Psychological factors in postoperative adjustment to stoma surgery.

Around one-quarter of stoma patients experience clinically significant psychological symptoms post-operatively. Psychological disorders are often not detected by those involved with the care of stoma patients. Past psychiatric history, dissatisfaction with preoperative preparation for surgery, postoperative physical symptomatology and the presence of negative stoma-related thoughts/beliefs have all been shown to be significantly associated with psychological morbidity after surgery. These findings suggest that healthcare professionals (especially surgeons involved with this patient population) should ask all patients about these factors before and after surgery. Questionnaires could be used to screen for difficulties and/or staff could undertake training aimed at improving the detection of psychological morbidity and endeavour to strengthen links with liaison mental health services. Future research in this area should be prospective, using psychometrically valid measures and be focused on the prediction, prevention, detection and treatment of poor psychological adjustment after stoma surgery.     

A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin.

OBJECTIVES: Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG. METHODS: A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20 ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion. RESULTS: Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642 mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates < or =1000 g and slightly higher in neonates 1001 to 1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm. CONCLUSIONS: Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.     

The inhibition of the oxidation of low density lipoprotein by (+)-catechin, a naturally occurring flavonoid.

(+)-Catechin inhibited the copper-catalysed oxidation of human low density lipoprotein (LDL) in a dose-dependent manner with complete inhibition at 20 micrograms/mL. The flavonoid at a concentration of 50 micrograms/mL also inhibited oxidation of LDL induced by the mouse transformed macrophage J774, human monocyte-derived macrophages and vascular endothelial cells isolated from human umbilical cords. LDL modified by copper-catalysed or cell-induced oxidation was endocytosed and degraded by human macrophages at a much greater rate than native LDL. LDL reisolated from copper or cell incubations in the presence of (+)-catechin was endocytosed and degraded at rates similar to native LDL. (+)-Catechin appeared to inhibit the uptake and degradation by macrophages of cell-modified LDL. The actions of (+)-catechin on cell-induced oxidation of LDL are consistent with the ability of flavonoids of similar structure to inhibit lipoxygenases and with a role for lipoxygenases in cell-induced modification of LDL in vivo.     

Extracellular adenosine,formed during low level NMDA receptor activation,provides an inhibitory threshold against further NMDA receptor-midiated neurotransmission in the cortex

In the cortex only a few of the available NMDA receptors must be activated to evoke maximal release of adenosine. In fact, maximal adenosine release occurs at 30 μM NMDA, a concentration at which noradrenaline release is only 20% maximal. NMDA-evoked noradrenaline release appears to require the generation of propagated action potentials, while adenosine release does not. Noncompetitive block of NMDA-evoked release of adenosine, but not noradrenaline, can be overcome by increasing NMDA concentrations. The above findings are consistent with the possibility that there are spare receptors for NMDA-evoked adenosine release, but not for nor-adrenaline release. These spare receptors are not due to elevated levels of glycine in the vicinity of those NMDA receptors mediating adenosine release. Functionally, it appears that low level NMDA receptor activation provides a purinergic inhibitory threshold against higher level NMDA receptor mediated processes. This could provide inhibitory tone and selectivity for critical functions, such as learning, memory, and synaptic plasticity in the cortex. © 1993 Wiley-Liss, Inc.     

Abrogation of IL-3 Requirements and Stimulation of Hematopoietic Cell Proliferationin Vitroandin Vivoby Carboxylic Acids

ABSTRACT: Short-chain fatty acids, such as butyrate and propionate, induce fetal globin gene expression and are under clinical investigation in the β-hemoglobinopathies. Limitations of the short-chain fatty acids as therapeutics include their rapid metabolism and a tendency to induce cell growth arrest if administered for prolonged periods. In studies described here, the cellular effects of other inducers of fetal globin, phenoxyacetic acid and derivatives of short-chain fatty acids and cinnamic acids, were investigated in the human erythroid cell line K562, the IL-3 dependent multi-lineage cell line (32D), and in mice and primates. Several test compounds supported 32D cell proliferation despite a 50-fold depletion of IL-3, which resulted in growth arrest and apoptotic death in control cells. The degree of proliferation induced by certain test compounds was similar to the degree of proliferation induced by Erythropoietin and G-CSF in the cells. Eight of ten compounds induced γ globin mRNA in K562 cells. A 2.5 to 6-fold increase in reticulocytosis was observedin vivoin mice treated with two prototype compounds. Pharmacokinetic studies of three prototype compounds demonstrated millimolar plasma concentrations after single oral doses for many hours in primates. These findings identify orally bioavailable compounds which induce γ globin gene expression and hematopoietic cell proliferation through an activity which partially abrogates requirements for IL-3. Such compounds provide potential for oral therapeutics which stimulate proliferation of hematopoietic cells of multiple lineages, as well as inducing fetal globin.     

Asthma and hyperthyroidism. A report of 4 cases

For many years it has been known that thyrotoxicosis can worsen asthma, increasing both the frequency and severity of asthma attacks and increasing requirements for medication. Clinical recognition of this association may be difficult. Thyrotoxic asthmatics frequently experience side-effects from medications, particularly beta-receptor agonists and theophyllines. Four case reports of asthmatics in whom thyrotoxicosis was diagnosed are presented. All 4 patients improved on returning to euthyroid status. The mechanism responsible for the harmful interaction is not known.