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Biomedical subjects

M H Samore

Publications and source records attributed to M H Samore.

51 records · Page 3Linked to original sources
PubMed1996

Pertussis toxin enhanced IgG1 and IgE responses to primary tetanus immunization are mediated by interleukin-4 and persist during secondary responses to tetanus alone.

Pertussis toxin (Ptx), the major toxin product of Bordetella pertussis, has potent immunologic effect including adjuvant effects on antibody responses and sensitization for anaphylaxis. In order to further define the effect of Ptx on the class and subclass of murine antibody response, we measured total and antigen specific IgG subclasses and IgE in Balb/c mice after primary and secondary immunization with tetanus toxoid (TT). Low doses of Ptx (100 ng) given intravenously at the time of primary immunization increased primary IgG1 and IgE anti-TT antibodies as well as total IgG1 and IgE concentrations compared to controls. The increase in IgG1 subclass and IgE response when Ptx was present during primary immunization was even more pronounced after secondary immunization with TT alone 3 weeks or 3 months later. Similar effects were noted after diphtheria toxoid immunization in the presence of Ptx. Administration of the anti IL-4 monoclonal antibody (11B11) suppressed the enhanced total and TT-specific IgE responses but not the enhanced IgG1 responses. The presence of low concentrations of Ptx during primary immunization primes for induction of IL-4 producing T-cell help which enhances IgGI and IgE responses to the primary exposure as well as to subsequent exposures of the antigen in the absence of Ptx. This phenomenon may have significance for the adjuvant activity of vaccines containing Ptx as well as for the immune response to natural pertussis.

Adjuvants, Immunologic↗
PubMed1996

Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial Clostridium difficile diarrhea.

PURPOSE: A prospective clinical and molecular epidemiologic study was conducted to define the frequency of nosocomial Clostridium difficile patient-to-patient transmission in an urban tertiary referral hospital. PATIENTS AND METHODS: Over a 6-month period, environmental cultures for C difficile were obtained from patients with new positive stool cytotoxin assay (index cases); stool samples were obtained from selected patient contacts (the roommate, occupants of adjacent rooms, and the patient occupying the index room after discharge of the index case); and hand cultures were obtained from personnel contacts. C difficile isolates were analyzed by pulse-field gel electrophoresis (PFGE) or, for isolates that were nontypeable by PFGE, by restriction enzyme analysis. RESULTS: During the study period, we identified 98 index cases of C difficile toxin-associated diarrhea, including focal outbreaks on two wards totaling 26 cases within a 2-month interval. Environmental contamination was detected at > or = 1 sites in 58% of rooms and often involved wide dispersed areas. Among 99 prospectively identified patient contacts, C difficile was cultured from the stool of 31 (31%), including 12 with diarrhea and 19 who were asymptomatic. C difficile was cultured from the hands of 10 (14%) of 73 personnel. Molecular analysis resolved 31 typing profiles among the index isolates; the most common profile (designated strain D1) was represented by 30 isolates. Among the isolates from patient contacts, 5 of 12 from symptomatic contacts matched the corresponding index isolate, and only 1 of 19 from asymptomatically colonized contacts matched. Transmission to personnel or patient contacts of the strain cultured from the corresponding index case was correlated strongly with the intensity of environmental contamination. Strain D1 was frequently represented among isolates associated with heavy environmental contamination, with personnel carriage, and with development of symptomatic illness among prospectively identified contacts. CONCLUSIONS: Intense environmental contamination and transmission to close personnel and patient contacts represented coordinated properties of an individual epidemic strain. For most epidemiologically linked contacts, positive cultures for C difficile did not result from transmission from the presumed index case.

Bacterial Toxins↗
PubMed1996

Pharmacokinetics of F105, a human monoclonal antibody, in persons infected with human immunodeficiency virus type 1.

F105 is a human monoclonal antibody that binds to the CD4 binding site of human immunodeficiency virus type 1 gp120 and neutralizes clinical and laboratory isolates of the human immunodeficiency virus. This phase I study investigated the disposition of the antibody in humans. F105 was administered over a 60-minute period at two dose levels, 100 and 500 mg/m2. Blood samples were obtained for up to 56 days. The clearance of the antibody was 0.33 ml/min with a corresponding half-life of approximately 13 days. Peak concentrations achieved at the higher dose level were 216.19 +/- 9.62 micrograms/ml. The disposition of the drug was linear for the doses studied. Simulations were performed to design future studies aimed at investigating the efficacy of the antibody. This study concluded that F105 can be administered as a bolus dose every 21 days.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Comparison of PCR-based approaches to molecular epidemiologic analysis of Clostridium difficile.

Representative isolates of the 10 serogroups of Clostridium difficile and 39 clinical isolates (30 toxigenic and 9 nontoxigenic), including 5 isolates from a confirmed nosocomial outbreak, were analyzed by using two previously described arbitrary-primer PCR (AP-PCR) molecular typing methodologies (AP-PG05 and AP-ARB11) and PCR ribotyping. The two AP-PCR methods investigated gave comparable results; AP-PG05 and AP-ARB11 identified 8 and 7 groups among the serogroup isolates and classified the clinical isolates into 21 and 20 distinct groups, respectively. PCR ribotyping also identified 8 unique groups among the serogroup isolates but classified the clinical isolates into 23 groups. In addition, when results obtained by the PCR methods were compared with typing data generated by pulsed-field gel electrophoresis (PFGE), PCR ribotyping and PFGE were found to be in agreement for 83% (29 of 35) of isolates typeable by both techniques while AP-PG05 was in agreement with PFGE for 60% (20 of 33) and AP-ARB11 was in agreement with PFGE for only 44% (17 of 36). These results indicate that PCR ribotyping is a more discriminatory approach than AP-PCR for typing C. difficile and, furthermore, that this technique generates results that are in higher concordance with those obtained by using an established method for differentiating isolates of this organism on a molecular level than are results generated by using AP-PCR.

Bacterial Typing Techniques↗
PubMed1995

Clinical correlates of secondary meningitis in HIV-infected adults.

BACKGROUND: Neurologic complaints are common in adults infected with the human immunodeficiency virus, but little is known about which clinical features are associated with secondary causes of meningitis. METHODS: A retrospective cross-sectional study of adults infected with the human immunodeficiency virus who received a diagnostic lumbar puncture (LP) in the infectious disease clinic, emergency department, and inpatient wards of the Deaconess Hospital, Boston, Mass, from 1989 through 1992 to determine which clinical features available at the time of LP are correlated with definite or probable secondary meningitis. RESULTS: Of the 491 LPs, 90% were performed in whites, 93% in men, and 11% in injection drug users. Cerebrospinal fluid test results revealed secondary meningitis in 39 (7.9%) of 491 LPs performed on 322 individuals. Cryptococcal meningitis was the predominant type (27 cases); no bacterial or tuberculous meningitis was found. In multivariate analyses, a history of non-Hodgkin's lymphoma (adjusted odds ratio [OR], 4.3; 95% confidence interval [CI], 1.5 to 12.5), a history of herpes simplex virus infection (OR, 2.5; 95% CI, 1.2 to 5.0), nausea and/or vomiting (OR, 2.0; 95% CI, 1.03 to 4.0), headache in a person with the acquired immunodeficiency syndrome (OR, 2.1; 95% CI, 1.03 to 4.4), and cranial nerve abnormalities (OR, 5.1; 95% CI, 1.8 to 14.1) were positive correlates of opportunistic meningitis; current fluconazole use (OR, 0.3; 95% CI, 0.1 to 0.8) conferred a lower risk. CONCLUSION: In similar clinical settings, physicians and their human immunodeficiency virus-infected patients should consider these features when assessing the risk of secondary meningitis and the necessity for immediate LP.

AIDS-Related Opportunistic Infections↗
PubMed1995

Staphylococcus aureus catheter-associated bacteremia. Minimal effective therapy and unusual infectious complications associated with arterial sheath catheters.

OBJECTIVE: To determine factors that predict complications and examine outcomes of Staphylococcus aureus bacteremia according to the duration of antibiotic therapy. METHODS: Clinical data were extracted from charts of patients with positive blood cultures for S aureus at a single institution during a 2-year period. RESULTS: Of 102 patients with S aureus bacteremia, 55 were considered to have bacteremia attributable to an intravascular catheter, including five patients who were bacteremic after percutaneous transluminal coronary angioplasty. Among the other 50 patients with S aureus catheter-associated bacteremia, infection was community acquired in 18 and nosocomial in 32. Septic pulmonary emboli were more common in patients with community-acquired S aureus catheter-associated bacteremia, most of whom had Hickman catheters or venous access disks. Delayed removal of the infected catheter was associated with persistence of bacteremia (P = .01). With patients with early complications excluded, patients treated for 10 to 15 days had clinical characteristics similar to those of patients treated with longer courses of antibiotics and had similarly low rates of relapse (0% vs 4.7%). In contrast, treatment with parenteral antibiotics for less than 10 days appeared to be inadequate in that relapse occurred in two of three such patients. Staphylococcus aureus catheter-associated bacteremia associated with percutaneous transluminal coronary angioplasty was complicated by a femoral artery mycotic aneurysm in two of five patients. CONCLUSION: Approximately one third of S aureus catheter-related bacteremias were community acquired, reflecting increased usage of intravascular devices for home parenteral support. A 10- to 15-day course of parenteral antibiotics was equivalent to longer courses of therapy in patients without early complications.

Adult↗
PubMed1995

Major infectious complications after orthotopic liver transplantation and comparison of outcomes in patients receiving cyclosporine or FK506 as primary immunosuppression.

A retrospective cohort study was conducted to determine the incidence of major infectious complications after orthotopic liver transplantation and to compare outcomes in patients receiving either cyclosporine (CsA) or FK506 (tacrolimus) as primary immunosuppression. Of 133 transplants performed in 118 patients, 124 transplant episodes were evaluated. Cytomegalovirus (CMV) infection (INF) and disease (DIS), deep fungal infection (DFI), and intraabdominal bacterial infections (IAI) were catalogued. The overall incidences of major infectious outcomes were: CMV INF = 33%; CMV DIS = 19%; DFI = 15%; and IAI = 25%. Cox proportional hazard analysis identified donor seropositivity, OKT3 as secondary immunosuppression and initial intensive care unit (ICU) duration as risk factors for CMV INF and DIS in the overall population. Fungal colonization was the dominant risk factor associated with deep fungal infection. A choledochojejunostomy anastomosis, the number of cellular blood products transfused at the time of transplantation surgery, and prior CMV INF were independent risk factors for both fungal colonization and deep infection. The single risk factor identified for intraabdominal bacterial infections was the number of cellular blood products transfused at the time of surgery. In the Cox proportional hazards model the relative risk (RR) for each category of infection was lower in the FK506 group (CMV: RR = .87, 95% confidence interval [C.I.] = [.32-2.4]; DFI: .58 [.13-2.6]; IAI: .51 [.15-1.7]), but the effect was not statistically significant. Survival was similar in patients receiving FK506 or CsA. CMV INF and DFI were independent predictors of death for all patients. Risk factors identified for CMV INF and DIS support the findings of others. Higher intraoperative blood product requirements and complicated intraoperative or postoperative courses increase the risk for IAI or DFI. The development of effective strategies to prevent CMV and fungal infections in liver transplant recipients remains a priority for future endeavors.

Bacterial Infections↗
PubMed1994

Clostridium difficile colonization and diarrhea at a tertiary care hospital.

Clostridium difficile is the major identifiable infectious cause of nosocomial diarrhea. A prospective study was conducted at New England Deaconess Hospital (Boston) to examine risk factors for C. difficile carriage at both admission and follow-up. Specimens from patients admitted to two wards (one medical, one surgical) and three intensive care units (two surgical, one medical) were cultured weekly until discharge. For 89 (18%) of 496 patient admissions, at least one culture was positive. The prevalence of culture positivity within 72 hours of admission was 11%. Risk factors for culture positivity at admission were prior C. difficile diarrhea (adjusted odds ratio [OR] = 9.5), renal insufficiency (OR = 6.7), and recent hospitalization elsewhere (OR = 3.1). Fifteen percent of patients for whom initial cultures were negative and for whom follow-up cultures were performed acquired C. difficile. Admission to the vascular surgery service (relative risk [RR] = 2.3) and liver transplantation (RR = 4.2) were significant risk factors for C. difficile acquisition. Patients asymptomatically colonized on admission had very low risk (1 in 44) for subsequent development of C. difficile diarrhea. In contrast, nine (47%) of 19 patients who acquired toxigenic strains developed C. difficile diarrhea, a finding suggesting that progression to diarrhea occurs early after acquisition or does not occur at all. The relatively high prevalence of culture positivity at admission may be characteristic of tertiary care hospitals and adds to the difficulty of controlling this nosocomial pathogen.

Aged↗
PubMed1994

Wide diversity of Clostridium difficile types at a tertiary referral hospital.

Nosocomial Clostridium difficile infection was investigated at a hospital with 15 cases of C. difficile diarrhea per 1000 discharges. From January 1991 to May 1991, patients admitted or transferred to five wards or units had weekly rectal swabs taken for culture; in addition, all cytotoxin-positive stools were cultured. Restriction enzyme analysis (REA) was used for molecular typing. Among 205 isolates from 39 patients with C. difficile diarrhea and 67 asymptomatically colonized, 55 distinct REA banding patterns were identified. Evidence for patient-to-patient transmission was limited, in that numerous strains were found even among clustered cases of diarrhea. Patients who acquired C. difficile in the community or other hospitals constituted 32% of culture-positive patients and contributed 44% of the REA types. Diversity of C. difficile strains was in part the result of patients acquiring C. difficile in the community or other hospitals. High incidences of nosocomial C. difficile diarrhea do not necessarily indicate clonal epidemics.

Aged↗
PubMed1994

Comparison of restriction endonuclease analysis, ribotyping, and pulsed-field gel electrophoresis for molecular differentiation of Clostridium difficile strains.

A combined clinical and molecular epidemiologic analysis of 46 strains of Clostridium difficile, including 16 nosocomial isolates from one ward (outbreak ward) plus 17 other nosocomial isolates and 13 community-acquired isolates, was performed. HindIII digests of total cellular DNA were analyzed by restriction enzyme analysis (REA) and ribotyping; SmaI digests were analyzed by pulsed-field gel electrophoresis (PFGE). Isolates were assigned to typing groups on the basis of the profiles detected; isolates with closely related profiles were assigned to subgroups. The 16 isolates from the outbreak ward were resolved by both REA and PFGE into five distinct groups; 13 isolates represented two REA groups and three PFGE groups and two isolates were resolved as distinct groups by both techniques. DNA obtained from one isolate was persistently partially degraded, precluding analysis by PFGE. Seventeen sporadic nosocomial isolates were resolved by REA and PFGE into comparable numbers of groups (i.e., nine groups) and subgroups (i.e., 15 and 14 subgroups, respectively), with two isolates not evaluable by PFGE. The 13 epidemiologically unrelated community-acquired isolates were assigned to 11 groups by REA and to 12 groups by PFGE. Overall, ribotyping identified only nine groups among the 46 isolates. We conclude that REA and PFGE have comparable discriminatory powers for epidemiologic typing of C. difficile isolates and that ribotyping is appreciably less discriminatory. For a few isolates, partial DNA degradation prevented analysis by PFGE but not by REA or ribotyping; the cause of the degradation is unknown.

Bacterial Proteins↗
PubMed1994

Risk factors for invasive fungal infections complicating orthotopic liver transplantation.

Risk factors for invasive fungal infection in patients undergoing orthotopic liver transplantation were examined. Thirty-four of 168 transplants were complicated within 100 days after transplantation by documented invasive fungal infection (Candida species, 28 patients; mycelial fungi, 5; both Candida and Aspergillus species, 1). In the multivariate Cox proportional hazards model, three baseline and two posttransplant variables were independently significant risk factors for infection: level of creatinine (hazard ratio = 1.4), length of transplant operation (HR = 1.2), retransplantation (HR = 3.2), abdominal or intrathoracic reoperations (HR = 2.5), and cytomegalovirus infection (HR = 8.5). Four predictors (creatinine of > 3.0 mg/dL, operative time of > or = 11 h, retransplantation, and early colonization) assessable at the time of transplantation or shortly thereafter were incorporated into a simple predictive model for risk stratification. The risk of invasive fungal infection ranged from 1% in patients with no predictors to 67% in patients with two or more predictors. Strategies to prevent invasive fungal infections after liver transplantation should be targeted to these high-risk groups.

Adrenal Cortex Hormones↗
PubMed1993

Epidemiology of nosocomial Clostridium difficile infection.

C. difficile is a frequent cause of nosocomial diarrhea and is associated with substantial morbidity. C. difficile carriage may arise either from overgrowth of endogenous organisms or from exogenous acquisition. Within hospitals, asymptomatically colonized patients typically outnumber symptomatic patients by a ratio of approximately 3:1. Patient-to-patient transmission of C. difficile has been well documented in studies of nosocomial outbreaks, utilizing typing methods to supplement epidemiologic investigations. The mechanisms and frequency of transmission probably vary between institutions, but contamination of environmental surfaces and personnel hand carriage both appear to be important. Nosocomial C. difficile infection can be remarkably difficult to control, particularly after it becomes endemic in an institution. Policies targeting both environmental contamination and personnel hand-washing/glove use practices may be most successful. Prophylaxis of C. difficile diarrhea in high-risk patients on antibiotics may also have merit if an effective and safe biologic agent can be identified. Asymptomatically colonized patients should not be treated because they are at low risk for the development of diarrhea and because further antibiotic treatment may prolong the carrier state.

Cross Infection↗
PubMed1992

Effect of pertussis toxin on susceptibility of infant rats to Haemophilus influenzae type b.

Pertussis toxin is an important virulence factor of Bordetella pertussis that may also contribute to the toxicity of pertussis vaccines. The effect of low doses of pertussis toxin on response to Haemophilus influenzae type b (Hib) infection was examined in infant rats. Pretreatment of rats with 10 or 100 ng of pertussis toxin increased blood bacterial concentration (P less than .01), serum endotoxin levels (P less than .01), and mortality (P less than .05) relative to saline pretreated controls challenged with 4 x 10(3) Hib intraperitoneally. The 100-ng dose of pertussis toxin, but not the 10-ng dose, increased the leukocyte count. Thus, doses of pertussis toxin less than the threshold dose for inducing leukocytosis may enhance the susceptibility of infant rats to Hib infections.

Animals↗