Pretreatment with small-dose ketamine reduces withdrawal movements associated with injection of rocuronium in pediatric patients

We evaluated the pretreatment of small-dose of ketamine or normal saline in the reduction of withdrawal movements induced by rocuronium injection. One-hundred pediatric patients (aged 1-6 yr) were randomly assigned into 2 groups. A 22-gauge IV cannula was inserted into the dorsum of the hand, and ketamine 0.2 mg/kg or normal saline was given, followed by a 5 mg/kg thiopental injection 10 s later. IV rocuronium (0.8 mg/kg) was injected over 5 s. The patient's response to rocuronium injection was graded by using a four-point scale in a double-blinded manner. We observed that the incidence of withdrawal movements was 83% in the saline group and 27% in patients pretreated with ketamine (P < 0.05). Some patients in both groups developed skin erythema at the site of injection. We conclude that pretreatment with small-dose ketamine significantly attenuates withdrawal movements associated with IV injection of rocuronium in pediatric patients anesthetized with thiopental. IMPLICATIONS: Pretreatment with small-dose ketamine 0.2 mg/kg provides a simple and safe means of reducing the incidence of withdrawal movements induced by the injection of rocuronium, a short-acting nondepolarizing muscle relaxant.     

Reversal of the effect of albumin on gut barrier function in burn by the inhibition of inducible isoform of nitric oxide synthase

HYPOTHESIS: The use of albumin in the early resuscitation formula after major burn has been forbidden because of its damaging effect on the gut barrier function. We hypothesize that inhibition of the inducible isoform of nitric oxide synthase to stabilize endothelial permeability and to retain albumin in the vascular space will ameliorate the major trauma-induced gut barrier dysfunction. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: In experiment 1, specific pathogen-free rats undergoing 35% total body surface area burn or sham burn were given equal volumes (7.5 mL/kg) of isotonic sodium chloride solution or albumin from femoral veins for fluid resuscitation at 0, 4, or 8 hours after burn. In experiment 2, intraperitoneal S-methylisothiourea sulfate (7.5 mg/kg) was given immediately after burn to rats from different groups, as in experiment 1 (SMT groups). At 24 hours after burn, the intestinal mucosa was assayed for myeloperoxidase activity as an index for neutrophil sequestration, the distribution of fluorescein isothiocyanate-dextran across the lumen of small intestine was determined to evaluate the intestinal permeability, and bacterial translocation (BT) to the mesenteric lymph nodes (MLNs) and histological findings in the ileum were also examined. RESULTS: Compared with sham burn, burn induced significant increases in intestinal mucosa myeloperoxidase activity, intestinal permeability, BT to the MLNs, and villi sloughing in rats. Albumin administration at 0 or 4 hours after burn enhanced the increases in neutrophil sequestration, permeability, and villi sloughing compared with saline injection at the same times. In contrast, injection of albumin in the burn-SMT group did not aggravate these changes in intestinal myeloperoxidase activity, intestinal permeability, BT to the MLNs, and villi edema. Burn-SMT rats with albumin injections at 4 or 8 hours after burn showed significant 35% and 52% decreases, respectively, in intestinal permeability compared with burn-SMT-saline rats. Use of albumin at 8 hours after burn in combination with S-methylisothiourea significantly attenuated BT to the MLNs and reduced villi edema. CONCLUSIONS: Early albumin resuscitation aggravated the burn-induced gut damage. Albumin administration and inhibition of the inducible isoform of nitric oxide synthase in combination decreased burn-induced gut barrier dysfunction and reversed the damaging effect of albumin on gut barrier function and decreased BT.     

Significance of intraoperative peritoneal culture of fungus in perforated peptic ulcer

BACKGROUND: The incidence of postoperative fungal infection is increasing and the gastrointestinal tract is the major source, but antifungal therapy in perforated peptic ulcer (PPU) is still controversial. The aim of this study was to determine the significance of intraoperative peritoneal fluid culture of fungus and establish the indications for treatment. METHODS: Between July 1997 and September 2001, all patients admitted with a PPU were studied. Clinical data and peritoneal fluid for culture were collected. Risk factors for a positive peritoneal fluid culture of fungus and outcome were evaluated, and related to the development of surgical site infection, duration of hospital stay and mortality rate. RESULTS: One hundred and forty-five patients with a PPU were included; 63 (43.4 per cent) had positive peritoneal fluid fungal culture. Age, preoperative organ failure, delay in operation, high Mannheim Peritonitis Index (MPI) and Acute Physiology And Chronic Health Evaluation (APACHE) II scores, and preoperative antibiotic therapy were risk factors for a positive fungal culture. Sex and an MPI score of 20 or more remained significant in multivariate analysis (P < 0.001). Patients with a positive fungal culture had a higher incidence of surgical site infection, a longer hospital stay and a significantly higher mortality rate, especially when this was combined with a high MPI score. CONCLUSION: Positive peritoneal fungal culture was common and was a significant risk factor for adverse outcome in patients with a PPU. A high MPI score could be used as an indicator for prophylactic antifungal therapy.     

Inhibition of hypoxia inducible factor 1alpha causes oxygen-independent cytotoxicity and induces p53 independent apoptosis in glioblastoma cells

PURPOSE: Hypoxia, which activates the hypoxia inducible factor-1 alpha (HIF-1alpha) pathway, is a common feature in malignant gliomas and has been linked with tumor cell survival and therapy resistance. In this study, we examined the effect of antisense inhibition of HIF-1alpha on the survival, apoptosis and responses to chemotherapy in U-87 malignant glioma cells. MATERIALS AND METHODS: Hypoxia (1% oxygen) was achieved in a tri-gas incubator with intermittent N(2) gas flushing or in a gas tight-module sealed with 94% N(2), 1% O(2) and balance CO(2). HIF-1alpha inhibition was achieved with antisense phosphorothioate oligodeoxynucleotide (AS-HIF ODN), delivered using cytofectin GSV3815. HIF-1alpha expression level was monitored by a hypoxia-responsive luciferase reporter assay and verified by northern blot and immunoblot analyses. Cell viability was quantified by a colorimetric microtiter plate MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. Apoptotic cell death was detected with a colorimetric caspase-3 assay, as well as using terminal transferase-catalyzed in situ end labeling (TUNEL) staining. RESULTS: Antisense HIF-1alpha phosphorothioate oligodeoxynucleotide (AS-HIF ODN) treatment suppressed HIF-1alpha expression by up to 80% under both normoxic and hypoxic conditions as measured by a hypoxia-responsive reporter assay and confirmed by northern and western blot analyses. Antisense knockdown of HIF-1alpha resulted in significant reduction in U-87 cells survival and an acceleration of apoptosis, which did not involve p53 transactivation. Pretreatment of cells with Z-Val-Ala-Asp (-OCH(3))-fluoromethylketone (Z-VAD), a broad-spectrum caspase inhibitor largely eliminated this effect of AS-HIF. Caspase-3 specific activity was markedly induced 3 days after AS-HIF treatment when increased cell death was also noted. Transient overexpression of HIF-1alpha in U-87 cells neutralized apoptosis-inducing effect of AS-HIF. AS-HIF treatment did not affect viability of primary astrocytes and was selectively more toxic to U-87 glioma cells than normal human fibroblasts. The HIF-1alpha antisense treatment exerted an oxygen-independent, and additive but not synergistic effect to the cytotoxicity of cisplatin, etoposide, and vincristine. CONCLUSIONS: These results together indicate that suppression of HIF-1alpha-expression may be a promising strategy that is selective for reducing the survival and facilitating chemotherapeutic efficacy of malignant glioma.     

Low-dose thalidomide treatment for advanced hepatocellular carcinoma

OBJECTIVE: To analyze the efficacy of oral thalidomide in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: Sixty-eight patients with unresectable and nonembolizable HCC were consecutively enrolled in a compassionate treatment program of oral thalidomide. Tumor response and treatment-related toxicity were prospectively followed. Thalidomide was given at a starting dose of 200 mg per day. The dose was gradually escalated in 100-mg steps up to 600 mg per day if no limiting toxicities developed. RESULTS: Sixty-three patients were evaluable for response. One complete and 3 partial responses, defined by World Health Organization criteria, were seen, with a response rate of 6.3% (95% CI 0-12.5). The duration of response was 50+, 24.6, 11.6+ and 8.7+ weeks, respectively. All 4 responders had a dramatic decrease in alpha-fetoprotein (alpha-FP) levels. Another 6 of the 42 patients with elevated alpha-FP levels before treatment had a more than 50% decrease in their alpha-FP levels after thalidomide treatment. Totally 10 patients had an objective response to thalidomide. The median overall survival for all of the 68 patients was 18.7 weeks (95% CI 11.8- 25.6) with a 1-year survival rate of 27.6%. The median overall survival of the 10 patients with an objective response to thalidomide was 62.4 weeks (95% CI 31.2-93.6 weeks). All responders responded at a dose equal to or less than 300 mg per day. Toxicities of thalidomide were generally manageable, and only 16, 6, and 0 patients developed grade 2, 3, and 4 toxicities, respectively. CONCLUSION: Low-dose thalidomide is safe and induces unequivocal tumor response in a minority of patients with advanced HCC.     

A novel method for single cell detection of in situ telomerase or histone H3 in combination with clonal analysis by FISH

A novel method for simultaneously detecting clonality by FISH, and presence of telomerase activity (telo+ cells) or histone H3 mRNA (H3+) in single cells from a mixed leukemic population is reported. The methods were validated using K562 cells mixed with peripheral blood granulocytes and bone marrow aspirate cells from newly diagnosed AML patients. Fifty patients with AML were analyzed for telo+ cells, while eight AML patients were analyzed for FISH-Telomerase and FISH-H3+ during remission induction therapy. Our results demonstrate that: (1). changes in the leukemic populations during therapy could be followed; (2). a favorable response to chemotherapy occurred when there was a reduction in both the cytogenetically abnormal cells along with reduction in telo+ cells within this abnormal population; (3). reduction of either telo+ cells or FISH+ cells alone did not correlate with good response. H3+ could be detected in only 4% of the leukemic population, most of which were cytogenetically abnormal. These newly established methods allow sub-populations of cells to be followed during disease progression and treatment and to elucidate factors that give a specific clone proliferative advantage.     

Implicit exchanges in family caregiving for frail elders in Taiwan

In this study, the authors use in-depth interviews with inductive analysis to develop a conceptual framework for exploring social exchanges and their implicit calculations for caregivers in Taiwan. They interviewed 12 caregivers, based on theory-based sampling and maximum variation. They found some components of implicit exchanges of the caregivers, and drew a framework to describe it. At the beginning of care, motivations were mostly from obligation accompanied by reciprocity or repaying motives. In the process of caregiving, some unique, implicit cultural implicit exchanges were found, such as karma, a demonstrative behavior to investment, equitable share of responsibility, and the pressure or rewards from public opinion. These implicit exchanges might be intermediary factors in helping caregivers cope with their burden or even in influencing their continuation of care. The findings are implicated to help family caregivers continue their care and not damage their quality of care.     

Severe acute respiratory syndrome: lessons from Singapore

An outbreak of severe acute respiratory syndrome (SARS) occurred in Singapore in March 2003. To illustrate the problems in diagnosing and containing SARS in the hospital, we describe a case series and highlight changes in triage and infection control practices that resulted. By implementing these changes, we have stopped the nosocomial transmission of the virus.An outbreak of severe acute respiratory syndrome (SARS) was first recognized in Singapore on March 12, 2003. The index patient was hospitalized at Tan Tock Seng Hospital, which has since become the country’s designated SARS hospital. The patient infected 20 other people (including patients and healthcare workers), who subsequently became the sources for secondary spread of the infection (1). As of June 12, 2003, a total of 206 cases and 31 deaths attributed to SARS had been reported in Singapore.We describe the important lessons learned during the triage and containment of SARS at the National University Hospital, Singapore. Both involved expanding isolation criteria to include all patients with undifferentiated fever (even in the absence of respiratory symptoms or chest x-ray changes), improving contact-tracing methods, enforcing the use of fit-tested personal protective equipment in all patient-care areas, avoiding aerosol-generating procedures, and carefully monitoring all healthcare workers for fever or respiratory symptoms. We also highlight the impact of these measures on preventing the entry and nosocomial spread of infection.