Effectiveness of the Kids in Control of Food (KICk-OFF) structured education course for 11-16 year olds with Type 1 diabetes.

AIM: To assess the effect of a 5-day structured education course (Kids in Control of Food; KICk-OFF) on biomedical and psychological outcomes in young people with Type 1 diabetes. METHODS: This was a cluster-randomized trial involving 31 UK paediatric centres. Participants were recruited prior to stratified centre randomization. Intervention centres delivered KICk-OFF courses, whereas control centres delivered usual care. Participants were 11-16 years of age and had Type 1 diabetes for at least one year. The KICk-OFF course was delivered by trained educators to eight participants per course. Glycaemic control and quality of life were measured at baseline, 6, 12 and 24 months. Secondary outcomes were hypoglycaemia, ketoacidosis, fear of hypoglycaemia and diabetes self-efficacy. RESULTS: Three hundred and ninety-six participants provided baseline data (199 intervention and 197 control). At 6 and 12 months the intervention group showed significantly improved total generic quality of life scores compared with controls (baseline: 80 vs. 82; 6 months: 82 vs. 82; P = 0.04). Across the whole intervention group mean HbA1c levels were not significantly different from controls; baseline HbA1c mean (95% confidence interval), 78 mmol/mol (75-81) vs. 76 mmol/mol (74-79) [9.3% (9-9.6%) vs. 9.1% (8.9-9.4%); 24 months: 77 mmol/mol (74-79) vs. 78 mmol/mol (75-81) (9.2% (8.9-9.4%) vs. 9.3% (9-9.6%)], adjusted mean difference, -2.0 mmol/mol (6.5-2.5) [2.3% (-2.7% to 2.4%)], P = 0.38. CONCLUSIONS: Attending a KICk-OFF course was associated with significantly improved total quality of life scores within 6 months. Glycaemic control, as measured by HbA1c , was no different at 24 months. (Clinical Trial Registry No: ISRCTN3704268).

Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage.

Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.

Prognostic indicators of mortality of mechanically ventilated patients with acute leukemia in a comprehensive cancer center.

BACKGROUND: The prognosis for adult acute leukemia patients that require intensive care unit (ICU) admission and invasive mechanical ventilation is poor. We aimed to identify prognostic indicators of 30-day hospital mortality in adult patients who had acute leukemia and respiratory failure, who had received invasive mechanical ventilation in the ICU but who had not received blood and marrow transplantation, were not admitted due to cardiopulmonary arrest or myocardial infarction and, had not recently undergone surgery. METHODS: In this case-control study, we retrospectively reviewed the medical records of relevant patients >16 year old who had been admitted to the ICU at our institution over a 4-year period. The main outcome measure was 30-day hospital mortality. Univariate and multivariate analyses were conducted to determine significant predictors of death. RESULTS: For the 167 patients meeting our eligibility criteria, the median age was 61 years. The majority was admitted due to respiratory insufficiency/failure (69%). The 30-day hospital mortality rate was 62%. Independent predictors of 30-day hospital mortality were advanced disease status (odds ratio [OR]=3.34; 95% confidence interval [CI], 1.65-6.77) and increased organ failure at the time of intubation (OR=1.17; 95% CI, 1.03-1.33) per point increase in the SOFA score. Patients who had received endotracheal intubation within the first 24 h of ICU admission were less likely than others to die (OR=0.46, 95% CI, 0.23-0.91) within the next 30 days after admission to the hospital. CONCLUSION: Advanced disease status and elevated SOFA scores at intubation are strong predictors of 30-day mortality in patients with acute leukemia and respiratory failure. The protective effect of early endotracheal intubation warrants further investigation.

Effects of isoflurane, pentobarbital, and urethane on apoptosis and apoptotic signal transduction in rat kidney.

BACKGROUND: Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Anesthetic agents have been shown to modulate apoptotic signal transduction in various tissues. We examined the effects of 6 h of different general anesthetic techniques on renal cell apoptosis in rat kidneys. METHODS: Twenty-one male Sprague-Dawley rats were randomly allocated into four groups: (i) control, non-anesthetized rats (n= 3) and rats anesthetized with (ii) inhaled isoflurane (n= 6), (iii) intraperitoneal pentobarbital (n= 6), and (iv) intraperitoneal urethane (n= 6). Animals were sacrificed 6 h after the induction of anesthesia. RESULTS: Apoptosis was assessed by terminal deoxynucleotidyl transferase-fluorescein end-labeling analysis. RNA was extracted from the left kidney to probe cDNA microarrays. Gene expression was measured as a percentage of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and subsequently confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with the control (no anesthesia), urethane significantly (P < 0.001) induced apoptosis in both the renal cortex and medulla. Isoflurane significantly (P < 0.001) inhibited apoptosis in the medulla. Microarray analysis revealed that urethane up-regulated more (74) genes than pentobarbital (16) and isoflurane (10). Isoflurane down-regulated more genes (85) than pentobarbital (74) and urethane (12). These anesthetic-induced modulations were significant (P < 0.05) for 60 isoflurane-, 30 pentobarbital- and 4 urethane-modulated genes. CONCLUSION: Our results suggest that general anesthetic drugs have an effect on renal cell apoptosis and apoptotic signal transduction, and thus may potentially affect the risk of subsequent acute renal failure.

Characteristics of cardiac arrest in cancer patients as a predictor of survival after cardiopulmonary resuscitation.

BACKGROUND: Despite advances in cardiopulmonary resuscitation and the education of its providers, survival remains dismal for cancer patients suffering in-hospital cardiac arrest. In an effort to determine if characteristics of cardiac arrest would represent a useful parameter for prognostication and recommendations regarding the suitability of ongoing resuscitation for various groups, this review was undertaken for patients who experienced in-hospital cardiac arrest. METHODS: A retrospective study of data gathered between January 1993 and December 1997 was undertaken in a 518-bed comprehensive cancer center. The records of 243 inpatients who experienced cardiac arrest and received cardiopulmonary resuscitation were reviewed, and their course observed until hospital discharge or death. RESULTS: Sixteen of 73 patients (22%) who had sudden, unanticipated cardiac arrests survived to be discharged from the hospital; however, none (0 of 171) of the patients who experienced an anticipated cardiac arrest survived (P < 0.001). Logistic regression analysis revealed that anticipated cardiac arrest associated with metabolic derangement was an independent predictor of hospital mortality. CONCLUSIONS: Patients experiencing an anticipated cardiac arrest, the course of which could not be interrupted through aggressive management in an intensive care unit, have an extremely poor prognosis. Ongoing resuscitative measures in these patients need not be routinely provided. The authors suggest an algorithm for resuscitation that evaluates the characteristics of the arrest as a prognostic factor. This algorithm should be implemented once progressive deterioration spirals toward cardiac arrest that cannot be prevented. Such an approach should avoid painful and costly interventions that are futile with the present techniques of cardiopulmonary resuscitation.

What is the role of stimulant laxatives in the management of childhood constipation and soiling?.

BACKGROUND: Constipation is extremely common in childhood and may lead to overflow soiling/encopresis. Standard treatment of the more severe case is to empty the bowels of impacted faeces by the use of oral or rectal laxatives and then maintain regular bowel movements by the continuation of osmotic and stimulant laxatives. OBJECTIVES: The objective of the review was to determine the effect of stimulant laxative treatment in children with chronic constipation who may also suffer from soiling / encopresis. SEARCH STRATEGY: The Cochrane database of randomised controlled trials was searched. Additional citations were sought by hand searching of paediatric journals and from contact with known professionals in the field. SELECTION CRITERIA: All identified randomised controlled trials (RCTs) which compare the administering of stimulant laxatives to children with either placebo or alternative treatment. DATA COLLECTION AND ANALYSIS: No trials were found that met the selection criteria. MAIN RESULTS: No trials were found that adequately met the selection criteria. REVIEWER'S CONCLUSIONS: The need exists to establish a secure footing for treatment decisions and adequately sized trials are required to provide comparative data on commonly used drugs.

End-of-life decisions in cancer care.

End-of-life decisions in critically ill patients with cancer are often complex and fraught with emotion. End-of-life care involves a multidisciplinary approach that takes into account the patient and family's desires and the goals of therapy. Decisions regarding the use of life-support technology at the end of life encompass an outcomes and goal-oriented approach. Ethical, medical, legal, and economic issues should be considered in the assessment of life-support technologies and directives for their appropriate use in the ICU.

Influence of an advance directive on the initiation of life support technology in critically ill cancer patients.

OBJECTIVE: To determine whether the presence of an advance directive at admission to an intensive care unit (ICU) influenced the decision to initiate life support therapy in critically ill cancer patients. DESIGN: Matched-pairs case-control design. SETTING: The University of Texas M. D. Anderson Cancer Center ICU. PATIENTS: Of 872 patients treated in the ICU from 1994 to 1996, 236 (27%) were identified as having advance directives. One hundred thirty five patients who had advance directives were successfully matched to 135 patients who did not on the basis of type of malignancy, reason for admission to ICU, severity of illness, and age. These pairs comprised the study group. INTERVENTIONS: Life-supporting interventions were compared between the matched groups using the McNemar and Wilcoxon matched-pairs signed ranks tests. MEASUREMENTS AND MAIN RESULTS: No significant difference was found in the frequency with which the following interventions were applied in patients with and without advance directives (respectively): mechanical ventilation, 44% vs. 42%; inotropic support, 31% vs. 31%; pulmonary artery catheterization, 11% vs. 12%; cardiopulmonary resuscitation, 7% vs. 12%; and renal dialysis, 3% vs. 7%. There were also no differences in ICU (75% vs. 73%, respectively) or hospital (56% vs. 59%, respectively) survival. More patients with advance directives than those without had do-not-resuscitate orders within the first 72 hrs (19% vs. 11%, p =.046) and patients with advance directives had shorter ICU durations and lower ICU charges than patients without advance directives. CONCLUSIONS: After controlling for type of malignancy, reason for admission to the ICU, severity of illness, and age, the decision to initiate life-supporting interventions did not differ significantly among patients with and without advance directives. The presence of an advance directive, however, may have helped guide decisions earlier regarding duration of therapy and resuscitation status.

An investigation of prospective memory in children with ADHD.

Prospective memory, defined as the ability to follow through on intended behavior, is believed to be subserved by a number of neuroanatomical substrates, but particularly dependent, at least in part, on the frontal lobes. Children with Attention-Deficit Hyperactivity Disorder (ADHD) traditionally have difficulty on tasks dependent on frontal lobe structures. The present study attempted to determine whether children with ADHD are impaired in prospective memory function. Two studies are described that use a new measure of time-based prospective memory, the CyberCruiser (Kerns, 2000), to compare children with ADHD to a control group consisting of participants who were matched in respect to age, gender, and IQ. The results document prospective memory deficits in ADHD. Prospective memory performance correlated significantly with clinical measures of ADHD as assessed by the Conners' Parent Rating Scale (Conners, 1990) Hyperactivity Index, but was unrelated to intellectual ability. Though psychometric measures of attention correlated with prospective memory performance, they did not account for the differences in prospective memory that were observed between the ADHD and control groups.

Identifying risk factors for imminent death in cancer patients with acute dyspnea.

A substantial proportion of cancer patients presenting to an emergency center (EC) or clinic with acute dyspnea survives fewer than 2 weeks. If these patients could be identified at the time of admission, physicians and patients would have additional information on which to base decisions to continue therapy to extend life or to refocus treatment efforts on palliation and/or hospice care alone. The purpose of this study was to identify risk factors for imminent death (survival

Advance directives in critically ill cancer patients.

Although advance directives have been used since the 1970s, the discussion of these documents has become more common since the enactment of the Patient Self-Determination Act in 1991. This study evaluated the frequency of advance directives in critically ill patients at a tertiary cancer center and found that cancer patients had a relatively low completion rate of advance directives (27%). The finding that advance directives were more common among Caucasians than other ethnic groups signifies the importance of considering cultural differences when addressing end-of-life issues with patients. The documents also were found more often in older patients with serious diseases. The relationship between hospital mortality and advance directives is complex. The most seriously ill patients and patients with leukemia had the highest mortality and the highest rate of advance directives. Further research on the interactions among mortality, advance directives, and severity of illness is needed. This research contributes to the body of knowledge available on advance directives and particularly sheds light on advance directives in critical ill cancer patients.

Prognostic indicators for blood and marrow transplant patients admitted to an intensive care unit.

Although hematopoietic stem cell transplantation (HSCT) can be curative in patients with certain malignancies, survival is poor if the recipient becomes critically ill. This prospective study examined the outcomes of 115 consecutive HSCT patients admitted to the medical intensive care unit (MICU) of a tertiary cancer center and identified variables associated with survival. The need for endotracheal intubation and mechanical ventilation ("intubation") had a profound adverse effect on survival. Overall, 9 of 48 (18.8%) intubated patients survived compared with a survival rate of 44 of 67 (65.7%) among patients not intubated (p < 0.001). This pattern persisted for nearly all patient subgroups. Among intubated patients, those receiving peripheral blood stem cell transplant (PBSCT) had significantly better survival than bone marrow transplant (BMT) patients (8 of 26, 31% versus 1 of 22, 4%; p = 0.028). Multiple logistic regression analyses indicated that the probability a patient admitted to the MICU survived decreased significantly if the patient was intubated, had an allogeneic rather than autologous transplant, had an infection or gastrointestinal bleeding, and also decreased with higher respiratory rate, higher heart rate, longer time from transplant to MICU admission or higher bilirubin. These results may be of value in deciding which critically ill patients will benefit from intubation following major complications after HSCT transplantation.

Nitric oxide synthase and arginase in cells isolated from the rat gastric mucosa.

Nitric oxide (NO) synthase activity, which converts arginine to citrulline and NO, is present in homogenates of rat gastric mucosal cells. The aims of this study were to identify the form of NO synthase expressed in gastric cells isolated from fed rats, and to investigate the metabolism of arginine by suspensions of intact mucosal cells. Antibodies directed against the neuronal form of NO synthase recognised a protein of 160 kDa on immunoblots of extracts of gastric cells, and stained isolated cells of approx. 8 microm in diameter. NO synthase was enriched in a cell fraction which banded at high-density in a Percoll gradient, and was inhibited (IC50) by N(G)-nitro-L-arginine (0.8 microM), N(G)-monomethyl-L-arginine (12.6 microM), L-canavanine (147 microM), trifluoperazine (140 microM) and by phosphorylation involving protein kinase C. Intact gastric cells converted exogenous arginine to ornithine and citrulline. Arginase was present in the cells, and was predominantly responsible for arginine metabolism because formation of ornithine and citrulline was reduced by the arginase inhibitors, N(G)-hydroxy-L-arginine and L-ornithine, but not by NO synthase inhibitors such as N(G)-nitro-L-arginine. In conclusion, NO synthase that resembles the neuronal isoform is present in gastric mucosal cells, but a pathway involving arginase seems to be largely responsible for citrulline formation from exogenous arginine in intact mucosal cells.

Dyspnea in cancer patients. Etiology, resource utilization, and survival-implications in a managed care world.

BACKGROUND: Dyspnea is the fourth most common symptom of patients who present to the emergency department (ED) at The University of Texas M. D. Anderson Cancer Center and may, in some patients with advanced cancer, represent a clinical marker for the terminal phase of their disease. This retrospective study describes the clinical characteristics of these patients, the resource utilization associated with the management of dyspnea, and the survival of patients with this symptom. METHODS: The authors randomly selected 122 of 1068 patients presenting with dyspnea for a retrospective analysis. The median age of the patients was 58 years (range, 23-90 years) and 53% were female. Underlying malignancies were breast cancer (30%), lung cancer (37%), and other cancers (34%). Approximately 94% of the patients had received prior cancer treatment and the majority (69%) had uncontrolled, progressive disease. RESULTS: The most common treatments administered in the ED were oxygen (31%), beta-2 agonists (14%), antibiotics (12%), and narcotics (11%). Approximately 60% of patients were admitted to the hospital from the ED for further treatment of dyspnea and the underlying malignancy, and the median length of stay was 9 days. The median overall survival after the ED visit for dyspnea was 12 weeks. Specific diagnoses were associated with different median survival rates: lung cancer patients: 4 weeks; breast cancer patients: 22 weeks (P = 0.0073, vs. lung cancer); and other cancer diagnoses: 27 weeks (P = 0.0027, vs. lung cancer). CONCLUSIONS: Lung cancer patients presenting to the ED with dyspnea have much shorter survival than patients with other malignancies. For some patients, the presence of dyspnea requiring emergency treatment may indicate a phase in their illness in which resources should be shifted from acute intervention with hospitalization to palliative and supportive care measures.

Localization of constitutive isoforms of nitric oxide synthase in the gastric glandular mucosa of the rat.

Nitric oxide has been implicated in the regulation of blood flow, mucosal integrity and mucus secretion in the gastric mucosa. An antiserum directed against the C-terminal hexadecapeptide of rat brain nitric oxide synthase (NOS) and monoclonal antibodies to the neuronal and endothelial forms of NOS were used to establish the location of isoforms of NOS in rat gastric glandular mucosa. Antibodies to the neuronal form of NOS reacted with a band of 160 kDa on immunoblots of brain and gastric mucosa, and the addition of the hexadecapeptide inhibited recognition by the antipeptide antiserum. The antibody to endothelial NOS detected a band of 140 kDa on protein blots of samples of intestinal mesentery and gastric mucosa. Immunohistochemistry using these antibodies demonstrated that material related to neuronal NOS was present in surface cells of the gastric mucosa, and showed a similar localization to intense NADPH diaphorase activity. The antibody to endothelial NOS did not stain the surface of the gastric mucosa but recognized blood vessels in the lower region of the gastric glands and in the sub-mucosa. This study suggests that nitric oxide might act both as an intra- and inter-cellular messenger to regulate mucus release, and that the NOS present in surface cells is related more closely to the neuronal than to the endothelial isoform.

Anatomic patterns of Fos immunostaining in rat brain following systemic endotoxin administration.

To identify brain neurons that participate in the acute phase response, rat brains were examined immunocytochemically for Fos protein following the intravenous administration of bacterial endotoxin (lipopolysaccharide, LPS). Two to three hours after the injection of LPS, 150 micrograms/kg body weight, to adult male Long-Evans rats, a consistent anatomic pattern of Fos immunostained cell nuclei is seen. In the brain stem, prominant Fos immunostaining is induced in tyrosine hydroxylase immunoreactive neurons of the caudal ventral-lateral medulla (the A1 cell group), in both tyrosine hydroxylase positive and negative neurons of nu. tractus solitarius, in the parabrachial nu., and in a few neurons of the locus ceruleus. In the hypothalamus, endotoxin induces Fos expression in magnocellular neurons of the paraventricular and supraoptic nuclei and internuclear cell groups. A higher percentage of oxytocin-immunoreactive cells is double labeled for Fos nuclear immunostaining than vasopressin-immunoreactive cells. A minority of somatostatin immunoreactive periventricular hypothalamic neurons are Fos positive. Other hypothalamic nuclei that contain endotoxin-induced Fos nuclear immunostaining include the parvocellular neurons of the paraventricular nu., the dorsomedial and arcuate nuclei, the lateral hypothalamus, the dorsal hypothalamic area (zona incerta), and the median nucleus of the preoptic area. LPS induces numerous Fos-positive neurons in regions known to respond to a variety of stressful stimuli; these regions include the preoptic area, bed nucleus of the stria terminalis, lateral septum, and the central and medial nuclei of the amygdala. Moreover, Fos nuclear immunostaining is seen in neurons of circumventricular organs: the organum vasculosum of the lamina terminalis, the subfornical organ, and the area postrema. The maximum intensity of Fos nuclear immunostaining occurs 2-3 h after endotoxin administration and declines thereafter. It is attenuated by pretreatment with indomethacin, 25 mg/kg body weight Sc, or dexamethasone, 1 mg/kg IP. These observations are consistent with the participation of a variety of brain neuronal systems in the acute phase response and elucidate the functional neuroanatomy of that response at the cellular level.

An experimental model of leptomeningeal metastases employing rat mammary carcinoma cells.

Five percent of patients dying with breast cancer have leptomeningeal metastases (LM) but current therapy is of only marginal benefit. Therefore, an experimental model of LM from breast cancer was developed to facilitate the development of novel therapies. Cell suspensions of 13762 MAT BIII rat mammary carcinoma cells are injected into the cisterna magna of adult, female Fischer 344 rats under general anesthesia. 10-12 days after the injection of 2 x 10(5) viable cells, animals develop neurologic signs, including ataxia, paralysis and spontaneous rotation. Histologically, tumor cells can be seen in the subarachnoid space over the surface of the brain and spinal cord and within the ventricles. Tumor cells do not invade the brain parenchyma. Collections of tumor cells are extensively infiltrated by macrophages and CD8-positive (suppressor/cytotoxic) T cells, but by few CD4-positive (helper) T cells. MAT BIII cells therefore provide a model of LM from breast cancer with a reproducible clinical course and histologic features. The tumor elicits a cellular immune response and can be useful in exploring biologic therapies for leptomeningeal metastases.

Stimulation by carbachol of mucus gel thickness in rat stomach involves nitric oxide.

Instillation of carbachol (150 micrograms/kg) into the gastric lumen in vivo increased the thickness of the mucus gel layer. Intravenous administration of the inhibitor of nitric oxide (NO) synthase, NG-nitro-L- arginine methyl ester (L-NAME, 0.4-5 mg/kg) dose-dependently reduced the stimulation by carbachol, the half-maximal inhibitory dose being 0.57 mg/kg. This effect of L-NAME was abolished by administration of L-arginine but not by D-arginine (100 mg/kg i.v.). By contrast L-NAME (5 mg/kg) did not reduce the stimulatory effect of intraluminal 16,16-dimethyl prostaglandin E2 (50 micrograms/kg) on mucus gel thickness. These results implicate NO in the cholinergic activation of gastric mucus secretion.