Anxiety and depression in adolescent cancer: findings in patients and parents at the time of diagnosis

Adolescent cancer is uncommon and presents an exceptional stress for the young patient and their parents. The emotional needs of adolescents with cancer are a major factor in the recommendation for the establishment of adolescent cancer units in major cancer centres in the U.K. However, there have been no prospective, longitudinal studies assessing the psychological impact of a diagnosis of cancer on the adolescent patient and their family. In 1994 we began a longitudinal study of the emotional impact of the diagnosis of cancer in patients and their families presenting to an adolescent cancer unit and of the coping strategies they employ. This first report presents the results of the study at the time of diagnosis in 42 adolescents, 34 mothers and 27 fathers. The Beck Depression Inventory (BDI) was used to assess depression and anxiety levels were measured using Spielberger's State Trait Anxiety Inventory (STAI). Adolescents and their parents completed the questionnaires on first admission to the adolescent cancer unit. The median time since cancer diagnosis was approximately 3 weeks. To provide normative data for the U.K. adolescent population, control values were obtained from 173 pupils of the same age and background. The results showed that, contrary to expectation, adolescents with cancer were no more anxious or depressed than the control adolescent population. Nevertheless, a substantial minority of patients and controls had elevated anxiety or depression scores. Girls were significantly more anxious (P = 0.011) and depressed (P < 0.0001) than boys. Mothers were the most anxious family members and were significantly more anxious than fathers (P = 0.038). Parental anxiety scores, especially mothers, were much higher than reported norms. There was no significant difference between mothers' and fathers' depression scores. Although at the time of diagnosis adolescent cancer patients are not more anxious or depressed than their healthy peers, many adolescents without cancer are anxious or depressed. Staff on adolescent cancer units should therefore be aware of the frequency of emotional disturbance in this population. Mothers are the most anxious family members. Although the findings are relatively reassuring at the time of diagnosis, follow-up data from this cohort will show whether anxiety and depression change with treatment involving intensive chemotherapy, surgery and radiotherapy and will indicate the coping strategies which patients and their families adopt in dealing with both the disease and its treatment.     

Activation of coagulation and fibrinolysis in open and laparoscopic cholecystectomy

BACKGROUND: Activation of coagulation and fibrinolysis occurs as a stress response to surgery and may predispose the patient to thromboembolic complications. Other components of the surgical stress response (cytokine release, neurohumoral response, etc.) have been shown to differ between laparoscopic and open cholecystectomy, and the aim of this study was to investigate the effects of laparoscopic and open surgery on the coagulation and fibrinolytic pathways. METHODS: Fourteen patients undergoing laparoscopic cholecystectomy and 12 patients undergoing open cholecystectomy had blood taken in the perioperative period for fibrinopeptide A (FPA) prothrombin fragment F1.2, antithrombin 3, tissue plasminogen activator (tPA) and its fast-acting inhibitor plasminogen activator inhibitor-1 (PAI-1 antigen and activity), and the euglobulin clot lysis time (ECLT). RESULTS: The only significant differences between the two groups occurred 6 h after surgery when the ECLT was longer (p < 0.005; Mann Whitney), and PAI-1 antigen and activity were higher (p < 0.01 and p < 0.001, respectively; Mann Whitney) after open cholecystectomy than laparoscopic cholecystectomy. CONCLUSIONS: Other changes in fibrinolysis and coagulation were similar for open and laparoscopic cholecystectomy. With respect to hemostasis, laparoscopic cholecystectomy does not increase the risk of thromboembolic complications compared to the conventional procedure.     

Morphological and pharmacological evidence for neuropeptide Y-galanin interaction in the rat hypothalamus

Galanin (GAL) and neuropeptide Y (NPY) have been shown to play important roles in the regulation of pituitary hormone secretion, as well as ingestive and sexual behaviors, by acting within the hypothalamus. While the mechanism of action of these regulatory peptides is under intensive investigation, less attention has been paid to the possible interaction between them in influencing these central regulatory processes. Because NPY and GAL augment pituitary gonadotropin release, the present study was undertaken to evaluate the nature of morphological and functional relationships between these excitatory hypothalamic peptidergic systems. Double immunolabeling for NPY and GAL was carried out on vibratome sections taken from the hypothalamus of colchicine-pretreated female rats. Avidinbiotin peroxidase technique and a dark blue diaminobenzidine reaction was used to visualize NPY profiles, while the GAL neurons were labeled with a light brown diaminobenzidine reaction using either the avidin-biotin peroxidase or the peroxidase antiperoxidase technique. Light microscopic examination of the immunostained material showed that in the arcuate nucleus, paraventricular nucleus, supraoptic nucleus, anterior hypothalamus, and medial preoptic area, an abundant network of NPY-immunoreactive axons surrounded GAL-immunostained cells. Numerous dark blue NPY-containing putative boutons were observed in close proximity to GAL-immunolabeled cell bodies and dendrites. Correlated light and electron microscopic examination revealed that most of the immunoreactive NPY axon terminals established synaptic connections with GAL-expressing cells. Synaptic connections were most frequently found in the medial preoptic area and in the magnocellular region of the paraventricular nucleus and arcuate nucleus. Fewer connections were observed in the supraoptic nucleus. These morphological observations demonstrate the existence of a strong NPY input to hypothalamic GAL neurons, thereby suggesting a modulatory role for NPY in monitoring GAL release. To evaluate the functional relevance of this anatomical relationship, the effects of intraventricular injection of a GAL receptor antagonist, galantide, were examined on NPY-induced LH release in ovarian steroid-primed ovariectomized rats. As expected, intraventricular injection of NPY readily stimulated LH release. Although, while on its own, galantide was ineffective in altering basal LH release, it markedly attenuated the NPY-induced LH response, thereby suggesting that GAL released in response to NPY administration may, in part, mediate the excitatory effects of NPY. These experimental results, taken together with the morphological observations, document the involvement of an NPY --> GAL signaling modality in the release of gonadotropins and, likewise, raise the possibility of a similar signaling process in the release of other pituitary hormones and elicitation of behavioral effects attributed to NPY and GAL.     

Factors associated with early onset pneumonia in the severely brain-injured patient

An analysis of 125 patients with closed head injury was completed in order to identify the risk factors involved in the development of early pneumonia. Pneumonia was diagnosed in 60% of the patients. Early pneumonia developed in 47.8% of the patients. Brain-injured patients who developed early pneumonia were found to have a lower Glasgow Coma Scale (GCS) score. Early pneumonia was found more often in patients with swallowing disorders and evidence of aspiration. Patients who had been intubated in the field were found to be at greater risk for the development of early pneumonia than those intubated in the hospital. Patients with early pneumonia had prolonged intubation times, intensive care unit stays, and hospital stays. This study suggests that a GCS score less than 5, evidence for swallowing disorders and aspiration, and field intubation are risk factors for early pneumonia in the brain-injured patient.     

Effects of diheptyldiselenide (DDS) on human tumor cell lines and on peripheral blood mononuclear cells

In vitro effects of graded concentrations of diheptyldiselenide (DDS) on human tumor cell proliferation, and on the proliferative responses and immunological functions of peripheral blood mononuclear cells (MNC) were investigated. The agent significantly decreased tumor cell proliferation in a dose and time dependent manner. Proliferative responses of MNC to phytohemagglutinin (PHA) and interleukin-2 (IL-2) were also significantly depressed when MNCs were exposed to DDS (250 microM for 18 h) led to a significant increase in NK activity only in MNC samples showing very limited baseline NK function. On the other hand, generation of LAK cells was significantly inhibited by DDS. However, when the agent was added to the effector and target cell mixture during the 4 h 51Cr release cytotoxicity assay, no influence was found on NK and LAK-mediated target cell lysis. These studies show that high concentrations of DDS inhibit tumor cell proliferation and could also impair certain proliferative-dependent immune functions, without directly affecting cell-mediated cytolytic activity of effector cells.     

Induction of 8-hydroxydeoxyguanosine in isolated DNA and HeLa cells exposed to fecapentaene-12: evidence for the involvement of prostaglandin H synthase and iron

The genotoxic/mutagenic mechanism(s) of action of fecapentaene-12 (fec-12) is complex but there is evidence to suggest that the generation of active oxygen species (AOS) may be involved. This has been assessed by measuring the formation of 8-hydroxydeoxyguanosine (8-OHdG) in isolated DNA and HeLa cells exposed in vitro to fec-12. The possibility that fec-12 may form AOS via peroxidative 'activation' by prostaglandin H synthase (PHS) has been investigated by measuring 8-OHdG in HeLa cells exposed to fec-12 in the absence or presence of PHS inhibitors. The role of iron as a catalyst in this pathway has also been investigated. A 4-fold increase in the level of 8-OHdG in isolated DNA was seen after exposure to fec-12 (1 mM) alone. This increase was enhanced synergistically by ferrous iron. Fec-12 exposure of HeLa cells at 50 and 100 microM induced 2- and 3-fold increases (P < 0.001) respectively in the level of 8-OHdG in cellular DNA. No increase was seen at 10 microM fec-12. The PHS inhibitors indomethacin and acetylsalicylate blocked the formation of 8-OHdG induced by fec-12 (50 microM) but did not inhibit the formation of 8-OHdG in these cells after exposure to H2O2 and Fe2+. Addition of the iron chelating agent o-phenanthroline to cells prior to fec-12 exposure blocked the increase in 8-OHdG induced by fec-12 (50 microM). Addition of the radical scavenging agent DMSO (10%) to cells prior to fec-12 exposure reduced the level of 8-OHdG to within 10% of control. Specific inhibition of fec-12 induced 8-OHdG formation in HeLa cells by PHS inhibitors suggests that this enzyme may be involved in 'activating' fec-12 to form AOS in cells. Inhibition of fec-12 induced 8-OHdG formation in cells by o-phenanthroline suggests a role for intracellular iron as a catalyst in this process.