Upper airway infection and pediatric anesthesia: how is the evidence based?

Anesthesia for the child with an upper respiratory infection remains one of the most common, yet contentious, issues facing the pediatric anesthesiologist. A general lack of evidence-based research has led to disparities in the manner in which children with upper respiratory infections have been traditionally managed. More recent research, however, suggests that children with uncomplicated infections can be managed safely, given that most complications can be anticipated, recognized, and treated. This review summarizes the evolving literature regarding cancellation of surgery for the child with an upper respiratory infection, perioperative outcomes, and anesthetic management.     

Six-month outcomes associated with a brief alcohol intervention for adult in-patients with psychiatric disorders

The objective of this study was to evaluate the 6-month outcomes of a brief intervention to reduce alcohol consumption by psychiatric in-patients in the general hospital setting and following resolution of psychiatric morbidity. Patients from the psychiatric wards of three general hospitals were screened using the Alcohol Use Disorders Identification Test. Of 144 people approached who matched the study criteria, 120 (83%) people aged 18-64 years (mean 31.7) were recruited. Participants were randomized to either a brief motivational interview or an information package to reduce alcohol consumption. Alcohol consumption was assessed as total weekly consumption and categorized on Australian National Health and Medical Research Council (NH&MRC) criteria. We delivered 62 motivational interviews and 58 information packages. At the 6-month follow-up 83 (69%), participants were reassessed. Both groups had significantly reduced alcohol consumption. However, the motivation group had a significantly greater reduction in weekly consumption than the information group (F = 6.8, (1,65) p < 0.025) after controlling for age, sex, SCL-90-R GSI and alcohol dependence (and baseline alcohol consumption). A greater proportion of the motivation group compared to the information group also 'improved' in their classification on NH&MRC criteria (chi(2) = 7.3, df 1, p < 0.01). Brief interventions, especially motivational interviews, are effective in reducing alcohol use in persons with psychiatric disorders. They are effective across the mid-range of GSI severity scores for in-patients. Screening and brief interventions can and should be incorporated into the routine assessment and management in psychiatric units.     

Validity and psychometric properties of the General Health Questionnaire-12 in young Australian adolescents

BACKGROUND: The General Health Questionnaire (GHQ) is a measure of current mental wellbeing that has been extensively validated with adults. The instrument has also been used with adolescents. OBJECTIVE: (i) To assess the psychometric properties of the GHQ-12 among school students in grades 7-10; (ii) to validate it against other psychological tests; and (iii) to suggest a threshold score. METHOD: The survey was conducted in single sex and mixed schools from the state and private system in Perth, Western Australia. The survey contained the GHQ-12 and measures of anxiety, depression, self-esteem, stress, generalized self-efficacy, social desirability and negative affectivity. RESULTS: There were 336 students (female 55%) with an age range of 11-15 years (median 13). The GHQ showed good internal consistency (alpha 0.88). Girls had higher mean GHQ-12 scores than boys (F (1,326) 15.0, p < 0.001) and scores for both genders increased with school grade (F (3,326) 4.2, p < 0.01). Multiple linear regression showed that depression, anxiety, self-esteem and stress were significant independent predictors of GHQ scores. The model accounted for 68% of the variance (adjusted R 2). Screening indices were calculated by comparison with a combined depression and/or anxiety category. Threshold scores of 13/14 for males and 18/19 for females appeared optimal. General Health Questionnaire scores were compared with two criterion groups: adolescents in hospital with alcohol or drug (AOD) related problems and those with problems not related to AOD use. Only the former group had significantly higher total scores. CONCLUSIONS: The GHQ-12 showed good structural characteristics and was appropriately correlated with other measures of related traits. Overall, the GHQ-12 appears to be a valid index of psychological wellbeing in this population and was considerably shorter than some of the other instruments.     

Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin

BACKGROUND: The role of dietary components in cancer progression and metastasis is an emerging field of clinical importance. Many stages of cancer progression involve carbohydrate-mediated recognition processes. We therefore studied the effects of high pH- and temperature-modified citrus pectin (MCP), a nondigestible, water-soluble polysaccharide fiber derived from citrus fruit that specifically inhibits the carbohydrate-binding protein galectin-3, on tumor growth and metastasis in vivo and on galectin-3-mediated functions in vitro. METHODS: In vivo tumor growth, angiogenesis, and metastasis were studied in athymic mice that had been fed with MCP in their drinking water and then injected orthotopically with human breast carcinoma cells (MDA-MB-435) into the mammary fat pad region or with human colon carcinoma cells (LSLiM6) into the cecum. Galectin-3-mediated functions during tumor angiogenesis in vitro were studied by assessing the effect of MCP on capillary tube formation by human umbilical vein endothelial cells (HUVECs) in Matrigel. The effects of MCP on galectin-3-induced HUVEC chemotaxis and on HUVEC binding to MDA-MB-435 cells in vitro were studied using Boyden chamber and labeling assays, respectively. The data were analyzed by two-sided Student's t test or Fisher's protected least-significant-difference test. RESULTS: Tumor growth, angiogenesis, and spontaneous metastasis in vivo were statistically significantly reduced in mice fed MCP. In vitro, MCP inhibited HUVEC morphogenesis (capillary tube formation) in a dose-dependent manner. In vitro, MCP inhibited the binding of galectin-3 to HUVECs: At concentrations of 0.1% and 0.25%, MCP inhibited the binding of galectin-3 (10 micro g/mL) to HUVECs by 72.1% (P =.038) and 95.8% (P =.025), respectively, and at a concentration of 0.25% it inhibited the binding of galectin-3 (1 micro g/mL) to HUVECs by 100% (P =.032). MCP blocked chemotaxis of HUVECs toward galectin-3 in a dose-dependent manner, reducing it by 68% at 0.005% (P<.001) and inhibiting it completely at 0.1% (P<.001). Finally, MCP also inhibited adhesion of MDA-MB-435 cells, which express galectin-3, to HUVECs in a dose-dependent manner. CONCLUSIONS: MCP, given orally, inhibits carbohydrate-mediated tumor growth, angiogenesis, and metastasis in vivo, presumably via its effects on galectin-3 function. These data stress the importance of dietary carbohydrate compounds as agents for the prevention and/or treatment of cancer.     

Severe congenital lead poisoning in a preterm infant due to a herbal remedy

A preterm infant born to a woman with chronic lead poisoning was found to have the highest blood lead level recorded for a surviving neonate. Parenteral calcium disodium edetate, but not oral succimer, was effective in reducing the infant's lead burden in the neonatal period. An exposure assessment revealed the mother's long-term ingestion of lead-contaminated herbal tablets as the source.     

Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections

BACKGROUND: Anesthesia for the child who presents for surgery with an upper respiratory infection (URI) presents a challenge for the anesthesiologist. The Current prospective study was designed to determine the incidence of and risk factors for adverse respiratory events in children with URTs undergoing elective surgical procedures. METHODS: The study population included 1,078 children aged 1 month to 18 yr who presented for an elective surgical procedure. Parents were given a short questionnaire detailing their child's demographics, medical history, and presence of any symptoms of a URT. Data regarding the incidence and severity of perioperative respiratory events were collected prospectively. Adverse respiratory events (any episode of laryngospasm, bronchospasm, breath holding > 15 s, oxygen saturation < 90%, or severe cough) were recorded. In addition, parents were contacted 1 and 7 days after surgery to determine the child's postoperative course. RESULTS: There were no differences between children with active URIs, recent URIs (within 4 weeks), and asymptomatic children with respect to the incidences of laryngospasm and bronchospasm. However, children with active and recent URIs had significantly more episodes of breath holding, major desaturation (oxygen saturation < 90%) events, and a greater incidence of overall adverse respiratory events than children with no URIs. Independent risk factors for adverse respiratory events in children with active URIs included use of an endotracheal tube (< 5 yr of age), history of prematurity, history of reactive airway disease, paternal smoking, surgery involving the airway, the presence of copious secretions, and nasal congestion. Although children with URIs had a greater incidence of adverse respiratory events, none were associated with any long-term adverse sequelae. CONCLUSIONS: The current study identified several risk factors for perioperative adverse respiratory events in children with lulls. Although children with acute and recent URIs are at greater risk for respiratory complications, these results suggest that most of these children can undergo elective procedures without significant increase in adverse anesthetic outcomes.     

Phase I study of docetaxel and topotecan in patients with solid tumors

Purpose: Both docetaxel (DOC), a promoter and stabilizer of microtubule assembly, and topotecan (TOPO), a topoisomerase I inhibitor, have shown antitumor activity in a variety of solid tumor malignancies. This phase I trial was conducted to determine the overall and dose-limiting toxicities (DLT), the maximum tolerated dose (MTD) and the pharmacokinetics of the combination of DOC and TOPO in patients with advanced solid tumor malignancies. Methods: DOC was administered first at 60 mg/m² without G-CSF and at 60, 70, and 80 mg/m² with G-CSF by 1-h infusion on day 1 of the odd-numbered cycles (1, 3, 5, etc.) and on day 4 of the even-numbered cycles (2, 4, 6, etc.). TOPO 0.75 mg/m² was administered as a 30-min infusion on days 1, 2, 3 and 4 of each cycle. G-CSF 300 μg was administered subcutaneously (s.c.) on days 5–14. Cycles were repeated every 21 days. All patients were premedicated with dexamethasone 8 mg orally every 12 h for a total of six doses starting on the day before DOC infusion. Results: A total of 22 patients were treated. Six patients were treated in cohort I with DOC and TOPO doses of 60 and 0.75 mg/m², respectively, without G-CSF, and two patients developed DLT (febrile neutropenia). Four patients were treated in cohort II with DOC and TOPO doses of 60 and 0.75 mg/m², respectively, with G-CSF, and no DLT was observed. Four patients were treated in cohort III with DOC and TOPO doses of 80 and 0.75 mg/m², respectively, with G-CSF, and three developed DLT (febrile neutropenia). DOC was then de-escalated to 70 mg/m² and delivered with TOPO 0.75 mg/m² and G-CSF (cohort IV). Eight patients were treated at this dose level, and one DLT (febrile neutropenia) was observed. Two patients developed a severe hypersensitivity reaction shortly after the DOC infusion was started, one in cycle 1 and one in cycle 2. Both patients were removed from the study. Two patients developed severe dyspnea in the presence of progressive pulmonary metastases. Other nonhematological toxicities were mild. One patient with extensively pretreated ovarian carcinoma had a partial response, and eight patients with various solid tumor malignancies had stable disease with a median time to progression of 12 weeks (range 9–18 weeks). Administration of TOPO on days 1–4 and DOC on day 4 resulted in increased neutropenia. Conclusions: DOC 80 mg/m² given first as a 1-h infusion on day 1 with TOPO 0.75 mg/m² given as a 0.5-h infusion on days 1, 2, 3 and 4 with G-CSF was considered the MTD. The recommended phase II dose for DOC given on day 1 is 70 mg/m² with TOPO 0.75 mg/m² given on days 1, 2, 3 and 4 every 21 days with G-CSF 300 μg s.c. on days 5–14. The alternative schedule with DOC given on day 4 and TOPO on days 1–4 is not recommended. Received: 18 February 2000 / Accepted: 19 July 2000     

Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies

Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack mutations in these genes, suggesting that the so-called gene correction strategies may have broader potential than initially believed. Increasing knowledge of cancer genetics has identified these and other genes as potential targets for gene replacement therapy. Initial patient trials of p53 and BRCA1 gene therapy have provided some indications of potential efficacy, but have also identified areas of basic and clinical research that are needed before these approaches may be widely used in patient care.