Temporal assessment of Candida risk factors in the surgical intensive care unit.

HYPOTHESIS: Risk factors for Candida infection in surgical intensive care units (SICUs) change over time. Risk factor progression may influence Candida colonization and infection. DESIGN: Multicenter cohort survey. SETTING: Three urban teaching institutions. PATIENTS: A total of 301 consecutively admitted patients in SICUs for 5 or more days. MAIN OUTCOME MEASURES: Assessment of patients on SICU days 1, 3, 4, 6, and 8 and SICU discharge for risk factors, Candida colonization, and antifungal use. Candida colonization status was categorized as noncolonized (NC), locally colonized (LC) if 1 site was involved, and disseminated infection (DI) if 2 or more sites or candidemia were involved. RESULTS: The most frequent risk factors in the 301 patients enrolled were presence of peripheral and central intravenous catheters, bladder catheters, mechanical ventilation, and lack of enteral or intravenous nutrition. Early risk factors included total parenteral nutrition or central catheter at SICU day 1 and previous SICU admissions or surgical procedures. Peak number of risk factors (mean +/- SD) were as follows: 7.2 +/- 2.6 in NC (n = 229), 9.2 +/- 2.3 in LC (n = 45), and 9.2 +/- 2.6 in DI (n = 27). These numbers were reached at day 8 in the NC and LC groups and day 4 in the DI group. The LC and DI groups had more risk factors on each SICU day than the NC group and longer median SICU length of stay (28 days in the DI group vs 11 and 19 days in the NC and LC groups, respectively). Antifungal therapy, while used most frequently in the DI group, was initiated later for this group than in NC and LC groups. CONCLUSIONS: Risk factors for Candida infection in SICU patients change over time. Patients with DI demonstrate a greater number of and more rapid increase in risk factors than patients in the LC and NC groups. Presence of early risk factors at the time of SICU admission, a high incidence of risk factors, or a rapid increase in risk factors should prompt clinicians to obtain surveillance fungal cultures and consider empirical antifungal therapy.

Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis.

Neuropeptides are implicated in many tumors, breast cancer (BC) included. Preprotachykinin-I (PPT-I) encodes multiple neuropeptides with pleiotropic functions such as neurotransmission, immune/hematopoietic modulation, angiogenesis, and mitogenesis. PPT-I is constitutively expressed in some tumors. In this study, we investigated a role for PPT-I and its receptors, neurokinin-1 (NK-1) and NK-2, in BC by using quantitative reverse transcription-PCR, ELISA, and in situ hybridization. Compared with normal mammary epithelial cells (n = 2) and benign breast biopsies (n = 21), BC cell lines (n = 7) and malignant breast biopsies (n = 25) showed increased expression of PPT-I and NK-1. NK-2 levels were high in normal and malignant cells. Specific NK-1 and NK-2 antagonists inhibited BC cell proliferation, suggesting autocrine and/or intercrine stimulation of BC cells by PPT-I peptides. NK-2 showed no effect on the proliferation of normal cells but mediated the proliferation of BC cells. Cytosolic extracts from malignant BC cells enhanced PPT-I translation whereas extracts from normal mammary epithelial cells caused no change. These enhancing effects may be protein-specific because a similar increase was observed for IL-6 translation and no effect was observed for IL-1alpha and stem cell factor. The data suggest that PPT-I peptides and their receptors may be important in BC development. Considering that PPT-I peptides are hematopoietic modulators, these results could be extended to understand early integration of BC cells in the bone marrow, a preferred site of metastasis. Molecular signaling transduced by PPT-I peptides and the mechanism that enhances translation of PPT-I mRNA could lead to innovative strategies for BC treatments and metastasis.

Postsurgical reduction of serum lipoproteins: interleukin-6 and the acute-phase response.

In a previous retrospective study, we reported a significant reduction in serum cholesterol levels following major surgery, and speculated on the possible role of cytokines in this reduction. The purpose of this article is to report a prospective study of the association of cytokines with postoperative changes in serum lipoprotein levels. Serum samples were obtained from 11 male patients before and at intervals for up to 10 days after surgery, and were assayed for total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), cortisol, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interferon-gamma (IFN-gamma). LDL-C was calculated. The TC showed a 27.9% decrease, from a mean of 4.27 mmol/L to 3.08 mmol/L (p < 0.001) after surgery, reaching a nadir at 24 hours and returning to preoperative values in 7 to 10 days. A similar decrease was noted in the HDL-C and LDL-C levels. IL-6 levels increased from a mean baseline value of 6 pg/ml to a peak of 143 pg/ml at 24 hours (p < 0.0006). There was an inverse relationship between TC and IL-6 levels, with r = -0.51 for the entire curve and r = -0.90 for the cholesterol nadir with the IL-6 peak. The other cytokines did not show significant changes. We conclude that TC and its fractions decrease to a nadir and that IL-6 increases to a peak approximately 24 hours after major surgery. There is a significant inverse correlation between TC and IL-6, suggesting a possible role of IL-6 in postoperative changes in serum lipoproteins.

Gamma radiation-sterilized, triple-lumen catheters coated with a low concentration of chlorhexidine were not efficacious at preventing catheter infections in intensive care unit patients.

In a randomized, double-blind trial, gamma radiation-sterilized, chlorhexidine-coated triple-lumen catheters were compared with uncoated control catheters for their ability to prevent catheter infection in 254 intensive care unit patients. The chlorhexidine coating was not efficacious, and a rabbit model demonstrated that reduction of chlorhexidine activity by gamma radiation sterilization was the likely explanation for the failure.

Sepsis and multiple organ dysfunction syndrome: a clinical-mechanistic overview.

Multiple organ dysfunction syndrome (MODS) is the primary cause of death in patients admitted to ICUs. Despite the development of better resuscitation, more powerful antibiotics, and more sophisticated methods for organ support, our ability to rescue patients from established MODS has not improved significantly since the syndrome was first described two decades ago. Rapid advancements in molecular biology have begun to unravel some of the potential mechanisms behind the development of this syndrome, and have suggested many potential therapeutic approaches. To effectively use these new treatment options as they become available, it is necessary to have a clear understanding of how these therapies fit into the current theories on the pathophysiology of MODS. Thus, the goal of this article is to integrate what is new in our understanding of the development of MODS with current concepts regarding potential therapies of this complex and perplexing syndrome.

Falls: epidemiology and strategies for prevention.

Injury secondary to falls is a largely preventable public health problem. The records of 356 patients admitted following a fall to a level I trauma center over a 32-month period were reviewed to determine the epidemiology and to define possible prevention strategies. Falls constituted 9% of total trauma admissions during this time period and had a mortality of 11% (38 of 356). Two hundred ninety-seven falls were accidental, 36 were due to violent criminal behavior, 16 were from suicide attempts, and 7 were from house fires. Sixty-one children under the age of 13 fell; only one died. Falls out of windows accounted for 36% of these falls with over three-quarters of children falling from three stories or less. Elderly patients (age more than 64 years) accounted for only 44 (14%) of falls but over 50% of the deaths. This mortality rate occurred despite the fact that the majority of these falls were from relatively low heights. There were 224 adult falls (ages 18 to 64 years); 36% were occupation-related, and most were by construction workers, roofers, or painters. The remaining adult fall victims had a high rate of unemployment and alcohol and drug use. This study identified several groups where risk factors for falling permit targeted prevention strategies. A large percentage of children who fell were preschool males who fell from windows and this may be related to the lack of window guard legislation in our area.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of lymphocele and lymphatic fistula following renal transplantation by laparoscopic peritoneal window.

Symptomatic lymphoceles that occur after renal transplantation are managed best by surgical marsupialization with drainage into the peritoneal cavity. We report a case of post-transplant lymphocele associated with a cutaneous lymphatic fistula, which was successfully treated using laparoscopic drainage without a major surgical incision. With this new technique we were able to remove an ellipse of peritoneal wall along with the adjacent lymphocele wall and to lyse all internal lymphocele loculations, allowing for the free flow of lymph into the peritoneal cavity and cessation of cutaneous leakage. We believe that, when technically possible, laparoscopic internal peritoneal drainage is an effective procedure for managing simple and complex symptomatic lymphoceles with or without associated lymphatic fistulas, provided there is no evidence of infection.

Fecal steroid 21-dehydroxylase, a potential marker for colorectal cancer.

Eubacterium lentum and phenotypically similar organisms synthesize a steroid 21-dehydroxylase which converts biliary tetrahydrodeoxycorticosterone to pregnanolone. Tetrahydrodeoxycorticosterone, in contrast to pregnanolone, is carcinogenic for hamster embryonic cells (HECT test). In patients with recently diagnosed, untreated sigmoidal or rectal cancer the fecal concentration of 21-dehydroxylating organisms is reduced by more than 99% as compared with age-matched controls. The lack of fecal 21-dehydroxylating organisms, therefore, is a potential marker for the disorder. The role of steroid 21-dehydroxylase in the pathogenesis of colorectal cancer is unknown.

Location of Campylobacter jejuni in infected chicken livers.

To determine whether chicken livers infected with Campylobacter jejuni are seeded in vivo or contaminated after slaughtering, 117 livers purchased in retail outlets in New York were examined for surface and tissue infections. Of 56 livers positive for C. jejuni, 36 yielded surface growth only, 18 both surface and tissue growth, and 2 tissue growth only. The scanty growth from tissue samples suggests a carry-over of organisms from the surface. It was concluded, therefore, that contamination is most likely due to unhygienic handling of offal. Infection rates of livers varied from retailer to retailer.

In vitro susceptibility of Campylobacter fetus subsp. jejuni to N-formimidoyl thienamycin, rosaramicin, cefoperazone, and other antimicrobial agents.

The activities of 11 antimicrobial agents against 36 strains of Campylobacter fetus subsp. jejuni were studied by a broth microdilution method. All strains were susceptible to 7 of the 11 antimicrobial agents. Of the newer agents tested N-formimidoyl thienamycin (MK0787) and rosaramicin had very good activity, whereas cefotaxime, moxalactam, and cefoperazone had poorer activity.