Healthy vaginal tissue was then opposed to the incised skin edges with 3-0 Vicryl in an interrupted pattern. Once healed, the vaginas remained patent, allowing normal mating and urination. Nine months after surgery, five baboons had healthy infants, and pregnancy was confirmed in the other two animals. The described procedure may allow female baboons previously infertile and at risk of urinary tract infections to be returned to a healthy reproductive state.

Efficacy and safety of Minipress XL, a new once-a-day formulation of prazosin.

The efficacy and safety of prazosin GITS (gastro-intestinal therapeutic system), a new extended-release once-a-day formulation, were assessed both as monotherapy in mild essential hypertension and in combination with a diuretic in moderate essential hypertension in two multicenter, double-blind, placebo-controlled trials. Prazosin GITS (Minipress XL) given once daily in doses of either 10 or 20 mg significantly reduced sitting and standing systolic and diastolic blood pressure compared with placebo in both mild and moderate essential hypertension. There were minimal, clinically insignificant changes in heart rate following prazosin-GITS treatment (2.5, 10, and 20 mg) compared with placebo treatment. Prazosin GITS was well tolerated; the most common adverse experiences reported were headache, dizziness, and fatigue. All adverse experiences in the moderate hypertension group and the majority (91 percent) in the mild hypertension group were mild-to-moderate in severity. The results from these multicenter trials demonstrate the efficacy and safety of this new extended-release once-a-day formulation of prazosin in the treatment of patients with mild and moderate essential hypertension.