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Biomedical subjects

G A Hall

Publications and source records attributed to G A Hall.

At least 19 recordsLinked to original sources
PubMed2000

Allogeneic red blood cell transfusion is an independent risk factor for the development of postoperative bacterial infection.

BACKGROUND AND OBJECTIVES: Allogeneic red blood cell transfusions may exert immunomodulatory effects in recipients including an increased rate of postoperative bacterial infection. It is controversial whether allogeneic transfusion is an independent predictor for the development of postoperative bacterial infection. METHODS: We analysed a prospectively collected database of 1,349 patients undergoing colorectal surgery in 11 centres across Canada. The primary outcome was the development of either a postoperative wound infection or intra-abdominal sepsis in transfused and nontransfused patients. The effect of allogeneic transfusion on postoperative infection was evaluated with adjustment for all the confounding factors in a multiple regression analysis. RESULTS: The 282 patients who received a total of 832 allogeneic units had a significantly higher frequency of wound infections and intra-abdominal sepsis than the patients who were not transfused (25. 9 vs. 14.2%, p = 0.001). A significant dose-response relationship between transfusion and infection rate was demonstrated. Multiple regression analysis identified allogeneic transfusion as a statistically significant independent predictor for postoperative bacterial infection (OR 1.18, 95% CI 1.05-1.33, p = 0.007). Other independent predictors were anastomotic leak, repeat operation, patient age and preoperative haemoglobin level. The mortality rate was also significantly higher in the transfused group. CONCLUSION: These data support the hypothesis that allogeneic red cell transfusion is an independent risk factor for the development of postoperative bacterial infection in patients undergoing colorectal surgery. This association provides further reason to minimise exposure to allogeneic transfusions in the perioperative setting.

Abdomen↗
PubMed1999

Prospective audit of cytomegalovirus-negative blood product utilization in haematology/oncology patients.

The transfusion management of immunocompromised patients often requires special blood product use such as cytomegalovirus (CMV)-negative cellular products, which are more costly than standard blood products and occasionally in short supply. We audited the use of CMV-negative products in haematology/oncology patients to determine the appropriateness of their use. A concurrent-prospective audit was conducted of all orders for CMV-negative packed red blood cell (PRBC) and platelet products in 201 haematology/ oncology patients. Once CMV serostatus was determined, orders for inappropriate CMV-negative units were cancelled, and filled as CMV untested units. During the 21-month period of this audit, the rates of inappropriate transfusions decreased for PRBC from 73.2% to 14.3% (chi2 = 68.4, P<0.001) and for platelets from 68.1% to 10.6% (chi2 = 65.6, P<0.001). The median time to cancellation of inappropriate CMV-negative orders was 11 days. This audit resulted in estimated cost savings of $16500 over the 21-month duration. Inappropriate requests for scarce and expensive blood products are substantially reduced by concurrent-prospective auditing of transfusion practice, in a manner that is both simple and cost effective.

Antibodies, Viral↗
PubMed1998

Detrimental effects on villus form during conventional oral rehydration therapy for diarrhoea in calves; alleviation by a nutrient oral rehydration solution containing glutamine.

This paper examines the possibility that treatment of diarrhoea with conventional oral rehydration solutions (ORSs) may be detrimental to villus structure by imposing nutrient deprivation and that such detrimental effects may be reduced or avoided by using a nutrient ORS. A conventional WHO-type ORS (W) was compared with two nutrient solutions (N and G) both containing high glucose concentrations and the latter containing glutamine; their effects on enteric structure were assessed by morphometric analysis of samples obtained from diarrhoeic calves after 96 h treatment. Comparisons were also made with samples from controls and diarrhoeic calves at the stage where oral rehydration would have begun in the treated groups. As in our previous ORS studies, diarrhoea was induced with enterotoxigenic Escherichia coli (09:K30:K99). We measured villus length and width, crypt depth and width and calculated villus surface area in proximal, mid and distal small intestine (PSI, MSI, DSI), using standard morphometric techniques. Proximal and distal spiral colon samples (PC, DC) were examined for crypt depth and width; mitoses per crypt were counted in samples from all regions. Non-diarrhoeic calves showed the expected gradient of villus length through PSI, MSI and DSI, hence data for each region are normalized as a percentage of the control value for that region. PSI showed the greatest loss of villus length and surface area (50%) with diarrhoea. In MSI and DSI the villus loss was greater with solution W and N or G, as were increased mitoses and crypt depth. Crypt depth and mitoses also increased in the colon with solution W. Colonic crypt width increased with diarrhoea and conventional oral rehydration but less so with G; there is reason to believe that such changes have functional significance. Crypt changes in colon, MSI and DSI were least with solution G. The changes developing in diarrhoeic calves prior to treatment were thus less apparent in those treated with a nutritional ORS, particularly if it contained glutamine.

Animals↗
PubMed1998

In vivo resistance to simian immunodeficiency virus superinfection depends on attenuated virus dose.

Infection of macaques with attenuated simian immunodeficiency virus (SIV) induces potent superinfection resistance that may be applicable to the development of an AIDS vaccine but little information exists concerning the conditions necessary for the induction of this vaccine effect. We report that only a high dose of attenuated SIVmac protected macaques against intravenous challenge with more virulent virus 15 weeks after primary infection. Three of four animals given 2000-20000 TCID50 of SIVmacC8, a molecular clone of SIVmac251(32H) with a 12 bp deletion in the nef gene, essentially resisted superinfection with uncloned SIVmac. In two animals challenge virus was never detected by PCR and in one animal challenge virus was detected on one occasion only. Although animals given 2-200 TCID50 of attenuated virus were superinfected they were spared from the loss of CD4 cells seen in infected naive controls. Protection from superinfection did not correlate with immune responses, including the levels of virus-specific antibodies or virus-neutralizing activity measured on the day of challenge; although, after superinfection challenge, Nef-specific CTL responses were detected only in animals infected with high doses of attenuated SIV. Unexpectedly, cell-associated virus loads 2 weeks after inoculation were significantly lower in animals infected with a high dose of attenuated SIV compared to those in animals infected with a low dose. Our results suggest that the early dynamics of infection with attenuated virus influence superinfection resistance.

Animals↗
PubMed1997

Experimentally assessed public health risks associated with pigs from farms experiencing anthrax.

Following an outbreak of anthrax in an intensive pig rearing unit in north Wales in 1989 a study was initiated by the Ministry of Agriculture, Fisheries and Food to assess public health risks during such an outbreak. Of 50 pigs infected by the addition of Bacillus anthracis spores to their feed, two died of anthrax six and eight days later. The remainder were observed for 21 days and exhibited only mild and transient clinical signs of disease. As judged by the results of bacteriological culture of appropriate tissues from the survivors, it was concluded that meat from healthy pigs killed 21 days after the latest case during an outbreak would not pose a public health risk.

Animal Feed↗
PubMed1997

Macaques infected with live attenuated SIVmac are protected against superinfection via the rectal mucosa.

Good protection against systemic challenge in the SIVmac model of AIDS has been provided by prior infection with attenuated virus. To determine if such protection extends to intrarectal mucosal challenge two molecular clones, SIVmacC8 and SIVmacJ5, were used in this study. SIVmacC8 has an attenuated phenotype in vivo, due to a 12-bp deletion in the nef/ 3'-LTR, whereas SIVmacJ5 has a full size nef open reading frame and induces AIDS in infected macaques. The J5 molecular clone was shown to infect rhesus macaques following atraumatic intrarectal inoculation. The dynamics were similar to those following intravenous inoculation resulting in early, high, cell-associated viremia and seroconversion. Four macaques previously infected with the attenuated SIVmacC8 resisted superinfection with SIVmacJ5, following intrarectal inoculation. These animals also resisted intrarectal infection with an HIV/SIV chimeric virus (SHIV) composed of SIVmac239 expressing the HXBc2 env, tat, and rev genes, suggesting that immunity to the envelope proteins was unlikely to be involved in the superinfection resistance. Infection with the attenuated SIVmac generated cytotoxic T lymphocytes (CTL) detectable in the peripheral circulation, serum neutralizing antibodies, and SIV-binding antibodies in rectal fluids. SIVmacC8 proviral DNA was found in lymph nodes removed at necropsy but there was no evidence for local sequestration of challenge virus. SIV-specific CTL, were detected in gut-associated lymph nodes and may have a role in limiting superinfection following mucosal exposure.

Animals↗
PubMed1997

Macaques infected with attenuated simian immunodeficiency virus resist superinfection with virulence-revertant virus.

Macaques infected with attenuated simian immunodeficiency virus (SIVmac) can resist superinfection challenge with virulent virus, showing the potential of live attenuated virus as an AIDS vaccine. Superinfection resistance does not, however, prevent the generation of virulent virus in vivo, suggesting that such virus may circumvent the resistance effect. Here, we show that three macaques already infected with the attenuated molecular clone SIVmacC8 were resistant to superinfection with virulent virus that arose in vivo following repair of a 12 bp attenuating lesion in the nef/3' LTR. In contrast, four naive animals became infected following inoculation with blood taken from the macaque in which virulent virus arose. Loss of nef-specific cytotoxic T lymphocyte (CTL) responses followed repair of the attenuating lesion within nef in the donor animal, suggesting the possibility of escape from CTL-driven selection pressure.

Animals↗
PubMed1995

Constitutive expression of major histocompatibility complex class II antigens on monocytes and B cells correlates with disease in simian immunodeficiency virus-infected rhesus macaques.

Constitutive host factors that influence progression to AIDS are understood poorly. In the macaque model for AIDS, 35 animals infected with simian immunodeficiency virus (SIV) were analyzed for major histocompatibility complex class II antigen expression on blood monocytes and B cells by immunostaining and flow cytometry. Expression varied widely between animals but was constant with time. Level of expression and the proportion of monocytes and B cells that expressed class II were not affected by SIV infection. Significantly more animals developed AIDS in the group with low class II expression than in the group with high expression (P < .001). Progression to disease was faster in animals that expressed poorly (P < .01), and opportunistic pathogens were more common (P < .05). Thus, the constitutive level of class II antigen expression may be a useful prognostic indicator for human immunodeficiency virus disease in humans and may be an important factor in the design of vaccine trials.

AIDS Vaccines↗
PubMed1995

Repair and evolution of nef in vivo modulates simian immunodeficiency virus virulence.

Experimental evidence from the simian immunodeficiency virus (SIV) model of AIDS has shown that the nef gene is critical in the pathogenesis of AIDS. Consequently, nef is of considerable interest in both antiviral drug and vaccine development. Preliminary findings in two rhesus macaques indicated that a deletion of only 12 bp found in the overlapping nef/3' long terminal repeat (LTR) region (9501 to 9512) of the SIVmacC8 molecular clone was associated with reduced virus isolation frequency. We show that this deletion can be repaired in vivo by a sequence duplication event and that sequence evolution continues until the predicted amino acid sequence of the repair is virtually indistinguishable from that of the virulent wild type. These changes occurred concomitantly with reversion to virulence, evidenced by a high virus isolation frequency and load, decline in anti-p27 antibody, substantial reduction in the CD4/CD8 ratio, and development of opportunistic infections associated with AIDS. These findings clearly illustrate the capacity for repair of small attenuating deletions in primate lentiviruses and also strongly suggest that the region from 9501 to 9512 in the SIV nef/3' LTR region is of biological relevance. In addition, the ability of attenuated virus to revert to virulence raises fundamental questions regarding the nature of superinfection immunity.

Amino Acid Sequence↗
PubMed1995

The lesions of rotavirus infection in 1- and 10-day-old gnotobiotic calves.

Age-related resistance to rotavirus disease has been described with some rotaviruses. In the present study, we investigated age-related resistance to rotavirus disease by defining extent of intestinal infection, virus replication, and severity of intestinal lesions in groups of three 1- and 10-day-old gnotobiotic calves of mixed breed inoculated orally with a cloned bovine rotavirus of low virulence for calves (strain C3-160) and in two groups of three uninoculated control calves of mixed breed. One-day-old calves inoculated with rotavirus developed diarrhea 26 hours after inoculation, and their feces contained 10(8.5)-10(9.2) TCID50/g feces; inoculated 10-day-old calves did not develop diarrhea, virus excretion commenced on the second or third day after inoculation, and peak concentrations of virus in feces were 10(5.7)-10(7.9) TCID50/g feces. Calves were euthanatized within 8-30 hours after the attainment of peak virus shedding while they were still shedding virus at peak levels. The mean percentage of small intestinal epithelium that was immunostained for rotavirus was three times greater in 1-day-old calves than in 10-day-old calves, and the large intestine was infected more extensively in 1-day-old calves. Immunostaining for rotavirus was maximal in the mid small intestine. Staining of mucin was substantially less in the epithelium of the small intestines and colon of rotavirus-inoculated 1-day-old calves than in age-matched controls. The mean height of villi was reduced to approximately half that of controls in the mid and distal small intestine of rotavirus-inoculated 1-day-old calves and was unchanged in 10-day-old calves. Mean crypt cell production rates were greater than that in controls in both groups of rotavirus-inoculated calves, indicating increased enterocyte loss. Age-related resistance to disease was not due to an inability of rotavirus to infect and replicate in enterocytes with lethal effects but appeared to be associated with a slowing of the pathogenic process, which occurred because insufficient enterocytes became infected and destroyed for lesions to develop.

Aging↗
PubMed1993

Histochemistry and morphology of porcine mast cells.

Mast cells have been described extensively in rodents and humans but not in pigs, and the objective of this study was to characterize porcine mast cells by histochemistry and electron microscopy. Carnoy's fluid proved to be a good fixative but fixation with neutral buffered formalin blocked staining of most mast cells. Alcian Blue stained more mast cells than did Toluidine Blue (pH 0.5), although Alcian Blue also stained goblet cells. In pigs, unlike rodents, the Alcian Blue method did not distinguish between mast cells in the intestinal mucosa and those in the connective tissue of the intestinal submucosa, tongue and skin. Mast cells were significantly larger in adult pigs than in piglets; in adult pigs and piglets, mast cells in the intestinal mucosa were significantly larger than those in submucosal connective tissue, and they were more varied in shape in piglets and adults. Granules in mast cells in the intestinal mucosa stained less intensely than those in mast cells in connective tissue of tongue, skin and intestinal submucosa. Mast cells in the connective tissue of the tongue, skin and intestinal submucosa fluoresced strongly when stained with berberine sulphate or with a mixture of berberine sulphate and Acridine Orange, but mast cells in the intestinal mucosa did not. All mast cells reacted positively in an enzyme-histochemical method previously used to detect human tryptase but not in a method previously used to detect human chymase. Mast cells in the medulla of thymus stained similarly to mast cells in the intestinal mucosa. Ultrastructural differences between mast cells were not detected.

Animals↗
PubMed1993

Number and distribution of T lymphocytes in the small intestinal mucosa of calves inoculated with rotavirus.

An understanding of the immune response to rotavirus is needed to develop effective prophylaxis. There is evidence that cell-mediated responses may be involved and to extend these observations, rotavirus antigen and the three major T cell subsets, BoCD4+, BoCD8+, and BoWC1+ gamma/delta lymphocytes were immunostained in tissue sections from calves killed at 2, 4, 6, 8 and 10 days post inoculation and quantified by image analysis. It was established that in control calves, BoCD4+ lymphocytes were predominantly in the lamina propria, while the majority of BoCD8+ and BoWC1+ gamma/delta lymphocytes were in the epithelium. Rotavirus infection was seen throughout the small intestine with the greatest amount of viral antigen detected at 4 days post inoculation in the mid and distal small intestine. Increased numbers of all subsets were detected; small increases in intraepithelial BoCD4+ and BoWC1+ gamma/delta T lymphocytes were observed especially in the distal small intestine, while larger increases in BoCD8+ cells were detected in the epithelium and lamina propria of the proximal, mid and distal small intestine. The timing and location of these increases in T lymphocyte subsets is indicative of a specific immune response involving BoCD8+ and BoWC1+ gamma/delta T lymphocytes.

Animals↗
PubMed1993

An investigation of temporary workshop clusters reacting with cells of the mononuclear phagocytic system.

Monoclonal antibodies (mAbs) within ten temporary workshop clusters (TC3, TC8, TC9, TC11, TC16, TC17, TC19, TC20, TC21 and TC31) which from preliminary evidence appeared to recognize molecules expressed by cells of the mononuclear phagocytic system were studied by immunohistology and flow cytometry. A number of mAbs were identified that were potentially useful for immunohistological studies of the mononuclear phagocytic system. The results confirmed the specificity of a number of CD11a, CD11b, CD11c and CD44 mAbs. The findings also indicated that for several TCs the mAbs could not be regarded as recognizing the same molecule.

Animals↗
PubMed1993

Variation in rotavirus virulence: a comparison of pathogenesis in calves between two rotaviruses of different virulence.

Variation in virulence between two bovine rotaviruses was investigated using ten female and ten male 10-day-old gnotobiotic calves of five breeds or cross breeds that were inoculated with a virulent strain or a strain of low virulence. Similar numbers of infectious viral particles were detected in feces of calves inoculated with either virus, but diarrhea, xylose malabsorption, and reduction of villus height occurred only after inoculation with virulent virus. The mean percentage of the area of the villus epithelium per villus immunostained for rotavirus antigen was eight times greater in calves inoculated with virulent virus, and the mean percentage of villi on which immunostained enterocytes were detected was twice as large in calves inoculated with virulent virus than in calves inoculated with the virus of low virulence. Mean crypt death and mean crypt cell production rates were increased after inoculation with either virus. Virulence was associated with extensive spread of infection through the small intestine, preferential colonization of the proximal small intestine, and marked damage to enterocytes and villi. The virus of low virulence infected the proximal small intestine poorly, and although it infected more enterocytes in the mid and distal small intestine and replicated in them, causing cytopathic effects, it did not damage intestinal structure and affect function.

Animals↗
PubMed1992

A study of the basis of virulence variation of bovine rotaviruses.

Rotaviruses are enteric pathogens of cattle but sub-clinical infections are common. Virulence variation has been identified with bovine rotaviruses and some rotaviruses replicated without clinical signs in non-immune calves. The rotavirus genome is composed of eleven segments of double-stranded RNA and the fourth largest segment codes for a non-glycosylated surface protein, VP4, which has been linked with virulence. In the present study the biological basis of rotavirus virulence variation was studied in vivo and compared with the known properties of the fourth gene. Calves were inoculated orally with a virulent rotavirus or a rotavirus of low virulence which multiplied but failed to cause diarrhoea. They were taken for necropsy at intervals of 2 days after inoculation. Clinical signs, virus in faeces and the percentage of infected small intestinal epithelium were determined. Damage to the small intestine was assessed by measurement of villus heights and crypt-cell production rates. Virulence was associated with a greater level of colonization of the small intestinal epithelium, greater enterocyte damage and preferential infection of the upper small intestine. The fourth gene determines the ability of rotaviruses to spread in vitro and the finding that virulence was associated with greater colonization in vivo raises the possibility that this gene may have an important role in rotavirus virulence.

Animals↗
PubMed1991

Follicle associated epithelium of the gut associated lymphoid tissue of cattle.

The morphology of the gut-associated lymphoid tissue of the small and large intestine in three gnotobiotic calves was examined by scanning and transmission electron microscopy, and the distribution of specialized membranous cells present in the follicle associated epithelium was defined. Isolated follicles remaining in the ileum of a cow after involution of the continuous Peyer's patch were examined by scanning electron microscopy. The presence of membrane-bound particles, reported to be exclusively associated with the continuous Peyer's patch, was investigated in other gut-associated tissue of the small and large intestine of the calf. The presence of two types of follicle associated epithelium in the small intestine of the calf was confirmed, and the follicle associated epithelium of the large intestine proved to be a homogeneous population of specialized membranous cells, similar to that of the continuous Peyer's patch of the small intestine. In the discrete Peyer's patches, some specialized membranous cells were completely hidden by adjacent enterocytes and could only be identified by cytoplasmic extensions into the intestinal lumen. In the proximal part of the continuous Peyer's patch, a transitional zone was detected where the follicle associated epithelium of some doomed villi was composed of a homogeneous population of specialized membranous cells, while the epithelium covering other doomed villi consisted of a mixture of absorptive and specialized membranous cells, usually only found in the discrete Peyer's patches. Membrane-bound particles were observed associated with gut-associated lymphoid tissue in the small and large intestine.

Animals↗
PubMed1990

Attaching and effacing lesions in vivo and adhesion to tissue culture cells of Vero-cytotoxin-producing Escherichia coli belonging to serogroups O5 and O103.

Certain isolates of Escherichia coli from humans and animals with enteric disease attach to enterocytes and cause 'attaching and effacing' (AE) lesions. E. coli strain S22-1, serotype O103:H2, isolated from a child with diarrhoea, contained two plasmids; one of these (pDEP12) hybridized with the CVD419 DNA probe derived from a plasmid found in E. coli O157:H7 and associated with expression of fimbriae and ability to adhere to Intestine 407 cells. Strain S102-9, serotype O5:H-, isolated from a calf with dysentery, contained six plasmids, one of which also hybridized with the CVD419 probe. Loss of pDEP12 coincided with reduced adhesion to HEp-2 or Intestine 407 cells cultured in vitro; reintroduction of this plasmid restored adhesiveness. Loss of the plasmid in strain S102-9 that hybridized with the CVD419 probe did not cause a decrease in adhesion. Accumulations of actin were seen in vitro in the fluorescence actin staining (FAS) test of strains S22-1, S102-9 and their derivatives, irrespective of the plasmid content of these strains or the prevalence of attached bacteria. Strain S22-1 and its plasmidless derivative caused AE lesions of equal severity in experimentally infected gnotobiotic piglets; piglets inoculated with an isolate from a healthy human or pig did not develop these lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesins, Escherichia coli↗