Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 73
Filter
1.
Can J Vet Res ; 87(4): 245-253, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37790267

ABSTRACT

Streptococcus suis (S. suis) and Glaesserella parasuis (G. parasuis) are ubiquitous colonizers of swine tonsils that can cause systemic disease and death, under undefined conditions. It is not known, however, whether these 2 species interact during initial infection. To investigate whether such interactions occur, the objective of this study was to assess phenotypic differences between mono-and co-cultures of S. suis and G. parasuis when representative strains with different virulence potential were co-cultured in vitro. In cross-streak screening experiments, some G. parasuis (GP) serovar strains (GP3, GP4, GP5) exhibited altered morphology with some S. suis (SS) serovar strains, such as SS2, but not with SS1. Co-culture with GP5 reduced hemolytic activity of SS1, but not of SS2. Although both SS strains outgrew GP isolates in biofilm co-cultures, strain type affected the number of planktonic or sessile cells in co-culture biofilms. Numbers of sessile SS1 increased in co-cultures, but not of GP3. Both planktonic and sessile SS2 increased in co-culture, whereas GP5 decreased. Sessile SS1 increased, but planktonic GP5 decreased in co-culture and planktonic SS2 increased, but sessile GP3 decreased when grown together. The SS2 strain had a competitive advantage over GP3 during mid-exponential co-culture in broth. Streptococcus suis is predicted to use more unique carbon sources, suggesting that S. suis outcompetes G. parasuis in growth and nutrient consumption. This work provides direction for future studies of phenotypic and genotypic interactions between these and other swine tonsil co-colonizers.


Streptococcus suis (S. suis) et Glaesserella parasuis (G. parasuis) sont des colonisateurs omniprésents des amygdales porcines qui peuvent provoquer des maladies systémiques et la mort, dans des conditions non définies. On ne sait pas cependant si ces 2 espèces interagissent lors de l'infection initiale. Pour déterminer si de telles interactions se produisent, l'objectif de cette étude était d'évaluer les différences phénotypiques entre les mono- et cocultures de S. suis et G. parasuis lorsque des souches représentatives ayant un potentiel de virulence différent étaient cocultivées in vitro. Dans les expériences de dépistage par stries croisées, certaines souches des sérotypes de G. parasuis (GP) (GP3, GP4, GP5) présentaient une morphologie altérée avec certaines souches de sérovars de S. suis (SS), telles que SS2, mais pas avec SS1. La coculture avec GP5 a réduit l'activité hémolytique de SS1, mais pas de SS2. Bien que la croissance des deux souches SS ait surpassé celle des isolats de GP dans les cocultures de biofilms, le type de souche a affecté le nombre de cellules planctoniques ou sessiles dans les biofilms de coculture. Le nombre de SS1 sessiles a augmenté dans les cocultures, mais pas de GP3. Les SS2 planctoniques et sessiles ont augmenté en coculture, tandis que GP5 a diminué. La SS1 sessile a augmenté, mais la GP5 planctonique a diminué en coculture et la SS2 planctonique a augmenté, mais la GP3 sessile a diminué lorsqu'elles sont cultivées ensemble. La souche SS2 avait un avantage compétitif sur GP3 lors de la coculture mi-exponentielle en bouillon. On prévoit que S. suis utilise plus des sources de carbone uniques, ce qui suggère que S. suis surpasse G. parasuis en termes de croissance et de consommation de nutriments. Ce travail fournit une orientation pour les études futures des interactions phénotypiques et génotypiques entre ces derniers et d'autres co-colonisateurs des amygdales porcines.(Traduit par Docteur Serge Messier).


Subject(s)
Streptococcal Infections , Streptococcus suis , Swine Diseases , Animals , Swine , Streptococcus suis/genetics , Coculture Techniques/veterinary , Serogroup , Virulence , Genotype , Streptococcal Infections/veterinary
2.
Int J Colorectal Dis ; 27(7): 927-30, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22274577

ABSTRACT

BACKGROUND: Percutaneous tibial nerve stimulation (PTNS) is an acceptable second line treatment for patients with faecal incontinence (FI) unresponsive to conservative measures. There is however a paucity of data in the literature regarding its efficacy. The aim of this prospective study was to evaluate the efficacy of PTNS in an exclusively female cohort of patients and to identify factors that may predict treatment response. METHOD: A prospective cohort of female patients with FI underwent evaluation of sphincter morphology, anorectal pressures and rectal sensation as part of their physiologic assessment prior to treatment. PTNS was performed according to a specific departmental protocol. The clinical outcomes measured were: (1) Cleveland Clinic incontinence scores, (2) deferment time and (3) weekly incontinence episodes. Outcomes were compared at baseline and following treatment using appropriate statistical tests. Clinical outcomes were correlated with the results of the anorectal physiology testing (i.e. sphincter morphology, rectal sensation). RESULTS: Eighty-eight female patients with a mean age of 58.0 ± 13.6 years were included in the analysis. FI was predominantly a late consequence of obstetric injury. The mean incontinence score improved from 12.2 ± 4.0 at baseline to 9.1 ± 4.6 following treatment (p < 0.0001). Statistically significant improvements were also seen in the median deferment time and median number of weekly incontinence episodes. Sphincter damage and altered rectal sensation did not appear to influence the outcomes. CONCLUSIONS: PTNS is an effective treatment in female patients with FI. Improvements in clinical outcomes were independent of damage to the anal sphincter complex in patients with normal rectal sensation.


Subject(s)
Anal Canal/innervation , Anal Canal/pathology , Fecal Incontinence/therapy , Rectum/innervation , Rectum/pathology , Transcutaneous Electric Nerve Stimulation , Anal Canal/physiopathology , Demography , Fecal Incontinence/physiopathology , Female , Humans , Middle Aged , Rectum/physiopathology , Sensation , Tibial Nerve/pathology , Treatment Outcome
4.
Colorectal Dis ; 14(9): 1101-5, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22145761

ABSTRACT

AIM: Percutaneous tibial nerve stimulation (PTNS) is increasingly being used as a treatment for faecal incontinence (FI). The evidence for its efficacy is limited to a few studies involving small numbers of patients. The aim of the study was to assess the efficacy of PTNS in patients with urge, passive and mixed FI. METHOD: A prospective cohort of 100 patients with FI was studied. Continence scores were determined before treatment and following 12 sessions of PTNS using a validated questionnaire [Cleveland Clinic Florida (CCF)-FI score]. The deferment time and average number of weekly incontinence episodes before and after 12 sessions of treatment were estimated from a bowel dairy kept by the patient. Quality of life was assessed prior to and on completion of 12 sessions of PTNS using a validated questionnaire [Rockwood Faecal Incontinence Quality of Life (QoL)]. RESULTS: One hundred patients (88 women) of median age of 57 years were included. Patients with urge FI (n=25) and mixed FI (n=60) demonstrated a statistically significant improvement in the mean CCF-FI score (11.0 ± 4.1 to 8.3 ± 4.8 and 12.8 ± 3.7 to 9.1 ± 4.4) with an associated improvement in the QoL score. This effect was not observed in patients with purely passive FI (n=15). CONCLUSION: The study demonstrates that PTNS benefits patients with urge and mixed FI, at least in the short term.


Subject(s)
Fecal Incontinence/therapy , Tibial Nerve , Transcutaneous Electric Nerve Stimulation/methods , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Quality of Life , Surveys and Questionnaires , Treatment Outcome
5.
Antonie Van Leeuwenhoek ; 97(2): 155-70, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19941164

ABSTRACT

Parsimony network analysis of rDNA sequences was used to delimit phylogenetic species of yeasts in an objective, formal manner. Many strains assigned to Candida apicola (Starmerella clade), when compared to the type, fell outside the inclusion limits proposed by Kurtzman and Robnett (1998) based on a pair-wise comparison of the large subunit rRNA gene D1/D2 domains. However, when these sequences were analyzed jointly with ITS rDNA sequences by parsimony network analysis, 28 of the 30 strains formed a cohesive set. Two strains, MUCL 45721 and CBS 4353, were excluded from the species, but there was no evident justification to subdivide the rest. A similar analysis of 81 isolates originally assigned to Candida azyma (Wickerhamiella clade) yielded dramatically different results, giving rise to six independent networks corresponding to Candida azyma sensu stricto (18 strains), Candida azymoides (2 strains), a pair of isolates from Australian hibiscus flowers, a single isolate from the same substrate, a single isolate from Malaysian bertam palm nectar, and 57 isolates that are assigned to the new species Candida parazyma (type = UWOPS 91-652.1(T) = CBS 11563(T) = NRRL Y-48669(T)). The strains retained in C. azyma sensu stricto differed from one another by up to four substitutions in their D1/D2 sequences, but their polymorphism at the level of the ITS was considerable and suggested a history of divergence resulting from dispersal. Strains of C. parazyma fell into seven variant haplotypes based on sequences of the rDNA ITS and D1/D2 regions. The most abundant haplotype occurred across the global range of the species. Others were either endemic to Belize, Costa Rica, Rarotonga, or Tennessee, suggestive of vicariance, or occurred across remote localities, offering partial support to the notion of rapid dispersal.


Subject(s)
Candida/classification , Candida/isolation & purification , Insecta/microbiology , Animals , Candida/genetics , Cluster Analysis , DNA, Fungal/chemistry , DNA, Fungal/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , DNA, Ribosomal Spacer/chemistry , DNA, Ribosomal Spacer/genetics , Molecular Sequence Data , Phylogeny , Polymorphism, Genetic , Sequence Analysis, DNA
6.
J Cyst Fibros ; 7(3): 252-7, 2008 May.
Article in English | MEDLINE | ID: mdl-18042441

ABSTRACT

BACKGROUND: Liver disease is an important cause of death in adults with cystic fibrosis (CF). Ursodeoxycholic acid (UDCA) may slow progression. Managing varices and timely evaluation for liver transplantation are important. METHODS: Adults with CF underwent annual review. Abnormalities of liver function tests or ultrasound prompted referral to the CF/liver clinic where UDCA was commenced. Endoscopic surveillance for varices was undertaken if ultrasound suggested portal hypertension. RESULTS: 154 patients were followed for a median 5 years. 43 had significant liver disease, 29 had cirrhosis with portal hypertension and 14 had ultrasound evidence of cirrhosis without portal hypertension. All started UDCA. Only one patient developed chronic liver failure and none required liver transplantation. 27 underwent endoscopy; 1 required variceal banding, the others had insignificant varices. Ultrasound was normal in 97 patients while five had steatosis; nine further patients had splenomegaly but no other evidence of portal hypertension. Neither spleen size nor platelet count correlated with portal hypertension. CONCLUSIONS: Liver disease was common in adults with CF but disease progression was rare. Thus liver disease detected and closely monitored in adults appeared to have a milder course than childhood CF. Splenomegaly, unrelated to portal hypertension may be a consequence of CF.


Subject(s)
Cholagogues and Choleretics/therapeutic use , Cystic Fibrosis/epidemiology , Liver Diseases/epidemiology , Ursodeoxycholic Acid/therapeutic use , Adult , Comorbidity , Female , Humans , Hypertension, Portal/epidemiology , Liver Cirrhosis/epidemiology , Liver Diseases/surgery , Liver Transplantation , Male , Platelet Count , Prospective Studies , Splenomegaly , Thrombocytopenia/epidemiology
7.
Dev Med Child Neurol ; 48(11): 877-82, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17044953

ABSTRACT

Gastrostomy tube (GT) feeding in children with cerebral palsy (CP) is associated with significant increases in weight gain and, potentially, with overfeeding. This study aimed to measure energy balance and body composition in children with CP who were fed either orally or by GT. Forty children (27 males, 13 females; median age 8y 6mo; range 1y 4mo-18y 11mo) with spastic quadriplegic CP, of whom 22 were gastrostomy-fed and 18 orally-fed, underwent anthropometry, indirect calorimetry, and total energy expenditure determination (doubly-labelled water method). Total body water content (estimated by the 18O dilution method) was used to determine body composition. The Gross Motor Function Classification System (GMFCS) was used to determine the degree of motor impairment. GMFCS levels ranged from I to V; in the gastrostomy group 19 out of 22 were Level V and two out of 22 were Level IV. Within the orally-fed group, 11 out of 18 were Level V and four out of 18 were Level IV. Resting metabolic rate and total energy expenditure of the gastrostomy-fed children were lower but they had a significantly larger triceps skinfold thickness (p=0.01) and fat mass index (p=0.02) than the orally-fed children. Both groups had consistently higher body-fat content and lower fat-free (i.e. muscle and bone) content than the reference population of age- and sex-matched children without disabilities. This study has demonstrated the relatively low energy expenditure and high body-fat content of children with severe CP and highlighted the potential risk of overfeeding with available enteral feeds administered via GT.


Subject(s)
Body Composition , Cerebral Palsy/metabolism , Cerebral Palsy/therapy , Energy Metabolism/physiology , Enteral Nutrition , Gastrostomy , Adolescent , Child , Child, Preschool , Energy Intake/physiology , Female , Food, Formulated , Humans , Infant , Male , Motor Activity/physiology
8.
Br J Radiol ; 79(945): 712-5, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16940371

ABSTRACT

Low carbohydrate diets are currently fashionable for inducing weight loss, but the metabolic effects at organ level are not well understood, especially the effect on liver fat storage. Such studies require serial hepatic fat measurements, for which liver biopsy is impractical. In 10 healthy volunteers we demonstrate the use of rapid (total 2 min acquisition time, 10 min magnet room time), non-invasive, quantitative MRI to serially measure hepatic fat changes induced by following a low carbohydrate diet for 10 days. A significant (p<0.01) reduction in hepatic fat after 3 days of dieting was observed in 5 subjects. All subjects demonstrated significant (p<0.01) reductions in hepatic fat by day 10. A strong correlation (kappa = 0.81) existed between the initial fat content and the percentage fat content reduction in the first 3 days of the diet. All subjects lost weight (average 1.7 kg at day 3 and 3.0 kg at day 10), but this was not correlated with hepatic fat loss after 3 days or 10 days of dieting. The results presented illustrate the potential value of MR hepatic fat quantification in longitudinal studies of hepatic fat content.


Subject(s)
Adipose Tissue/anatomy & histology , Diet, Carbohydrate-Restricted , Liver/anatomy & histology , Adult , Body Mass Index , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Weight Loss
9.
Colorectal Dis ; 8(1): 46-55, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16519638

ABSTRACT

OBJECTIVE: A Colorectal Development Unit (CDU) was established to treat patients with end stage faecal incontinence with the electrically stimulated gracilis neoanal sphincter (ESGN). The aim of this study was to investigate the impact of the CDU on functional outcome and complications. METHODS: From March 1997 to March 2003, 53 patients underwent ESGN formation. Results were compared with 65 patients undergoing ESGN surgery prior to the establishment of the unit (pre-CDU) between 1988 and 1997, which were similar with regard to age, sex, aetiology and follow-up. RESULTS: Thirty-three (70%) CDU patients had a good functional outcome defined as continence to solid and liquid stool, a significant improvement when compared to the pre-CDU group, successful in 29 (45%) (P = 0.01). Episodes of technical complications leading to stimulator replacement were significantly reduced, from 25 to 3 over time (P < 0.001). Severe septic episodes were significantly reduced from 21 to four (P = 0.003) but there was no significant change in the incidence of postoperative evacuatory dysfunction. CONCLUSION: Since setting up a CDU, a successful outcome has been achieved in 33 (70%) of 47 patients undergoing ESGN surgery, which represents a significant improvement over time. This is probably related to improved patient assessment and selection, more reliable equipment and increased operative and peri-operative experience that come with a multidisciplinary team approach.


Subject(s)
Anal Canal/physiopathology , Electric Stimulation Therapy/methods , Fecal Incontinence/therapy , Surgery Department, Hospital , Adolescent , Adult , Aged , Anal Canal/surgery , Colectomy/adverse effects , Fecal Incontinence/etiology , Fecal Incontinence/physiopathology , Female , Humans , Male , Middle Aged , Postoperative Complications , Rectal Diseases/surgery , Retrospective Studies , Treatment Outcome
10.
Br J Surg ; 92(5): 598-604, 2005 May.
Article in English | MEDLINE | ID: mdl-15779072

ABSTRACT

BACKGROUND: The results of conventional treatment for rectal intussusception and rectocele are unpredictable. The aim was to develop a less invasive surgical approach and to evaluate outcome in selected patients. METHODS: Seventeen patients (13 women; median age 47 (range 20-67) years) with rectal evacuatory dysfunction and rectal intussusception, 13 of whom had a rectocele, were selected. The intussusception was corrected by external pelvic suspension of the rectum, using collagen strips attached to the rectal wall and pubis. The rectocele was repaired with a collagen patch. Patients were assessed before and 6 months after surgery by symptom and quality of life questionnaires, anorectal physiological investigation and proctography, and were followed up for a median of 12 months. RESULTS: Sepsis requiring exploration occurred in two patients but there was no extrusion or need to remove the collagen. Of the 15 patients assessed after surgery, total symptom scores were significantly decreased (P < 0.001) and quality of life scores improved (P < 0.001). Proctographically, the degree of intussusception was improved in ten patients; six patients had normal postoperative proctograms. The rectocele was reduced in size in all patients, and was not demonstrable in eight. CONCLUSION: An effective procedure for rectal intussusception and rectocele has been developed in a selected group of patients with marked evacuatory symptoms.


Subject(s)
Intussusception/surgery , Rectal Diseases/surgery , Adult , Aged , Collagen , Female , Humans , Male , Middle Aged , Quality of Life , Rectocele/surgery , Surgical Flaps , Treatment Outcome
11.
Dev Med Child Neurol ; 47(2): 77-85, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15707230

ABSTRACT

We report a longitudinal, prospective, multicentre cohort study designed to measure the outcomes of gastrostomy tube feeding in children with cerebral palsy (CP). Fifty-seven children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) were assessed before gastrostomy placement, and at 6 and 12 months afterwards. Three-quarters of the children enrolled (43 of 57) had spastic quadriplegia; other diagnoses included mixed CP (6 of 57), hemiplegia (3 of 57), undiagnosed severe neurological impairment (3 of 57), ataxia (1 of 57), and extrapyramidal disorder (1 of 57). Only 7 of 57 (12%) could sit independently, and only 3 of 57 (5%) could walk unaided. Outcome measures included growth/anthropometry, nutritional intake, general health, and complications of gastrostomy feeding. At baseline, half of the children were more than 38D below the average weight for their age and sex when compared with the standards for typically-developing children. Weight increased substantially over the study period; the median weight z score increased from -3 before gastrostomy placement to -2.2 at 6 months and -1.6 at 12 months. Almost all parents reported a significant improvement in their child's health after this intervention and a significant reduction in time spent feeding. Statistically significant and clinically important increases in weight gain and subcutaneous fat deposition were noted. Serious complications were rare, with no evidence of an increase in respiratory complications.


Subject(s)
Cerebral Palsy/nursing , Cerebral Palsy/surgery , Enteral Nutrition/methods , Gastrostomy/methods , Adolescent , Anthropometry/methods , Body Height/physiology , Cerebral Palsy/classification , Child , Child Development/physiology , Child, Preschool , Demography , Female , Head/growth & development , Humans , Infant , Infant, Newborn , Longitudinal Studies , Male , Nutritional Status/physiology , Retrospective Studies , Time Factors , Treatment Outcome , Weight Gain/physiology
12.
Dev Med Child Neurol ; 46(12): 796-800, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15581151

ABSTRACT

The aim of this prospective cohort study was to evaluate the impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy (CP). Short-Form 36 version II was used to measure quality of life in carers of 57 Caucasian children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) six and 12 months after insertion of a gastrostomy tube. Responses were calibrated against a normative dataset (Oxford Healthy Life Survey III). Six months after gastrostomy feeding was started, a substantial rise in mean domain scores for mental health, role limitations due to emotional problems, physical functioning, social functioning, and energy/vitality were observed. At 12 months after gastrostomy placement, carers reported significant improvements in social functioning, mental health, energy/vitality (mean increase >9.8 points;p<0.03), and in general health perception (mean increase 6.35 points;p=0.045) compared with results at baseline. Moreover, the values obtained for these domains at 12 months were not significantly different from the normal reference standard. Carers reported a significant reduction in feeding times, increased ease of drug administration, and reduced concern about their child's nutritional status. This study has demonstrated a significant, measurable improvement in the quality of life of carers after insertion of a gastrostomy feeding tube.


Subject(s)
Attitude of Health Personnel , Caregivers/psychology , Cerebral Palsy , Disabled Children , Gastrostomy/methods , Parenteral Nutrition/psychology , Quality of Life , Adolescent , Adult , Cerebral Palsy/epidemiology , Child , Child, Preschool , Disability Evaluation , Female , Follow-Up Studies , Health Status , Humans , Infant , Male , Mental Disorders/epidemiology , Mental Disorders/psychology , Nutritional Status , Patient Care Team , Prospective Studies , Surveys and Questionnaires
13.
Nephrol Dial Transplant ; 16(3): 552-5, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11239030

ABSTRACT

BACKGROUND: Intracellular calcium [Ca](i) has been found to be elevated in hypoxic cells in vitro and in erythrocytes and lymphocytes from patients who are septic. Loop diuretics decrease [Ca](i) in platelets from patients with hypertension and in red blood cells from normal volunteers. We report the results of a study designed to measure [Ca](i) in platelets from patients with acute renal failure (ARF) before and after the administration of loop diuretics. METHODS: Sixteen healthy adults and seven patients with ARF were enrolled into the study. Intraplatelet calcium was measured using a fluorescent probe (quin2). Patients with ARF all received intravenous (i.v.) dopamine, 2 microg/kg body weight, and 20% mannitol, 100 ml every 6 h and, in double-blind manner, either torasemide, frusemide, or placebo, 3 mg/kg body weight i.v. every 6 h. Data from subjects given either frusemide or torasemide have been considered together and termed the diuretic group. RESULTS: Basal levels of [Ca](i) in platelets from patients with ARF were significantly higher than in controls (126.9 +/-3 5.7 nmol/l vs 85.7 +/- 22.2 nmol/l, P = 0.02), but were not affected by the administration of loop diuretic (126.9 +/- 35.7 nmol/l vs 165.9 +/- 49.7 nmol/l, P = 0.09, pre- vs post-diuretic). CONCLUSIONS: Intraplatelet calcium is raised in patients with ARF. Loop diuretics have no significant effect on intraplatelet calcium in these patients.


Subject(s)
Acute Kidney Injury/blood , Acute Kidney Injury/drug therapy , Blood Platelets/metabolism , Calcium/blood , Diuretics/therapeutic use , Furosemide/therapeutic use , Sulfonamides/therapeutic use , Adult , Arginine Vasopressin/pharmacology , Chelating Agents/pharmacology , Double-Blind Method , Egtazic Acid/pharmacology , Female , Humans , Male , Torsemide
14.
Eur J Immunol ; 30(10): 2881-7, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11069070

ABSTRACT

Innate immunity directs the adaptive immune response by identifying antigens that are associated with infectious agents. Although some microbial antigens can be recognized by innate immune receptors, most cannot, and these require identification by some other means. The introduction of aldehydes into antigens by glycolaldehyde, which can be produced by activated neutrophils reacting with serine, or by the oxidation of an N-linked oligosaccharide with NaIO4, enhances by several orders of magnitude their immunogenicity in mice. The augmented immunogenicity requires the presence of an aldehyde on the antigen, and is not dependent on protein aggregation. An in vitro correlate of augmented immunogenicity is the enhanced presentation of glycolaldehyde-modified antigen to T cells by macrophages and bone marrow-derived dendritic cells. The potential clinical importance of this form of antigen modification is twofold: glycolaldehyde renders a model self antigen immunogenic, and it converts a relatively non-immunogenic malaria antigen, merozoite surface protein-1, into an effective immunogen. Thus, the tagging of antigens by the addition of aldehydes, which may be an innate immune mechanism to facilitate their recognition by the adaptive immune system, may have a role in the genesis of autoimmunity and the development of vaccines.


Subject(s)
Acetaldehyde/analogs & derivatives , Aldehydes/immunology , Antibody Formation/immunology , Antigens/immunology , Immunity, Innate/immunology , Acetaldehyde/immunology , Animals , Antigens/chemistry , Antigens, Protozoan/chemistry , Antigens, Protozoan/immunology , Autoantigens/chemistry , Autoantigens/immunology , Autoimmunity/immunology , Chickens , Columbidae , Cytochrome c Group/chemistry , Cytochrome c Group/immunology , Merozoite Surface Protein 1/chemistry , Merozoite Surface Protein 1/immunology , Mice , Muramidase/chemistry , Muramidase/immunology , Neutrophils/immunology , Ovalbumin/chemistry , Ovalbumin/immunology , Oxidation-Reduction , Periodic Acid/pharmacology , Serine/metabolism , Structure-Activity Relationship , Vaccines
15.
Nephrol Dial Transplant ; 13(1): 67-71, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9481717

ABSTRACT

BACKGROUND: The object of the study was to develop an artificial neural network (ANN) to identify patients with IgA nephropathy (IgAN) with a poor prognosis and to compare the predictions of the ANN with the predictions of six experienced nephrologists. METHODS: The following data from the time of renal biopsy were retrieved from the records of 54 patients with IgAN: age, sex, systolic and diastolic blood pressure, number of prescribed antihypertensive drugs, 24-h urine protein excretion, and serum creatinine. Patients aged less than 14 years, or who had serum creatinine > 350 mumol/l at presentation, liver disease or concomitant kidney disease were excluded. Outcome was assigned as 'stable' if serum creatinine was < 150 mumol/l after 7 years and 'non-stable' if serum creatinine was > or = 150 mumol/l. The ANN was trained and tested using a 'jack-knife' sampling technique and performance evaluated in terms of number of correct predictions, sensitivity and specificity. The six nephrologists were asked to predict outcome at 7 years for each patient using the same data as the ANN and their performance was assessed in the same manner. RESULTS: The ANN assigned the correct outcome to 47/54 (87.0%) patients: sensitivity 19/22 (86.4%), specificity 28/32 (87.5%). The mean score for nephrologists was 37.5/54 (69.4%, range 35-40), mean sensitivity 72% and mean specificity 66%. CONCLUSIONS: An ANN trained using routine clinical information obtained at the time of diagnosis can potentially predict 7-year outcome for renal function in IgAN more accurately than experienced nephrologists, and can therefore identify a group of high-risk patients requiring close follow-up.


Subject(s)
Glomerulonephritis, IGA/diagnosis , Neural Networks, Computer , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Nephrology , Sensitivity and Specificity
16.
Nephrol Dial Transplant ; 12(12): 2592-6, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9430857

ABSTRACT

BACKGROUND: Studies on the role of loop diuretics in patients with acute renal failure (ARF) are largely retrospective, anecdotal, and poorly controlled. We report the results of a prospective, randomized, placebo-controlled, double-blind study examining the effect of loop diuretics on renal recovery, dialysis, and death in patients with ARF. METHODS: Ninety-two patients with ARF were enrolled into the study. All received intravenous dopamine, 2 micrograms/kg body weight/min throughout, 20% mannitol, 100 ml every 6 h for the first 3 days, and, in a double-blind manner, either torasemide, frusemide, or placebo, 3 mg/kg body weight i.v. every 6 h for 21 days or until renal recovery or death. RESULTS: Renal recovery, the need for dialysis, and death were no different in the three groups. Patients given a loop diuretic had a significant rise in urine flow rate in the first 24 h compared to placebo (P = 0.02). Based on the urine flow rate during the first post-medication day patients were divided into two groups--oliguric (< 50 ml/h) and non-oliguric (> or = 50 ml/h). Non-oliguric patients had a significantly lower mortality than oliguric patients (43% vs 69%, P = 0.01). However, they were less ill (APACHE II score 17.2 vs 20.6, P = 0.008) and had less severe renal failure at entry (creatinine clearance 14 ml/min vs 4 ml/min, P < 0.0001). CONCLUSION: The use of loop diuretics in oliguric patients with ARF can result in a diuresis. There is no evidence that these drugs can alter outcome.


Subject(s)
Acute Kidney Injury/drug therapy , Diuretics/therapeutic use , Furosemide/therapeutic use , Sulfonamides/therapeutic use , Acute Kidney Injury/mortality , Acute Kidney Injury/physiopathology , Adult , Aged , Creatinine/metabolism , Diuresis/drug effects , Diuretics/adverse effects , Double-Blind Method , Female , Furosemide/adverse effects , Humans , Male , Middle Aged , Placebos , Prospective Studies , Sulfonamides/adverse effects , Torsemide
17.
Science ; 271(5247): 348-50, 1996 Jan 19.
Article in English | MEDLINE | ID: mdl-8553069

ABSTRACT

An optimal immune response should differentiate between harmful and innocuous antigens. Primitive systems of innate immunity, such as the complement system, may play a role in this distinction. When activated, the C3 component of complement attaches to potential antigens on microorganisms. To determine whether this alters acquired immune recognition, mice were immunized with a recombinant model antigen, hen egg lysozyme (HEL), fused to murine C3d. HEL bearing two and three copies of C3d was 1000- and 10,000-fold more immunogenic, respectively, than HEL alone. Thus, C3d is a molecular adjuvant of innate immunity that profoundly influences an acquired immune response.


Subject(s)
Adjuvants, Immunologic , Antibody Formation , Complement C3d/immunology , Immunity, Innate , Animals , Antigens, CD19/immunology , Antigens, CD19/metabolism , B-Lymphocytes/immunology , Complement C3d/metabolism , Freund's Adjuvant/immunology , Hemocyanins/immunology , Humans , Immunoglobulin G/biosynthesis , Male , Mice , Mice, Inbred CBA , Mice, Transgenic , Muramidase/immunology , Receptors, Complement 3d/immunology , Receptors, Complement 3d/metabolism , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/metabolism , Tumor Cells, Cultured
18.
J Hepatol ; 22(4): 399-403, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7665858

ABSTRACT

Monitoring treatment efficacy in patients with portal venous hypertension has been limited by the difficulty of direct or indirect assessment of portal vein pressure. The majority of currently available haemodynamic tests, such as hepatic vein wedge pressure or azygos vein flow measurement by thermodilution catheter, are invasive which has restricted their application. We describe a non-invasive cine phase contrast magnetic resonance technique for quantitative measurements of bulk volume flow and for demonstrating flow changes during the cardiac cycle in the azygos vein. The technique was used to analyse the azygos vein flow in seven adult volunteers and five patients with biopsy-confirmed chronic liver disease, portal hypertension and endoscopically proven oesophageal varices. In the volunteers the mean volume flow rates varied between 81 and 241 ml/min with a mean for the group of 171 ml/min. The patients had a significantly higher mean volume flow rate of 628 ml/min (p < 0.01), with a range of 339 to 945 ml/min. These preliminary results suggest that cine phase contrast magnetic resonance angiography is a practical non-invasive method for measuring absolute azygos vein flow, and may provide a non-invasive method of monitoring portal hypertension.


Subject(s)
Blood Circulation , Magnetic Resonance Angiography , Adult , Atrial Function , Blood Flow Velocity , Cineangiography , Female , Heart/physiology , Humans , Hypertension, Portal/diagnosis , Hypertension, Portal/physiopathology , Magnetic Resonance Angiography/methods , Male , Microscopy, Phase-Contrast , Myocardial Contraction , Reference Values , Veins
19.
J Hepatol ; 21(6): 1135-9, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7699240

ABSTRACT

Abnormalities of carbohydrate metabolism, including hyperinsulinaemia and insulin resistance, are well recognised complications of cirrhosis. While diabetes mellitus can be explained in many instances on the basis of coincident pancreatic disease, in most the characteristic glucose intolerance of cirrhosis is not readily explicable. A previous clinical observation that hepatitis C virus infection and diabetes mellitus appeared to be associated was formally tested by a retrospective review of 100 consecutive adult patients with cirrhosis undergoing assessment for liver transplantation. Hepatitis C virus was diagnosed by conventional serological and histological criteria. Twenty-three patients had diabetes mellitus, of whom 18 were being treated with insulin. Of the 34 patients with hepatitis C virus-related cirrhosis, 17 (50%) had diabetes mellitus, in contrast to just six (9%) of the 66 patients with cirrhosis unrelated to hepatitis C virus (chi2 = 19.1, p < 0.0001) with an odds ratio for hepatitis C virus by diabetes mellitus status 10.0 (95% confidence interval 3.4 to 29.3). Hierarchical loglinear model analysis of those factors of potential relevance to the development of diabetes mellitus revealed that only hepatitis C virus interacted significantly with diabetes mellitus while the relation between diabetes mellitus and origin, sex, body mass index and severity of cirrhosis was conditional. By multiple logistic regression analysis of diabetes mellitus status in relation to the same variables, only hepatitis C virus status was statistically significant (p < 0.0001). Origin, sex, severity of cirrhosis, body mass index and therapy were not significantly associated.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Diabetes Complications , Diabetes Mellitus/epidemiology , Hepatitis C/complications , Liver Cirrhosis/complications , Adult , Female , Humans , Incidence , Male , Middle Aged , Regression Analysis , Retrospective Studies
20.
Nephrol Dial Transplant ; 9(3): 291-5, 1994.
Article in English | MEDLINE | ID: mdl-7519762

ABSTRACT

A survey of all 483 adult dialysis patients in the three renal units in Glasgow using second-generation ELISA was carried out to determine hepatitis C virus (HCV) seroprevalence in the summer of 1991 before the introduction of blood donor screening for antibody to HCV in the UK. Supplementary testing of ELISA positive sera was by second-generation immunoblot assay (RIBA-2, Chiron). Retrospective case note analysis and testing of stored sera were performed to assess liver function and the risk factors for acquisition of the virus. Nineteen of the 483 patients (3.9%) were seropositive. Sixteen patients had been transfused and 12 had previous transplants. Seropositivity was associated with current haemodialysis (P < 0.01) rather than continuous ambulatory peritoneal dialysis (CAPD). Of those on haemodialysis, the time since first dialysis was longer for seropositives (13.6 years) than for seronegatives (6.3 years) (P < 0.01) but this did not apply to those on CAPD. Twelve of 19 (63.2%) seropositives had persistent elevations of alanine transferase compared to seven of 38 (18%) seronegative controls (P < 0.01). This large group of dialysis patients is at special risk of HCV infection but the seroprevalence is less than that reported from outside the UK despite the use of more sensitive techniques. The risk is associated with haemodialysis and is probably largely due to blood transfusion. The introduction of screening of donated blood for HCV antibody should reduce the incidence of new infection in dialysis patients.


Subject(s)
Hepatitis C/etiology , Peritoneal Dialysis, Continuous Ambulatory/adverse effects , Renal Dialysis/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Base Sequence , DNA Primers/genetics , Female , Hepacivirus/genetics , Hepacivirus/immunology , Hepatitis Antibodies/blood , Hepatitis C/epidemiology , Hepatitis C/transmission , Hepatitis C Antibodies , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Molecular Sequence Data , RNA, Viral/blood , RNA, Viral/genetics , Risk Factors , Scotland/epidemiology , Transfusion Reaction
SELECTION OF CITATIONS
SEARCH DETAIL
...