Predictors of adverse outcome from candidal infection in a tertiary care hospital.

OBJECTIVES: To retrospectively delineate predictors of adverse outcome by looking at the demographic features, therapy and outcome of systemic candida infection in a large tertiary care university-affiliated medical center. METHODS: We reviewed the clinical data on 186 inpatients with candidemia over a 6-year period. The major reason for their hospital admission was an underlying malignancy or an infection other than candidemia. RESULTS: Candida albicans, tropicalis, parapsilosis, glabrata and krusei caused 54, 22, 13, 8 and 3% of the candidemia episodes, respectively. The overall mortality was 42% and it was highest in patients suffering from candidemia of the glabrata species (73%). Forty-eight (63%) of the 76 patients who received no anti-fungal treatment died compared to 38 (34%) of 110 patients who were treated (P < 0.05). Predictors of adverse outcome were intensive care unit stay, renal failure, thrombocytopenia and the need for mechanical ventilation or inotropic support. CONCLUSIONS: We identified four predictors of mortality from candidemia infection. Their validity should be further assessed and the specific candida strains and their susceptibility need to be methodically identified. Our data support immediate initiation of therapy at first identification of infection.

Invasive group A streptococcal infections in a large tertiary center: epidemiology, characteristics and outcome.

BACKGROUND: Invasive group A streptococcal (GAS) infections are increasing alarmingly worldwide. PATIENTS AND METHODS: To determine the clinical and epidemiologic characteristics of invasive GAS in a large tertiary medical center, we retrospectively surveyed microbiology and medical records of patients with invasive GAS infections (isolation of Group A Streptococcus from a normally sterile site) treated in our hospital from January 1995 to December 1997. RESULTS: 70 patients with a median age of 48 years (range 2 months-88 years) were identified. Of the 70 identified, 53 (76%) were adults (age > or = 19 years). The most common co-morbid diseases for invasive GAS in adults were diabetes mellitus, congestive heart failure (CHF), malignancy and immunosuppression. A probable port of entry was identified in 31 (44%) of the cases. In children, varicella lesions were the major port of entry. Overall mortality rate was 17%: The difference in mortality between pediatric and adult cases was significant (0/17 vs 12/53, respectively; p = 0.03). Toxic shock syndrome (TSS) and necrotizing fasciitis were identified in 8.6% and 5.7% of the cases, respectively, with mortalities of 83.3% and 25%. Hyponatremia and hypocalcemia were more frequently observed among the severely ill. CONCLUSION: Invasive GAS infections tend to have an unexpected course and a broad clinical spectrum, ranging from local skin or pharyngeal involvement to deeply invasive fasciitis with TSS and high mortality. The elderly and those with underLying medical conditions are at utmost rsk for invasive GAS. Clear-cut guidelines for early therapeutic strategy, i.e. antibiotic administration and preemptive hospital admission are needed for community-based physicians.

Acute respiratory distress syndrome in children with malignancy--can we predict outcome?

PURPOSE: The purpose of this study was to delineate early respiratory predictors of mortality in children with hemato-oncology malignancy who developed acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: We conducted a retrospective chart review of children with malignant and ARDS who needed mechanical ventilation and were admitted to a pediatric intensive care unit from January 1987 to January 1997. RESULTS: Seventeen children with ARDS and malignancy aged 10.5 +/- 5.1 years were identified. Six of the 17 children (35.3%) survived. Sepsis syndrome was present in 70.6% of all the children. Peak inspiratory pressure, positive end-expiratory pressure (PEEP), and ventilation index values could distinguish outcome by day 3. A significant relationship between respiratory data and outcome related to efficiency of oxygenation, as determined by PaO(2)/FIO(2) and P(A-a)O(2), was present from day 8 after onset of mechanical ventilation. CONCLUSIONS: Peak inspiratory pressure, PEEP, and ventilation index values could distinguish survivors from nonsurvivors by day 3. This may assist in early application of supportive nonconventional therapies in children with malignancy and ARDS.

Beta-chemokine secretion patterns in relation to clinical course and outcome in children after cardiopulmonary bypass: continuing the search to abrogate systemic inflammatory response.

BACKGROUND: Surgery involving cardiopulmonary bypass (CPB) is frequently accompanied by a systemic inflammatory response partly triggered by neutrophils and monocyte-macrophages. Certain cytokines that are powerful leukocyte-chemotactic factors have recently been characterized and shown to be important in evoking inflammatory responses: monocyte chemoattractant protein-1 (MCP-1) has monocyte-macrophage chemotactic activity, and regulated-upon-activation normal T-cell expressed and secreted (RANTES) has a potent chemoattractant activity for mononuclear phagocytes. This prospective cohort study investigated possible roles of these chemokines in the inflammatory response to CPB and relationships between the changes in chemokine levels and the clinical course and outcome. METHODS: Systemic blood of 16 children undergoing CPB was collected after induction of anesthesia (base line); at 15 minutes after bypass onset; at CPB cessation; and at 1, 2, 4, 8, 12, and 24 hours afterward to measure MCP-1 and RANTES. RESULTS: The significant changes of plasma beta chemokine levels following CPB were associated with patient characteristics, operative variables, and postoperative course. Cardiopulmonary bypass of more than 2 hours, longer surgical times, inotropic support, and reoperation were associated with higher MCP-1 levels and lower RANTES levels. CONCLUSIONS: Our results suggest a relation between CPB-induced mediators and clinical effects, implying pathogenic roles for chemokines following CPB. These molecules should be considered as possible targets for therapeutic intervention.

Metabolic and clinical markers of prognosis in the era of CT imaging in children with acute epidural hematomas.

Acute epidural hematoma (AEH), a relatively common complication of head injury in children, persists in bearing high morbidity and mortality. Early establishment of prognosis could guide optimal patient allocation, and early identification of predictive signs could assist in choosing appropriate therapeutic interventions. This study aimed to delineate expeditiously obtainable prognostic markers for determining outcome in a subset of children with AEH. We reviewed our 11-year experience with 61 consecutive children <16 years old with head trauma and isolated AEH. Treatment followed a standard advanced trauma life support protocol. A medical history was obtained, and all patients underwent neurosurgical and physical evaluations. CT scans were performed, as were laboratory tests which included arterial blood gases, glucose, electrolytes (K(+), Na(+)), hemoglobin and coagulation studies. Evaluation of the data collected on cause of injury, interval between trauma occurrence and presentation, clinical symptoms, Glasgow Coma Scale (GCS) scores, vital signs, laboratory test results, physical findings and surgical versus conservative management revealed that the best single predictors of outcome following AEH were the GCS and focal neurological deficits. Of all laboratory data obtained on admission, the blood potassium, pH and glucose test results correlated significantly with prognosis. Prognosis can be adequately and expeditiously estimated by selected markers within a comprehensive evaluation of children with AEH.

Negatively charged quantum well polaritons in a GaAs/AlAs microcavity: An analog of atoms in a cavity

The negatively charged exciton (X-) is observed to strongly couple with the microcavity- (MC-)confined photons in a GaAs quantum well containing a two-dimensional electron gas with 0

Adapting prognostic respiratory variables of ARDS in children to small-scale community needs.

PURPOSE: The clinical literature on the incidence and subsequent mortality of adult respiratory distress syndrome (ARDS) has come primarily from the experiences of large tertiary referral centers, particularly in Western Europe and North America. Consequently, very little has been published on the incidence, management, and outcome of ARDS in smaller community-based intensive care units. We aimed to delineate early clinical respiratory predictors of death in children with ARDS on the modest scale of a community hospital. MATERIALS AND METHODS: A retrospective chart review of children with ARDS needing conventional mechanical ventilation admitted to our pediatric intensive care unit from 1984 to 1997. The diagnosis of ARDS was based on acute onset of diffuse, bilateral pulmonary infiltrates of noncardiac origin and severe hypoxemia defined by partial pressure of oxygen <200 mm Hg during positive end-expiratory pressure (PEEP) of 6 cm H2O or greater for a minimum of 24 hours. Demographic, clinical, and physiological data including PaO2/ FIO2, A-aDo2, and ventilation index were retrieved. RESULTS: Fifty-six children with ARDS aged 8 +/- 5.5 years (range, 50 days to 21 years) were identified. The mortality rate was 50%. Early predictors of death included the peak inspiratory pressure (PIP), ventilation index, and PEEP on the third day after diagnosis: Nonsurvivors had significantly higher PIP (35.3 +/- 10.5 cm H2O vs 44.4 +/- 10.7 cm H2O, P < .001), PEEP (8 +/- 2.8 cm H2O vs 10.7.0 +/- 3.5 cm H2O, P < .01), and ventilation index (49.14 +/- 20.4 mm Hg x cm H2O/minute vs 61.6 +/- 51.1 mm Hg cm H2O/minute) than survivors. In contrast, PAO2/FIO2 and A-a DO2 were capable of predicting outcome by day 5 and thereafter. CONCLUSIONS: A small-scale mortality outcome for ARDS is comparable to large tertiary referral institutions. The PIP, PEEP, and ventilation index are valuable for predicting outcome in ARDS by the third day of conventional therapy. The development of a local risk profile may assist in decision-making of early application of supportive therapies in this population.

Early prediction of neurological outcome after falls in children: metabolic and clinical markers.

Falls are the foremost reason for non-fatal injuries and are second only to motor vehicle accidents in causing accidental death. The purpose of this study was to identify the clinical and metabolic predictors of the outcome of head injury caused by falls from a height. Medical records of 61 children who had been admitted to the paediatric intensive care unit from 1990 to 1993 after falling from a height were reviewed retrospectively. Outcomes were categorised as good, moderate, severe, and poor. Glasgow coma scores, pupillary responses, brain oedema, and midline shift are significantly associated with poor outcome (p < 0.05). Metabolic markers associated with poor outcome included hyperglycaemia and hypokalaemia. Children with a poor outcome had, at admission, significantly higher glucose concentrations compared with children with good outcomes (mean SD): 20.0 (7.1) v 9.31 (4.0) mmol/l, p < 0.01), and lower potassium concentrations compared with children with good, moderate, and severe outcomes (mean (SD): 2.8 (0.4) v 3.7 (0.4) mmol/l, p < 0.001, 3.5 (0.3) mmol/l, p < 0.01, and 3.41 (0.3) mmol/l, p < 0.05, respectively). These findings allow for an early allocation of effort and resources to children injured from such falls.

[Head injuries in children--clinical characteristics as prognostic factors].

An unselected series of 200 consecutive cases of major head trauma in children aged 6 months to 16 years, seen during 4 years, was studied. Injuries were due to road accidents (40%), falls (30.5%) and other causes (29.5%), and were assessed clinically and by cranial CT. On admission the Glasgow Coma Score ranged from 4.72-11.65 and in addition to pupillary responses and brain stem reflexes, was a significant predictor of outcome. Brain edema, midline shift, intracranial hemorrhage and also hyperglycemia, hypokalemia and coagulopathy, were associated with poor outcome. While 17% died, 53% were discharged in good functional condition. Early identification of clinical features related to prognosis can help the caring team provide maximal support for patient and family.

A newly-synthesized GPI-anchored protein, TAG-1/axonin-1, is inserted into axonal membranes along the entire length of the axon and not exclusively at the growth cone.

Evidence exists that some newly-synthesized membrane components are inserted into the membrane of the growing axon at the growth cone. We now examine the site of insertion of a glycosylphosphatidylinositol-anchored protein, TAG-1/axonin-1. The protein was cleaved from the plasma membrane by phosphatidylinositol-specific phospholipase C. Newly-synthesized TAG-1/axonin-1 was subsequently detected along the entire length of the axonal membrane, with no evidence for preferential insertion at the distal end. These results raise the possibility that different subsets of proteins are inserted at different locations in axonal membranes.

Inhibition of sphingolipid synthesis affects axonal outgrowth in cultured hippocampal neurons.

Neuronal growth is regulated by both extracellular and cellular determinants and is believed to proceed by the addition of new membrane material at the growth cone. To determine whether lipid synthesis is necessary to maintain neuronal growth, we have examined the effect of Fumonisin B1, an inhibitor of ceramide synthesis, on the development of cultured hippocampal neurons. Fumonisin B1 inhibits ceramide synthesis in hippocampal neurons both in vivo and in vitro. Ganglioside synthesis and content was reduced after Fumonisin B1 treatment, and ganglioside GD1b was not detectable at the cell surface by immunofluorescence. Inhibition of sphingolipid synthesis by Fumonisin B1 had a significant effect on axonal growth. Between days 2-3 in culture, mean axon length increased from 170 to 240 microns, but in Fumonisin-treated cells, no increase in axon length was observed. Addition of a fluorescent derivative of ceramide together with Fumonisin B1 reversed this effect, confirming that Fumonisin B1 acts via inhibition of ceramide synthase. Further, ceramide by itself caused a significant increase in axon length. We discuss three possible mechanisms by which inhibition of sphingolipid synthesis could disrupt axonal growth, among them the possibility that ongoing sphingolipid synthesis is necessary to provide new membrane material to the growing axon.

The N- and C-terminal regions regulate the transport of wheat gamma-gliadin through the endoplasmic reticulum in Xenopus oocytes.

Following sequestration into the endoplasmic reticulum (ER), wheat storage proteins are naturally either retained and packaged into protein bodies within this organelle or exported to the Golgi apparatus. To identify protein domains that control the sorting of wheat storage proteins within the ER, a wild-type gamma-gliadin storage protein as well as two of its deletion mutants, each bearing either of the two autonomous N- and C-terminal regions, were expressed in Xenopus oocytes. Our results demonstrated that the N-terminal region of the gliadin, which is composed of several tandem repeats of the consensus sequence PQQPFPQ, was entirely retained within the ER and accumulated in dense protein bodies. In contrast, the C-terminal autonomous region was efficiently secreted to the medium. The wild-type gamma-gliadin, containing both regions, was secreted at a lower rate and less efficiently than its C-terminal region. These results suggest that sorting of the wheat gamma-gliadin within the ER may be determined by a balance between two opposing signals: one functions in the retention and packaging of the storage protein within the ER, while the second renders the protein competent for export from this organelle to the Golgi apparatus.