Tacrolimus dosage requirements after initiation of azole antifungal therapy in pediatric thoracic organ transplantation

Azole antifungals inhibit the metabolism of tacrolimus mediated by CYP3A4. Upon initiation of azole therapy, the required dose reduction of tacrolimus is unknown. We reviewed our experience with azole antifungals in our pediatric thoracic transplant population receiving tacrolimus. Tacrolimus levels and dosage requirements were compared before and during azole therapy. Thirty-one patients received both tacrolimus and an azole antifungal (fluconazole = 9, itraconazole = 22). The tacrolimus dose was empirically reduced by approximately one-third when azole therapy was initiated. Mean tacrolimus dose requirements decreased by 68% within the first month of therapy (pre-azole: 0.27 +/- 0.14 mg/kg/day; 30 day post-azole: 0.087 +/- 0.069 mg/kg/day; p < 0.001). Despite a mean decrease in tacrolimus dose from baseline of 33, 42, and 55% on day 1, 2, and 4 of azole therapy, respectively, there was still an unintended 38% increase in tacrolimus levels during the first month of azole therapy. A calculated dose-reduction protocol of 50% on day of azole initiation, 70% on day 3, and 75% on day 14 should result in minimal mean changes in the tacrolimus levels. There was no difference in tacrolimus dose reduction between fluconazole and itraconazole groups. Azole antifungals markedly decrease tacrolimus requirements within the first few days of therapy. An initial reduction in tacrolimus dose by one-third is insufficient, and dose reduction of at least 50% upon azole initiation seems warranted. Once azole antifungal therapy is initiated, frequent therapeutic drug monitoring is required.     

Survival with hypopituitarism from congenital syphilis

Congenital syphilis continues to occur despite the advances in testing of pregnant women in many countries and the availability of penicillin since 1943. This is a report of a child with multiple systemic manifestations of congenital syphilis. This is one of the few cases of survival with pituitary involvement from congenital syphilis and the first noted case in which diabetes insipidus developed. Institution of routine testing in all countries might have prevented the severe manifestations of syphilis seen in this child.     

Effect of excisional therapy and highly active antiretroviral therapy on cervical intraepithelial neoplasia in women infected with human immunodeficiency virus

OBJECTIVE: Our purpose was to determine the rates of recurrence, persistence, and progression of cervical intraepithelial neoplasia in women who were seropositive for human immunodeficiency virus after excisional therapy with and without highly active antiretroviral therapy.Study Design: The records of 118 women with cervical intraepithelial neoplasia, 56 of whom were infected with human immunodeficiency virus and 62 of whom were not infected, were examined to compare outcomes. Demographic, behavioral, and clinical indices were analyzed. RESULTS: Of 54 women infected with human immunodeficiency virus, 31 (57.4%) had persistent or recurrent cervical intraepithelial neoplasia, in comparison with 10 (16.7%) of 60 noninfected women (P <.01). Progression occurred in 4 (16.7%) of 54 in the infected group and in 3 (5.0%) of 60 in the noninfected group (P <.05). In 21 (60.0%) of 35 infected women, in comparison with 8 (32%) of 25 noninfected women, disease persisted 6 months after diagnosis if treatment was not given (P <.05). Of 19 infected women, 10 (52.6%) had recurrent disease after treatment, compared with 2 (5.7%) of 35 noninfected women (P <.01). Risk factors for recurrence in women who were seropositive for human immunodeficiency virus included margin involvement of specimens obtained by loop electrosurgical excision (87.5% vs 20.0%l; P <.05). Exposure to highly active antiretroviral therapy, including therapy with protease inhibitors, was associated with a lower recurrence or persistence rate (17.6% vs. 70.3%; P <.05) and a lower progression rate (0% vs. 24%; P <.05). CONCLUSION: Women infected with human immunodeficiency virus had high rates of recurrent and persistent cervical intraepithelial neoplasia despite standard therapy. Low CD4(+) levels and margin involvement of specimens obtained by loop electrosurgical excision are risk factors for recurrence. The use of highly active antiretroviral therapy is associated with a lower risk of recurrence, persistence, and progression of cervical intraepithelial neoplasia.     

Bacterial transfer and cross-contamination potential associated with paper-towel dispensing

BACKGROUND: The role of hands in disease transmission is well established, and the importance of handwashing is recognized. However, the exits of paper-towel dispensers used in hand drying may be contaminated, and the functionality of handwashing equipment increasingly is being questioned. OBJECTIVES: We sought to study the transfer and cross-contamination potential between hands, towels, and dispenser exits if one or more is contaminated using bacteria representative of the skin's flora. MATERIALS AND METHOD: A generic wall-mounted paper-towel dispenser and a range of different paper towels were used. Volunteers with either clean or contaminated hands were asked to remove, using a range of protocols, towels from dispensers which themselves were either clean or contaminated. Previously clean surfaces were then microbiologically tested. RESULTS: Recoverable bacterial transfer rates from a contaminated hand to clean dispenser exits ranged from 0.01% to 0.64% depending on the bacteria used with an even higher transfer rate for clean towels. The reverse transfer (ie, from contaminated exits to clean hands) was between 12.4% and 13.1%. CONCLUSIONS: The results indicate that zig-zag transfer of bacteria between paper-towel dispensers and hands can take place if either one is contaminated. This potential should be considered in the design, construction, and use of paper-towel dispensers.     

Environmental surface cleanliness and the potential for contamination during handwashing

Effective handwashing (including drying) is important in infection control. The ability of the various stages of handwashing to decrease skin-surface microbial counts has been documented. However, an important element, environmental surface cleanliness, and the potential for contamination of hands during the process has not been well studied or quantified. An examination of the adenosine triphosphate (a measure of residual organic soil), bacterial, and staphylococcal load on ward handwash station surfaces, which could be touched during handwashing, is reported. Hand contact surfaces tested consisted of approximately 620 each of: faucet handles, soap dispenser activator mechanisms, and folded paper-towel dispenser exits. Failure rates in excess of benchmark clean values were higher with adenosine triphosphate assays than microbial counts. This could indicate the presence of a higher level of general organic debris (eg, skin cells) as opposed to microbial contamination or could reflect greater assay sensitivity. Faucet handles were more likely to be contaminated and be in excess of benchmark values than paper-towel dispenser exits. However, the latter are likely to be the final surface touched during the handwashing process and overall nearly 20% were above microbiologic benchmark values. Many of the organisms isolated were staphylococci and the results are discussed within the context of microbial cross-contamination and potential pathogen spread.     

Reboxetine: a review of efficacy and tolerability

Clinical data on the efficacy and tolerability of the novel selective noradrenergic reuptake inhibitor reboxetine are reviewed. Reboxetine appears to have almost no pharmacological activity other than potently blocking the reuptake of noradrenaline. Clinical studies show reboxetine to be highly effective for the treatment of major depression. Reboxetine is more effective than placebo and comparable in efficacy to tricyclic antidepressants and selective serotonin reuptake inhibitors. Some studies suggest that reboxetine may have slightly better efficacy than fluoxetine and imipramine. Reboxetine is effective in severely depressed patients as well as elderly depressed persons. Reboxetine is remarkably well tolerated, having very few side effects. Reboxetine appears to cause little sexual dysfunction. The most common side effects are dry mouth and constipation. The drug does not inhibit or induce hepatic cytochrome P450 enzymes and is safe in overdose. Reboxetine may prove to be as effective and better tolerated than any other antidepressant currently available.     

The FLK2/FLT3 ligand synergizes with interleukin-7 in promoting stromal- cell-independent expansion and differentiation of human fetal pro-B cells in vitro

The effects of a novel cytokine FLK2/FLT3 ligand (FL) on human fetal bone marrow-derived CD34+CD19+ pro-B cells were analyzed in a stromal- cell-independent, serum-deprived culture system. FL, like interleukin-3 (IL-3), synergized with IL-7 in promoting pro-B cell growth, and differentiation of these cells into CD34-CD19+clgM+slgM- pre-B cells, whereas a small proportion of these cells even differentiate into more mature slgM+ B cells. In contrast, KIT ligand (KL) and granulocyte- macrophage colony-stimulating factor (GM-CSF) were ineffective in promoting IL-7-dependent pro-B cell growth and differentiation. Maximal levels of pro-B cell expansion, generally resulting in 15- to 30-fold increases in cellularity, were obtained in cultures supplemented with optimal doses of FL + IL-7 + IL-3. The addition of mouse bone marrow stromal cells further enhanced the proliferation and differentiation of pro-B cells obtained in the presence of these three cytokines. Under these conditions, cultures could be maintained for more than 4 weeks, and in general 40- to 50-fold increases in cell numbers were observed by 3 weeks of culture. The percentages of clgM+ and slgM+ B cells increased 1.5- to 3-fold and 2-fold, respectively, suggesting that stromal cells may provide additional costimulatory signals for human B- cell growth and differentiation that are different from IL-7, IL-3, and FL. Collectively, our results indicate that FL, in contrast to KL, strongly promotes long-term expansion and differentiation of human pro- B cells in the presence of IL-7 or in combination of IL-7 and IL-3, which is a novel property of this hematopoietic growth factor.     

Obstetric and nonmalignant gynecologic bleeding: treatment with angiographic embolization

Eight patients (seven post partum, one post abortion) with massive pelvic hemorrhage related to pregnancy and one patient with uncontrollable bleeding following a cervical biopsy underwent angiography to facilitate the identification and treatment of bleeding sites. In all nine patients pelvic hemorrhage was successfully controlled with embolization under angiographic guidance. Angiographic embolization allowed preservation of the uterus in six patients referred prior to hysterectomy, and one patient subsequently became pregnant. When conservative measures and minor surgical repairs have failed, embolization should be the next step in the treatment of postpartum hemorrhage to avoid major surgery in an unstable patient and to maintain reproductive function.     

Managing chronic conditions for elderly adults: the VNS CHOICE model

Chronic illness combined with functional impairment often results in an increased need for medical care and supportive long-term care (LTC) services. Navigating the health care system is challenging and complex, and even more so for patients with complex needs. Traditional fee-for-service care does not support and facilitate coordination and collaboration between providers and service settings. In New York State, managed LTC, a model of coordinated care for the chronically ill, endeavors to provide a bridge between primary, acute, home and community-based, and institutional LTC services for a medically complex and functionally frail nursing home eligible population.