Striatal D(2) receptor occupancy in bipolar patients treated with olanzapine.

We explored the relationship between striatal dopamine-2 (D(2)) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2) receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40-68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes.     

Norepinephrine modulates glutamatergic transmission in the bed nucleus of the stria terminalis.

The bed nucleus of the stria terminalis (BNST) and its adrenergic input are key components in stress-induced reinstatement and maintenance of drug use. Intra-BNST injections of either beta-adrenergic receptor (beta-AR) antagonists or alpha2-adrenergic receptor (alpha2-AR) agonists can inhibit footshock-induced reinstatement and maintenance of cocaine- and morphine-seeking. Using electrophysiological recording methods in an in vitro slice preparation from C57/Bl6j adult male mouse BNST, we have examined the effects of adrenergic receptor activation on excitatory synaptic transmission in the lateral dorsal supracommissural BNST (dBNST) and subcommissural BNST (vBNST). Alpha2-AR activation via UK-14,304 (10 microM) results in a decrease in excitatory transmission in both dBNST and vBNST, an effect predominantly dependent upon the alpha2A-AR subtype. Beta-AR activation via isoproterenol (1 microM) results in an increase in excitatory transmission in dBNST, but not in vBNST. Consistent with the work with receptor subtype specific agonists, application of the endogenous ligand norepinephrine (NE, 100 microM) elicits two distinct effects on glutamatergic transmission. In dBNST, NE elicits an increase in transmission (62% of dBNST NE experiments) or a decrease in transmission (38% of dBNST NE experiments). In vBNST, NE elicits a decrease in transmission in 100% of the experiments. In dBNST, the NE-induced increase in synaptic transmission is blocked by beta1/beta2- and beta2-, but not beta1-specific antagonists. In addition, this increase is also reduced by the alpha2-AR antagonist yohimbine and is absent in the alpha2A-AR knockout mouse. In vBNST, the NE-induced decrease in synaptic transmission is markedly reduced in the alpha2A-AR knockout mouse. Further experiments demonstrate that the actions of NE on glutamatergic transmission can be correlated with beta-AR function.     

Rigid rods with flexible side chains — A route to molecular reinforcement?

Liquid-crystalline main-chain polyesters with polystyrene side chains of different length and number per main chain were synthesized using aromatic hydroxyfunctional polystyrene (PS) macromonomers, terephthalic acid derivatives and tert-butylhydroquinone as co-diol. The molecular weight of the polystyrene side chain was varied in the range from 1000 to 20000. The influence of this novel type of substituent on the solubility, thermal behaviour and miscibility with PS as a flexible matrix polymer is discussed. The properties of the new compounds are compared to those of the respective homopolyester. The graft copolyesters are, depending on the characteristics of the polymeric substituent, soluble in common organic solvents and their thermal transition points are lowered compared to the homopolyester. Compared to blends of the homopolyester, the improvement of miscibility of the polymer-substituted rigid rods with PS as an example for a flexible matrix polymer can be valued as a step to molecular reinforcement.     

Specific selection of osteosynthetic material in the treatment of thoracic or lumbar spinal injuries by the posterior approach

Summary The authors report 165 cases of thoraco-lumbar lesions with neurological dysfunction. All the patient were operated. They analyze the neurological and mechanical results and indicate the use of different osteosynthesis apparatus according to the type and level of lesions.Harrington's rods seem to give more precise repositioning while Roy Camille's plates give more stability. When the posterior wall of the spinal canal is intact, Kempf's compression rods can be used.Thoraxic spine injuries seem to be an indication for Harrington's rods, while lumbar injuries seem to call for Camille's plates.     

Mechanics and function in heart morphogenesis.

For years, biomechanical engineers have studied the physical forces involved in morphogenesis of the heart. In a parallel stream of research, molecular and developmental biologists have sought to identify the molecular pathways responsible for embryonic heart development. Recently, several studies have shown that these two avenues of research should be integrated to explain how genes expressed in the heart regulate early heart function and affect physical morphogenetic steps, as well as to conversely show how early heart function affects the expression of genes required for morphogenesis. This review combines the perspectives of biomechanical engineering and developmental biology to lay out an integrated view of the role of mechanical forces in heart development.     

Inhibin and renin in follicular fluids of patients with one or two ovaries stimulated with a GnRH agonist and gonadotrophins

Follicular fluids from eight patients with one ovary and from ten patients with two ovaries were investigated for bioactive inhibin, total renin, oestradiol (E2) and progesterone (P4) concentrations. Four follicular fluids were pooled per patient before assessment. All women had been stimulated similarly using a protocol including a GnRH agonist, HMG and HCG. Renin levels were significantly lower and P4 significantly higher in pools of follicular fluid from patients with one ovary, whereas inhibin and E2 concentrations were similar in both patient groups. A significant negative correlation was found in the pools of follicular fluid between inhibin and E2 in both groups. These results suggest a role for inhibin and renin in the paracrine and autocrine control of stimulated follicular development.     

A study of the use of intravenous cannulas for medical emergencies in Newham--implications for financial savings

A study of intravenous (i.v.) cannula usage for medical emergencies admitted to hospitals in the Newham Health District was undertaken during two defined periods (24 and 35 days). Almost half the cannulas inserted (47%) were not flushed following an initial bolus injection of heparinized saline. The duration that cannulas remained in a vein ranged from 24 hours to 8 days (median 2 days) and inflammation around the cannula site was related to the length of time since insertion but unrelated to whether the cannula was flushed regularly or to the type of fluid used. Our findings indicate a substantial wastage of i.v. cannulas due to difficulties with insertion and suggest that isotonic saline, without heparin, is effective in maintaining cannula patency for 48 hours. It is concluded that these findings are not unique to the Newham Health District and worthwhile financial savings should be achieved throughout the NHS if clinicians reconsider the indications and use of i.v. cannulas for their patients.     

Hirschsprung's disease in young adults

Hirschsprung's disease is rarely seen in the young adult, and presents unique problems in management because of the massive dilatation and hypertrophy that occur proximal to the aganglionic rectum or the rectosigmoid colon. The diagnosis, which may be suspected by barium enema, is confirmed by suction or full-thickness biopsy of the rectum that may be complemented by anal manometry. Based on our experience with eight patients, a two-stage surgical reconstruction is recommended, with a preliminary sigmoid colostomy through the normally innervated colon and an associated defunctionalized stoma constituting the initial operation. The distal colonic stoma permits cleansing of the caudal colon while the normally innervated proximal colon reverts to near normal caliber, usually within 2 to 6 months. This approach is in accord with the recommendation of Fairgrieve. Reconstruction using a Duhamel or Soave procedure has given good results. The Duhamel procedure seems preferable when a considerable discrepancy remains between the ganglionic and aganglionic segments of rectum.