Incomplete or failed thrombectomy in acute stroke patients with Alberta Stroke Program Early Computed Tomography Score 0-5 - how harmful is trying?

BACKGROUND AND PURPOSE: It is currently unknown whether mechanical thrombectomy (MT) for ischaemic stroke patients with low initial Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is clinically beneficial or even harmful. The purpose of this study was to investigate whether failed or incomplete MT in acute large vessel occlusion stroke with an initial ASPECTS ≤ 5 is associated with worse clinical outcome compared to patients not undergoing MT. METHODS: This observational cohort study included a consecutive sample of patients with anterior circulation stroke and initial ASPECTS ≤ 5 admitted between March 2015 and August 2019. Failed recanalization was defined as Thrombolysis in Cerebral Infarction (TICI) score 0-2a, and incomplete recanalization as TICI 2b. Clinical outcome was assessed using the modified Rankin Scale (mRS) at 90 days defining very poor clinical outcome as mRS > 4. RESULTS: One hundred and seventy patients were included. Ninety-nine patients underwent MT and 71 patients received best medical treatment only. Clinical outcome after failed or incomplete MT (TICI 0-2b) was significantly better compared to patients with medical treatment only (median mRS 5, interquartile range 4-6 vs 5-6, P = 0.03). In multivariable logistic regression analysis, failed or incomplete MT (TICI 0-2b) showed a significantly reduced likelihood for very poor outcome (odds ratio 0.39, 95% confidence interval 0.19-0.83, P = 0.01). Failed MT (TICI 0-2a) was not associated with a worse outcome compared to best medical treatment. CONCLUSIONS: Patients with failed or incomplete recanalization results (TICI 0-2b) showed a reduced likelihood for very poor outcome compared with those who did not receive MT. Evidence from randomized trials is needed to confirm that even failed or incomplete MT is not harmful in these patients.

S100ß as a novel and accessible indicator for the presence of monocyte-driven encephalitis in AIDS.

AIMS: The pathogenesis of human/simian immunodeficiency virus encephalitis (HIVE/SIVE) remains incompletely understood, but is associated with alterations in the blood-brain barrier. At present, it is not possible to easily determine if an individual has HIVE/SIVE before post mortem examination. METHODS: We have examined serum levels of the astroglial protein S100ß in SIV-infected macaques and show that it can be used to determine which animals have SIVE. We also checked for correlations with inflammatory markers such as CCL2/MCP-1, IL-6 and C-reactive protein. RESULTS: We found that increased S100ß protein in serum correlated with decreased expression of the tight junction protein zonula occludens-1 on brain microvessels. Furthermore, the decrease in zonula occludens-1 expression was spatially related to SIVE lesions and perivascular deposition of plasma fibrinogen. There was no correlation between encephalitis and plasma levels of IL-6, MCP-1/CCL2 or C-reactive protein. CONCLUSIONS: Together, these data indicate that SIVE lesions are associated with vascular leakage that can be determined by S100ß protein in the periphery. The ability to simply monitor the presence of SIVE will greatly facilitate studies of the neuropathogenesis of AIDS.

Expression of serotonin transporters by peripheral blood mononuclear cells of rhesus monkeys (Macaca mulatta).

It has been well established that serotonin (5-hydroxytryptamine, 5-HT) plays a key role in neuro-endocrine-immune networks, mostly through its receptors and/or transporters. Although the presence of 5-HT receptor mRNAs in peripheral blood mononuclear cells (PBMCs) of rhesus monkeys has been reported, there is little information about serotonin transporter (SERT) expression by these cells. To examine SERT expression at the transcription and translation level, one-step RT-PCR, confocal microscopy and flow cytometry were used to detect SERT mRNA and protein expression by rhesus monkey PBMCs. It was found that SERT mRNA could be detected by RT-PCR from all of the rhesus macaque PBMC RNA samples and the nucleotide sequence of the amplicons was identical to the published SERT mRNA sequence. Low level SERT immunoreactivity was also demonstrated on the surface of rhesus PBMCs by confocal microscopy. Almost all lymphocytes and most monocytes were positive for SERT by flow cytometry. In the 2 rhesus macaques examined by multicolor flow cytometry, SERT(bright) cells were more than 84%, 94%, and 96% among CD20+, CD3+, and CD3+CD4+ lymphocytes respectively. These data demonstrate expression of SERT by rhesus macaque PBMCs, and indicate that rhesus macaques would be suitable models to test the in vivo immune regulatory effects of 5-HT or drugs targeting SERT.

Differential reduction of plasma cholesterol by the American Heart Association Phase 3 Diet in moderately hypercholesterolemic, premenopausal women with different body mass indexes.

The ability of a low-fat, low-cholesterol diet to improve the risk-factor profiles of moderately hypercholesterolemic, premenopausal women was evaluated. Nineteen women were fed a typical American diet for 1 mo, after which a low-fat diet consisting of 21% of total energy (en%) as fat, 59 en% carbohydrates, 19 en% protein, and 96 mg cholesterol/d (P:S 1.8) was given. After 5 months, total and low-density lipoprotein (LDL) cholesterol was decreased by 7% and 11%, respectively, and total triglycerides increased by approximately 30%. High-density-lipoprotein (HDL) cholesterol was decreased by 12% at month 2 and 5% at month 5 (P less than 0.05). Although HDL2 cholesterol decreased progressively throughout the diet period to -35% by month 5, HDL3 cholesterol, which decreased to -5% at month 1, increased to +7% by month 5. Of the plasma apolipoproteins only apo A-II was altered (+15%) by the diet. Body mass index correlated to baseline values and affected response to diet; only the leanest women had significant decreases in total, LDL, and HDL2 cholesterol in response to the low-fat diet.

Changes in body weight, body composition, and energy intake in women fed high- and low-fat diets.

The effects of a 20%-fat diet (LF) on total body weight, lean body weight, and adiposity were studied in 18 premenopausal women with body mass index (BMI) of 18-44. Subjects were fed a 37%-fat (HF) control diet for 4 wk followed by the LF diet for 20 wk. Total body weight, lean body weight, and fat weight were measured at the end of the HF and LF dietary periods by hydrostatic weighing. Despite adjustments in energy intake to maintain weight throughout the study, subjects exhibited a 2.8% decrease in total body weight (P less than 0.0006), an 11.3% decrease in fat weight (P less than 0.0001), and a 2.2% increase in lean body weight (P less than 0.0149) by the end of the LF period. Similar changes were observed in obese (BMI greater than 30) and non-obese women (BMI less than 30). By the end of the LF period, energy intake had increased significantly in comparison with the HF diet (119% of the HF intake, P less than 0.0001). Results could not be explained by changes in daily activity levels and suggest that macronutrient composition plays a role in energy requirements for weight maintenance.

Developmental expression patterns of CCR5 and CXCR4 in the rhesus macaque brain.

Emerging data indicate that chemokine receptors on neurons and glia in the central nervous system (CNS) play a role in normal CNS development, intercellular communication, and the neuropathogenesis of AIDS. To further understand chemokine receptors in the brain and explore their potential role in HIV neuropathogenesis, particularly in pediatrics, we examined the regional and cellular distribution of CCR5 and CXCR4 in normal fetal, neonatal, and adult rhesus macaques. CCR5 and CXCR4 were detected by immunohistochemistry and immunofluorescence within the cytoplasm of subpopulations of neurons in the neocortex, hippocampus, basal nuclei, thalamus, brain stem, and cerebellum and by flow cytometry on the surface of neurons and glia. Interestingly, expression of CCR5 and CXCR4 increased significantly (p<0.05) from birth to 9 months of age. We further characterize this dynamic developmental pattern of CCR5 and CXCR4 expression in resident cells of the CNS.

Effects of hyperoxia and diet on murine tissue levels of vitamin E and polyunsaturated fatty acids.

One hundred eighty-six adult female mice were studied to examine the effect of manipulating dietary vitamin E and fractional inspired oxygen concentrations (FiO2) on tissue levels of vitamin E, total polyunsaturated fatty acids (TPUFA) and conjugated dienes (CD) as an index of lipid peroxidation. Animals were fed custom diets containing either 0, 50 or 150 ppm DL-alpha-tocopheryl acetate. Once plasma vitamin E levels of mice fell below 0.2 mg/dl (at week 19), all mice were placed in chambers containing either room air (FiO2 approximately 0.21) or FiO2 greater than 0.95 for the next 72 hr. Dietary manipulation had a major impact on the levels of vitamin E in plasma, lung and perirenal adipose tissues (p less than 0.0001, p less than 0.0001 and p less than 0.005, respectively). Dietary vitamin E deprivation was associated with significant reductions in lung glutathione peroxidase (GPX) activities (p less than 0.05) and in plasma TPUFA levels (p less than 0.05). No significant effect attributable to either diet or FiO2 was observed for liver vitamin E, liver TPUFA or lung TPUFA levels, or for those of CD in any tissue examined. Adipose TPUFA levels were depressed in all dietary groups exposed to FiO2 greater than 0.95, when compared with those of groups exposed to room air. The high FiO2 exposures also were associated with marked reductions in lung to body weight ratios (p less than 0.01). These data suggest that dietary vitamin E treatment after long-term feeding can modify vitamin levels in plasma, lung and adipose tissues, and lung GPX activities. Vitamin E levels in liver seemed less responsive to our dietary manipulations in adult female mice, though expressing liver vitamin E levels in terms of TPUFA revealed significant differences between the ratios from 0 and 150 ppm vitamin E groups (p less than 0.05).

Evaluation of an avian-specific probiotic and Salmonella typhimurium-Specific antibodies on the colonization of Salmonella typhimurium in broilers.

Salmonella typhimurium colonizes the intestinal tract of poultry and causes food-borne illness in humans. Reduction of S. typhimurium colonization in the intestinal tract of poultry reduces potential carcass contamination during slaughter. The purpose of this study was to determine the effect of an avian-specific probiotic and S. typhimurium-specific antibodies on the colonization of S. typhimurium in broilers and on body weights. Broiler chicks were spray-vaccinated at the hatchery with the commercial product. Avian Pac Plus, which contains Lactobacillus acidophilus, Streptococcus faecium, ad S. typhimurium-specific antibodies. At placement, these chicks were administered Avian Pac plus in the water. Six hours postplacement, chicks were orally challenged with 1.8 x 10 (7) CFU of S. typhimurium. Chicks were administered Avian Pac Plus for two additional days postchallenge. Chicks were evaluated for S. typhimurium colonization and shedding every 3 to 4 days for the first 2 weeks and every 7 days for 6 weeks. The mean cecal and colonic concentration of S. typhimurium from the Avian Pac Plus-treated group was significantly lower at day 31 (P = 0.0001), day 38 (P = 0.0005), and day 43 (P = 0.0001) than the nontreated control group. These results indicated that a combination of Lactobacillus acidophilus, Streptococcus faecium, and S typhimurium-specific antibodies have a beneficial effect in reducing the colonization of S. typhimurium in market-aged broilers.

The effect of hypovitaminosis A on the pathogenesis of Pasteurella multocida in turkeys.

It has been proposed that Pasteurella multocida can invade the host tissues via the mucous membrane. Vitamin A (VitA) deficiency has been associated with mucous membrane damage, such as squamous metaplasia. The objective of this study was to determine the early stages in the pathogenesis of P. multocida in VitA-deficient turkeys and clinically healthy turkeys. Fifteen-week-old VitA-deficient and clinically healthy turkeys were inoculated with P. multocida P-1059, a virulent strain, and the portal of entry, invasion, and localization of P. multocida were studied by microbial examination of the trachea, liver, and lung and histologic examinations of internal organs. Higher mortality was found in VitA-deficient turkeys. Pasteurella multocida was first reisolated from the trachea, secondarily from the liver and blood, and finally from the lung in both groups. Invasion of P. multocida into tissues occurred between 3 hr and 24 hr postinoculation in both groups. Our findings suggest that altered membrane integrity in VitA-deficient birds did not appear to change the time course of the systemic spread of P. multocida infection in turkeys and that the increased mortality seen in the VitA-deficient turkeys may be associated with immune system impairment.

Virulence of raptor-origin Pasteurella multocida in domestic chickens.

Pasteurella multocida belonging to somatic serotype 1 and capsular type A has been known to cause avian cholera in domestic poultry. Pasteurella multocida serotype 1 has also been isolated from raptorial birds. However, the capsular type for these raptorial isolates remains unknown. Moreover, the virulence of these raptorial isolates for domestic poultry has not been determined. The objectives of this study were to determine the capsular type of raptorial P. multocida serotype 1 isolates and to determine if these isolates were virulent for domestic chickens. Study chickens were inoculated with one of three P. multocida isolates. Isolate WESO-1 was obtained from a western screech owl (Otus kennicottii) and isolates RTHA-2 and RTHA-4 were isolated from two red-tailed hawks (Buteo jamaicensis). These isolates were given by either the oral, intravenous, or intraocular route. Control birds were given brain-heart infusion broth. The capsular serotypes of three isolates were also determined. The RTHA-2 and RTHA-4 isolates belonged to P. multocida capsular type A. The WESO-1 isolate belonged to capsular type F. Results also demonstrated that, for the isolates examined, the intraocular route did not cause mortality in chickens. There was mortality in all groups for the intravenous route. However, various mortality patterns were observed when P. multocida was given orally for the three different isolates. The RTHA-4 isolate (serotype 1:A) was the most virulent for domestic chickens. The WESO-1 isolate (serotype 1:F) was the least virulent for chickens among the raptorial isolates examined.

Crop impaction resulting from feather ball formation in caged layers.

Abnormal behaviors in commercial poultry, including feather pulling and pica, have been known to occur when birds are exposed to an unfamiliar environment. We report here the development of crop impactions resulting from feather ball formation. Twelve specific-pathogen-free (SPF) chickens were placed in one of three cages housed among a commercial layer flock in three different buildings on a farm site. Three weeks after placement, the birds were removed from the cages and given a physical exam. Chickens were thin, and one bird in each of the three caged groups had a palpable mass at the level of the thoracic inlet. At necropsy, a mass was noted in the crop. Upon further dissection, a wet, foul-smelling mass consisting of feathers and feed debris was recovered. Results from our case indicate that unfamiliar surroundings can cause pica in birds. Hence, avian researchers and veterinarians planning to introduce new birds into a flock, i.e., SPF birds, should consider the birds' previous environmental conditions prior to placement because sudden placement in unfamiliar surroundings can result in pica.

Evaluation of an avian-specific probiotic to reduce the colonization and shedding of Campylobacter jejuni in broilers.

Campylobacter jejuni has often been responsible for human gastroenteritis. Poultry have often been implicated as a source for these human infections. Intestinal colonization of C. jejuni in the chicken plays a role in carcass contamination during slaughter. Thus, reducing C. jejuni colonization in chickens can potentially reduce the incidence of C. jejuni infections in humans. The use of probiotics to competitively exclude the colonization of intestinal pathogens has been proposed for poultry. Hence, the purpose of this study was to evaluate the use of an avian-specific probiotic containing Lactobacillus acidophilus and Streptococcus faecium for reducing the shedding and colonization of C. jejuni in the chicken intestinal tract. Day-old chicks were randomly allocated into either a probiotic-treated group or a control group. The treated group was given probiotic from day 1 to day 3, and the control group was not given any probiotic. Six hours after the first oral administration of probiotics (treatment) or double distilled water (control), these chicks were challenged with C. jejuni. The frequency of the C. jejuni shedding was monitored until market age. Intestinal colonization was determined for the two experimental groups at slaughter. Results indicated that chickens given probiotics from day 1 to day 3 had a 70% reduction in the frequency of C. jejuni shedding in colonized chicks (P = 0.0001) and a 27% reduction in jejunal colonization in colonized chicks (P = 0.0001) at slaughter when compared with the control group. Thus, the use of the avian-specific probiotic containing L. acidophilus and S. faecium can reduce the colonization and frequency of fecal shedding of C. jejuni in market-aged broilers.

Encephalomalacia associated with vitamin E deficiency in commercially raised emus.

Thirteen of 64 emus on a commercial emu farm in Ohio exhibited neurological signs that included backward staggering, incoordination, generalized weakness, and sitting on their hocks with head retracted backward. Eight of the birds showing such signs were found dead. Two of these emus were necropsied, and no significant gross lesions were observed. Major histopathological lesions were found in the cerebellum and included multiple malacic foci in association with neuropil rarefaction and astrogliosis within the white matter of folia. In addition, the hepatic vitamin E level of one emu was determined at the Michigan State University Animal Health Diagnostic Laboratory (MSU-AHDL) to be 14.61 micrograms/g dry weight. This vitamin E level was in the lower percentile (35%) of 30 emu liver samples examined at MSU-AHDL. A diagnosis of vitamin E-associated encephalomalacia was made based on clinical signs, gross and histological lesions, and liver vitamin E levels.

Prevalence and characteristics of Pasteurella multocida in commercial turkeys.

The oropharyngeal regions of 680 meat turkeys and 55 breeder turkeys from nine outbreak farms, three history-outbreak farms, and 19 nonoutbreak farms in Ohio, Indiana, and Pennsylvania were cultured to determine the prevalence of Pasteurella multocida in turkeys. Pasteurella multocida was recovered from 32 out of 105 turkeys belonging to outbreak farms. Pasteurella multocida was not recovered from either history-outbreak or nonoutbreak farms. Characterization via capsular and somatic serotyping, biotyping, restriction endonuclease analysis, and antimicrobial susceptibility testing was performed on all recovered P. multocida isolates. Pasteurella multocida serotype A:1 and somatic serotype 1 with an un-typable capsular serogroup (UT:1) were the most common serogroups found. All isolates belonged to biotype P. multocida ssp. multocida. EcoRI, HpaII, and HindIII restriction enzyme digestions identified three, five, and five restriction fragment length polymorphism profiles, respectively. A majority of the isolates were susceptible to amikacin, ampicillin, ceftiofur, cephalothin, enrofloxacin, florfenicol, gentamicin, neomycin, novobiocin, oxacillin with 2% NaCl, sarafloxacin, tilmicosin, and trimethoprim with sulphadiazine and resistant to clindamicin, penicillin, tiamulin, and tylosin.

Survey of pathogens and blood parasites in free-living passerines.

To determine the disease prevalence of free-living passerines, 1709 passerines were sampled from 38 different field sites in Ohio. Choanal and cloacal swabs were collected from each bird and cultured for the presence of Pasteurella multocida, Salmonella spp., and Escherichia coli by standard microbiologic techniques. In addition, the serum from each bird was analyzed for the presence of antibodies to Mycoplasma gallisepticum, Mycoplasma synoviae, Newcastle disease virus, and avian influenza virus. A blood smear was also made to examine for the presence of blood parasites. Results indicated that the isolation of E. coli varied with bird species, with the European starling having a higher (21.4%) isolation of E. coli. Salmonella spp. were also isolated from these free-living passerines. Pasteurella multocida was not isolated from any of the sampled passerines. These birds did not have antibodies to M. gallisepticum, M. synoviae, Newcastle disease virus, or avian influenza virus. Blood parasites were not detected in any of the birds sampled.

Induction of vitamin A deficiency in turkeys.

The objective of this study was to determine the relationship between the hepatic vitamin A (VitA) level and the pathologic changes in the oropharynx and esophagus of VitA-deficient turkeys. Study turkeys were provided with a diet sufficient (11,000 IU/kg) or deficient (2750 IU/kg) in VitA from 4 to 17 wk of age. Body weight, bacterial culture, and tissues from internal organs were collected at weekly intervals. VitA deficiency causes epithelial tissue damage in poultry. This epithelial damage was seen grossly as white plaques in the oropharynx and esophagus and histologically as squamous metaplasia of mucosal glands and keratinization of epithelium. No significant difference in body weights was seen among the groups. Moreover, no pathogenic bacteria was isolated during sampling periods. Liver VitA levels declined significantly after consumption of low VitA diet for 3 wk and were depleted after 5 wk. Squamous metaplasia due to VitA deficiency developed in the esophagus after 3 wk and in the oropharynx after 4 wk of consuming a VitA-deficient diet.

The effect of route of inoculation on the virulence of raptorial Pasteurella multocida isolates in Pekin ducks (Anas platyrhynchos).

The purpose of this study was to determine the virulence of raptorial Pasteurella multocida for ducks and the effect of various routes of inoculation on virulence. Four-week-old Pekin ducks (Anas platyrhynchos) were challenged with one of three raptorial isolates (RTHA-2, RTHA-4, or WESO-1) by one of five inoculation routes (intranasal, intraocular, intravenous, oral, and subcutaneous). Ducks were monitored daily for mortality until 2 wk postchallenge. Results indicated that the intravenous route caused the most mortality for all isolates and that significant variation existed in the virulence among the sources of P. multocida, with WESO-1 causing the least mortality of the isolates tested.

Serologic survey of free-living nestling prairie falcons (Falco mexicanus) for selected pathogens.

Serum samples from 34 free-living nestling prairie falcons (Falco mexicanus) in southwestern Idaho were negative for antibodies to avian influenza virus, Newcastle disease virus, and three Aspergillus species. Serum from a single bird had hemagglutinating inhibition activity in response to Mycoplasma synoviae, and another bird's serum had slight activity in response to M. gallisepticum.

Substance P receptor antagonist reverses intestinal pathophysiological alterations occurring in a novel ex-vivo model of Cryptosporidium parvum infection of intestinal tissues derived from SIV-infected macaques.

BACKGROUND: Cryptosporidium infection leads to life-threatening diarrhea in AIDS patients. Pathogenesis of cryptosporidiosis is due to intestinal physiological alterations. We devised an ex-vivo model using ex-vivo Cryptosporidium parvum infection of jejunal tissues derived from SIV-infected macaques and studied the role of substance P (SP) in the pathogenesis of cryptosporidiosis. METHODS: We measured jejunal SP protein levels using ELISA, and electrophysiological alterations using the Ussing chamber technique in an ex vivo model of Cryptosporidium infection. Paraformaldehyde-fixed jejunum from SIV-infected macaques with and without naturally occurring cryptosporidiosis was studied for SP protein expression by immunohistochemistry and fluorescence deconvolution microscopy. RESULTS: Ex-vivo Cryptosporidium-infected tissues and tissues from SIV-infected macaques with naturally occurring cryptosporidiosis demonstrated elevated SP protein levels compared with tissues from SIV-infected animals without ex-vivo C. parvum infection or tissues from SIV-infected animals that have no evidence of cryptosporidiosis. In our ex-vivo model of Cryptosporidium infection, we demonstrated pathophysiological alterations that were blocked by SP-receptor antagonist treatment. CONCLUSIONS: These studies suggest that SP-receptor antagonists could prove useful for treatment of AIDS-related cryptosporidiosis.