[H](+)S 14297: A novel, selective radioligand at cloned human dopamine D3 receptors

The selective dopamine D₃ receptor antagonist [³H](+)S 14297 ((+)-[7-(N,N-dipropylamino)-5,6,7,8-tetrahydro-naphtho(2,3b)dihydro,2,3-furane]), labelled to high specific activity (145 Ci/mmol), bound to cloned human dopamine D₃ receptors but displayed negligible binding to cloned human D₂ receptors. [³H](+)S 14297 exhibited rapid association and dissociation, high affinity saturable binding (K_d = 7.0 nM) and a competition binding profile highly correlated with that of [¹²⁵I]iodosulpride (r = 0.98).     

Intracellular Ca2+ buffers disrupt muscarinic suppression of Ca2+ current and M current in rat sympathetic neurons.

The role of intracellular Ca2+ concentration ([Ca2+]i) in the muscarinic suppression of Ca2+ current and M-type K+ current has been investigated in isolated rat sympathetic neurons using the whole-cell patch-clamp technique and fura-2 fluorescence measurements. Muscarinic stimulation suppressed currents without raising [Ca2+]i. Nonetheless, intracellular bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) (11-12 mM), a Ca2+ chelator, reduced Ca2(+)-current suppression from 82 to 15%. For the latter, we explain the BAPTA action by a requirement for a certain minimum [Ca2+]i for continued operation of the pathway coupling muscarinic receptors to M-type K+ channels. The pathway coupling muscarinic receptors to Ca channels also showed some dependence on [Ca2+]i, but there may also be a blocking action of BAPTA that is independent of Ca2+ chelation.     

Sterile surgical technique for shunt placement reduces the shunt infection rate in children: preliminary analysis of a prospective protocol in 115 consecutive procedures

Objective The objective of this study was to evaluate whether the rigid application of a sterile protocol for shunt placement was applicable on a routine basis and allowed the reduction of shunt infections (SI) in children. Materials and methods Since 2001, a rigid sterile protocol for shunt placement in children using neither antibiotic-impregnated catheters nor laminar airflow was prospectively applied at Erasme Hospital, Brussels, Belgium. For assessing the protocol efficacy before continuation, we preliminarily analyzed the results of the first 100 operated children (43 females, 57 males, 49 aged <12 months; 115 consecutive shunt placement/revision procedures). All procedures were performed by the same senior surgeon, one assistant, one circulating nurse, one anesthesiologist. The sterile protocol was rigidly imposed to these four staff members: uniformed surgical technique; limited implant and skin edge manipulation; minimized human circulation in the room; scheduling surgery as first morning operation; avoiding postoperative cerebrospinal fluid (CSF) leak; double gloving; procedures of less than 30-min duration; systemic antibiotics prophylaxis. We analyzed separately: (1) children carrying an increased risk of SI (n = 38) due to preoperative external ventricular drainage, CSF leak, meningitis, glucocorticoids, chemotherapy; (2) children aged <12 months; (3) procedures for shunt revision. Results Errors in protocol application were recorded in 71/115 procedures. They were mainly done by non-surgical staff, decreased with time and were medically justified in some young children. Surprisingly, no SI occurred (follow-up, 4 to 70 months). One child developed an appendicitis with peritonitis (Streptococcus faecalis) after 6 months. No SI was found. After peritonitis was cured, shunt reinsertion was uneventful. Conclusion These preliminary results suggest that a uniform and drastic sterile surgical technique for shunt placement: (1) can be rigidly applied on a routine basis; (2) can lower the early SI rate below 1%; (3) might have a stronger impact to reduce SI than using antibiotic-impregnated catheters and optimizing the operative environment such as using laminar airflow and reducing the non-surgical staff. This last issue will be evaluated further in the present ongoing protocol.     

Reconstruction of upper digestive tract: reducing morbidity by laparoscopic pull-up.

BACKGROUND: Gastric pull-up is a useful method for reconstruction of the upper digestive tract, with considerable morbidity/mortality, especially in esophageal cancers (EC). OBJECTIVE: To analyze the experience of a multidisciplinary team with a laparoscopic gastric pull-up (LGPU) method, with or without thoracoscopy, in a series of 120 patients with EC. STUDY DESIGN: Retrospective. PATIENTS AND METHODS: From 1992 to 2004, 120 EC [cervical/cervicothoracic (3.0%), middle third (15.0%), and inferior third (82.0%)]. Most were squamous cell carcinomas (47.0%) and adenocarcinomas (34.0%). Stomach was dissected and mobilized exclusively by laparoscopy. Occasionally, laparoscopic approach was extended cranially, until connecting with cervical dissection. In other cases, dissection of thoracic esophagus was accomplished through a thoracoscopic approach. RESULTS: Eighty-one patients (68.0%) had LGPU; 39 (32.0%) needed thoracoscopy. Mortality was 5.9%. Complications were fistula (10.0%) and pneumonia (10.0%). All fistulae closed spontaneously; 89.2% of patients could swallow a normal oral diet. CONCLUSION: Low morbidity/mortality of LGPU for EC compared favorably with conventional techniques.     

Release of newly synthesized h-dopamine in the striatum: An adaptation of the push-pull cannula method to awake restrained and anesthetized rats

The release of newly synthesized ³H-dopamine (³H-DA) was measured in the rat striatum superfused, through a push-pull cannula, with a physiological medium enriched in ³H-tyrosine. The level of spontaneous ³H-DA release was dependent on the topographical localisation of the cannula in the striatum (anterior parts displayed higher levels than posterior ones) and on the anesthetic state (halothane anesthetized rats demonstrated higher levels than awake ones). Inhibition of DA inactivation processes by local application of benztropine (a DA reuptake inhibitor, 10⁻⁶ M) or by IV administration of pargyline (a MAO inhibitor, 100 mg/kg) enhanced the detectable outflow of ³H-DA from the striatum in both halothane anesthetized and awake rats. Local application of D-amphetamine (10⁻⁵ M) or acetylcholine (5 × 10⁻⁵ M) in the presence of eserine (5 × 10⁻⁵ M) evoked respectively a fivefold and a 30% increase in spontaneous ³H-DA release in halothane anesthetized rats. Inhibition of the firing of dopaminergic neurons by IV injection of gamma-hydroxybutyrate (400 mg/kg) produced a 30% decrease in striatal ³H-DA release. The present results demonstrate that the push-pull cannula method is suitable for the study of DA release in both the anesthetized and the awake rat.     

Salvage immunotherapy of malignant glioma

We present the preliminary results of a phase I trial of adoptive immunotherapy for recurrent or residual malignant glioma. The protocol is based on surgical debulking followed by implantation into the tumor bed of autologous lymphocytes that have been stimulated with phytohemagglutinin-P and then cultured in vitro in the presence of interleukin 2. Fifty-five patients with a mean Karnofsky rating of 64 were treated between February 1985 and March 1987. No significant toxicity was associated with the immunotherapy. Fifty patients had a positive initial response to therapy, nine patients had early recurrence (two to four months after treatment), and 22 patients died. We comment on major differences between the protocol described and other immunotherapy protocols.     

The role of the nurse in active euthanasia and physician-assisted suicide

The researchers wanted to obtain insight into the cooperation between physicians and nurses with regard to active euthanasia and physician-assisted suicide (EAS). In study I a stratified random sample of 203 clinical specialists, 152 general practitioners (GPs) and 50 nursing home physicians (NHPs) participated. In study II a random sample of 521 GPs was drawn from the province of North Holland and a random sample of 521 GPs was drawn from the rest of the Netherlands. For study III all NHPs were approached. Data were collected by means of an interview in study I. In studies II and III an anonymous, postal questionnaire was used. Approximately half of the GPs did not consult with nurses about a patient's request for EAS, the intention to administer EAS, and the actual administration. In 5% of cases, the NHPs and the specialists did not consult with nurses concerning these aspects. The GPs and NHPs indicated in 4% and 3% of the cases, respectively, that nurses administered the lethal drug(s) to the patients; the corresponding figure for the specialists was 21%. Almost all GPs and NHPs and about three-quarters of the specialists thought that nurses should never be allowed to administer EAS.