Divergent blood pressure responses during short-term sodium restriction in hypertension.

In untreated patients with essential hypertension, daily sodium intake was reduced from 197 to 70 mEq/day in 82 outpatients and from 124 to 14 mEq/day in 25 patients in a metabolic ward. During the 10 days of sodium restriction 17% of the outpatients and 40% of the inpatients had mean blood pressure decreases of at least 10 mm Hg, but in 17% of the outpatients and 28% of the inpatients mean pressure rose at least 5 mm Hg. Most blood pressure decreases occurred in the group with high-renin hypertension. Our short-term experience suggests that dietary salt deprivation may not be effective treatment for all patients with hypertension and may even be counterproductive in some.

Fungal prosthetic valve endocarditis in 16 patients. An 11-year experience in a tertiary care hospital.

Fungal prosthetic valve endocarditis (PVE) is an infrequent but serious complication of valve replacement surgery. To examine its long-term outcome, we retrospectively studied 16 patients with 19 episodes of definite fungal PVE. The mean age was 51 years (range, 27-71 yr). Onset of fungal PVE ranged from 8 days to 3.4 years after valve replacement. Candida albicans was the most common (56%) pathogen isolated. A portal of entry was identified in only 25% of the patients; the presence of intravascular catheters (50%) and prior bacterial endocarditis (38%) were leading predisposing factors. Fever (83%) was the most consistent clinical finding. Potentially serious embolic events, particularly strokes (32%), were common at presentation. Transesophageal echocardiography (sensitivity = 100%) was more useful than transthoracic echocardiography (sensitivity = 60%) in detecting lesions due to fungal PVE. Combined valve replacement surgery and amphotericin B (mean total dose of 1.8 g) in 15 patients resulted in an 87% in-hospital survival and 67% overall survival with a mean follow-up of 4.5 years (range, 5 mo to 16 yr). Two patients had 3 late relapses of fungal PVE up to 9 years after the preceding episode. Each relapse was treated with repeat valve replacement and amphotericin B; in addition, oral azole was utilized for chronic suppression, although the efficacy of this strategy remains unproven. Because of the possibility of relapse, long-term follow-up is essential even after surgical and prolonged antifungal therapy.

Ibuprofen-induced meningitis: detection of intrathecal IgG synthesis and immune complexes.

We report a case of ibuprofen-induced meningitis in an otherwise healthy individual. This is the 1st case documenting intrathecal IgG synthesis and immune complex formation in this disorder. The immunopathogenesis remains obscure, but is suggestive of an antigen-specific process requiring the presence of or exposure to ibuprofen.

Incidence and risk of developing fungal prosthetic valve endocarditis after nosocomial candidemia.

PURPOSE: To determine the incidence of prosthetic valve endocarditis (PVE) in fungemic patients with prosthetic heart valves (PHV), estimate risk of subsequent PVE, and describe risk factors and diagnostic and therapeutic management issues in such patients. PATIENTS AND METHODS: This is a retrospective chart review in a 1,100-bed tertiary referral center with an active cardiothoracic surgical service. Forty-four patients with PHVs developed nosocomial fungemia between January 1985 and April 1995. RESULTS: Of 44 patients, 33 never developed evidence of PVE (group 1), 7 (16%) had evidence of PVE at the time of candidemia (group 2), and 4 (9%) developed PVE a mean of 232 days after candidemia (group 3). Predisposing factors including intravascular lines, prior antibiotic therapy, and an identifiable portal of entry for fungemia were common in group 1 but not group 2. Candidemia occurred significantly later after PHV surgery in group 2 (mean 270 days) as compared to groups 1 and 3 (means 48 and 15.5 days, respectively; P = 0.02). Ten of 11 patients with Candida PVE (group 2 and 3) were treated with amphotericin B and valve replacement. Three relapses after combined therapy were documented in two patients. Mortality was significantly higher for patients without Candida PVE (group 1) as compared to patients with Candida PVE (groups 2 and 3) at 1 month (53% vs 9%), 2 months (69% vs 20%) and 1 year (83% vs 25%) after candidemia. CONCLUSIONS: Patients with prosthetic heart valves who develop nosocomial candidemia are at notable risk of either having or developing Candida PVE months or years later. Late onset candidemia and lack of an identifiable portal of entry should heighten concern about Candida PVE in such patients.

Infections of the cardiac suture line after left ventricular surgery.

PURPOSE: Infections of the cardiac suture line after left ventricular surgery are rare but may be fatal if not diagnosed promptly and treated effectively. In order to alert physicians to this entity, we reviewed data from three patients who presented at the Cleveland Clinic Hospital and from 22 patients in the literature. PATIENTS AND METHODS: The three patients in the current report underwent treatment at the Cleveland Clinic Hospital. Additional cases of infection of the left ventricular suture line were identified by reviewing the English literature pertaining to surgery for left ventricular aneurysms, pseudoaneurysms, and postoperative cardiac infections. RESULTS: Infection presented on average 16 months after surgery with cardiocutaneous fistulae, chest wall masses, hemoptysis or other pleuropulmonary symptoms, or systemic illness with bacteremia resembling endocarditis. Staphylococci and gram-negative bacilli were the most frequent pathogens. Diagnosis was often delayed and mortality was high. Left ventricular false aneurysms were identified in 15 of the 25 patients. Bleeding from sinuses in the chest wall or epigastrium or repeated hemoptysis were important clinical clues. In some instances, ill-advised surgical or instrumental procedures precipitated life-threatening hemorrhage. Treatment with antibiotics alone was insufficient. Excision of all infected sutures and Teflon pledgets and adequate debridement of the infected suture line were required to achieve cures. CONCLUSION: Since infection of the left ventricular suture line has protean clinical manifestations and may present months or years after the initial surgery, a high index of suspicion is of paramount importance in diagnosing the condition. Institution of cardiopulmonary bypass and reoperation through median sternotomy is recommended to achieve a cure.

Rapid uptake and esterification of arachidonic acid and other fatty acids by microfilariae of Brugia malayi.

We have examined the differential incorporation and esterification of exogenous fatty acids by microfilariae of the human filarial parasite Brugia malayi. Microfilariae incubated with 2 nM [3H]arachidonic acid over 1 h rapidly took up this fatty acid. Palmitic, oleic and linoleic acids were also incorporated by parasites. In contrast to these other fatty acids, little incorporated arachidonic acid remained as free fatty acid within microfilariae. Arachidonate was rapidly esterified into phospholipids, with 66% of incorporated arachidonate esterified into phospholipids at 1 min. Esterification of other fatty acids into phospholipids was quantitatively lesser and occurred into phosphatidylcholine and phosphatidylethanolamine. Arachidonate was preferentially esterified into phosphatidylinositol, which constituted only 10% of the total parasite phospholipid pool, and into phosphatidylcholine. By 1 min these two phospholipid classes, respectively, comprised 53% and 43% of [3H]arachidonyl-phospholipids. Neither the microfilarial incorporation of arachidonate nor its esterification into parasite phospholipids could be saturated by noncytotoxic concentrations of up to 600 microM. Microfilariae, which in vivo are exposed to arachidonate in blood, can rapidly, avidly and with high capacity incorporate exogenous arachidonate and esterify it preferentially into specific classes of phospholipids, including phosphatidylinositol. Like many mammalian cells, these phylogenetically distinct metazoan parasites possess efficient means for utilizing host-derived arachidonic acid.

Endobronchial Mycobacterium avium-intracellulare infection in a patient with AIDS.

The pulmonary manifestations of AIDS are well described in the medical literature; however, MAI infection presenting as an endobronchial lesion has not, to our knowledge, been reported in a patient with AIDS. We report a unique case of an AIDS patient who developed endobronchial polypoid lesions secondary to MAI infection. Complications resulting from these lesions included hemoptysis and later bronchiectasis.

A survey of allogeneic bone marrow transplant programs in the United States regarding cytomegalovirus prophylaxis and pre-emptive therapy.

Despite an extensive literature, no consensus has emerged regarding the optimal preventive strategy for CMV in allogeneic bone marrow transplantation (BMT). No survey of CMV prevention in BMT centers in the United States has yet been published. A questionnaire was sent to all allogeneic BMT programs in the United States, as listed in the November 1998 National Marrow Donor Program (NMDP) address roster. Questions included whether universal prophylaxis, pre-emptive therapy, or some other strategy was used for CMV prevention, and which CMV diagnostic tests were utilized. Eighty-one of 96 programs (86%) responded to the survey. Of these, 46 (56%) utilize a pre-emptive ganciclovir strategy, whereas 17 (21%) utilize universal prophylaxis, and 15 (19%) utilize a hybrid strategy based on risk stratification. The most commonly utilized CMV diagnostic tests are CMV-DNA by PCR (55 centers), shell vial centrifugation culture (52), tissue culture (42), pp65 antigenemia assay (38), and CMV-DNA by Digene hybrid capture (14). Of these, the CMV-DNA by PCR, pp65 antigenemia assay, and shell vial culture are the most frequently utilized as triggers for pre-emptive therapy. Quantitative assays are common (PCR 42%, Digene 64%). We conclude that centers currently performing allogeneic BMT in the United States employ a variety of strategies for CMV prevention, and differ in their diagnostic tests of choice for CMV monitoring. These results emphasize the need for large-scale studies to identify optimal diagnostic and management protocols. Bone Marrow Transplantation (2000) 26, 763-767.

Early infectious complications in autologous bone marrow transplantation: a review of 219 patients.

The objective of this study was to define the incidence, type and timing of early infectious complications, occurring within the first 30 days, in autologous bone marrow transplant (autoBMT) recipients over a 45-month period, and in addition to assess the effects of growth factors and primed peripheral blood progenitor cells on the rate of infectious complications. The paper describes a retrospective and observational study, carried out at the bone marrow transplantation unit at a tertiary referral center. The subjects were two hundred and nineteen patients who underwent autologous bone marrow transplantation for a variety of indications from April 1989 to December 1992. The median duration of neutropenia after autologous bone marrow transplantation was 12 days. There was a direct correlation between the duration of neutropenia and the incidence of infectious complications. The overall incidence of infections and isolated febrile episodes was 35%. Septicemia occurred in 7.8% of patients, pneumonia in 2.7%, skin infection in 1.8%, other infections in 2.7% and isolated febrile episodes in 20.1%. Viridans streptococci were the most common cause of septicemia. Invasive fungal infections occurred in only 2.3% of patients. There were no documented viral infections. The use of growth factors and primed peripheral blood progenitor cells was associated with a shorter duration of neutropenia; a decrease in the overall incidence of infections, particularly septicemia and fungal infections; a shorter length of stay in the hospital and a lower mortality rate in the first 30 days after transplantation. We found a lower incidence of bacterial and fungal infections compared to previous studies. The critical factor associated with the occurrence of any early infection was the duration of neutropenia, which was significantly shortened by the use of growth factors and peripheral blood progenitor cells. Septicemia was uncommon in our population and viridans streptococci were the most common bloodstream isolates.

Infectious complications within the first year after nonmyeloablative allogeneic peripheral blood stem cell transplantation.

Nonmyeloablative peripheral blood stem cell transplantation (PBSCT) is a novel therapeutic strategy for patients with malignant and non-malignant hematologic diseases. Infectious complications of this procedure have not been previously well described. Data on 12 patients transplanted at a tertiary care center were collected prospectively and verified retrospectively. Neutropenia developed in a third of patients, lasting for a median of 5 days. All patients developed some degree of graft-versus-host disease, as intended. Most patients achieved full chimerism by week 5. Bacterial infections occurred in two patients (17%). Cytomegalovirus (CMV) viremia occurred in five patients (42%) at a median of 80 days; none had received CMV prophylaxis. Viremia was associated with fever and fatigue in three patients, possible gastrointestinal involvement in one patient and was asymptomatic in one patient. All viremic patients responded to intravenous ganciclovir therapy. No fungal infections were documented. No patients died as a result of infection. The incidence of CMV viremia in our patients was high, but the incidence of invasive disease due to CMV was low. The best strategy to prevent CMV in patients undergoing nonmyeloablative PBSCT remains to be determined, but strategies employed in traditional allogeneic bone marrow transplantation should be considered in these patients.

The efficacy of prophylactic outpatient antibiotics for the prevention of neutropenic fever associated with high-dose etoposide (VP-16) for stem cell mobilization.

High-dose etoposide (2 g/m(2)) plus G-CSF is a very effective regimen for peripheral blood progenitor cell (PBPC) mobilization. Unfortunately, neutropenia is common. The infectious complications associated with high-dose etoposide have not been previously described. After noting a high incidence of hospitalizations for neutropenic fever, we began a vigorous prophylactic antibiotic regimen for patients receiving high-dose etoposide plus G-CSF, attempting to reduce infectious complications. Ninety-eight patients underwent etoposide mobilization between December 1997 and June 2000. Three chronological patient groups received: (1) no specific antibiotic prophylaxis (n = 44); (2) vancomycin i.v., cefepime i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27); and (3) vancomycin i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27). The patients not receiving antibiotic prophylaxis had a 68% incidence of hospitalization for neutropenic fever. In the patients receiving prophylaxis, the incidence was reduced to 26% and 15% respectively, for an overall incidence of 20% (P < 0.001 for comparison between prophylaxed and unprophylaxed groups). We conclude that etoposide mobilization is associated with a significant incidence of neutropenic fever, which can be substantially reduced by a vigorous antimicrobial prophylactic program.

Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined.

Unpredictability of commercially available exoantigen culture confirmation tests in confirming the identity of five Blastomyces dermatitidis isolates.

Colonial and microscopic features of five fungal isolates from three patients suggested Blastomyces dermatitidis. Extracts from the mold forms of all isolates were tested on several occasions with commercially available Exoantigen immunodiffusion culture-confirmation test reagents and Nolan reagents. All three isolates from patient 1 were negative on four separate attempts with Exoantigen reagents using conventional ("slant") and "broth" extraction methods, and were also negative on one attempt with the Nolan reagents. The isolate from patient 3 was negative on three attempts using both reagent kits. The isolate from patient 2 was negative on four of five attempts with Exoantigen test reagents and positive on one attempt with Nolan reagents. Commercially prepared chemiluminescence-labeled DNA probes (Gen-Probe, San Diego, CA) directed at ribosomal RNA from B. dermatitidis and Histoplasma capsulatum confirmed all five isolates as B. dermatitidis. The cost and labor of the exoantigen and DNA Probe culture confirmation tests were evaluated. New methods for confirming the identity of cultural isolates of B. dermatitidis that are sensitive, specific, and commercially available are greatly needed.

Leukotriene C4 synthesis catalyzed by Dirofilaria immitis glutathione S-transferase.

The biologically active sulfidopeptide leukotriene, leukotriene C4, is formed by the enzymatic action of leukotriene C4 synthase, which conjugates glutathione with leukotriene A4. We have found that a filarial glutathione S-transferase can function as a leukotriene C4 synthase. Glutathione S-transferase was purified from the cytosol of adult Dirofilaria immitis by glutathione-agarose affinity chromatography and was reacted with 25 microM leukotriene A4 methyl ester and 10 mM glutathione. The filarial enzyme catalyzed the formation of leukotriene C4 methyl ester, as shown by reverse phase high pressure liquid chromatographic analyses. The finding that filarial glutathione S-transferase can function as leukotriene C4 synthase provides a mechanism whereby filarial parasites could form lipoxygenase pathway derived sulfidopeptide leukotrienes.

Corneal microsporidiosis in a patient with AIDS.

Microsporidia are obligate intracellular protozoan parasites that are becoming increasingly recognized as opportunistic pathogens in patients with AIDS. They have been associated with enteritis, hepatitis, and peritonitis and recently keratoconjunctivitis. Gram stain demonstrates the presence of these organisms on light microscopic sections. The specific diagnostic features that distinguish microsporidia from other small nonspore-forming organisms are best demonstrated by electron microscopy, which is also used to characterize the members of Microsporea. In this study, salient histopathologic features of microsporidia in corneal epithelium obtained from an HIV-seropositive individual who developed AIDS are illustrated and discussed.

Coagulase-negative staphylococcal sternal wound infections after open heart operations.

BACKGROUND: Coagulase-negative staphylococci are commonly isolated from wounds of patients after median sternotomy; however, the epidemiology of these infections is poorly described and the morbidity, mortality, and cost of care remain undefined. METHODS: Retrospectively, we studied all patients with sternal wound infections attributable to coagulase-negative staphylococci after 22,180 open heart procedures performed at the Cleveland Clinic between January 1, 1988, and December 31, 1994 (84 months). In an assessment of potential risk factors for sternal wound infections caused by coagulase-negative staphylococci, 17 patients with coagulase-negative staphylococcal sternal wound infections were compared with 29 patients who underwent open heart operations without subsequent sternal wound infections, as well as with another 22 patients in whom sternal wound infections attributable to other pathogens developed. RESULTS: A total of 436 sternal wound infections were identified (19 per 1,000 procedures), of which 100 (23%) were attributable to coagulase-negative staphylococci (4.5 per 1,000). Fifty-six percent of coagulase-negative staphylococcal sternal wound infections were superficial, 27% were deep, and 17% represented mediastinitis; 14% of patients had a concomitant secondary bloodstream infection. Ninety-two percent of coagulase-negative staphylococcal isolates were methicillin resistant. The mean interval from operation to onset of infection was 24 days (range, 4 to 388 days), and most patients had purulent discharge from the chest wound, fever, and leukocytosis. Adverse outcomes included reexploration (39%), flap operation (12%), and sternectomy (5%); 89% required parenteral antibiotics for a mean of 22 days. This resulted in 2,600 additional hospital days, with an average additional direct cost per case of $20,000. In both case-control studies, insulin-dependent diabetes mellitus was the only risk factor significantly associated with sternal wound infections attributable to coagulase-negative staphylococci (p value = 0.02 by two-tailed Fisher's exact test). CONCLUSIONS: Sternal wound infections attributable to coagulase-negative staphylococci had a substantial impact on cardiothoracic surgery-related morbidity.

Oral disease burden in patients undergoing prosthetic heart valve implantation.

BACKGROUND: Valvular heart disease predisposing to endocarditis and requiring prosthetic valve implantation is common among the elderly. Spontaneous bacteremias associated with acute or chronic oral/odontogenic infections may represent a far greater cumulative risk for the development of endocarditis than do occasional health care procedures administered in a professional setting. METHODS: To determine the oral disease burden in patients undergoing mechanical or bioprosthetic heart valve implantation, we performed a comprehensive clinical and radiographic regional examination on 156 consecutive patients, with emphasis on identifying acute and chronic oral/odontogenic infections and conditions. RESULTS: The mean number of remaining teeth in the cohort was 19.32; of these, 1.07 were carious, involving a mean number of 2.51 tooth surfaces. In addition, 15.38% of the patients had evidence of acute or chronic periapical abscesses, and 43.6% of the patients had moderate to advanced periodontitis. CONCLUSIONS: In view of the substantial morbidity and mortality associated with prosthetic valve endocarditis and based upon the high incidence of dental disease identified in patients undergoing valvular operations, routine preoperative dental assessment should be deemed a "medical necessity" by third-party payors. Appropriate therapeutic intervention should be initiated whenever possible before valve implantation.

Early onset prosthetic valve endocarditis: the Cleveland Clinic experience 1992-1997.

BACKGROUND: We reviewed all cases of early onset prosthetic valve endocarditis (EO-PVE) occurring less than 12 months after valve operation among 7,043 patients undergoing heart valve replacements or repairs at The Cleveland Clinic between 1992 and 1997. METHODS: Cases were defined by the Duke criteria and identified through prospective surveillance. RESULTS: Seventy-seven cases of EO-PVE were identified (1 per 100 procedures), and during the study period the incidence of EO-PVE decreased from 1.5% (1992 to 1994) to 0.7% (1995 to 1997) (p < 0.01). The incidence of EO-PVE for rings (0.2%; 4 of 1,992) was significantly lower than for mechanical (1.6%; 28 of 1,731) and bioprosthetic valves (1.1%; 41 of 3,320) (p < 0.001). The incidence of EO-PVE was also significantly lower for mitral valve versus aortic valve surgeries (0.6% versus 1.4%, p < 0.001). The most common pathogens causing EO-PVE were coagulase-negative staphylococci (52%), fungi (13%), Staphylococcus aureus (10%), and enterococci (8%). Patients undergoing combined surgical and medical treatment of EO-PVE had a significantly higher 30-day, 2-year, and 3-year survival than medically treated patients, although patients judged to be too ill to survive surgery accounted for two-thirds of the patients treated medically. CONCLUSIONS: There is a 1% incidence rate of EO-PVE among patients undergoing valve operations at our institution, usually caused by coagulase-negative staphylococci, and combined surgical and medical treatment is associated with improved survival compared with medical treatment alone.

Viral pulmonary infections in thoracic and cardiovascular surgery.

Viral respiratory infections are uncommon causes of pulmonary infiltrates in immunocompetent patients who undergo cardiothoracic surgery. In winter months, however, influenza can be acquired in the community preoperatively or in the hospital setting. The recognition of influenza cases is essential to prevent nosocomial transmission. Respiratory syncytial virus is also an important pulmonary pathogen in pediatric patients who undergo cardiothoracic surgery and may produce serious disease in children with underlying pulmonary or congenital heart disease. Viral infections of the respiratory tract are important causes of morbidity and mortality in heart and lung transplant recipients, especially cytomegalovirus (CMV). Other herpes viruses such as varicella zoster virus and herpes simplex virus may also occasionally involve the lung. Epstein-Barr virus has been incriminated in the pathogenesis of post-transplant lymphoproliferative disease, an uncommon but severe complication of transplantation. Except for Epstein-Barr virus, effective therapy exists for CMV and the other herpes viruses. Prophylaxis with ganciclovir is effective in preventing serious CMV infections in seropositive heart transplant recipients. However, better strategies are needed to prevent primary CMV infection in these patients.