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Biomedical subjects

L Kyne

Publications and source records attributed to L Kyne.

12 recordsLinked to original sources
PubMed2001

Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea.

BACKGROUND: We have reported that symptom-free carriers of Clostridium difficile have a systemic anamnestic immune response to toxin A. The aim of this study was to determine whether an acquired immune response to toxin A, during an episode of C. difficile diarrhoea, influences risk of recurrence. METHODS: We prospectively studied 63 patients with nosocomial C. difficile diarrhoea. Serial serum IgA, IgG, and IgM concentrations against C. difficile toxin A, toxin B, or non-toxin antigens were measured by ELISA. Individuals were followed for 60 days. FINDINGS: 19 patients died (30%). Of the 44 who survived, 22 had recurrent C. difficile diarrhoea. Patients with a single episode of C. difficile diarrhoea (n=22) had higher concentrations of serum IgM against toxin A on day 3 of their first episode of diarrhoea than those with recurrent diarrhoea (n=22, p=0.004). On day 12, serum IgG values against toxin A were higher in patients who had a single episode of diarrhoea (n=7) than in those who subsequently had recurrent diarrhoea (n=9, p=0.009). The odds ratio for recurrence associated with a low concentration of serum IgG against toxin A, measured 12 days after onset of C. difficile diarrhoea, was 48.0 (95% CI 3.5-663). INTERPRETATION: A serum antibody response to toxin A, during an initial episode of C. difficile diarrhoea, is associated with protection against recurrence.

Aged↗
PubMed2001

Clostridium difficile.

Clostridium difficile is a major cause of antibiotic-associated diarrhea and colitis. The incidence of infection with this organism is increasing in hospitals worldwide, consequent to the widespread use of broad-spectrum antibiotics. Pathogenic strains of C. difficile produce two protein exotoxins, toxin A and toxin B, that cause colonic mucosal injury and inflammation. Many patients who are colonized are asymptomatic, and recent evidence indicates that diarrhea and colitis occur in those individuals who lack a protective antitoxin immune response. In patients who do develop symptoms, the spectrum of C. difficile disease ranges from mild diarrhea to fulminant pseudomembranous colitis. Prevention of nosocomial C. difficile infection involves judicious use of antibiotics and multidisciplinary infection control measures to reduce environmental contamination and patient cross-infection. Ultimately, active or passive immunization against C. difficile may be an effective means of controlling the growing problem of nosocomial C. difficile diarrhea and colitis.

Anti-Bacterial Agents↗
PubMed2000

Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A.

BACKGROUND: Clostridium difficile infection can result in asymptomatic carriage, mild diarrhea, or fulminant pseudomembranous colitis. We studied whether antibody responses to C. difficile toxins affect the risks of colonization, diarrhea, and asymptomatic carriage. METHODS: We prospectively studied C. difficile infections in hospitalized patients who were receiving antibiotics. Serial stool samples were tested for C. difficile colonization by cytotoxin assay and culture. Serum antibody (IgA, IgG, and IgM) levels and fecal antibody (IgA and IgG) levels against C. difficile toxin A, toxin B, and nontoxin antigens were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Of 271 patients, 37 (14 percent) were colonized with C. difficile at the time of admission, 18 of whom were asymptomatic carriers. An additional 47 patients (17 percent) became infected in the hospital, 19 of whom remained asymptomatic. The baseline antibody levels were similar in the patients who later became colonized and those who did not. After colonization, those who became asymptomatic carriers had significantly greater increases in serum levels of IgG antibody against toxin A than did the patients in whom C. difficile diarrhea developed (P<0.001). The adjusted odds ratio for diarrhea was 48.0 (95 percent confidence interval, 3.4 to 678) among patients with colonization who had a serum level of IgG antibody against toxin A of 3.00 ELISA units or less, as compared with patients with colonization who had a level of more than 3.00 ELISA units. CONCLUSIONS: We find no evidence of immune protection against colonization by C. difficile. However, after colonization there is an association between a systemic anamnestic response to toxin A, as evidenced by increased serum levels of IgG antibody against toxin A, and asymptomatic carriage of C. difficile.

Aged↗
PubMed2000

Neutrophilia and congestive heart failure after acute myocardial infarction.

BACKGROUND: Inflammation associated with acute myocardial infarction (AMI) is frequently marked by a peripheral leukocytosis and relative neutrophilia. Whether this process may contribute to the development of postinfarction congestive heart failure (CHF) is not established. The objective of this study was to examine the association between hospital admission peripheral total leukocyte count and the neutrophil percentage and the subsequent development of CHF in patients with AMI. The study was designed as a retrospective cohort study in the setting of a tertiary referral hospital. Participants included 185 patients discharged with a diagnosis of AMI between May 1 and Sept 30, 1996. METHODS AND RESULTS: Outcome measures included clinical episodes of CHF with confirmatory chest roentgenogram findings and/or echocardiographic evidence of contractile dysfunction. Multivariable logistic regression analyses were performed to examine the relation between the total leukocyte count, neutrophil percentage, and the development of CHF in the first 4 days after AMI while controlling for baseline characteristics and early therapeutic interventions. Thirty-one percent of the cohort had a leukocyte count >11.0 x10(9)/L on admission to the hospital; 65% had a neutrophil percentage >65%, and 61% had a lymphocyte percentage </=25%. CHF developed in 43% of the cohort. Of these, 92. 5% had relative neutrophilia (neutrophil percentage >65%) compared with 45% of those in whom CHF did not develop. Multivariable analysis revealed a highly significant association between relative neutrophilia and the subsequent development of CHF (odds ratio 14.3; 95% confidence interval 5.2 to 39.3). CONCLUSIONS: Relative neutrophilia on admission to the hospital in patients with AMI is significantly associated with the early development of CHF. This association may help in the identification of individuals at high risk who might benefit from more aggressive interventions to prevent or reduce the risk of CHF.

Adult↗
PubMed1999

Factors associated with prolonged symptoms and severe disease due to Clostridium difficile.

OBJECTIVE: toxigenic Clostridium difficile is responsible for a spectrum of disease severity ranging from mild diarrhoea to fulminant colitis. This study attempts to determine the proportion of patients in each category of severity and evaluate the risk factors for a more prolonged and complicated course. DESIGN: prospective cohort study. SETTING: university teaching hospital. SUBJECTS: all patients with symptomatic C. difficile infection during 4 months of an outbreak (January-April 1995); n=73; median age 74 years (range 17-91). MEASUREMENTS: incidence of C. difficile-associated disease (CDAD); severity of disease; percentage of patients in each category of severity; risk factors for severe disease/prolonged symptoms (univariate and multivariable analyses). RESULTS: the incidence of CDAD was 0.93%. Of the cases identified, 18 (24.7%) had mild, self-limiting disease; 26 (35.6%) had moderately severe disease; 23 (31.5%) had prolonged symptoms and six (8.2%) had a complicated course. Although CDAD was more common in older patients (P < 0.001), increasing age was not a risk factor for severity. Significant risk factors for severe CDAD included low Barthel and abbreviated mental test scores (P < 0.01, P < 0.001 respectively) and recent endoscopy (P=0.03). Logistic regression analysis revealed the following independent predictors of severe CDAD: endoscopy [odds ratios (OR) 4.0, P=0.03] and cognitive impairment (OR 11.0, P < 0.01). A trend towards significance was noted for nasogastric tube insertion (OR 3.1, P=0.08). Complications of infection included dehydration, malnutrition and faecal incontinence (which was statistically significantly associated with more severe disease; P < 0.01). CONCLUSION: risk factors for severity of CDAD include functional disability, cognitive impairment, and recent endoscopy. Anticipation of severe CDAD may limit morbidity and mortality.

Adolescent↗
PubMed1999

Is age a negative prognostic indicator in HIV infection or AIDS?

To better understand disease progression in older persons with human immunodeficiency virus (HIV infection or acquired immunodeficiency syndrome (AIDS), we studied patients aged 50 years and older hospitalized with a diagnosis of HIV infection or AIDS between January 1985 and October 1995. Data collected included demographics, opportunistic infections, comorbid disease, neurologic dysfunction, and antiretroviral therapy. A total of 86 patients with a mean age of 54.3 years was identified. Pneumocystis carinii pneumonia was the most frequent opportunistic infection (43%). Hypertension was the most common previous medical condition (38%). Other comorbid disease was present in less than 15% of the subjects. Fifty-seven patients (66%) had neurologic impairment, with 30 requiring treatment for delirium. In these 30, 23 (77%) had anemia, infection, or both. The median length of survival following the diagnosis of AIDS was 18.5 months, for HIV it was 48 months. The median survival following the diagnosis of AIDS in patients who received antiretroviral therapy was 22 months compared with 11 months for those who did not receive antiretroviral therapy (p < 0.0004). Multivariable analysis found that antiretroviral therapy was the only independent predictor of survival after the diagnosis of AIDS. In contrast to previous studies, the present findings suggest that older age may not necessarily be associated with more rapid disease progression and reduced survival times in persons with HIV infection or AIDS. In those patients with delirium, many may have readily treatable conditions (anemia and/or infection). The absence of significant comorbid disease and the access to antiretroviral therapy may be in part responsible for the longer survival times obtained in this cohort compared to that reported previously.

Aging↗
PubMed1998

Community-acquired Clostridium difficile infection.

Clostridium difficile-associated disease (CDAD) is primarily a nosocomial condition. Community-acquired disease has been reported but the incidence is felt to be low and the rate of disease resulting in hospitalization is reported as negligible. We recently experienced a 6-month outbreak of CDAD (January to June 1995): 139 patients were involved and four deaths were attributable to pseudomembranous colitis. Early in the outbreak period we were aware that many new admissions presented with C. difficile cytotoxin B positive diarrhoea: in some cases this was the sole reason for hospitalization. This observation forms the basis of this report.

Adult↗
PubMed1998

Simultaneous outbreaks of two strains of toxigenic Clostridium difficile in a general hospital.

We report an outbreak of Clostridium difficile-associated disease (CDAD) in a large Dublin hospital. From January to June 1995, inclusive, 139 patients were affected; the mean age of cases was 68.8 +/- 19 years. Clinical information is available for 73 cases identified during the first four months of the outbreak. The majority of patients presented with abrupt onset of watery diarrhoea; however, 19.2% presented with an unexplained pyrexia following a course of antimicrobial therapy and 5.5% presented with a surgical acute abdomen. Twenty patients (27.4%) experienced relapsing disease and seven (9.6%) patients died. Seventy-six percent of cases received a cephalosporin prior to the onset of disease, the highest relative risks occurring with third-generation agents; however, 9.6% of patients affected had not been exposed to antimicrobial therapy in the preceding eight weeks. Pyrolysis mass spectrometry identified two clusters of isolates, representing two strains of C. difficile. There was marked spatial clustering of these strains, with each confined to a separate area of the hospital. Infection control measures and an antibiotic policy were introduced. Throughout the outbreak period the use of the most frequently used cephalosporin in the hospital increased; this was accompanied paradoxically by a reduction in the number of new cases of CDAD.

Aged↗
PubMed1998

Timing of surgery for fulminating pseudomembranous colitis.

BACKGROUND: With increasing antibiotic usage Clostridium difficile colitis is becoming more common. Surgery for fulminating C. difficile colitis, however, is rare because of the effectiveness of specific anticlostridial chemotherapy. Surgical outcome in five patients with fulminating C. difficile colitis involved in a recent outbreak of this disease is reported. METHODS: Five of 138 patients developed fulminating C. difficile colitis unresponsive to medical therapy. All patients had antibiotics in the preceding period. Indications for operation in those who underwent surgery were systemic toxicity with a pyrexia, marked leukocytosis and abdominal signs leading to progressive organ failure, despite appropriate anticlostridial antibiotic therapy. RESULTS: At operation all patients had a markedly oedematous colon with normal serosa but with acute mucosal colitis. All underwent subtotal abdominal colectomy and ileostomy. Progressive organ failure persisted in four, leading to death, giving a mortality rate of four in five in the operated group in comparison with 3.8 per cent (five of 133 patients) in those treated medically. CONCLUSIONS: These results indicate that this increasingly common disease frequently leads to a fatal outcome in patients requiring surgery and implies that earlier surgical consultation may be necessary to improve survival in patients with fulminating C. difficile colitis unresponsive to antibiotic therapy.

Abdomen, Acute↗
PubMed1998

Familial craniosynostosis, anal anomalies, and porokeratosis: CAP syndrome.

We report on the occurrence of coronal craniosynostosis, anal anomalies, and porokeratosis in two male sibs. A third male sib was phenotypically normal as were the parents. The occurrence of these three clinical features has, to our knowledge, not been reported before. Cutaneous or anal anomalies or both have been reported in a number of syndromes associated with craniosynostosis, including Crouzon, Pfeiffer, Apert, and Beare-Stevenson syndromes. These syndromes are associated with mutations in the fibroblast growth factor receptor genes FGFR1, FGFR2, and FGFR3. They are inherited in an autosomal dominant fashion. In contrast, the cases we report do not carry any of the common FGFR mutations and the pedigree suggests autosomal or X linked recessive inheritance.

Abnormalities, Multiple↗