Approximately 40–70% of treatment-resistant schizophrenic patients fail to benefit from clozapine monotherapy or are partial responders. During the last years several clozapine adjunctive agents have come into clinical practice. This study aims to critically review all published randomized, double-blind, placebo-controlled clinical trials (RCTs) regarding the efficacy and safety of adjunctive agents in clozapine-resistant schizophrenic or schizoaffective patients. A MEDLINE search for RCTs on clozapine adjunctive agents published from January 1980 to February 2004 was conducted. All identified papers were critically reviewed and examined against several methodological features as well as clinical and pharmacological parameters. Eleven trials including 270 patients, partial or non-responders to clozapine, assessed the efficacy of sulpiride, lithium, lamotrigine, fluoxetine, glycine, d-serine, d-cycloserine and ethyl-eicosapentanoate (E-EPA) as clozapine adjuncts. There were eight parallel-group and three crossover trials. The inclusion criteria varied widely. The duration as well as the dosage of clozapine monotherapy were reported adequate in only one trial. Plasma clozapine levels were assessed in only three trials. Main side-effects reported were hypersalivation, sedation, diarrhea, nausea, hyperprolactinaemia. The outcome favored clozapine augmentation with sulpiride, lamotrigine and E-EPA. Lithium was shown to benefit only schizoaffective patients. However, the methodological shortcomings of trials analyzed limit the impact of evidence provided.

The past 50 years have seen an accumulation of evidence suggesting that associative learning depends on high-level cognitive processes that give rise to propositional knowledge. Yet, many learning theorists maintain a belief in a learning mechanism in which links between mental representations are formed automatically. We characterize and highlight the differences between the propositional and link approaches, and review the relevant empirical evidence. We conclude that learning is the consequence of propositional reasoning processes that cooperate with the unconscious processes involved in memory retrieval and perception. We argue that this new conceptual framework allows many of the important recent advances in associative learning research to be retained, but recast in a model that provides a firmer foundation for both immediate application and future research.

Background: This study was designed to determine the effectiveness of a psychosocial intervention for family caregivers in delaying nursing home placement of individuals with dementia.

Methods: The participants comprised 153 family caregivers of persons with dementia who underwent intervention and 155 family caregivers who did not. The intervention consisted of five weekly counselling sessions and a three-month conversation group. All patients with dementia underwent a standardized assessment of cognitive and functional ability. The degree of burden and the subjective health of family caregivers were assessed. Participation continued until the patient moved to a nursing home or died, or until five years of living at home had passed.

Results: There were significant delays (6 months) in nursing home placement, and a longer time at home for persons with dementia with adult children as caregivers in the intervention group compared to the control group at follow-up (p = 0.004). A greater delay of institutionalization was found where intervention-group caregivers were daughters (p = 0.028). The proportional hazards regression showed factors associated with nursing home placement to be the family caregiver's influence on intervention (OR = 1.55, p = 0.019), caregiver gender (OR = 0.66, p = 0.033) and the patient's severity of dementia (OR = 1.45, p = 0.002).

Conclusion: Family caregiver intervention for adult children was significantly associated with prolonged time to nursing home placement.

Objective: To conduct a prospective randomized controlled trial describing and investigating the efficacy and safety of radiosurgical excision of benign superficial vocal fold lesions.

Materials and methods: Fifty patients with benign superficial vocal fold lesions (20 vocal nodules, 27 vocal polyps and three Reinke’s oedema) who failed conservative therapy were included in the study. They were equally randomized into cold knife or radiosurgical excision. Clinical and voice assessments were done pre-operatively and after surgery. Voice analysis included a subjective visual analogue scale (VAS) and a perceptual assessment with a simplified version of the GRBAS scale (GRB) consisting of G (grade), R (roughness), and B (breathiness). Acoustic voice evaluation included jitter and shimmer. Post-operative voice therapy was provided for all patients. Complications, smoothness of post-operative recovery, and administration of analgesia were reported.

Results: Both groups experienced significant improvement in VAS, perceptual evaluation and acoustic analysis after surgery, with no evidence of significant differences between the cold knife and radiofrequency groups. The radiofrequency group showed a decrease of 17 per cent in the mean operative time when compared with the cold knife group, but this was not statistically significant. No evidence of a significant difference was noticed in the smoothness of post-operative recovery, administration of analgesia and complication rate.

Conclusion: Radiophonosurgery opens a new therapeutic approach for patients with benign superficial vocal fold lesions. It combines the advantages of both cold knife and laser phonosurgery, being easy, safe, precise and effective, and having excellent tactile and haemostatic properties.

Background and objective: Controlled hypotension may alter organ blood flow and tissue oxygenation. The aim of the study was to investigate whether induced hypotension using sodium nitroprusside alters pancreatic function assessed by pancreatitis-associated protein concentrations in the blood.

Methods: Thirty patients undergoing elective radical prostatectomy were allocated randomly into two groups: (a) hypotension group: sodium nitroprusside was administered to lower mean arterial pressure to approximately 50 mmHg; (b) control group: no hypotension was used, mean arterial pressure was kept >70 mmHg. Pancreatitis-associated protein and lipase were measured in arterial blood samples: after induction of anaesthesia (T1), at the end of surgery (T2), 2 h (T3) and 24 h (T4) postoperatively.

Results: Pancreatitis-associated protein plasma concentrations increased significantly in patients in the hypotensive group (from 2.8 ± 1.1 to 5.5 ± 2.0 µg L−1 at T4) and pancreatitis-associated protein plasma concentrations were significantly higher in comparison with controls (5.5 ± 2.0 versus 3.5 ± 2.4 µg L−1) at T4. Lipase concentrations showed a similar course in both groups. None of the patients showed clinical signs of pancreatitis.

Conclusions: Controlled hypotension during surgery was associated with a small but significant increase in pancreatitis-associated protein compared with controls. The absence of concomitant elevation in lipase concentrations and a lack of clinical evidence of pancreatitis damage suggest that hypotension induces mild pancreatic stress.

We investigated the effects of controlled hypotension with haemodilution under isoflurane anaesthesia on splanchnic perfusion in elderly patients. We determined the intramucosal pH using gastric tonometry in 28 patients scheduled for hip surgery. Patients without cardiac disease were assigned to two groups according to age. Group A (adult patients, n=14) included patients aged less than 60 years (range 29–58 years, 47±11 years, mean±SD) and group B(elderly patients, n=14) more than 65 years (68–78 years, 72±5 years). Anaesthesia was maintained with N2O-O2-isoflurane. After induction of anaesthesia, haemodilution was produced by drawing 800–1000 mL of blood and replacing it with the same amount of hydroxyethyl starch. Final haematocrit values were 23–24% in all groups. Controlled hypotension was induced with prostaglandin E1 (PGE1) and mean blood pressure was maintained at approximately 60 mmHg for approximately 80 min. Measurements, including gastric intramucosal pH (pHi), arterial blood pH (pHa) and serum lactate were measured before haemodilution (T0), after haemodilution (T1), 80 min after starting hypotension (T2), 60 min after recovery from hypotension (T3) and on the 1st post-operative day (T4). The values of pHa and lactate showed no change in the groups throughout the time course. The gastric pHi values showed significant decreases from 7.418±0.035 to 7.334±0.024 (P < 0.05) in group A and from 7.428±0.029 to 7.320±0.039 (P < 0.05) in group B after haemodilution, while no further decreases were found at 80 min after starting the hypotension (7.329±0.038 in group A and 7.322±0.031 in group B) and 60 min after recovery from hypotension (7.331±0.029 in group A and 7.328±0.034 in group B). It can be concluded that moderate haemodilution under isoflurane anaesthesia might impair splanchnic perfusion in adult and elderly patients. The addition of controlled hypotension with PGE1 or an increase in age did not further impair splanchnic perfusion nor the splanchnic oxygen supply.

The effects of controlled hypotension induced with trimethaphan (TMP), nitroglycerin (TNG) or prostaglandin E1 (PGE1) during sevoflurane anaesthesia on hepatic function were studied in 28 patients undergoing spinal fusion surgery. Patients were randomly divided into three groups to receive TMP (group A, n=10), TNG (group B, n=10) or PGE1 (group C, n=8). Anaesthesia was maintained with N2O and sevoflurane. The mean arterial blood pressure was maintained at 60 mmHg for 90 min. Measurements included arterial ketone body ratio (AKBR-acetoacetate/3-hydroxybutyrate), SGOT, SGPT, LDH, blood glucose and blood gases were made. Measurements were taken before hypotension, 60 min and 90 min after starting hypotension, 60 min after recovery from hypotension and on the post-operative day. AKBR showed no significant change. SGOT, SGPT and LDH were within normal limits. Controlled hypotension induced with TMP, TNG or PGE1 under sevoflurane anaesthesia in surgical patients did not cause hepatocellular damage.