Psychological defenses and coping styles in patients following a life-threatening attack of asthma

Twenty-five patients who have suffered a near miss asthma death (NMAD) have undergone a comprehensive psychiatric evaluation on average 13 months following this event. Forty percent of the patients were judged to have psychiatric disorders at the time of assessment. All patients had very high levels of denial and following the NMAD, patients appeared to either decompensate psychiatrically, usually exhibiting symptoms of anxiety disorders, or further increase their levels of denial. Those patients who had psychiatric illnesses at the time of the study were more constitutionally vulnerable towards developing these disorders and had a reduced perception of their quality of life compared with the patients who increased their levels of denial following the NMAD. The effects of the NMAD on patients and their families ranged from mutual anger and anxiety, although the anger was often repressed, to mutual overinvolvement and overdependence. The presence of high levels of denial of asthma and a history of psychiatric illness in the patient appear to be factors that may increase the likelihood of death from asthma.     

Spontaneous Tumor Regression in a Syngeneic Rat Model of Liver Cancer: Implications for Survival Studies

PurposeTo characterize tumor growth of N1S1 cells implanted into the liver of Sprague–Dawley rats to determine if this model could be used for survival studies. These results were compared with tumor growth after implantation with McA-RH7777 cells.Materials and MethodsN1S1 or McA-RH7777 cells were implanted into the liver of Sprague–Dawley rats (n = 20 and n = 12, respectively) using ultrasound (US) guidance, and tumor growth was followed by using US. Serum profiles of 19 cytokines were compared in naive versus tumor-bearing rats.ResultsBoth types of tumors were visible on US 1 week after tumor implantation, but the mean tumor volume of N1S1 tumors was larger compared to McA-RH7777 tumors (231 mm³ vs 82.3 mm³, respectively). Tumor volumes in both groups continued to increase, reaching means of 289 mm³ and 160 mm³ in N1S1 and McA-RH7777 groups, respectively, 2 weeks after tumor implantation. By week 3, tumor volumes had decreased considerably, and six tumors (50%) in the McA-RH7777 had spontaneously regressed, versus two (10%) in the N1S1 group. Tumor volumes continued to decrease over the following 3 weeks, and complete tumor regression of all tumors was seen 5 weeks and 6 weeks after tumor implantation in the McA-RH7777 and N1S1 groups, respectively. In an N1S1-implanted rat, multiple cytokines that have been shown to correlate with the ability of the tumor to survive in a hostile environment were increased by as much as 50%, whereas the average increase in cytokine levels was 90%. These findings suggest that the net cytokine environment favors an antitumor immune response. A similar trend was observed in a rat with a McA-RH7777 tumor, and the increase in cytokine levels was considerably more pronounced, with an average increase of 320%.ConclusionsThe model of N1S1 cell implantation in the liver of Sprague–Dawley rats is not ideal for survival studies and should only be used with great caution in short-term studies that involve cancer therapies.     

Repurposing the Open Access Malaria Box To Discover Potent Inhibitors of Toxoplasma gondii and Entamoeba histolytica

Toxoplasmosis and amebiasis are important public health concerns worldwide. The drugs currently available to control these diseases have proven limitations. Therefore, innovative approaches should be adopted to identify and develop new leads from novel scaffolds exhibiting novel modes of action. In this paper, we describe results from the screening of compounds in the Medicines for Malaria Venture (MMV) open access Malaria Box in a search for new anti-Toxoplasma and anti-Entamoeba agents. Standard in vitro phenotypic screening procedures were adopted to assess their biological activities. Seven anti-Toxoplasma compounds with a 50% inhibitory concentration (IC₅₀) of <5 μM and selectivity indexes (SI) of >6 were identified. The most interesting compound was MMV007791, a piperazine acetamide, which has an IC₅₀ of 0.19 μM and a selectivity index of >157. Also, we identified two compounds, MMV666600 and MMV006861, with modest activities against Entamoeba histolytica, with IC₅₀s of 10.66 μM and 15.58 μM, respectively. The anti-Toxoplasma compounds identified in this study belong to scaffold types different from those of currently used drugs, underscoring their novelty and potential as starting points for the development of new antitoxoplasmosis drugs with novel modes of action.     

Kinetics of Bupivacaine After Nicorandil Treatment in Mice

Previous studies have reported interactions between potassium-channel agonists and bupivacaine. This study was designed to document possible changes in the pharmacokinetic behaviour of bupivacaine and its main metabolite, N-desbutylbupivacaine, in mice after a single 1 mg kg^?1 intraperitoneal injection of nicorandil. The kinetic variables of bupivacaine were determined after a single 20 mg kg intraperitoneal dose of bupivacaine in controls (group 1) and in nicorandil-treated mice (group 2). The maximal concentration in the serum (C_max 0.618 ± 0.051 vs 0.408 ± 0.041 μg mL^?1 for group 1 vs 2, P = 0.01) and the area under the concentration curve (AUC 1.039 ± 0.051 vs 0.758 ± 0.072 μg mL^?1 h for group 1 vs 2, P = 0.013) of bupivacaine were significantly lower in nicorandil-treated mice, while CL (0.579 ± 0.025 vs 0.815 ± 0.079 for group 1 vs 2, P = 0.022) and V_d (0.506 ± 0.054 vs 0.981 ± 0.117 for group 1 vs 2, P = 0.1006) were increased in nicorandil-treated animals. The ratio of AUC for N-desbutylbupivacaine to AUC for bupivacaine, which may partially indicate the rate of metabolism, was higher in the presence of nicorandil (1.142 ± 0.017 compared with 0.877 ± 0.013, P = 0.0001). Our data may indicate an increased metabolism of bupivacaine in nicorandil-treated mice. These results do not explain the previously reported enhanced anaesthetic activity of bupivacaine in the presence of nicorandil, but may participate, at least in part, in the relative protective effect of nicorandil against the previously reported bupivacaine-induced toxicity.     

Psychiatric and medical features of near fatal asthma.

BACKGROUND--The associations between psychiatric caseness, denial, and self reported measures of handicap and morbidity due to asthma in patients suffering a near fatal attack of asthma have not been fully explored. METHODS--Seventy seven consecutive subjects who presented to Adelaide teaching hospitals with a near fatal attack of asthma were assessed with a validated semi-structured interview following discharge from hospital. RESULTS--43% of the patients scored > or = 5 on the GHQ-28 questionnaire. There was a positive correlation between GHQ-28 score and limitation to daily activities due to asthma, and between GHQ-28 score and days lost from work, school or usual daily activities, both of which were retained after adjusting for age and sex. Asthma severity did not show a clear association with GHQ-28 score. The asthmatic patients reported high levels of denial, 57% scoring more than 3 out of 5 on the denial scale of the Illness Behaviour Questionnaire. Presentation with a history of progressive respiratory distress was negatively associated with denial score. This persisted after adjustment for age and sex--that is, those with high denial scores were more likely to report presentation as sudden collapse than progressive respiratory distress. CONCLUSIONS--Psychiatric caseness (GHQ score > or = 5) is associated with high levels of morbidity in asthmatic patients who survive a near fatal attack of asthma. High levels of denial in asthmatic subjects may be life threatening. The link between morbidity associated with asthma and psychiatric features, along with other psychosocial issues, warrants further investigation. A broader paradigm than the traditional medical model should be considered when assessing patients with asthma.