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Biomedical subjects

J A Carton

Publications and source records attributed to J A Carton.

At least 19 recordsLinked to original sources

The Toll-like receptor 4 (Asp299Gly) polymorphism is a risk factor for Gram-negative and haematogenous osteomyelitis.

Osteomyelitis is a bone infection caused mostly by Staphylococcus aureus but also by Gram-negative bacteria. Toll-like receptors (TLRs), after recognizing microbial products, induce a signal in neutrophils, leading to NF-kappaB activation and transcription of pro-inflammatory genes. Polymorphisms in TLR2 (Arg753Gln) and TLR4 (Asp299Gly, Thr399Ile) genes are associated with bacterial infections, we therefore studied these polymorphisms in osteomyelitis patients. Homozygotes for the TLR4 (Asp299Gly) polymorphism were significantly more frequent among the 80 osteomyelitis patients than in the 155 healthy controls (3/80, 3.8%versus 0/155, 0%; P = 0.038). Carriers of one or two G alleles of this tlr4 polymorphism were more likely to have Gram-negative, haematogenous and/or chronic osteomyelitis than those without this mutation (P < 0.031). Patients with the TLR4 (Thr399Ile) mutant, which cosegregates with the TLR4 (Asp299Gly), were also carriers of this second polymorphism. No differences for the TLR2 (Arg753Gln) genotypes were found between patients and controls. Neutrophils of patients homozygous for the TLR4 (Asp299Gly) polymorphism showed lower LPS-induced apoptosis reduction, phosphorylation of the inhibitor of NF-kappaB, and lower IL-6 and TNF-alpha levels (P < 0.05). We report here for the first time an association between this TLR4 polymorphism and susceptibility to Gram-negative bacteria and haematogenous osteomyelitis.

Adolescent↗

Eikenella corrodens brain abscess after repeated periodontal manipulations cured with imipenem and neurosurgery.

Eikenella corrodens is a facultatively anaerobic gram-negative rod that colonizes the oral cavity and very rarely produces central nervous system (CNS) infections. Frontal lobe abscesses are occasionally associated with a dental source of infection. We report a case of an adult man with overzealous dental cleaning habits who developed a right frontal brain abscess caused by E. corrodens. He underwent neurosurgical drainage of the pus and was successfully treated with imipenem 4 g/i.v./day for 4 weeks with no complications. Repeated periodontal trauma could explain the Eikenella brain abscess in this case.

Anti-Bacterial Agents↗

Successful intrathecal ethanol block for intractable spasticity of AIDS-related progressive multifocal leukoencephalopathy.

OBJECTIVE: To study the efficacy of intrathecal ethanol block to relieve intractable spasticity in AIDS-related progressive multifocal leukoencephalopathy (PML) when long-term intrathecal baclofen infusion cannot be used. METHODS: A 33-year-old man with AIDS-related PML developed very severe spastic paraparesis (Ashworth rigidity score, 4) and painful muscle spasms. The patient was unable to sit in his wheelchair and remained bed bound. Combined oral baclofen and tizanidine at therapeutical doses were used without any effect on the spasticity. The patient refused the placement of an intrathecal catheter for long-term baclofen infusion. A single intrathecal ethanol (6 ml) injection in the L2-L3 intervertebral space with the patient placed in a lateral Trendelenburg (40 C) position was performed. RESULTS: The procedure was very effective in improving the stiffness (Ashworth rigidity score. 2, after the technique) and the muscle spasms disappeared. No side effects during or after the injection were observed. CONCLUSION: Intrathecal ethanol block is a last but very useful choice for treatment of intractable spasticity in PML and other neurologic disorders in AIDS patients when other oral treatments have failed and intrathecal baclofen infusion is not suitable.

Acquired Immunodeficiency Syndrome↗

Cytomegalovirus antigenemia surveillance in the treatment of cytomegalovirus disease in AIDS patients.

OBJECTIVE: Surveillance of quantitative cytomegalovirus (CMV) antigenemia among AIDS patients with CMV treated complications in order to determine its value in assessing the response to treatment and survival. METHODS: A longitudinal follow-up of antigenemia measurement at diagnosis, after induction therapy with ganciclovir or foscarnet, and every 3 months during maintenance therapy was carried out in 25 patients with CMV retinitis and in 8 with extraocular CMV disease. Positive antigenemia was defined as the presence of any amount of immunofluorescent pp65-positive leukocytes/10(5) cells. RESULTS: Mean antigenemia values were: 77+/-148/10(5) leukocytes at retinitis diagnosis; 45+/-114 after induction therapy; and 7+/-18 and 1.5+/-4 after 6 months and one year of therapy, respectively. Patients achieving undetectable antigenemia increased from 44% at baseline to 68% at postinduction and 80% during follow-up. Seven patients (28%) who remained free of relapses presented significant minor baseline antigenemias and became negative after induction therapy. Patients with extraocular disease showed erratic antigenemia values and absent therapeutic response. CMV blood cultures before and after induction therapy were positive in 39% and 21% of patients, respectively. Kaplan-Meier analysis revealed a significantly longer survival for patients with retinitis when compared to those with extraocular complications, and for patients with negative antigenemia after induction in comparison with those who failed to achieve it. CONCLUSIONS: Low basal antigenemia and antigenemia clearance after induction therapy are variables directly related to good response to treatment and survival. Continuous surveillance of antigenemia during treatment could permit designing of individual strategies to obtain a better response.

AIDS-Related Opportunistic Infections↗

Bactericidal effect of ADP and acetic acid on Bacillus subtilis.

Bacillus subtilis is a ubiquitous soil bacterium used for measuring the beta-lysin activity and in other bioassays. We observed a complete bactericidal effect of ADP on B. subtilis at concentrations of 50-100 microM at pH values <5.5, which disappeared at pH values above 6. The effect was also found for acetic acid at concentrations >17.4 microM and similar pH values. ATP, adenosine, and HCl were not bactericidal. We used BCECF-AM, a pH-sensitive probe, and found that the killing of B. subtilis was due to a change in the intracellular pH caused by the passage across the cell membrane of these weak organic acids when incubated with B. subtilis at pH values near the pK. More experiments are needed to determine the biological meaning of these in vitro findings.

Acetic Acid↗

[Bacteremia in patients undergoing chronic hemodialysis in a 16-year period].

OBJECTIVE: To determine the incidence of bacteremia among patients on hemodialysis, the responsible microorganisms and to describe the predisposing and prognostic factors. METHODS: A retrospective analysis was conducted of 85 episodes of bacteremia occurred from 1979-1994; the episodes involved 71 patients (male/female ratio: 27/44) with a mean age of 58 years (29-80). RESULTS: Eighty-seven microorganisms were recovered, which included 61 grampositive cocci (67% Staphylococcus aureus), 25 gramnegative bacilli (52% Escherichia coli) and 1 anaerobe. The mean incidence was 3.1/100 patients on hemodialysis/year (range: 1.1-8.3), higher in patients with interstitial and cystic renal disease. In 52% of cases an intravascular source was detected, associated with vein access for hemodialysis (in 91% there were inflammatory signs at the fistula). In 16 cases (19%) no portal of entry was detected and in the remaining patients the portal of entry had an extravascular origin. Eighty patients received antibiotic therapy and 35 patients required the substitution of the vein access. Thirteen patients died (15%) as a result of bacteremia. The mortality rate was higher among patients developing shock (50%), endocarditis (75%) and in those who had remained for longer than 1,000 days on hemodialysis (45%). Bacteremia accounted for the third known cause of death on dialysis, and was responsible for 11% of deaths occurred during the time of the study. CONCLUSIONS: Bacteremia among hemodialysed patients was mainly associated with Staphylococcus aureus infections at the vascular access. Bacteremia was the direct responsible for 11% of deaths occurred on dialysis.

Adult↗

Imipenem therapy of brain abscesses.

The efficacy of imipenem versus standard chemotherapy (both in addition to neurosurgery) in the treatment of brain abscess was compared in a retrospective study. Cure was obtained in 52 of 60 (86.7%) patients in the standard group, and in 15 of 15 (including 5 patients with multiple brain abscesses) in the imipenem group. Cure without neurosurgery was observed in 2 of 60 (3.3%) and 3 of 15 (20%) of the cases, respectively (p = 0.08). Levels of imipenem in blood, cerebrospinal fluid, and brain pus were above the minimum inhibitory concentrations of most of the abscess isolates. Side effects of imipenem were rare and tolerance was excellent. Imipenem monotherapy (3-4 g/day) for five weeks seems a reasonable therapeutic choice for treatment of bacterial brain abscesses.

Adolescent↗

[Severe orbital cellulitis: therapeutic results in 9 patients and review of the literature].

BACKGROUND: Orbital cellulitis can produce severe neuromeningeal infections. Modern antimicrobial agents such as imipenem can be a valid therapeutical choice. METHODS: Patients with severe or complicated orbital cellulitis admitted to our hospital from 1986 through 1994 were retrospectively studied. RESULTS: Nine patients with severe orbital cellulitis, seven of them older than 14 years, are reported. Cellulitis was secondary to different forms of sinusitis in five of them. The incriminated microorganisms were: Streptococcus viridans alone or combined to gram negative bacilli (3 cases), Prevotella melaninogenica and other anaerobes (2 cases), Enterococcus faecalis and Staphylococcus aureus (one case each). Three patients developed brain abscesses, one an acute bacterial meningitis and another a subdural empyema. Eight patients underwent a surgical drainage. Seven patients were treated with IV imipenem at doses of 2-3 g/day with complete cure of the orbital cellulitis and of the associated infectious complications and no secondary effects. Two patients died. CONCLUSIONS: Imipenem is an effective antibiotic in the combined medical-surgical treatment of the severe or complicated orbital cellulitis.

Adolescent↗

[Infectious endocarditis of the native valve: its epidemiological profile and an analysis of its mortality between the years 1984 and 1993].

BACKGROUND: The description of the epidemiologic profile and analysis of the mortality of infectious endocarditis (IE) observed from 1984-1993. METHODS: One hundred thirty episodes of IE in a native valve (30 in drug addicts [IVDA] and 20 cases of nosocomial acquisition) were analyzed with right/left/bilateral localization (42/84/4, respectively), infection of the mitral/aortic/tricuspid valve (52/47/34, respectively) and the etiology was determined as Staphylococcus aureus in 52 cases, 41 Streptococcus, 13 negative coagulase Staphylococcus, and 11 Enterococcus. High risk IE were identified by uni and multivariate analysis (MVA). RESULTS: The incidence of IE ranged from 0.36 and 0.70 cases x 1.000 admitted adults/year (mean: 0.50). Transthoracic echocardiography detected bacterial vegetations in 67% of the cases with the validity to predict the development of embolisms being 55%. MVA showed the embolic episodes (present in 45% of the IE) to be associated with the IVDA patients and prolonged fever. The latter complication, being defined as > or = 10 days of fever under appropriate treatment, was observed in 32% of the cases and was due to mild (n = 15) and severe causes (n = 27). Postembolic septic complications were associated to fever with MVA. Twenty three patients died (18%), 2 IVDA and 5 nosocomial IE, mainly due to heart failure (n = 13). The independent risk factor predictors for death (p < 0.05) were: age > or = 60 years (mortality 34%), cerebral embolisms (55%), severe heart failure (37%), and the exclusion of the patient as a candidate for surgery (73%). To the contrary, right IE (mortality 0%) and cardiac surgery (5%) favoured survival. CONCLUSIONS: To improve the prognosis of infectious endocarditis in high risk patients more opportune cardiac surgery accepting greater risks should be performed.

Adult↗

[Antiphospholipid antibodies in human immunodeficiency virus infection].

BACKGROUND: The frequency, clinical significance and prognosis of the lupic anticoagulant and the anticardiolipin antibodies were analyzed in patients with the human immunodeficiency virus infection. METHODS: A group of 34 consecutive patients seropositive to HIV with lupic anticoagulant was studied in relation with 75 seropositive subjects without circulating anticoagulant and a control group of plasma of 23 seronegative individuals. The lengthening of thromboplastin time (relation > 1.3) was used as a screening test. The anticardiolipin antibodies IgG were studied by commercial enzymoimmunoassay. RESULTS: Lupic anticoagulant was detected in 21% of the patients with AIDS and in 3% of the seropositive patients without AIDS. The anticoagulant was found in 13 of 53 cases with tuberculosis, in 8 of 57 with pneumonia by Pneumocystis carinii, in 4 of 32 with bacteremia and in 3 out of 8 with lymphoma. In another six patients other minor processes and/or HIV seropositivity were coexistent. Thrombosis was not seen in any case, and the rate of thrombocytopenia (18%) was that to be expected in this population. The patients with anticoagulant had a greater prevalence to developing AIDS, opportunistic infections and tuberculosis with respect to the seropositive group without anticoagulant, however, no differences were observed in the prevalence and levels of anticardiolipin antibodies and other nonspecific autoimmune phenomena. Periodic follow up of the patients with anticoagulant demonstrated persistence of the anticoagulant in 31% and reappearance of the same in 23% with new infections. CONCLUSIONS: No correlation was found between the different antiphospholipid antibodies in the patient infected by the human immunodeficiency virus. Low titers of anticardiolipin antibodies are indicative of disease progression.

Acquired Immunodeficiency Syndrome↗

[Replication indexes of the human immunodeficiency virus: predictive value of viral culture and blood antigens].

BACKGROUND: To investigate the relation between markers of load and replication of the HIV [viral culture in plasma and in mononuclear cells of peripheral blood (MCPB) and antigen p24 (p24Ag) with the number of CD4+ cells and the prognosis of the patients. METHODS: A retrospective study was performed in 188 patients who were analyzed and followed over a mean period of 431 days. The criteria of clinical progression (AIDS related complex, and new opportunistic infections), immunologic progression (CD4+ < 0.1 and < 0.05 + 10(9)/l) and death. Cocultures of HIV in free plasma and in MCPB were performed with the detection of complete AgHIV in the supernatant of the culture being used for analysis. Circulating p24Ag was determined by an ELISA technique without previous dissociation of the immunocomplexes. RESULTS: HIV cultures in plasma, in MCPB and p24Ag were positive in 27, 48 and 33% of the patients, respectively. The sensitivity of the indexes increased in agreement with the clinical progression of the patients and was inversely proportional to the depletion of the CD4+ lymphocytes (79% of the patients with CD4+ lymphocytes < 0.05 x 10(9)/l presented positive HIV culture in plasma). Viremia in plasma and to a lesser measure p24Ag correlated with variables recognized as bad prognosis and were found to be predictive of unfavorable evolution. Multivariate analysis demonstrated that pertenence to a symptomatic group and the presentation of a number of CD4+ lymphocytes of less than 0.2 x 10(9)/l were independent factors associated to the positivity of the viral culture in plasma and p24Ag. The culture positive in MCPB was principally related with the volume of blood analyzed. The risk of death was 6.38 fold greater in the presence of a positive plasma culture and 2.02 fold greater in the presence of positive p24Ag. In contrast, the unquantified positive HIV culture in MCPB showed no statistical significance in relation with patient survival. CONCLUSIONS: Positive HIV culture in plasma was the greatest prognostic index in patients with a number of CD4+ lymphocytes less than 0.2 x 10(9)/l. Unquantified cell culture had no predictive significance. To establish the prognosis of patients, the indexes of viral replication should not be used in isolation.

Acquired Immunodeficiency Syndrome↗

[Hospital infection caused by enterococci. The previous use of antibiotics as risk factors in a case-control study].

BACKGROUND: Nosocomial infection by enterococci is of growing importance and recognition. The risk factors, morbidity and prognosis of the same were investigated by a case and control study in a third level university hospital. METHODS: One hundred patients with nosocomial infection by enterococci were compared with 100 randomly selected control patients with non enterococcic nosocomial infection. Cases and controls were taken from a series of 10,926 patients examined in search of nosocomial infection by successive cut offs of prevalence. RESULTS: The prevalence of nosocomial infection by enterococci was found to be 9.9 per 1,000 admissions. Analysis among cases and controls by the odds ratio indicated a positive association for nosocomial infection by enterococci for the following risk factors: male sex (1.8), receipt of intensive care (3.6), predisposing diseases (3.1), urinary catheter (3), abdominal-genital surgery (2.4) or nephro-urologic surgery (4.6), other previous infections (1.9) and previous exposure to antibiotics (3.7), mainly aminoglucosides (4.2). Urinary infections and those of the surgical wound predominated, 15 patients had bacteremia, with mortality related with infection being 2%, preinfection hospital stay was 34.7 days and the mean stay was of 8.3 days but these data were not statistically different in the control group. The enterococcic infections were most frequently polymicrobian (odds ratio 5.5) received worse antibiotic coverage (5.1) and presented greater number of therapeutic failures or recurrences (2.5). CONCLUSIONS: Nosocomial infection by enterococci is relatively frequent and virulent. The risk factors identified in this study are in agreement with those found in most series. The previous use of aminoglucosides was specially capable of selecting enterococci but only 13% demonstrated high level resistance to gentamicin.

Adult↗

[Trends observed in the use of antimicrobial agents at a Spanish hospital from 1986 and 1991].

BACKGROUND: The recent introduction of new antimicrobials allows important changes in the controversial field of their prescription. Longitudinal analysis of the quality and tendencies of the use of antibiotics constitutes one of the basic tools for adapting antibiotic policy. METHODS: This study was undertaken in a university hospital with antibiotic policy plans and institutional protocols of antibiotic prophylaxis. The use of antimicrobials with prophylactic and therapeutic aims has been analyzed by 12 prevalence studies over 6 years in a sample equivalent to 10.2% of the population admitted. A comparison between the first three counts (1986-1987) and the last three (1990-1991) was performed. RESULTS: A mean of 26.6% of the patients admitted used antibiotics. Nonetheless, while its use as treatment grew with progressive deterioration in the quality of use, its use for prophylaxis decreased and improved. Parallel, the use of restricted antibiotics grew from 12 to 19%. The comparison of the habits of prescription between the onset and the end of the study showed the following important changes: decrease in the use of aminopenicillins and cotrimoxazole and increase in the use of first and third generation cephalosporins, antifungal drugs, tobramycin, vancomycin, the group of urinary antiseptics and quinolones and the miscellaneous group of antimicrobials of minor use. CONCLUSIONS: Antibiotics for therapy have been used more and worse, despite the restrictive barriers. The control methods have been effective in prophylaxis with the exception of its excessive prolongation which remains the principal problem. Changes have been registered in the pattern of use of antibiotics in favor of new more effective drugs against multiresistant flora.

Anti-Bacterial Agents↗