Severe postoperative haemorrhage and airway obstruction following high-dose enoxaparin

Unfractionated heparin infusion may be a more suitable choice of anticoagulant treatment in patients with venous thromboembolism in the immediate postoperative period.     

Radiographic analysis of lumbar lordosis: centroid, Cobb, TRALL, and Harrison posterior tangent methods

STUDY DESIGN: Delayed, repeated measures, with three examiners each twice digitizing thirty lateral lumbar radiographs. OBJECTIVES: To determine the reliability and clinical utility of the centroid, Cobb, tangential radiologic assessment of lumbar lordosis (TRALL), and Harrison posterior tangent line-drawing methods for analysis of lumbar lordosis. BACKGROUND DATA: Cobb's method is commonly used for curvature analysis on lateral lumbar radiographs, whereas the centroid, TRALL, and Harrison posterior tangent methods are not widely used. METHODS: Thirty lateral lumbar radiographs were digitized twice by each of three examiners. To evaluate reliability of determining global and segmental alignment, all four vertebral body corners of T12-S1 and the superior margin of the femur head were digitized. Angles created were segmental and global centroid, (two-line) Cobb angles, and intersections of posterior tangents. A global TRALL angle was determined. Means, standard deviations, mean absolute differences, interclass and intraclass correlation coefficients (ICC), and confidence intervals were calculated. RESULTS: The interobserver and intraobserver reliabilities of measuring all segmental and global angles were in the high range (ICCs > 0.83). The mean absolute differences of observers' measurements were small (0.6 degrees -2.0 degrees ). Distal segmental (L4-S1) and global angles of lumbar curvature were dependent on the method of measurement. CONCLUSIONS: All four radiographic methods had high reliability and low mean absolute differences of observers' measurements. Because it lacks a segmental analysis, the TRALL method is not recommended. The centroid, Cobb, and Harrison posterior tangent methods provide global and segmental angles. However, the centroid segmental method requires three segments and is less useful for a stability analysis.     

Pharmacokinetics of human growth hormone administered subcutaneously with two different injection systems

The bioavailability of recombinant human growth hormone (somatropin, CAS 12629-01-5) was compared between a transcutaneous jet injection device and subcutaneous cannula injection. Thirteen healthy male subjects received 8.64 IU somatropin once with jet and once with cannula injection in a randomized cross-over study. Baseline-corrected somatropin serum concentrations were evaluated with non-compartmental and compartmental methods. The 90% confidence intervals with two one-sided t-tests around the ratios of injection devices were 91-120% for maximum concentration, 94-110% for area-under-curve until 14 h, and 92-103% for area-under-curve to infinity. Somatropin has a known metabolic half-life of ca. 20-30 min while the observed terminal half-lives were 2-4 h. Absorption and elimination rate constants were similar. Times of maximum concentrations, terminal half-lives and lag times to start of absorption appeared to be shorter and the absorption rate constant appeared to be larger for jet than for cannula injection. In conclusion, the kinetics of somatropin from subcutaneous tissue had a "flip-flop" characteristic. Bioavailability of somatropin after jet injection was equivalent to cannula injection.     

Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.

The trace amine para-tyramine is structurally and functionally related to the amphetamines and the biogenic amine neurotransmitters. It is currently thought that the biological activities elicited by trace amines such as p-tyramine and the psychostimulant amphetamines are manifestations of their ability to inhibit the clearance of extracellular transmitter and/or stimulate the efflux of transmitter from intracellular stores. Here we report the discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta-phenethylamine, tryptamine, and octopamine. An extensive pharmacological survey revealed that psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of the catecholamine neurotransmitters are also good agonists at the rat trace amine receptor 1 (rTAR1). These results suggest that the trace amines and catecholamine metabolites may serve as the endogenous ligands of a novel intercellular signaling system found widely throughout the vertebrate brain and periphery. Furthermore, the discovery that amphetamines, including 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"), are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.     

Phenobarbitone-induced ploidy changes in liver occur independently of p53

Liver polyploidisation, characterised by accumulation of tetraploid and octaploid cells, is found with increasing age and after administration of various drugs. The significance and mechanisms controlling polyploidisation are not understood but p53 is a candidate gene to be involved. We have investigated the effect of p53 on sodium phenobarbitone (PB)-induced liver proliferation and polyploidisation. Using p53 wild type (+/+), heterozygous (+/-) and homozygous (-/-) C57BL/6J mice, we measured ploidy and proliferation (BrdU incorporation) after 21 days oral administration of PB. Administration of PB caused a striking ploidy change compared with untreated controls, with an increase in 8n cells, and no difference noted comparing the p53 genotypes. BrdU positivity also increased significantly compared with controls, with the increase in BrdU positivity occurring in 8n cells. Our results confirm that PB is a hepatic mitogen that causes liver polyploidisation with a striking increase in 8n cells within the liver. p53 status does not appear to have any effect on this PB-induced ploidy change.     

Enhanced sensitivity of human oral carcinomas to induction of apoptosis by selenium compounds: involvement of mitogen-activated protein kinase and Fas pathways

Prospective studies and recent intervention trials suggest that the risk of some cancers, including respiratory tract cancers, may be inversely related to selenium (SE) intake, and this is supported by strong experimental evidence with chemical-induced animal cancer models. How this cancer-protective effect is mediated is unclear, but interference with the balance of growth/apoptosis during tumor outgrowth is one plausible hypothesis. In general, there is a correlation between the effectiveness of SE compounds as chemopreventive agents in vivo and their ability to inhibit cell growth and induce apoptosis in vitro. This study has investigated the signal transduction pathways affected by SE compounds in biopsies of normal human oral mucosa cells and human oral squamous carcinoma cells (SCCs), using a primary culture system. Two SE compounds were tested: selenodiglutathione (SDG), the primary metabolite of selenite and the most commonly used cancer-protective SE compound in animal models, and the synthetic SE compound, 1,4-phenylenebis(methylene)selenocyanate (p-XSC), one of the most potent chemopreventive pharmacological SE compounds. Three novel findings are reported: (a) SCCs were found to be significantly more sensitive to induction of apo ptosis by SDG than normal human oral mucosa cells, though the differences were marginal with p-XSC; (b) both SE compounds induced the expression of Fas ligand (Fas-L) in oral cells to a degree that correlated with the extent of apoptosis induction; and (c) both SDG and p-XSC induced the stress pathway kinases, Jun NH2-terminal kinase (JNK) and p38 kinase, at concentrations causing apoptosis; p-XSC, and to a lesser extent SDG, also activated extracellular regulated kinases 1&2 (ERKs 1&2) and protein kinase-B or Akt. To test their functional involvement, the effect of inhibiting each of these pathways on induction of apoptosis by SDG and p-XSC was determined in SCCs. Inhibiting the ERKs 1&2 or Akt pathways with specific chemical inhibitors (PD98059 or LY294002, respectively) did not affect the extent of apoptosis induced by SDG or p-XSC (with the exception of LY294002, which actually enhanced the level of induction of apoptosis by SDG). The JNK pathway appeared to be most important for induction of Fas-L and apoptosis because concentrations of SB202190 that inhibited activation of both the JNK and p38 kinase (but not ERKs 1&2) in SCC reduced the extent of induction of Fas-L and apoptosis by SDG and p-XSC, whereas lower concentrations that inhibited activation only of p38 kinase did not. This was confirmed by the fact that exogenous expression of a dominant negative deletion mutant of c-Jun (TAM67) reduced the induction of both apoptosis and Fas-L by SDG.     

Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins

There are several reports of ultrastructural and protein changes affecting synapses in the anterior cingulate cortex in schizophrenia. Altered cytoarchitecture has also been described in this region in schizophrenia as well as in mood disorders. In this paper we review the literature and present a new study investigating synaptic abnormalities in the anterior cingulate cortex (area 24) in the Stanley Foundation brain series. We used Western blotting to assess four synaptic proteins: synaptophysin, growth-associated protein-43 (GAP-43), complexin I and complexin II, which inform about somewhat different aspects of the synaptic circuitry. Synaptophysin, complexin II and GAP-43 were reduced in bipolar disorder. The decreases correlated with the duration of illness and tended to be greater in subjects without a family history. Complexin II was also reduced in major depression. Complexin I and the housekeeping protein beta-actin did not differ between groups. None of the proteins changed significantly in schizophrenia. The results indicate the presence of a synaptic pathology in the anterior cingulate cortex in mood disorders, especially bipolar disorder. The abnormalities may contribute to the dysfunction of cingulate neural circuits. The loss of synaptophysin is suggestive of decreased synaptic density whilst the decrease in GAP-43 may denote impaired synaptic plasticity and the reduction of complexin II but not complexin I implies that the alterations particularly affect excitatory connections. The reductions may be progressive.     

Health gain and outcome predictors during inpatient and related day treatment in child and adolescent psychiatry

OBJECTIVE: To investigate health gain and its predictors during inpatient and associated day patient treatment. METHOD: Consecutive admissions to two inpatient units for children and young adolescents in northwest England were studied (N = 55). Ascertainments were made from multiple perspectives, including family, teacher, clinician, and an independent researcher. Measures were taken at referral, admission, discharge, and 6-month follow-up; health gain was inferred from change scores on measures. Recruitment lasted from late 1995 to 1997; follow-up was completed during 1998. Independent variables tested as predictors included assessments of presenting symptoms, therapeutic alliance, and family functioning. RESULTS: Significant health gain during hospitalization was found on most measures and sustained to follow-up. There was no symptom change during the waiting-list control condition. Health gain was predicted independently by child and parental therapeutic alliance with the unit early in hospitalization and by preadmission family functioning. Externalizing problems did well if accompanied by good alliance. CONCLUSIONS: Assessment of health gain from multiple perspectives is possible and valuable. Inpatient treatment has significant therapeutic effect. Predictors for health gain lie in process variables of therapeutic alliance and family functioning rather than presenting symptoms. The results are discussed in relation to clinical practice and future research.     

Observation of feeding in the diagnosis of posttraumatic feeding disorder of infancy

OBJECTIVES: To delineate diagnostic criteria for posttraumatic feeding disorder (PTFD) of infancy and to differentiate PTFD from infantile anorexia (IA) via observation of feeding interactions. METHOD: Three groups of infants (aged 6-32 months) participated: PTFD (n = 30), IA (n = 30), and healthy eater controls (n = 30). The three groups were matched with regard to age, gender, ethnicity, and socioeconomic status. Child psychiatrists used infants' medical and feeding histories and observed 20-minute mother-infant feeding interactions to determine diagnoses and group placement. Feeding interactions were also videotaped, and two raters assessed infants' resistance to feeding situations and to swallowing, as well as specific qualities of mother-infant feeding interactions. RESULTS: Overall, the clinical groups (PTFD and IA) demonstrated more problematic feeding interactions than did the control group. However, the PTFD group exhibited more resistance during feeding interactions than did the other two groups. In particular, the PTFD group displayed the most resistance to swallowing food. CONCLUSIONS: Infants' medical and feeding histories, as well as observations of feeding, are important to making the diagnosis of PTFD and differentiating it from other feeding disorders. Implications for treatment of PTFD are discussed.