Intravenous lidocaine improves postoperative analgesia, fatigue, and bowel function after laparoscopic colectomy. These benefits are associated with a significant reduction in hospital stay.
In experienced hands, laparoscopic sigmoidectomy may be a safe and effective procedure for fistulized sigmoiditis.
Purpose: We studied the pharmacokinetics of heated intraoperative intraperitoneal (i.p.) oxaliplatin (LOHP) solution and its safety profile in increasingly hypotonic solutions. This is the first clinical study of i.p. chemohyperthermia with hypotonic solutions. Methods: Patients with peritoneal carcinomatosis (PC) underwent complete cytoreductive surgery followed by intraoperative i.p. chemohyperthermia (IPCH) with successive dextrose solutions of 300, 200, 150 and 100 mosm/l. LOHP (460 mg/m2) was administered in 2 liters of solution/m2 at an i.p. temperature of 42–44°C for 30 min. IPCH was performed using an open procedure (skin pulled upwards) with a continuous closed circuit. Patients received intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2) just before IPCH to maximize the effect of LOHP. i.p. plasma and tissue samples were analyzed by means of atomic absorption spectrophotometry. Sixteen consecutive patients with PC of either gastrointestinal or peritoneal origin were treated. The safety of the procedure was studied. Results: Pharmacokinetics: The mean duration of the entire procedure was 7.7 ± 2.6 h. Half the LOHP dose was absorbed within 30 min at all dose levels. Absorption was not higher with hypotonic solutions than with isotonic solutions. The area under the curve of LOHP in plasma did not increase with decreasing osmolarity of the i.p. solutions. Intratumoral LOHP penetration was high; it was similar to that at the peritoneal surface, and about 18 times higher than that in nonbathed tissues. LOHP penetration was not significantly increased by using hypotonic solutions. Safety: There was a very high incidence of unexplained postoperative peritoneal bleeding (50%) and unusually severe thrombocytopenia in the 150 and 100 mosm/l groups. Conclusion: Contrary to experimental studies, this clinical study showed no increase in tumoral or systemic penetration of LOHP with i.p. hypotonic solutions (200, 150 or 100 mosm/l) during IPCH. A high incidence of i.p. hemorrhage and thrombocytopenia was observed.
Molecular and biophysical properties of GABAA receptors of dopaminergic (DA) neurones of the pars compacta of the rat substantia nigra were studied in slices and after acute dissociation. Single‐cell reverse transcriptase‐multiplex polymerase chain reaction confirmed that DA neurones contained mRNAs encoding for the α3 subunit of the GABAA receptor, but further showed the presence of α4 subunit mRNAs. α2, β1 and γ1 subunit mRNAs were never detected. Overall, DA neurones present a pattern of expression of GABAA receptor subunit mRNAs containing mainly α3/4β2/3γ3. Outside‐out patches were excised from DA neurones and GABAA single‐channel patch‐clamp currents were recorded under low doses (1‐5 μM) of GABA or isoguvacine, a selective GABAA agonist. Recordings presented several conductance levels which appeared to be integer multiples of an elementary conductance of 4‐5 pS. This property was shared by GABAA receptors of cerebellar Purkinje neurones recorded in slices (however, with an elementary conductance of 3 pS). Only the 5‐6 lowest levels were analysed. A progressive change in the distribution of occupancy of these levels was observed when increasing the isoguvacine concentration (up to 10 μM) as well as when adding zolpidem (20‐200 nM), a drug acting at the benzodiazepine binding site: both treatments enlarged the occupancy of the highest conductance levels, while decreasing that of the smallest ones. Conversely, Zn2+ (10 μM), a negative allosteric modulator of GABAA receptor channels, decreased the occupancy of the highest levels in favour of the lowest ones. These properties of α3/4β2/3γ3‐containing GABAA receptors would support the hypothesis of either single GABAA receptor channels with multiple open states or that of a synchronous recruitment of GABAA receptor channels that could involve their clustering in the membranes of DA neurones.
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