Progressive plasticity during colorectal cancer metastasis.

As cancers progress, they become increasingly aggressive-metastatic tumours are less responsive to first-line therapies than primary tumours, they acquire resistance to successive therapies and eventually cause death1,2. Mutations are largely conserved between primary and metastatic tumours from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression and therapy resistance3-5. However, we lack an understanding of metastatic cell states and the mechanisms by which they transition. Here, in a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that, although primary tumours largely adopt LGR5+ intestinal stem-like states, metastases display progressive plasticity. Cancer cells lose intestinal cell identities and reprogram into a highly conserved fetal progenitor state before undergoing non-canonical differentiation into divergent squamous and neuroendocrine-like states, a process that is exacerbated in metastasis and by chemotherapy and is associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues compared with their intestinal lineage-restricted primary tumour counterparts. We identify PROX1 as a repressor of non-intestinal lineage in the fetal progenitor state, and show that downregulation of PROX1 licenses non-canonical reprogramming.

Low viscosity silicone with less shrinkage for brain slices.

Plastination consists of replacing lipid and water with a curable polymer. This technique has numerous advantages, of which the production of non-toxic, inert, highly durable, dry, and easy maintenance and storage specimens stand out. Like all anatomical techniques, plastination also has disadvantages, and one of them is tissue shrinkage. The feasibility of using low viscosity domestic silicone (0,1Pa.s at 20°C) to plastinate brain slices was examined. Twenty humans, 10 millimeters (mm) brain slices were impregnated, ten slices each with two polymers [10 with domestic low viscosity polymer - P1 and 10 slices with Biodur® (0,45-0,6Pa.s at 20°C) S10]. Shrinkage was accessed by volume and area measurements. Volume shrinkage was significantly less in the slices impregnated with low viscosity domestic polymer, demonstrating the feasibility to plastinate brain slices with domestic low viscosity silicone polymer.

Evaluation of Hygienic Quality of Food Served in Universities Canteens of Northem Portugal.

Mass catering services have increased in the last years since people need to eat out mainly by work or study reasons. Microbiological quality of foodstuffs (n = 156) was evaluated in 20 food establishment (cafes and canteens) of two universities of northern Portugal. Overall, data revealed a high level of microbiological quality of foods served. No safety risks for consumers were detected since Clostridium spp., Listeria monocytogenes and Salmonella spp. were not detected. Among food types, hot meals displayed better microbiological results than cold foods (p < 0.05) as expected. Regarding hot meals, no differences were observed among different types (p > 0.05). Among cold meals, salads displayed the highest microbiological counts for hygiene indicators as well for food foodborne pathogens such as Staphylococcus aureus, Escherichia coli and Bacillus cereus. Although the risk of foodborne disease is scarce since counts were low. In cafes' meals, higher counts were observed than in canteens' meals which indicates that monitoring measures should be improved to avoid potential foodborne outbreaks related to the ready-to-eat products (salads, sandwiches and pastry). Results could be used as microbiological guidelines for canteens. Results indicated that proper food handling and adequate conservation of fresh foods along the food chain is essential in mass catering services to guarantee the food safety.

[Self-administration of a "mole removal pen"]. / Eigenanwendung eines "Muttermal-Entfernungs-Stifts".

A 31-year-old woman used a "mole removal pen" purchased from the internet for cosmetic reasons to remove numerous pigmentary moles. After self-application there was multiple scarring. Sequential videodermatoscopic documentation was performed. The purchase of medical-cosmetic products, their use, and the possible risks are discussed.

Progressive plasticity during colorectal cancer metastasis.

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

Ventral hernia repair in patients with abdominal loss of domain: an observational study of one institution's experience.

PURPOSE: Abdominal wall hernias are a common problem. The success of abdominal wall reconstruction decreases with increasing hernia size. This study summarizes the outcomes of one surgeon's experience using a "sandwich" technique for hernia repair in patients with loss of abdominal domain. METHODS: We reviewed our ventral hernia repair (VHR) experience from 2008 to 2015 among patients with loss of domain, as defined by a hernia defect greater than 300 cm2. The percent of herniation through the defect, defined by a hernia sac-to-abdominal cavity volume ratio, was measured on preoperative CT scans by four independent reviewers and averaged. Outcomes were compared among those with giant ventral hernias (hernia sac-to-abdominal cavity volume >30%) and those with smaller defect ratios. RESULTS: Over the study period, 21 patients underwent VHR. In 17 patients (81%), a "sandwich" technique was utilized. Ten patients had hernia sac-to-abdominal cavity defects less than 30%, and 11 had defects greater than 30%. Preoperative characteristics were similar in both groups with the exception of a higher ASA score in those with giant ventral hernias and more Ventral Hernia Working Group Grade 3 hernias in those without giant ventral hernias. Postoperative outcomes were similar in both groups. There were no mortalities. There were two recurrences (18%) in the giant VHR group and none in the smaller defect group (p = 0.16). Surgical site occurrences were noted in 48% of patients and did not differ between giant and non-giant VHR groups (50 vs 45%, p = 0.84). Average postoperative length of stay was significantly longer in the giant VHR group (31 vs. 17 days, p = 0.03). CONCLUSIONS: Our results suggest that the "sandwich" technique for VHR is a safe and durable method to restore abdominal wall integrity in those with LOD, even in patients with giant ventral hernias.

A validated, risk assessment tool for predicting readmission after open ventral hernia repair.

BACKGROUND/PURPOSE: To present a validated model that reliably predicts unplanned readmission after open ventral hernia repair (open-VHR). STUDY DESIGN: A total of 17,789 open-VHR patients were identified using the 2011-2012 ACS-NSQIP databases. This cohort was subdivided into 70 and 30% random testing and validation samples, respectively. Thirty-day unplanned readmission was defined as unexpected readmission for a postoperative occurrence related to the open-VHR procedure. Independent predictors of 30-day unplanned readmission were identified using multivariable logistic regression on the testing sample (n = 12,452 patients). Subsequently, the predictors were weighted according to ß-coefficients to generate an integer-based Clinical Risk Score (CRS) predictive of readmission, which was validated using receiver operating characteristics (ROC) analysis of the validation sample (n = 5337 patients). RESULTS: The rate of 30-day unplanned readmission was 4.7%. Independent risk factors included inpatient status at time of open-VHR, operation time, enterolysis, underweight, diabetes, preoperative anemia, length of stay, chronic obstructive pulmonary disease, history of bleeding disorders, hernia with gangrene, and panniculectomy (all P < 0.05). ROC analysis of the validation cohort rendered an area under the curve of 0.71, which demonstrates the accuracy of this prediction model. Predicted incidence within each 5 risk strata was statistically similar to the observed incidence in the validation sample (P = 0.18), further highlighting the accuracy of this model. CONCLUSION: We present a validated risk stratification tool for unplanned readmissions following open-VHR. Future studies should determine if implementation of our CRS optimizes safety and reduces readmission rates in open-VHR patients.

Efeitos do propofol administrado por via intracelomática em cágados-de-barbicha (Phrynops geoffroanus) Schweigger, 1812 / Effects of propofol administered by intracelomatic route in Geoffroy's toadhead turtle (Phrynops geoffroanus) Schweigger, 1812

O presente estudo avaliou a influência do regime hídrico sobre efeitos do propofol em Phrynops geoffroanus, bem como a qualidade da contenção farmacológica produzida. Foram utilizados 10 animais, anestesiados em dois momentos com propofol, na dose de 35mg/kg, por via intracelomática, com intervalo de 15 dias. O grupo 1 fora retirado da água 12 horas antes do procedimento e o grupo 2 permaneceu dentro da água até o momento da indução anestésica. Foram mensuradas frequência cardíaca, pressão arterial sistólica, temperatura, frequência respiratória e saturação de oxi-hemoglobina, e avaliados duração do período de latência, período hábil, período de recuperação e qualidade da contenção farmacológica. Houve diferença significativa entre grupos apenas quanto à frequência cardíaca. No grupo 1, as médias dos períodos de latência, hábil anestésico e de recuperação foram de 16,8±8,4, 86,5±79,4 e 1,5±3,8 minutos, respectivamente. Já no grupo 2, as médias foram de 19,9±9,8, 110,9±104,7 e 28,8±58,2 minutos, respectivamente. Concluiu-se que o regime hídrico de 12 horas não influenciou os parâmetros anestésicos e fisiológicos dos animais e que a qualidade da contenção farmacológica foi considerada boa em ambos os grupos.(AU)

The present study evaluated the influence of the water regime on the effects of propofol on Phrynops geoffroanus, as well as the quality of the pharmacological containment produced. Ten animals, anesthetized at two times with propofol at a dose of 35mg / kg, were used intracelomatically with a 15 day interval. Group 1 was withdrawn from the water 12 hours prior to the procedure and Group 2 remained in the water until the time of anesthetic induction. Heart rate, systolic blood pressure, temperature, respiratory rate and oxyhemoglobin saturation were measured and the duration of the latency period, skill period, recovery period and quality of pharmacological containment were measured. There was a significant difference between groups only regarding heart rate. In Group 1, the means of the latency, skillful anesthesia and recovery periods were 16.8±8.4, 86.5±79.4 and 1.5±3.8 minutes, respectively. In Group 2, the mean values were 19.9±9.8, 110.9±104.7 and 28.8±58.2 minutes, respectively. It was concluded that the 12-hour water regime did not influence the anesthetic and physiological parameters of the animals, and the quality of the pharmacological restraint was considered good in both groups.(AU)

The effect of TISSEEL fibrin sealant on seroma formation following complex abdominal wall hernia repair: a single institutional review and derived cost analysis.

PURPOSE: The authors evaluated the ability of a fibrin sealant (TISSEEL™: Baxter Healthcare Corp, Deerfield, IL, USA) to reduce the incidence of post-operative seroma following abdominal wall hernia repair. METHODS: We performed a 4-year retrospective review of patients undergoing abdominal wall hernia repair, with and without TISSEEL, by a single surgeon (FEE) at The Johns Hopkins Hospital. Demographics, surgical risk factors, operative data and 30-day outcomes, including wound complications and related interventions, were compared. The quantity and cost of Tisseel per case was reviewed. RESULTS: A total of 250 patients were evaluated: 127 in the TISSEEL group and 123 in the non-TISSEEL control group. The average age for both groups was 56.6 years (P = 0.97). The majority of patients were female (TISSEEL 52.8%, non-TISSEEL 56.1%, P = 0.59) and ASA Class III (TISSEEL 56.7%, non-TISSEEL 58.5%, P = 0.40). There was no difference in the average defect size for both groups (TISSEEL 217 ± 187.6 cm(2), non-TISSEEL 161.3 ± 141.5 cm(2), P = 0.36). Surgical site occurrences occurred in 18.1% of the TISSEEL and 13% of the non-TISSEEL group (P = 0.27). There was a trend towards an increased incidence of seroma in the TISSEEL group (TISSEEL 11%, non-TISSEEL 4.9%, P = 0.07). A total of $124,472.50 was spent on TISSEEL, at an average cost of $995.78 per case. CONCLUSIONS: In the largest study to date, TISSEEL™ application offered no advantage for the reduction of post-operative seroma formation following complex abdominal hernia repair. Moreover, the use of this sealant was associated with significant costs.

The treatment of tardive dyskinesia--a systematic review and meta-analysis.

This systematic review aimed to collate randomized controlled trials (RCTs) of various interventions used to treat tardive dyskinesia (TD) and, where appropriate, to combine the data for meta-analysis. Clinical trials were identified by electronic searches, handsearches and contact with principal investigators. Data were extracted independently by two reviewers, for outcomes related to improvement, deterioration, side-effects and drop out rates. Data were pooled using the Mantel-Haenzel Odds Ratio (fixed effect model). For treatments that had significant effects, the number needed to treat (NNT) was calculated. From 296 controlled clinical trials, data were extracted from 47 trials. For most interventions, we could identify no RCT-derived evidence of efficacy. A meta-analysis showed that baclofen, deanol and diazepam were no more effective than a placebo. Single RCTs demonstrated a lack of evidence of any effect for bromocriptine, ceruletide, clonidine, estrogen, gamma linolenic acid, hydergine, lecithin, lithium, progabide, seligiline and tetrahydroisoxazolopyridinol. The meta-analysis found that five interventions were effective: L-dopa, oxypertine, sodium valproate, tiapride and vitamin E; neuroleptic reduction was marginally significant. Data from single RCTs revealed that insulin, alpha methyl dopa and reserpine were more effective than a placebo. There was a significantly increased risk of adverse events associated with baclofen, deanol, L-dopa, oxypertine and reserpine. Meta-analysis of the impact of placebo (n=485) showed that 37.3% of participants showed an improvement. Interpretation of this systematic review requires caution as the individual trials identified tended to have small sample sizes. For many compounds, data from only one trial were available, and where meta-analyses were possible, these were based on a small number of trials. Despite these concerns, the review facilitated the interpretation of the large and diverse range of treatments used for TD. Clinical recommendations for the treatment of TD are made, based on the availability of RCT-derived evidence, the strength of that evidence and the presence of adverse effects.

Clonal relationships among Escherichia coli serogroup O6 isolates based on RAPD.

The genetic diversity in a group of Escherichia coli strains belonging to serogroup O6 but expressing different H antigens was investigated by random amplification of polymorphic DNA (RAPD). Isolates of serotypes H16, H1, H31, and non-motile (NM) strains were typed using a set of 3 primers with different G + C contents. The amplified band arrays allowed the identification of 3 main clonal clusters corresponding to each O:H serotype analyzed. Based on their RAPD profiles NM strains could be assigned to either H1 or H31 serotypes. The results indicate that the flagellar antigen and the RAPD fingerprint represent reliable clonal markers in this E. coli group.

Vitamin E for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Vitamin E has been proposed as a treatment to prevent or decrease the severity of TD. OBJECTIVES: To determine the clinical effects of vitamin E for people with schizophrenia or other chronic mental illnesses who also developed neuroleptic-induced tardive dyskinesia. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-2001), The Cochrane Schizophrenia Group's Register (January 2001), EMBASE (1980-2001), LILACS (1982-2001), MEDLINE (1966-2001), PsycLIT (1974-2001), SCISEARCH (1997), hand searching the references of all identified studies and contacting the first author of each included trial. SELECTION CRITERIA: Reports identified in the search were included if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia or other chronic mental illness who had been randomly allocated to either vitamin E or to a placebo or no intervention. DATA COLLECTION AND ANALYSIS: Data were independently extracted from these trials by each reviewer and relative risks (RR) or weighted mean differences (WMD), with 95% confidence intervals (CI) were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Ten studies were included. The overall results for 'clinically relevant improvement' found no benefit of vitamin E against placebo (6 trials, 256 people, RR 0.95 CI 0.89 to 1.02). For the outcome of 'any improvement in TD symptoms', again, no clear difference in favour of vitamin E was found (7 trials, 311 people, RR 0.86 CI 0.75 to 1.00). However, people who had not been allocated vitamin E, showed more deterioration of their symptoms (5 trials, 98 people, RR 0.38 CI 0.16 to 0.9). There was no difference in the incidence of adverse effects (8 trials, 163 people, RR 1.3 CI 0.5 to 3.2) or leaving the study early (medium term 5 trials, 133 people, RR 1.5 CI 0.8 to 2.7). There is no trial-based information regarding the effect of vitamin E for those with early onset of TD. REVIEWER'S CONCLUSIONS: Small trials with uncertain quality of randomisation indicate that vitamin E protects against deterioration of TD but there is no evidence that vitamin E improves symptoms of TD.

Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD. OBJECTIVES: To determine the effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP)) for people with antipsychotic-induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: We updated the previous Cochrane review by searching the Cochrane Schizophrenia Group Register (September 2003). We searched references for further trial citations and, where possible, contacted authors. SELECTION CRITERIA: Randomised controlled trials comparing use of non-benzodiazepine GABA agonist drugs with placebo or no intervention, involving people with schizophrenia or other chronic mental illnesses with signs of antipsychotic-induced TD. DATA COLLECTION AND ANALYSIS: Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to treat (NNT). For continuous data Weighted Mean Differences (WMD) were calculated. MAIN RESULTS: We identified eight small poorly reported studies for inclusion. For the outcome of 'no clinically important improvement in tardive dyskinesia' GABA agonist drugs were not clearly better than placebo (n = 108, RR 0.83 CI 0.6 to 1.1). Deterioration in mental state was more likely to occur in people receiving GABA medication (n = 95, RR 2.47 CI 1.1 to 5.4), but this effect was influenced by the decision to assign a negative outcome to those who dropped out before the end of the study. A greater proportion of people allocated GABA medication may fail to complete the trial compared with those allocated placebo (20% versus 9%), but this difference was not statistically significant (n = 136, RR 1.99 CI 0.8 to 4.7). There is a suggestion of an increase in ataxia (loss of power of muscular coordination) for both baclofen and sodium valproate (n = 95, RR 3.26 CI 0.4 to 30.2), and in sedation (n = 113, RR 2.12 CI 0.8 to 5.4) compared with placebo, but this was not significant. Withdrawal of tetrahydroisoxazolopyridine (THIP) may cause seizures. REVIEWERS' CONCLUSIONS: Evidence of the effects of baclofen, progabide, sodium valproate, or THIP for people with antipsychotic-induced TD is inconclusive and unconvincing. Any possible benefits are likely to be outweighed by the adverse effects associated with their use.

Anticholinergic medication for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Neuroleptic medication is used extensively to treat people with chronic mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders. Because of this, many acutely psychotic patients being treated with neuroleptic medication also receive anticholinergic drugs in order to reduce some of the associated movement side-effects. OBJECTIVES: To determine whether the use or the withdrawal of anticholinergic drugs (benzhexol or benztropine or biperiden or orphenadrine or procyclidine or scopolamine or trihexylphenidyl) were clinically effective for the treatment of people with both neuroleptic-induced TD and schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1995), Cochrane Schizophrenia Group's Register of trials (1995), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995), PsycLIT (1974-1995), and SCISEARCH (1995) were undertaken. References of all identified studies were searched for further trial citations. Principle authors of trials were contacted. SELECTION CRITERIA: Reports identified in the search were included if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia or other chronic mental illness who had been randomly allocated to either an anticholinergic agent or to a placebo (or no intervention). DATA COLLECTION AND ANALYSIS: No data could be extracted from the seven randomised controlled trials identified. MAIN RESULTS: No data were synthesized. The authors have been contacted to provide the relevant information. Two studies were excluded because no data are available and six others are still awaiting further information from the authors. REVIEWER'S CONCLUSIONS: Based on currently available information, no confident statement can be made about the effectiveness of anticholinergics to treat people with neuroleptic-induced tardive dyskinesia. The same applies for the withdrawal of such medications. Whether the withdrawal of anticholinergics may benefit people with neuroleptic-induced TD, this should be evaluated in a parallel-group, placebo-controlled randomised trial, with adequate sample size and at least 6 weeks of follow up.

Benzodiazepines for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) is a potentially disfiguring movement disorder of the orofacial region often caused by use of neuroleptic drugs. A wide range of strategies have been used to help manage TD and, for those who are unable to have their antipsychotic medication stopped or substantially changed, the benzodiazapine group of drugs has been suggested as a useful adjunctive treatment. OBJECTIVES: To determine the clinical efficacy of benzodiazepines for people with neuroleptic-induced tardive dyskinesia (TD) schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1995), the Cochrane Schizophrenia Group's Register of trials (1995), EMBASE (1980-1995), LILACS (1982-1995), MEDLINE (1966-1995), PsycLIT (1974-1995), SCISEARCH (1995) and handsearching the references of all identified studies. SELECTION CRITERIA: The inclusion criteria for all randomised studies were that they should focus on people with schizophrenia or other chronic mental illnesses and neuroleptic-induced TD and compare the use of benzodiazepines to placebo or no intervention. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and the odds ratio (95% CI) or the average difference (95% CI) were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Two trials were able to be included in this review. The results of this review do not allow any confident interpretations on the clinical utility of benzodiazepines for the treatment of neuroleptic-induced TD. From the data combined in this review, benzodiazepines have no distinct advantages over placebo in the treatment of TD. Data on side effects were not reported in the included trials. REVIEWER'S CONCLUSIONS: No clear statement about the efficacy of benzodiazepines drugs, to treat neuroleptic-induced TD, could be provided.

Diltiazem, nifedipine, nimodipine or verapamil for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) is a potentially disfiguring movement disorder of the orofacial region often caused by use of neuroleptic drugs. A wide range of strategies have been used to help manage TD and, for those who are unable to have their antipsychotic medication stopped or substantially changed, the calcium-channel blocking group of drugs (diltiazem, nifedipine, nimodipine, verapamil) has been suggested as a useful adjunctive treatment. OBJECTIVES: To determine the clinical efficacy of calcium-channel blockers in people with neuroleptic-induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1995), Cochrane Schizophrenia Group's Register of trials (1995), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995), PsycLIT (1974-1995), and SCISEARCH were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted. SELECTION CRITERIA: The inclusion criteria for all relevant randomised studies were that they should focus on people with schizophrenia or other chronic mental illnesses, with neuroleptic-induced TD and compare the use of calcium-channel blockers to placebo or no intervention. DATA COLLECTION AND ANALYSIS: No data could be extracted from the two randomised controlled trials that are currently awaiting assessment. The authors have been contacted to provide the relevant information. MAIN RESULTS: No studies met the entry criteria. No data were synthesized. REVIEWER'S CONCLUSIONS: Based on currently available information, no confident statement can be made about the effectiveness of calcium-channel blockers for treating people with neuroleptic-induced tardive dyskinesia. Before evaluation of these drugs in larger randomised controlled trials, clinicians should carefully weigh up their possible benefits against their potential adverse effects.

Cholinergic medication for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Since the 1950's neuroleptic medication has been extensively used to treat people with chronic mental illnesses, such as schizophrenia. These may cause tardive dyskinesia (TD), abnormal, repetitive and involuntary movements, in up to 20% of those using the medication for longer than three months. One theory of causation supports the use of cholinergic drugs for the management of TD. OBJECTIVES: To determine whether the use of cholinergic agents (arecoline, choline, deanol, lecithin, meclofenoxate, physostigmine, RS 86) were associated with clinical improvement in neuroleptic-induced TD in people with schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1995), Cochrane Schizophrenia Group's Register of trials (1995), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995), PsycLIT (1974-1995), and SCISEARCH (1995) were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted. SELECTION CRITERIA: Reports identified in the search were included if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia or other chronic mental illnesses who had been randomly allocated to either a cholinergic agent or to a placebo (or no intervention). DATA COLLECTION AND ANALYSIS: Seven different studies (8 references) were included in this review, and another ten trials are currently awaiting further data from authors. Data were independently extracted from these trials by each reviewer and odds ratios (OR) or average differences, with the 95% confidence intervals (95% CI) were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: The studies failed to detect any significant advantage of deanol or lecithin when compared to placebo. Data from two deanol trials demonstrated an excess of side effects in the active treatment group. People on cholinergic compounds report a range of gastrointestinal adverse effects (anorexia, nausea, vomiting, diarrhea, abdominal pain), sedation, and undesirable body odour. One person died of acute aspiration in a deanol versus placebo cross-over study. REVIEWER'S CONCLUSIONS: This review provides no strong evidence for the use of cholinergic agents in the treatment of neuroleptic-induced tardive dyskinesia. While people receiving cholinergic treatment had a marginal benefit compared to placebo, because of the small sample size, the cumulative data must be interpreted as inconclusive. Clinicians and trialists considering using cholinergic agents to treat TD should balance the lack of evidence for the efficacy against the excess of side effects associated with these compounds.

Miscellaneous treatments for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of neuroleptic medication. This review, one in a series examining the treatment of tardive dyskinesia, will cover miscellaneous treatments not covered elsewhere. OBJECTIVES: The primary objective of this review was to determine whether the following interventions were associated with a reduction of TD in people with schizophrenia, or others chronic mental illnesses: botulin toxin, endorphin, estrogen, essential fatty acid, EX11582A, ganglioside, lithium, naloxone, periactin, phenylalanine, piracetam, stepholidine, tryptophan, neurosurgery, or ECT. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1995), Cochrane Schizophrenia Group's Register of trials (1995), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995), PsycLIT (1974-1995), and SCISEARCH (1995) were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted. SELECTION CRITERIA: The inclusion criteria for all relevant randomised studies were that they should focus on people with schizophrenia or other chronic mental illnesses, with neuroleptic-induced TD and compare the use of the interventions listed above versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: Forty references describing 31 different trials were identified by the search strategy. Of 31 trials, 15 trials were excluded, six trials were included, eight awaiting assessment and a further two trials are pending (awaiting translation, unable to locate). Data were independently extracted by each reviewer and the odds ratio or the average differences were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Data were available about the efficacy and safety of cerultide, essential fatty acids, estrogen, lithium and insulin. There was a significant improvement in TD associated with the use of insulin compared to placebo (OR = 0.04, 95%CI 0.01-0.24). No significant differences between the other compounds and placebo were identified. REVIEWER'S CONCLUSIONS: There is no strong evidence to support the use of any of the agents included in this review, however because of the small sample sizes, all results must be considered inconclusive. The association between low dose insulin and improvement of TD requires replication.

Vitamin E for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Neuroleptic (antipsychotic) medication is used extensively to treat people with chronic mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Vitamin E has been proposed as a treatment to prevent or decrease the severity of TD. OBJECTIVES: To determine the clinical effects of vitamin E for people with schizophrenia or other chronic mental illnesses who also developed neuroleptic-induced tardive dyskinesia. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1998), The Cochrane Schizophrenia Group's Register (September 1998), EMBASE (1980-98), LILACS (1982-96), MEDLINE (1966-98), PsycLIT (1974-98), SCISEARCH, handsearching the references of all identified studies and contacting the first author of each included trial. SELECTION CRITERIA: Reports identified in the search were included if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia or other chronic mental illness who had been randomly allocated to either vitamin E or to a placebo or no intervention. DATA COLLECTION AND ANALYSIS: Data were independently extracted from these trials by each reviewer and Peto odds ratios (OR) or average differences, with the 95% confidence intervals (CI) were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Eight studies were included, and another three are currently awaiting further data from authors. The overall results for both, 'clinically relevant improvement' and 'any improvement' of TD symptoms, were in favour of vitamin E (OR 0.16, CI 0.04-0.7, NNT 5 CI 2.-32 and OR 0.23, CI 0.10-0.55, NNT 4 CI 2. 5-12 respectively). People who had not used vitamin E showed more deterioration of their symptoms (OR 0.20, CI 0.04-0.93). No difference could be found regarding the presence of adverse effects or leaving the study early before the end of study. There is no trial-based information regarding the effect of vitamin E for those with early onset of TD. REVIEWER'S CONCLUSIONS: Small trials with uncertain quality of randomisation, tend to suggest that vitamin E improves the symptoms of TD. Methodological problems such as small sample size, short term interventions, and inappropriate use of crossover design need to be dealt with in any future studies. The results of a recently completed trial involving 158 participants are eagerly awaited.