A cluster of parvovirus B19 infections in renal transplant recipients: a prospective case series and review of the literature.

Up to 9% of renal transplant recipients have severe multifactorial erythropoietin-resistant anemia. Human parvovirus B19 (PVB19) infection can cause severe anemia and is likely underreported. Sparse information on epidemiology and management in this population exists. To address these issues, after our first index case, we modified our clinical practice to prospectively screen patients with persistent hemoglobin (Hb) <10 mg/dL for PVB19 infection after excluding common causes of anemia including erythropoietin resistance. Potentially infected patients were further evaluated by serology, qualitative polymerase chain reaction (quPCR) and bone marrow biopsy (BMB) for cytomegalovirus, Epstein-Barr virus, PVB19 and other etiologies. Over 3 months, 212 kidney recipients visited outpatient clinics. Of 52 recipients with anemia, 8 had an Hb <10 mg/dL with erythropoietin resistance and were screened for PVB19 infection. Three cases had PVB19 infection by quPCR and often-inconclusive serology/BMB results. Cases had immunosuppression reduced and received IVIG (0.5 gm/kg x 4 doses) with recovery from anemia, viral clearance in two cases and one recurrence. PVB19-mediated anemia occurred in up to three out of eight (38%) screened kidney recipients with Hb <10 mg/dL resistant to erythrypoietin. We recommend prospective risk stratification for this population, high indices of suspicion using at least qualitative techniques for diagnosis and treatment goal for viral eradication.

Does valganciclovir hydrochloride (valcyte) provide effective prophylaxis against cytomegalovirus infection in liver transplant recipients?

INTRODUCTION: Cytomegalovirus (CMV) infection after solid organ transplantation is one of the most common viral infections, causing significant morbidity and mortality if not treated promptly. Ganciclovir has proven to be effective for the prophylaxis and treatment of CMV. However, oral absorption of ganciclovir is poor. Recently, oral administration of valganciclovir hydrochloride (Valcyte) has been observed to display 10-fold better absorption than oral ganciclovir. Valganciclovir has increasingly been used as prophylaxis against CMV after solid organ transplantation. The purpose of this study was to examine the efficacy of valganciclovir prophylaxis therapy after primary liver transplantation. PATIENTS AND METHODS: Between July 2001 and May 2003, 203 consecutive liver transplant recipients, including 129 men and 74 women of overall mean age 53 +/- 11 years, received valganciclovir (900 mg/d or 450 mg every other day depending on renal function) for 3 to 6 months after primary liver transplantation. All patients were followed up for a minimum of 6 months. Mean follow-up was 19 +/- 5.8 months. CMV DNA in peripheral blood was tested using polymerase chain reaction (PCR) amplification. Symptomatic CMV was stratified according to the CMV immunoglobulin (Ig)G status of the donor and recipient at the time of liver transplantation. Donors and recipients were classified preoperatively into groups according to the presence or absence of CMV as follows: group 1 (n = 73; donor CMV+, recipient CMV+); group 2 (n = 41; donor CMV-, recipient CMV+); group 3 (n = 54; donor CMV+, recipient CMV-; high-risk group); and group 4 (n = 35; donor CMV-, recipient CMV-). RESULTS: Twenty-nine patients (14.3%) developed symptomatic CMV disease at 169 +/- 117 days after liver transplantation: group 1, 16.4% versus group 2, 7.3% versus group 3, 25.9% versus group 4, 0%. Of these patients, 5 also had invasive CMV on liver biopsy, which was performed owing to abnormal liver functions. All 29 patients were treated with intravenous ganciclovir. One patient died owing to disseminated CMV, whereas the remaining 28 patients responded to treatment. Interestingly, 8 patients, including 1 who had invasive CMV hepatitis, developed symptomatic CMV within 90 days of liver transplantation even while on prophylactic valganciclovir. CONCLUSION: Valganciclovir failed to provide adequate prophylaxis following liver transplantation in our patients. The overall rate of CMV in seropositive donors and/or recipients was 17%, and in the high-risk group was 26%. Further prospective studies with measurement of ganciclovir concentrations are needed to elucidate the reasons for this unexpected failure.

Absence of gender differences in clinical outcomes in patients with cardiogenic shock complicating acute myocardial infarction. A report from the SHOCK Trial Registry.

OBJECTIVES: The aim of this study was to assess the impact of gender on clinical course and in-hospital mortality in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). BACKGROUND: Previous studies have demonstrated higher mortality for women compared with men with ST elevation myocardial infarctions and higher rates of CS after AMI. The influence of gender and its interaction with various treatment strategies on clinical outcomes once CS develops is unclear. METHODS: Using the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK? (SHOCK) Registry database of 1,190 patients with suspected CS in the setting of AMI, we examined shock etiologies by gender. Among the 884 patients with predominant left ventricular (LV) failure, we compared the patient demographics, angiographic and hemodynamic findings, treatment approaches as well as the clinical outcomes of women versus men. This study had a 97% power to detect a 10% absolute difference in mortality by gender. RESULTS: Left ventricular failure was the most frequent cause of CS for both gender groups. Women in the SHOCK Registry had a significantly higher incidence of mechanical complications including ventricular septal rupture and acute severe mitral regurgitation. Among patients with predominant LV failure, women were, on average, 4.6 years older, had a higher incidence of hypertension, diabetes and a lower cardiac index. The overall mortality rate for the entire cohort was high (61%). After adjustment for differences in patient demographics and treatment approaches, there was no significant difference in in-hospital mortality between the two gender groups (odds ratio = 1.03, 95% confidence interval of 0.73 to 1.43, p = 0.88). Mortality was also similar for women and men who were selected for revascularization (44% vs. 38%, p = 0.244). CONCLUSIONS: Women with CS complicating AMI had more frequent adverse clinical characteristics and mechanical complications. Women derived the same benefit as men from revascularization, and gender was not independently associated with in-hospital mortality in the SHOCK Registry.

Invasive Group C Streptococcus infection associated with rhabdomyolysis and disseminated intravascular coagulation in a previously healthy adult.

Infections with Group C Streptococci can lead to severe disease, particularly in individuals with underlying illnesses such as cardiovascular disease, malignancy or immunosuppression. We report the first case of rhabdomyolysis and disseminated intravascular coagulation secondary to Group C Streptococcus in a previous healthy male. A toxic shock-like syndrome associated with Group C and Group G Streptococci has been reported. However, unlike with Group A Streptococci, production of endotoxins by these organisms is less well defined. We tested the patient's isolate for its ability to produce superantigenic toxins and to induce a mitogenic response. Although it is not known whether Group C Streptococci require special growth conditions for the production of superantigens, we could not demonstrate either the production of exotoxins or the induction of a mitogenic response.

One-year survival following early revascularization for cardiogenic shock.

CONTEXT: Cardiogenic shock (CS) is the leading cause of death for patients hospitalized with acute myocardial infarction (AMI). OBJECTIVE: To assess the effect of early revascularization (ERV) on 1-year survival for patients with AMI complicated by CS. DESIGN: The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) Trial, an unblinded, randomized controlled trial from April 1993 through November 1998. SETTING: Thirty-six referral centers with angioplasty and cardiac surgery facilities. PATIENTS: Three hundred two patients with AMI and CS due to predominant left ventricular failure who met specified clinical and hemodynamic criteria. INTERVENTIONS: Patients were randomly assigned to an initial medical stabilization (IMS; n = 150) group, which included thrombolysis (63% of patients), intra-aortic balloon counterpulsation (86%), and subsequent revascularization (25%), or to an ERV group (n = 152), which mandated revascularization within 6 hours of randomization and included angioplasty (55%) and coronary artery bypass graft surgery (38%). MAIN OUTCOME MEASURES: All-cause mortality and functional status at 1 year, compared between the ERV and IMS groups. RESULTS: One-year survival was 46.7% for patients in the ERV group compared with 33.6% in the IMS group (absolute difference in survival, 13.2%; 95% confidence interval [CI], 2.2%-24.1%; P<.03; relative risk for death, 0.72; 95% CI, 0.54-0.95). Of the 10 prespecified subgroup analyses, only age (<75 vs >/= 75 years) interacted significantly (P<.03) with treatment in that treatment benefit was apparent only for patients younger than 75 years (51.6% survival in ERV group vs 33.3% in IMS group). Eighty-three percent of 1-year survivors (85% of ERV group and 80% of IMS group) were in New York Heart Association class I or II. CONCLUSIONS: For patients with AMI complicated by CS, ERV resulted in improved 1-year survival. We recommend rapid transfer of patients with AMI complicated by CS, particularly those younger than 75 years, to medical centers capable of providing early angiography and revascularization procedures.

Clinical and laboratory diagnosis of influenza virus infections.

Influenza epidemics account for more than 20,000 deaths in the United States each year, as well as substantial morbidity, medical costs, and time away from work and school. Since the 1950s, the principal weapon against these seasonal epidemics has been killed virus vaccine formulations. Despite massive efforts to immunize at-risk individuals against influenza, not everyone receives the vaccine. In addition, use of some drugs, such as amantadine and rimantadine, can lead to the development of drug resistant viruses in infected individuals and to transmission of these viruses to susceptible individuals. The many factors that contribute to the high annual incidence of influenza virus infections mandate prompt clinical recognition and appropriate patient management. Rapid diagnostic tests have been developed that may make it possible to avoid the use of antibacterial drugs, quickly decide whether isolation of infected patients is needed, and discharge hospitalized patients sooner.

Cardiogenic shock due to cardiac free-wall rupture or tamponade after acute myocardial infarction: a report from the SHOCK Trial Registry. Should we emergently revascularize occluded coronaries for cardiogenic shock?

OBJECTIVES: We sought to compare the characteristics and outcomes of patients with acute myocardial infarction (MI) and cardiogenic shock (CS) caused by rupture of the ventricular free wall or tamponade versus shock from other causes. BACKGROUND: Free-wall rupture is a recognized cause of mortality in patients with acute MI. Some of these patients present subacutely, which provides an opportunity for intervention. Recognition of factors that distinguish them from the overall shock cohort would be beneficial. METHODS: The international SHOCK Trial Registry enrolled patients concurrently with the randomized SHOCK Trial. Thirty-six centers consecutively enrolled all patients with suspected CS after MI, regardless of trial eligibility. RESULTS: Of the 1,048 patients studied, 28 (2.7%) had free-wall rupture or tamponade. These patients had less pulmonary edema, less diabetes, less prior MI, and less prior congestive heart failure (all p < 0.05). They more often had new Q waves in two or more leads (51.9% vs. 31.5%, p < 0.04), but MI location and time to shock onset after MI did not differ. Of patients with rupture or tamponade, 75% had pericardial effusions. No hemodynamic characteristics identified patients with rupture/tamponade. Most patients with rupture/tamponade had surgery and/or pericardiocentesis (27/28); their in-hospital survival rate was identical to that of the group overall (39.3%). Women and older patients with rupture/tamponade tended to survive intervention less often. CONCLUSIONS: Free-wall rupture and tamponade may present as CS after MI, and survival after intervention is similar to that of the overall shock cohort. All patients with CS after MI should have echocardiography in order to detect subacute rupture or tamponade and initiate appropriate interventions.

Oral hairy leukoplakia: a manifestation of primary infection with Epstein-Barr virus?

Oral hairy leukoplakia (OHL) is a characteristic lesion presumably secondary to Epstein-Barr virus (EBV) reactivation. It is frequently seen in individuals infected with the human immunodeficiency virus (HIV) and less often in other immunosuppressed individuals. The frequent association of this lesion with HIV infection and its rare occurrence in normal individuals usually motivates the search for immunosuppression, particularly secondary to HIV, when this lesion is found. We describe here a healthy HIV-negative individual with OHL and clinical and laboratory data suggestive of acute EBV infection.

Role of cytomegalovirus in the T cell changes seen in elderly individuals.

The effect of prior cytomegalovirus (CMV) infection on the immune system was evaluated in young and elderly volunteers. Prevalence of IgG antibodies to CMV was higher in the elderly volunteers. In both age groups, there was a strong association with CMV seropositivity and increased number of CD28- CD4 or CD8 T cells, as well as with increased numbers of T cells expressing CD56 or DR. Although these changes have previously been reported to be age-related, they were independent of age when CMV serological status was taken into account. In contrast, both age group and CMV status were important determinants of the total number of T cells, the number of CD8 T cells, and the number of CD8 T cells expressing CD45RA or CD28. These findings indicate that prior infection with CMV, as reflected by CMV serological status, has important effects on T cell subsets and surface markers and must be considered whenever evaluating age-related changes in immunological parameters.

Polymerase chain reaction and restriction fragment length polymorphism analysis of varicella-zoster virus isolates from the United States and other parts of the world.

A polymerase chain reaction (PCR) assay that identifies and differentiates wild-type (wt) and vaccine strains of varicella-zoster virus (VZV) was used to determine if VZV strains with restriction fragment length polymorphisms resembling those of the Japanese Oka vaccine strain were present in the wt pool outside of Japan. Virus samples (n = 114) from patients with chickenpox and zoster from various parts of the United States and Australia were analyzed. The assay correctly identified 113 samples as wt strain. The 1 sample identified as Oka vaccine strain came from a child with leukemia who developed a vaccine-associated rash after receiving the live attenuated varicella vaccine. At this point, there is no evidence that wt strains resembling the vaccine are circulating outside of Japan. This indicates that this PCR assay can be utilized to distinguish rashes due to vaccine and wt VZV.

Cytomegalovirus-specific IFNgamma and IL-4 are produced by antigen expanded human blood lymphocytes from seropositive volunteers.

The cytokine responses to cytomegalovirus (CMV) antigen in seropositive and seronegative individuals were measured using a combination of antigenic expansion and intracellular staining. Intracellular IFNgamma and IL-4 were produced in a dose-dependent manner by T cells in response to CMV only in the seropositive population. The potential for individual cells to produce both Th1 and Th2 cytokines simultaneously was clear, as IL-4 was most often produced in those cells with the highest IFNgamma production. The cytokine-specific nature of this response was demonstrated by fluorescence microscopy, which showed granular cytoplasmic staining, and at the mRNA level by ribonuclease protection assays. These methods expand our ability to evaluate the immune response to CMV, and can now be correlated to a number of clinical conditions.

Clinical and economic impact of enterovirus illness in private pediatric practice.

OBJECTIVE: To characterize the acute clinical course and economic burden of nonpolio enteroviral (NPEV) illness in the summer/fall season as seen in private pediatric practice. METHODS: We prospectively studied 380 children aged 4 to 18 years with systemic NPEV syndromes presenting to private suburban pediatric practices. Seventy-three asymptomatic controls were concurrently enrolled. Clinical diagnosis of NPEV illness was based on the presence of fever plus at least one of the following: headache and stiff neck (n = 2); myalgia and malaise (n = 105); nonpuritic maculopapular rash (n = 10); papulovesicular stomatitis (n = 214); papular rash of the hands, feet, and mouth (H/F/M) (n = 30); or pleurodynia (n = 11). Study participants were enrolled during a 4-month time span (July-October, 1994) and followed daily for 14 days. A parent symptom diary card and twice weekly phone contacts by study nurses characterized the illness to include the frequency of health care contacts, the necessity for laboratory tests, medication use, and school/work absenteeism. RESULTS: Three hundred seventy-two (98%) children completed the study; 122 (33%) of the patients were confirmed to be infected with NPEV. Confirmed NPEV infection was more frequently observed in Rochester, NY (85/147 = 58%) than in Scottsdale, AZ (32/224 = 14%). The age group 4 to 12 years comprised 79% to 90% of the enrollees, depending on the syndrome. Median duration of illness and median number of missed days of school/summer camp/work for the enrolled patients was: meningitis (7 days ill, 2 days missed), myalgia/malaise (9 days ill, 3 days missed), rash (6 days ill, 4 days missed), stomatitis (7 days ill, 2 days missed), H/F/M (7 days ill, 1 day missed), and pleurodynia (8 days ill, 3 days missed). Direct medical costs varied from $69 per case to $771 per case and indirect costs, attributable primarily to parent missed work and/or sick-child care, varied from $63 per case to $422 per case for H/F/M and meningitis, respectively. In households, H/F/M spread to 50% of siblings and 25% of parents. CONCLUSIONS: In our study population, NPEV infection: 1) caused sufficient illness to prompt physician visits in summer and fall; 2) occurred more frequently in 4 to 12 year olds than in adolescents; 3) produced various clinical syndromes concurrently during the same months in the same season of a given year; 4) varied in occurrence geographically; 5) was characterized by numerous symptoms of longer duration than previously recognized; and 6) produced a significant economic impact by generating both direct and indirect costs.

Successful intracoronary thrombolysis in cocaine-associated acute myocardial infarction.

We describe a case of cocaine-associated acute myocardial infarction managed by cardiac catheterization and intracoronary thrombolysis. Based on this and other reported cases, it appears that an invasive approach to the management of cocaine-associated acute myocardial infarction is advantageous over intravenous thrombolysis. Such a strategy would define the pathophysiology of acute myocardial infarction in the setting of cocaine use and allow mechanical intervention should pharmacologic therapy be unsuccessful.

Successful treatment of a generalized human papillomavirus infection with granulocyte-macrophage colony-stimulating factor and interferon gamma immunotherapy in a patient with a primary immunodeficiency and cyclic neutropenia.

BACKGROUND: We describe a patient with generalized verrucosis secondary to human papillomavirus (HPV) type 2 infection and a primary immunodeficiency and cyclic neutropenia. Treatment, which was well tolerated, included granulocyte-macrophage colony-stimulating factor and interferon gamma (IFN-gamma). In vitro assays to assess responses of T lymphocytes to mitogens (ie, proliferation assay and IFN-gamma enzyme-linked immunosorbent assay) were performed. In situ hybridization and polymerase chain reaction were used to detect HPV DNA in skin biopsy specimens. OBSERVATIONS: The T lymphocytes of the patient showed a significant (P < .05, unpaired Student t test) defect in IFN-gamma production (the basis for initiating IFN-gamma therapy). The response to immunotherapy was confirmed by using molecular methods. Six months after the completion of immunotherapy, HPV DNA was undetectable in skin samples from clinically regressed warts (according to the results of in situ hybridization and polymerase chain reaction). CONCLUSIONS: Our patient had treatment-resistant generalized verrucosis for 13 years. Treatment with granulocyte-macrophage colony-stimulating factor and IFN-gamma may have reconstituted an immune response against HPV, resulting in the dramatic regression of her widespread warts.

Placental examination in intrauterine coinfection with herpes simplex virus and cytomegalovirus.

Intrauterine coinfections have rarely been reported. However, pregnancies exposed to multiple sexually transmitted infectious agents and drugs are likely to occur with increasing frequency and lead to complex pathology in the newborn. Often it will be difficult to establish a diagnosis, above all when this has to be done retrospectively. A premature (34 weeks) newborn presented with a complex clinical picture after exposure to multiple infectious and noninfectious teratogens during gestation. Immunocytochemical staining of the placental membranes and parenchyma suggested intrauterine coinfection by herpes simplex virus (HSV) type 2 and cytomegalovirus. This case illustrates the importance of careful placental investigation with modern techniques for the diagnosis of intrauterine HSV infection and coinfections.

Early postoperative angiographic assessment of radial grafts used for coronary artery bypass grafting.

UNLABELLED: Despite a revival of interest in using the radial artery as an alternative conduit for myocardial revascularization, little angiographic documentation of early postoperative results has been presented, particularly in North America. Accordingly, 60 of 150 patients who underwent coronary artery bypass with radial arteries from November 1993 to July 1995 have had postoperative cardiac catheterization at our institution. The patency rate of the radial artery grafts was 95.7% (90 of 94 grafts patent) with an average internal diameter of 2.51 mm. Four radial artery grafts showed diffuse narrowing. The patency rate of the internal thoracic artery grafts was 100% with an average internal diameter of 2.25 mm. Three of 62 grafts demonstrated diffuse narrowing. Two of 24 (7.7%) saphenous vein grafts were occluded; the average internal diameter was 3.23 mm. The internal thoracic artery, the radial artery, and saphenous vein grafts were, respectively, 7.5%, 19.5%, and 53.3% larger than the anastomosed native coronary arteries. Graft-dependent flow was found in 81.1% of the radial artery grafts. CONCLUSION: The results of this study demonstrate that the short-term patency rate of radial artery grafts is excellent.

Prognostic significance of nonfatal reinfarction during 3-year follow-up: results of the Thrombolysis in Myocardial Infarction (TIMI) phase II clinical trial. The TIMI Investigators.

OBJECTIVES: This study sought to assess the independent contribution of nonfatal reinfarction to the risk of subsequent death in patients with acute myocardial infarction undergoing thrombolytic therapy. BACKGROUND: A composite of "unsatisfactory outcomes" as an end point has increased statistical power and facilitated evaluation of evolving treatment regimens in acute myocardial infarction. The significance of nonfatal reinfarction as a component of a composite end point has not been evaluated in the thrombolytic era. METHODS: Event rate of nonfatal reinfarction over 3-year follow-up was evaluated in patients with acute myocardial infarction entered into the Thrombolysis in Myocardial Infarction Phase II trial. The independent risk of nonfatal reinfarction for subsequent death within various time intervals of follow-up was determined. The mortality rate after nonfatal reinfarction was compared with that of a matched control group. RESULTS: During 3-year follow-up, 349 of 3,339 patients had a nonfatal reinfarction. Univariate predictors were history (antedating the index event) of angina (p = 0.01), hypertension (p = 0.01), multivessel disease (p = 0.007) and not a current smoker (p = 0.003); the latter was an independent predictor (relative risk [RR] 1.3, 99% confidence interval [CI] 1.0 to 1.8). Forty-three of the 349 patients with a nonfatal reinfarction died: RR for death (vs. patients without a nonfatal reinfarction) was 1.9 (99% CI 1.1 to 3.2) if reinfarction occurred within 42 days of study entry, 6.2 (99% CI 3.0 to 12.9) if reinfarction occurred between 43 and 365 days and 2.9 (99% CI 0.6 to 13.4) if reinfarction occurred between 366 days and 3 years. The cumulative 3-year death rate was 14.1% in patients with a nonfatal reinfarction compared with 7.9% (p < 0.01) in a matched control group. Univariate predictors of death after nonfatal reinfarction were age > or = 65 years (p < 0.001), not low risk category (p = 0.015) and history of heart failure before the index event (p < 0.001). Age > or = 65 years was the only independent predictor (RR 5.4, 99% CI 2.3 to 12.4). CONCLUSIONS: Nonfatal reinfarction is a strong and independent predictor for subsequent death. It represents a powerful component for a composite end point in patients who received thrombolytic therapy after acute myocardial infarction.