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Biomedical subjects

E A Blumberg

Publications and source records attributed to E A Blumberg.

At least 19 recordsLinked to original sources

A prospective cross-sectional study of BK virus infection in non-renal solid organ transplant recipients with chronic renal dysfunction.

BACKGROUND: Polyomavirus (primarily BK virus [BKV]) infection is an important cause of chronic renal dysfunction in renal transplant recipients, but its possible contribution to chronic renal dysfunction in non-renal solid organ transplant (NRSOT) recipients has not been fully explored. METHODS: We performed a prospective, cross-sectional study of consecutive NRSOT recipients with unexplained chronic renal dysfunction of at least a 3 months duration. Medical records were reviewed, and polymerase chain reaction was used to amplify BKV-specific sequences from serum and urine samples. The potential associations between various demographic and transplant variables and BKV infection were assessed. RESULTS: Thirty-four consecutive NRSOT recipients (23 lung, 8 liver, 2 heart, 1 heart-lung) with chronic renal dysfunction were enrolled at a median of 3.5 years (range 0.3-12.5 years) post transplantation. Five of the 34 (15%) patients had BKV viruria (range 1040-1.8 x 10(6) copies/mL), but none had BKV viremia. BK viruria was associated with mycophenolate mofetil use (5 of 19 [26%] vs. 0 of 15, P = 0.03) and a history of cytomegalovirus disease (3 of 4 [75%] vs. 2 of 30 [7%], P < 0.01). However, the mean estimated creatinine clearance was similar in patients with or without BKV viruria (49 vs. 47 mL/min). CONCLUSIONS: BKV viruria was present in a proportion of NRSOT patients with otherwise unexplained chronic renal dysfunction. The possibility that BKV infection might contribute to chronic renal dysfunction in this setting warrants further investigation.

Adult↗

Immunogenicity of pneumococcal vaccine in heart transplant recipients.

To assess the immunogenicity of pneumococcal vaccine in recipients of heart transplants, we immunized 35 long-term transplantation survivors with pneumococcal vaccine and measured the pre- and postvaccination IgG antibody titers to 5 representative vaccine capsular polysaccharides. Responses of heart transplant recipients to pneumococcal vaccine antigens were generally suppressed.

Adult↗

Hepatitis C transmission and infection by orthotopic heart transplantation.

BACKGROUND: The transmission and clinical consequences of hepatitis C viral (HCV) infection acquired by orthotopic heart transplantation (OHT) from an HCV-infected donor to an HCV-naive recipient have not been well described. We report our experience in 5 HCV-naive patients who were transplanted with hearts from HCV-positive donors. All transplants occurred within a 1-year period. METHODS: After cardiac transplantation we retrospectively examined the recipients' clinical course, liver-associated enzymes, HCV-antibody serology, quantitative HCV RNA level, and HCV genotype. RESULTS: Five subjects with rapidly deteriorating heart failure and negative serum antibodies to HCV received an emergent OHT from a donor known to be infected with HCV. Liver-associated enzymes peaked at 2 to 6 weeks post-transplant: mean peak alanine aminotransferase was 180 U/L (normal, 9 to 52) and aspartate aminotransferase was 111 U/L (normal, 14 to 36). Liver enzymes had returned to normal limits by 6 and 12 months post-OHT. At a mean 15 months after transplantation, only 1 of 5 patients has developed antibodies to HCV, but 4 of 5 have evidence of infection, as shown by serum HCV RNA. No patient has developed evidence of liver failure. CONCLUSIONS: (1) Transmission of HCV from an HCV-positive donor to an HCV-naive recipient at the time of OHT is likely. (2) Antibodies to HCV post-OHT may remain negative for more than 1 year in these patients. (3) Hepatitis C viral RNA using polymerase chain reaction should be the test of choice for diagnosis of HCV infection post-OHT. (4) Hepatitis C viral donor hearts should be limited to critically ill patients in extremis until the long-term consequences of acquisition of HCV by an OHT recipient are known.

Aged↗

Prevention of primary cytomegalovirus disease in organ transplant recipients with oral ganciclovir or oral acyclovir prophylaxis.

BACKGROUND: Optimal prophylaxis against cytomegalovirus (CMV) disease for organ transplant patients at risk for primary infection (donor seropositive, recipient seronegative, D+R-) remains to be determined. We hypothesized that prolonged oral ganciclovir therapy following intravenous therapy would provide increased protection. METHODS: A total of 155 evaluable D+R- organ transplant recipients from 13 transplant centers were entered into the study: all received intravenous ganciclovir (5 mg/kg/day) for 5-10 days and then either oral acyclovir (400 mg tid) or oral ganciclovir (1 g tid) for an additional 12 weeks. Patients were assigned to their treatment groups at a central randomization site, with a separate randomization scheme for each of the organs transplanted (kidney, heart, or liver). In the case of kidney transplants, the patients were stratified according to source of the kidney (living related vs. cadaveric donor). The primary endpoint was the incidence of CMV disease in the first six months post-transplant. RESULTS: Treatment with oral ganciclovir was associated with a significant decrease in the incidence of symptomatic disease or viremia when compared with the oral acyclovir group (32% vs. 50%, P<0.05). This difference was most marked in terms of tissue invasive disease: only 3 of 15 symptomatic patients in the ganciclovir group vs. 10 of 21 in the acyclovir group developed tissue-invasive infection (P<0.05). There was a significant difference in the time to CMV disease or viremia in the two groups: mean time 212+/-17 days post-transplant for the acyclovir group vs. 291+/-13 days for the ganciclovir group (P<0.001). The incidence of allograft rejection was 34% in the ganciclovir group and 46% in the acyclovir group (P=NS). Leukopenia was more common in the ganciclovir group (P<0.05), but in no case did it require drug discontinuation. Ganciclovir resistance did not develop in this study. CONCLUSION: Prophylaxis with oral ganciclovir following a brief course of intravenous ganciclovir provides useful protection against primary CMV disease.

Acyclovir↗

The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium. Synercid Emergency-Use Study Group.

A progressive increase in the incidence of vancomycin resistance in strains of Enterococcus faecium (VREF) has severely constrained treatment options for patients with infection caused by this emerging pathogen. Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic, is active in vitro against VREF, with an MIC90 of 1.0 mg/L. We studied the clinical efficacy and safety of quinupristin/dalfopristin in the treatment of VREF infection. Two prospective studies were conducted simultaneously. The first enrolled only patients with VREF infection; the second included patients with infection caused by other gram-positive bacterial pathogens in addition to VREF. Patients were enrolled if they had signs and symptoms of active infection and no appropriate alternative antibiotic therapy. The recommended treatment regimen of quinupristin/dalfopristin was 7.5 mg/kg i.v. every 8 h for a duration judged appropriate by the investigator. A total of 396 patients with VREF infection were enrolled. The most frequent indications for treatment included intra-abdominal infection, bacteraemia of unknown origin, urinary tract infection, catheter-related bacteraemia, and skin and skin structure infection. This patient population had a high prevalence of severe underlying illness, including a history of diabetes mellitus, transplantation, mechanical ventilation, dialysis, chronic liver disease with cirrhosis and oncological disorders. The mean (+/- S.D.) duration of treatment was 14.5 +/- 10.7 days (range: 1-108). The majority of patients (82.1%) were treated every 8 h, as assessed on day 2 of treatment, while 15.9% were treated every 12 h. The clinical success rate was 73.6% [142/193 clinically evaluable patients; 95% confidence interval (CI): 67.4%, 79.8%], the bacteriological success rate 70.5% (110/156 bacteriologically evaluable patients; 95% CI: 63.4%, 77.7%) and the overall success (both clinical and bacteriological success) rate 65.8% (102/156 bacteriologically evaluable patients; 95% CI: 57.9%, 72.9%). VREF bacteraemia at entry, mechanical ventilation and laparotomy were associated with a worse outcome. Quinupristin/dalfopristin was generally well tolerated. The most common systemic adverse events related to treatment were arthralgias (9.1%) and myalgias (6.6%). Related laboratory abnormalities were infrequent. In these severely ill patients with VREF infection and no other clinically appropriate therapeutic alternatives, quinupristin/dalfopristin demonstrated substantial efficacy and a good nervous system, cardiovascular, gastrointestinal, renal and hepatic tolerability.

Adolescent↗

Safety of influenza vaccine in heart transplant recipients.

BACKGROUND: Influenza vaccine is recommended for heart transplant recipients, but its administration is often deferred because of anecdotal reports of rejection associated with the vaccine. We evaluated the safety of influenza vaccine in a group of stable heart transplant recipients over a 2-year period. METHODS: During the 1993 to 1994 influenza season, stable heart transplant recipients who had undergone transplantation a minimum of 1 year before study entry were randomized to vaccination with a single dose of influenza vaccine versus no vaccination. Routine endomyocardial biopsies and postvaccination influenza serologic studies were performed between 2 and 6 weeks after enrollment/immunization. During the 1994 to 1995 season, patients were given 2 doses of influenza vaccine, separated by 3 weeks; endomyocardial biopsies and serologic studies were performed between 2 and 6 weeks after the second immunization or enrollment (if control subject). Biopsy results were evaluated with respect to vaccine response, immunosuppressive regimens, and patient demographics. RESULTS: Eighteen patients were enrolled in the single vaccine trial and 10 in the booster vaccine trial. Four of 14 vaccine recipients had biopsy specimens consistent with International Society for Heart and Lung Transplantation grades 2 to 3A as compared with 1 of 14 control subjects (grade 2) (p = .326). All episodes of rejection in the vaccine recipients were asymptomatic and responded to a single course of treatment. Rejection was unrelated to the time from transplantation, doses of immunosuppression, age, or number of doses of or response to vaccine. CONCLUSIONS: Influenza vaccine can be safely administered to most heart transplant recipients but may be associated with low-level histologic rejection.

Adult↗

Polymicrobial brain abscess in a patient infected with human immunodeficiency virus.

Although intracranial mass lesions that occur as a result of infection have commonly been reported in patients infected with human immunodeficiency virus, polymicrobial pyogenic brain abscess has not been described in this setting. We report the first case of a patient with a polymicrobial brain abscess involving Streptococcus bovis, Fusobacterium necrophorum, Peptostreptococcus, and group G Streptococcus, and we review the relevant world literature.

AIDS-Related Opportunistic Infections↗

The immunogenicity of influenza virus vaccine in solid organ transplant recipients.

We monitored the responses of solid organ transplant recipients (SOTs) to influenza vaccine during consecutive influenza seasons. Standard 1993-1994 trivalent influenza vaccine was given to 68 SOTs and 29 healthy young adults, and hemagglutination-inhibition (HI) antibody titers were determined pre- and post-immunization. Significant rises in geometric mean antibody titers occurred post-immunization for all three antigens in both groups. However, the magnitude of the rise was lower in SOTs (1.5-2.3-fold vs. 8.7-10.4-fold, depending on the antigen) (P < .05), and significantly fewer SOTs had protective HI titers (> or = 1:40) for B/Panama/45/90 antigens (50% of SOTs vs. 76% of healthy subjects) and for A/Texas/36/91 (H1N1) antigens (60% vs. 90%). After exclusion of persons with high preimmunization titers, SOTs had significantly reduced frequencies of > or = 4-fold antibody responses compared with those of healthy subjects (23%-38% vs. 86%-100%) (P < .05 for each antigen). When a series of two injections of standard 1994-1995 vaccine was given to 23 SOTs, there was no significant improvement in vaccine response with the second dose. Some SOTs have deficient responses to inactivated influenza vaccines.

Adult↗

Failure of systemic empirical treatment with amphotericin B to prevent candidemia in neutropenic patients with cancer.

We undertook a retrospective review of all patients with hematologic malignancies in whom candidemia developed during chemotherapy-induced neutropenia in 1989 and 1990. Candidemia developed in 11 patients; five were receiving therapeutic doses of amphotericin B at the time of infection. Disseminated infection occurred in 2 of 5 patients with breakthrough infection and 3 of 6 patients with candidemia before receipt of amphotericin B. Among patients with breakthrough candidemia there was a trend toward more-prolonged neutropenia prior to infection (P = .069), but otherwise they were indistinguishable from other candidemic patients with regard to risk factors for candidemia. Amphotericin B-susceptible Candida albicans was isolated from two patients and Candida krusei from three patients with breakthrough infection. All patients were treated with amphotericin B; all breakthrough infections responded to treatment. Neutropenic patients with breakthrough candidemia were clinically similar to those whose candidemia preceded amphotericin B therapy, and there was no increase in morbidity and mortality among individuals with breakthrough infection.

Acute Disease↗

Endocarditis-associated paravalvular abscesses. Do clinical parameters predict the presence of abscess?

STUDY OBJECTIVE: To determine whether standard clinical and transthoracic echocardiographic criteria considered to be suggestive of the presence of endocarditis-associated paravalvular abscess are predictive of which patients would benefit from reliable but invasive transesophageal echocardiographic investigations for abscess. DESIGN: Retrospective chart review. SETTING: A 630-bed university hospital. PATIENTS: Forty-eight patients with 51 episodes of definite endocarditis and 24 paravalvular abscesses. MEASUREMENTS AND RESULTS: A comparison of abscess and nonabscess populations revealed that clinical parameters (patient demographics, valvular involvement, presence of a prosthesis, infection with a virulent organism, pericarditis, persistent fever, persistent bacteremia, congestive heart failure, history of intravenous drug use, embolization) and transthoracic echocardiographic parameters were insensitive predictors of the presence of abscess. The only statistically significant correlate was the presence of previously undetected atrioventricular or bundle branch block. Paravalvular abscesses were common in our population and were associated with increased mortality. Improved survival correlated with the absence of mitral valve involvement and the absence of moderate-to-severe congestive heart failure. CONCLUSIONS: Given the accuracy and safety of transesophageal echocardiography and the unreliability of clinical and transthoracic echocardiographic criteria, we recommend that transesophageal echocardiography be considered in all endocarditis patients with previously unrecognized conduction disturbances, aortic or prosthetic valve involvement, or both, or indications for valve replacement, or all of the foregoing.

Abscess↗

Cryptococcus albidus and mucormycosis empyema in a patient receiving hemodialysis.

C albidus and mucormycosis were cultured simultaneously from the pleural space of a patient with end-stage renal disease receiving long-term hemodialysis. There have been only nine previous reports of infection with C albidus, with only one involving the lung. This organism has never before been isolated from the pleural space, and none of the previously reported cases included a coinfection with mucormycosis. We have reviewed and compared all known cases of infection with C albidus.

Adult↗

Infections of implantable cardioverter defibrillators: approach to management.

Implantable cardioverter defibrillators are being used with increasing frequency for the treatment of life-threatening ventricular arrhythmias. Nevertheless, no guidelines exist for the management of infections of these devices. We report our experience with infections of these devices and review the English-language literature. In all cases, patients presented with local signs of generator infection; systemic signs of infection and bacteremia were often absent. Most infections are due to staphylococcus. Risk factors for the development of infection include placement of the device via median sternotomy during another cardiac surgical procedure, reoperation, and intercurrent infection at another site. Infections are most reliably treated with full explantation of the device and antibiotics. In rare cases, patients may respond to a combination of intravenous antibiotics and removal and replacement of only the generator.

Adult↗

Persistent fever in association with infective endocarditis.

Fever persisting despite adequate antimicrobial therapy for endocarditis can be an ominous sign. To evaluate the significance of persistent fever in this situation, we reviewed the records of patients at three hospital affiliates of Albert Einstein College of Medicine. Twenty-six patients with 27 episodes of endocarditis and fever lasting for > or = 2 weeks despite appropriate antimicrobial therapy were identified and compared with a matched cohort of 26 patients with endocarditis but without prolonged fever. The median duration of fever in the former group was 35 days. Cardiac infection caused fever in 13 of these patients, seven of whom had myocardial abscesses. Additional causes of infection included drug treatment, nosocomial transmission of pathogens, and pulmonary emboli. Sixteen patients required cardiac surgery (seven on an emergent basis), whereas only two controls underwent such a procedure (P < .001). Twenty-two patients with persistent fever and five controls developed nosocomial complications (P < .001). Six patients with fever died, five from endocarditis-related complications. Thus persistent fever often indicates complicated endocarditis. We present an approach for the evaluation of the patients affected by this condition.

Adolescent↗

Seven-pathogen tricuspid endocarditis in an intravenous drug abuser. Pitfalls in laboratory diagnosis.

Polymicrobial endocarditis is being reported with increasing frequency in drug abusers. However, the full extent of infection may be unrecognized with routine blood culture techniques because of the overgrowth of more fastidious organisms by other pathogens. This report documents an intravenous drug abuser with the first reported case of tricuspid valve endocarditis involving seven pathogens, discusses pitfalls of routine blood cultures and examines the role of the laboratory in microbiologic diagnosis.

Adult↗

Prognostic significance of valvular regurgitation in patients with infective endocarditis.

PURPOSE: Doppler ultrasound is a sensitive modality for detecting and quantitating valvular regurgitation in patients with infective endocarditis. Because valvular regurgitation leads to heart failure, we evaluated the prognostic significance of Doppler-detected valvular regurgitation in patients with endocarditis who had not yet developed clinical heart failure. PATIENTS AND METHODS: We reviewed the medical records of 65 patients with a clinical diagnosis of infective endocarditis from May 1985 to March 1990. A total of 49 patients were included in the study: 33 patients with native valve endocarditis and 16 patients with prosthetic valve endocarditis. The initial Doppler echocardiogram was examined in these patients to determine the presence and degree of valvular regurgitation. RESULTS: Significant (moderate to severe) valvular regurgitation was detected in 23 (47%) patients. The presence or absence of significant valvular regurgitation did not predict the development of congestive heart failure, the need for surgery, or death (p = NS). The development of congestive heart failure was significantly associated with the need for surgery (p less than 0.0001) and death (p less than 0.05). CONCLUSION: We conclude that the detection of significant valvular regurgitation in patients with infective endocarditis who have not yet developed heart failure is not predictive of future complications nor does the absence of significant valvular regurgitation identify a group of patients with a more favorable prognosis. In our series, patients who developed congestive heart failure had a significantly higher incidence of surgery and death. Therefore, decisions regarding clinical management in patients with infective endocarditis should not be made solely on the presence or absence of echocardiographically detected valvular regurgitation.

Adult↗

Staphylococcus aureus infection of human endothelial cells potentiates Fc receptor expression.

Vasculitis, a recognized complication of staphylococcal-endovascular infections, may result in part, from the expression of FcR by Staphylococcus aureus-infected endothelial cells. FcR were measured using [51]Cr labeled SRBC preincubated with rabbit anti-SRBC IgG. FcR were not detected on uninfected endothelial cells, but were demonstrated on S. aureus infected cells using IgG, but not IgM labeled SRBC. FcR expression was dependent on the initial bacterial density (greater than or equal to 8 x 10(7) cfu/ml) and on phagocytosis of the staphylococci, but not on new protein synthesis. IgG labeled SRBC binding was blocked by aggregated IgG but not IgM. SRBC coated with the F(ab')2 portion of IgG did not bind, thus confirming that FcR were specifically involved in this interaction. FcR are expressed after S. aureus invasion of human endothelial cells and may contribute to the vasculitis which often accompanies S. aureus-endovascular infections.

Cells, Cultured↗