Rosiglitazone versus bedtime insulin in the treatment of patients with conventional oral antidiabetic drug failure: a 1-year randomized clinical trial.

This study was conducted to evaluate the efficacy and tolerability of rosiglitazone in the treatment of patients with secondary oral antidiabetic drug (OAD) failure and to directly compare its use with bedtime insulin. A total of 112 Chinese patients with type 2 diabetes and conventional OAD failure were recruited. Patients were randomly assigned to treatment with rosiglitazone or bedtime isophane insulin; they continued to take their original oral antidiabetic drugs. Glycemic index, other clinical profiles, and tolerability were assessed during treatment and 1 y after add-on treatment was provided. Among the 112 patients, mean age (+/-SD) was 58.2+/-11.0 y (median, 58 y; range, 37 to 84 y). Both rosiglitazone (n=56) and insulin (n=56) significantly improved fasting glucose (2.4 and 3.7 mmol/L, respectively) and hemoglobin A1c concentrations (1.1% and 1.3%, respectively). Both therapies increased body mass index after 1 y of treatment (0.9 and 0.8 kg/m2, respectively). Only rosiglitazone increased high-density lipoprotein cholesterol concentrations (0.1 mmol/L). Four patients (7.1%) who were given rosiglitazone developed adverse effects (2, ankle edema, and 2, gastrointestinal disturbance). Six insulin-treated patients (10.7%) described adverse effects (5, early morning hypoglycemia, and 1, anxiety). Investigators concluded that in Chinese patients with type 2 diabetes and secondary conventional OAD failure, 1 y of treatment with rosiglitazone or bedtime insulin added to the regular regimen resulted in similar improvements in glycemic control. Rosiglitazone was also associated with improved high-density lipoprotein cholesterol levels. The addition of rosiglitazone may offer a safe and effective alternative to bedtime insulin treatment.

A 10-week Tai-Chi program improved the blood pressure, lipid profile and SF-36 scores in Hong Kong Chinese women.

BACKGROUND: Physical activity is associated with a better longevity and reduced morbidity. In addition, exercise has a mood-elevating effect, which improves self-esteem. Tai-Chi is a traditional Chinese aerobic exercise. We aimed to assess the short-term effects of Tai-Chi on the clinical parameters and health-related quality of life (QOL) in Hong Kong Chinese. MATERIAL/METHODS: Twenty Chinese healthy female subjects were recruited. There were 2 Tai-Chi sessions per week for 10 weeks. Each session lasted for one hour. Health-related QOL was assessed with SF-36 questionnaire. RESULTS: Of the 20 subjects, their mean age was 40.8 +/- 5.9 years (median 42.5 years, range 30-50 years). At the end of the study, systolic blood pressure, total cholesterol and low-density lipoprotein cholesterol levels significantly reduced (114 +/- 9 to 108 +/- 9 mmHg, p = 0.012; 4.7 +/- 0.8 to 4.4 +/- 0.5 mmol/L, p = 0.020 and 2.7 +/- 0.6 to 2.2 +/- 0.5 mmol/L, p = 0.001, respectively). Among all SF-36 items, Vitality and Mental Health significantly improved after the 10-week Tai-Chi program (64.9 +/- 8.1 to 68.4 +/- 6.6, p = 0.038 and 64.4 +/- 6.9 to 69.1 +/- 1.4, p = 0.003, respectively). CONCLUSIONS: A 10-week Tai-Chi exercise program improved systolic blood pressure, lipid profiles and some of the parameters of health-related QOL in Hong Kong Chinese women. Tai-Chi is likely to be a useful choice of physical activity. We need a larger study that covers a wider range of populations to confirm our results.

Respiratory virus infections in pediatric hematopoietic stem cell transplantation.

Respiratory virus infections (RVI) have become an increasingly appreciated problem in the hematopoietic stem cell transplant (HSCT) population. A retrospective analysis of 274 patients undergoing 281 HSCT at St. Jude Children's Research Hospital from January 1994 through December 1997 was performed. Medical and clinical laboratory records were reviewed beginning at the onset of conditioning through the year following each HSCT, and the analysis was done for the first RVI only. Thirty-two (11%) of 281 HSCT cases developed a RVI during the first year post-HSCT. The most frequent cause of RVI was human parainfluenza virus type 3. Univariate analysis was performed to determine the association between risk factors and the cumulative incidence of RVI. Respiratory viruses are frequent causes of infections in the first year post-HSCT in the pediatric population. Only allogeneic transplant and the degree of acute or chronic graft versus host disease were found to be statistically significant risk factors for RVI.

Bacillus cereus bacteremia and meningitis in immunocompromised children.

Two cases of Bacillus cereus meningitis in immunocompromised children at our hospital within a 2-month period prompted us to review B. cereus--related invasive disease. We identified 12 patients with B. cereus isolated in blood cultures from September 1988 through August 2000 at our institution. Three of these patients also had B. cereus isolated from CSF specimens; 1 additional patient had possible CNS involvement (33%, group A), whereas 8 patients had no evidence of CNS involvement (67%, group B). Patients in group A were more likely to have neutropenia at the onset of sepsis and were more likely to have an unfavorable outcome. They were also more likely to have received intrathecal chemotherapy in the week before the onset of their illness. Two patients from group A died. One survived with severe sequelae. The fourth patient had mild sequelae at follow-up. No sequelae or deaths occurred among patients in group B. In patients with unfavorable outcomes, the interval from the time of recognition of illness to irreversible damage or death was short, which demonstrates a need for increased awareness, early diagnosis, and more-effective therapy, particularly that which addresses B. cereus toxins.

Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer.

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.

Hepatitis C infection among survivors of childhood cancer.

Preliminary reports have suggested that survivors of childhood cancer and aplastic anemia who are infected with the hepatitis C virus (HCV) have a low risk for progression to significant liver disease. Among our surviving patients who were transfused between 1961 and March 1992, 77 (6.6% of surviving patients tested thus far) have evidence of HCV infection, whereas 4 surviving patients who were transfused after March 1992 are HCV-infected. One patient chronically infected with HCV died of liver failure, and 2 patients died of hepatocellular carcinoma. To characterize the risk for these and other complications, 65 patients are enrolled in a longitudinal study of HCV infection, of whom 58 (89.2%) had circulating HCV RNA at the time of protocol enrollment, with genotypes 1A and 1B most commonly isolated. Most enrolled patients have few or no symptoms, carry out normal activities, and have normal liver function. To date, 35 patients have undergone liver biopsy for abnormal liver function since the diagnosis of primary malignancy; central pathology review shows 28 (80%) have chronic active hepatitis, 25 (71%) have fibrosis, and 3 (9%) have cirrhosis. These preliminary data suggest that though most survivors of childhood cancer who are infected with HCV are clinically well, some are at risk for clinically significant liver disease. Identification of other HCV-infected patients and prospective monitoring of this cohort are ongoing to determine the risk for, and to identify factors associated with the progression of, liver disease.

Fungal susceptibility testing.

The utility of antifungal susceptibility testing has not been broadly determined. Thus, susceptibility testing of fungal isolates is not recommended on a routine basis. For instance, susceptibilty testing may be considered for some Candida species and for patients with Pseudallescheria boydii infections. Testing of yeasts for susceptiblity to azoles is of particular value due to their variability in response to these agents. It may also be important to test the susceptibility of new fungal organisms not previously identified or known to cause human disease because in these situations there are no clinical reports of efficacy to guide the choice of antifungal therapy.

Stability and sterility of a recombinant factor VIII concentrate prepared for continuous infusion administration.

Minipumps may facilitate cost-effective and convenient continuous infusion (CI) therapy for severe hemophilia A. This study evaluated the in vitro sterility, ability to support bacterial growth, and specific activity stability of a recombinant factor VIII (FVIII; Bioclate, Centeon) delivered by simulated CI at a variety of temperatures and after the addition of heparin or antibiotic. Closed system CIs of Bioclate (89.5 IU/ml) with and without heparin were sampled and cultured over a 6 day period. Bioclate (53.7 IU/ml) with and without heparin or vancomycin was inoculated with 102-105 CFU/ml of S. aureus, S. epidermidis, Escherichia coli, E. cloacae, or Y. enterocolitica and assessed by quantitative culture after 1 and 3 days. The stability of Bioclate (50, 100, and 250 IU/ml) at three temperatures (21 degrees C, 37 degrees C, and 39 degrees C) with and without heparin or vancomycin was tested over a period of 28 days. FVIII activity was measured in triplicate by a chromogenic assay (Coamatic Factor VIII, Chromogenix) and purity evaluated by Western blot. No bacterial growth was detected during CI of FVIII for up to 6 days. Following bacterial inoculation, there was rapid growth (>3 log increase) of all tested bacterial species except S. aureus which only displayed a 1 log expansion at 3 days. The addition of heparin containing 9.45 microg/U benzyl alcohol had no effect on bacterial growth. The addition of vancomycin caused a modest suppression of S. aureus growth but not of E. coli. Diluent alone did not support bacterial growth. Neither concentration, increased temperature, nor the addition of heparin or vancomycin had a significant effect on FVIII activity stability. Samples retained >75% baseline activity for between 3 and 7 days, except the infusion of Bioclate 50 IU/ml plus heparin maintained at 21 degrees C which remained stable for 28 days. Western blot analysis supported the activity assay findings. Standard and concentrated preparations of Bioclate are suitable for CI when delivered by the MiniMed 404-SP minipump. Because of the observed nutritive capability of this FVIII concentrate for sustaining bacterial growth, any contamination could result in systemic infection.

Adenovirus infection after pediatric bone marrow transplantation.

Retrospective analysis of 206 patients undergoing 215 consecutive bone marrow transplants (BMT) at St Jude Children's Research Hospital between November 1990 and December 1994 identified 6% (seven male, six female) with adenovirus infection. The affected patients had a median age of 7.9 years (range 3-24 years) at time of transplantation. Although transplants were performed for hematologic malignancies, solid tumors or nonmalignant conditions, only patients with hematologic malignancies had adenoviral infections. Adenovirus was first detected at a median of 54 days (range -4 to +333) after BMT. Adenovirus developed in eight of 69 (11.6%) patients receiving grafts from matched unrelated or mismatched related donors, in four of 52 (7.7%) receiving grafts from HLA-matched siblings, and in one of 93 (1.1%) receiving autografts. The most common manifestation of adenovirus infection was hemorrhagic cystitis, followed by gastroenteritis, pneumonitis and liver failure. The incidence of adenovirus infection in pediatric BMT patients at our institution is similar to that reported in adult patients. Using univariate analysis, use of total body irradiation and type of bone marrow graft were significant risk factors for adenovirus infection. Only use of total body irradiation remained as a factor on multiple logistic regression analysis.

Viridans streptococcal isolates from patients with septic shock induce tumor necrosis factor-alpha production by murine macrophages.

Viridans streptococci are an important cause of bacteremia and septic shock in neutropenic patients, especially patients receiving chemotherapeutic agents that induce severe mucositis. The mechanisms by which viridans streptococci cause septic shock are unclear. We hypothesized that septic shock due to viridans streptococci is attributable to host cytokine production. Three clinical isolates of viridans streptococci were evaluated for their ability to induce production of tumor necrosis factor-alpha (TNF-alpha) by RAW 264.7 murine macrophages. These three strains of viridans streptococci induced TNF-alpha in a dose-dependent fashion, and the kinetics of TNF-alpha induction were similar to those observed with a clinical isolate of Escherichia coli.

The role of esophagoscopy in diagnosis and management of esophagitis in children with cancer.

Esophagitis is a common complication in patients treated for cancer; however, difficulty in determining its etiology on the basis of noninvasive clinical information limits the implementation of specific therapies. We reviewed our experience with esophagoscopy and biopsy as an aid in the diagnosis and management of esophagitis in children with cancer. Of eleven episodes of esophagitis evaluated by esophagoscopy with biopsy, four (36%) had an infectious etiology (two with Candida, one with Herpes simplex virus, and one with viridans streptococci). The absolute neutrophil count, presence of oropharyngeal colonization, and appearance of the esophagus at esophagoscopy were not predictive of the etiology of esophagitis. Esophagoscopy with biopsy affected the management of 4 (36%) patients. We believe this procedure to be a valuable aid in managing esophagitis in children with cancer by providing objective data not otherwise available to the clinician.

Use of fluoroquinolones as prophylactic agents in patients with neutropenia.

BACKGROUND: The use of fluorinated quinolone antibiotics to selectively decontaminate the gastrointestinal tract is a reasonable alternative to prevent infection in neutropenic patients. The fluoroquinolones represent ideal antibiotics with which to achieve the principles of selective decontamination by allowing colonization of anaerobes to inhibit the adherence, colonization and proliferation of potentially pathogenic aerobic flora. OBJECTIVE: This report describes the prophylactic use of fluoroquinolones in neutropenic patients. RESULTS: The majority of studies of fluoroquinolone prophylaxis in neutropenic patients have shown a reduction in documented Gram-negative bacterial infections. However, Gram-positive infections, particularly those with viridans streptococci, present a major impediment to the use of single agent prophylaxis with a quinolone. CONCLUSION: Prophylaxis with fluoroquinolones in neutropenic patients was found to be advantageous, but it must be balanced against the risk of Gram-positive infections and the potential for antibiotic resistance.

Lipoteichoic acid from viridans streptococci induces the production of tumor necrosis factor and nitric oxide by murine macrophages.

Bacterial endotoxin or lipopolysaccharide is the major proinflammatory component of gram-negative bacteria, but the components of gram-positive bacteria that trigger the inflammatory cascade are poorly understood. Lipoteichoic acid (LTA) purified from 2 strains of viridans streptococci induced the accumulation of tumor necrosis factor (TNF) mRNA and protein by the murine macrophage cell line RAW 264.7 in a dose- and time-dependent manner. Furthermore, in the presence of recombinant interferon-gamma, LTA from both strains of viridans streptococci provoked the accumulation of inducible nitric oxide (NO) synthase mRNA and the production of NO. Together these observations indicate that LTA can trigger macrophage activation and the production of TNF and NO and suggest that LTA may be an important determinant of the host inflammatory response to gram-positive infection.

Diagnostic utility of thoracentesis for neutropenic children with cancer.

Thoracentesis is a procedure often performed in children with pleural effusions to assist in diagnosis and management. Its safety and utility for immunocompromised patients with neutropenia (absolute neutrophil count, <1,500 polymorphonuclear leukocytes and band forms per microL) is unclear. We reviewed our experience over a 10-year period to evaluate the role of thoracentesis for neutropenic children with cancer who had pulmonary effusions of presumed infectious etiology. Twenty-two patients were identified, and 18 had absolute neutrophil counts of < or = 500/microL. Empirical antibiotics had been administered to 95% of these patients and antifungal agents to 72%. Two patients' cultures were positive for fungal organisms: Aspergillus terreus in one case and Candida albicans in the other. Both of these patients had been receiving antifungal therapy. Therapy was altered for these two patients plus one additional patient in whose pleural fluid tumor cells were unexpectedly found. Eight of the remaining 19 patients underwent another diagnostic procedure, yielding five additional diagnoses. In conclusion, thoracentesis is safe and should be considered as a diagnostic test for febrile neutropenic patients with pulmonary effusions of presumed infectious etiology, although more invasive tests may be warranted.

Sequence and analysis of the rpoB gene of Mycobacterium smegmatis.

The rpoB gene encodes the beta subunit of the DNA-dependent RNA polymerase of bacteria. Mutations in defined areas result in resistance to rifampin. Mycobacterium smegmatis is naturally resistant to rifampin, but analysis of the rpoB gene revealed no identifiable rifampin resistance mutations. Another mechanism of resistance may be present.