Reduction of aggression during benzodiazepine withdrawal: effects of flumazenil.

Benzodiazepine withdrawal has been associated with hostile and aggressive behavior. The benzodiazepine antagonist flumazenil has reduced, increased or not affected hostility and aggression in animal and human studies. In the present study we analyzed data collected in a placebo-controlled study of the effects of the benzodiazepine antagonist flumazenil in patients previously treated for benzodiazepine dependency, and healthy controls. The aim was to analyze the effects of flumazenil on hostility and aggression. Ten patients and 10 controls received, on two separate occasions, cumulative doses of flumazenil (0.05, 0.1, 0.25, 0.5 and 1mg at 15min intervals) or placebo. Withdrawal symptoms were rated after each injection. Patients had been free from benzodiazepines for 47 (4-266) weeks on the first occasion. A three-way interaction (groupxtreatmentxdose) was found, and was explained by: 1) patients rating aggression and hostility higher than controls at all times during placebo, while 2) during the flumazenil provocation i) the initial significant difference between patients and controls was no longer significant above the 0.5mg dose, and ii) patients rated aggression and hostility significantly lower above the 0.5mg dose compared to base-line. The results suggest that self-rated aggression and hostility in patients treated for benzodiazepine dependency was reduced by the partial benzodiazepine agonist flumazenil.

Visual scoring of atherosclerosis in chest computed tomography: findings among male construction workers.

BACKGROUND: Standard chest computed tomography (CT) examinations may contain valuable and underused information on atherosclerosis. PURPOSE: To study the retrospective scoring of chest atherosclerosis in CT studies performed for reasons other than cardiovascular. MATERIAL AND METHODS: Unenhanced CT images originally used for lung cancer screening of 505 male construction workers were retrospectively analyzed for chest atherosclerotic calcifications (coronary, aortic, and precervical artery origins). Findings were compared between those with a prediagnosed cardiovascular disease or diabetes (n = 180) and disease-free subjects (n = 325). RESULTS: Arterial calcifications (all) occurred among 96.6% of the subjects and coronary calcifications among 91.7%. The average total calcium score of the diseased subjects was 8.34 vs. 5.13 in the disease-free group (P<0.001). All calcification scores increased with age. In multivariable analyses, systolic blood pressure, erythrocyte sedimentation rate, and smoking were generally associated with high scores, while high stature and high diastolic blood pressure were mainly associated with low scores. Nonsignificant positive associations between asbestos exposure and coronary calcifications were found. CONCLUSION: Our scoring method agreed well with preknown cardiovascular risk factors, indicating the method's usability. Chest CT examinations contain valuable information concerning atherosclerosis. This can be used epidemiologically or to reveal occult atherosclerotic disease.

Patellar tendon shortening after treatment of patellar instability with a patellar tendon medialization procedure.

Patellar instability is a multifactorial disorder. Patella alta is strongly associated with patellar instability. We hypothesize that procedures of the patellar tendon such as medialization may shorten the patellar tendon. In this retrospective study, 41 patients with patellar instability were treated operatively with a patellar tendon medialization procedure. Twenty-eight knees were treated using a modified Roux-Goldthwait method and 16 using a modified Elmslie-Trillat method. The patients were followed 2-7 years after the operation. Pre- and post-operative x-rays were analyzed with particular emphasis on patellar tendon length, patellofemoral congruence angle and osteoarthritis. The final clinical outcome was assessed using the Lysholm score and clinical examination. In both groups patients were generally satisfied with the result of the operation and there was no significant difference in Lysholm scores at follow-up. However, patellofemoral osteoarthritic changes increased in both groups compared with the pre-operative status. The patellar tendon length was reduced in both groups, but significantly, by 7%, in the Roux-Goldthwait group. We conclude that patellar tendon shortens after a Roux-Goldthwait procedure.

The reliability of diagnosis of infection during revision arthroplasties.

BACKGROUND: Follow up studies have shown that 0.5 to 4% of the total joint arthroplasties will be complicated by infection. Distinction between aseptic loosening and infection is important for prediction of the final outcome after revision arhtroplasty but also for the choice of operative treatment. However, diagnosis of low grade chronic infection is extremely demanding. MATERIALS AND METHODS: 68 hip and knee revision arthroplasties were reviewed retrospectively in order to evaluate the reliability of pre- and perioperative analysis of infection during total joint revision arthroplasties. The sensitivity and specificity for clinical signs, blood white-cell count, C-reactive protein level, radiographic analysis, bone and leukocyte scans, joint aspirations, and gram staining were determined. Tissue sample were harvested and cultured in all cases. Positive cultures were regarded as a true infection. RESULTS: We were not able to characterize the infection by clinical signs. Also no single test was able to show the presence of infection in all cases. The best results were obtained from pre- and perioperative joint aspirations. Joint aspiration showed 1.0 specificity and 0.75 sensitivity. CONCLUSION: It is clear from this study that no single test is able to show the presence of infection in every case. Classical clinical signs, laboratory tests, special imaging studies and joint aspirations have all yielded a notable rate of false negative results. Therefore, we recommend that, if arthroplasty patients have pain in prosthetic joint without clear radiological evidence of loosening, bone scans and preoperative joint aspirations should be undertaken. Also, if radiological evidence of loosening is accompanied with one or more of following criteria; C-reactive protein level elevated, radiologic evidence of infection, loosening within the first five years after implantation. In case of infection a delayed two-stage reconstruction should be managed.

Acute traumatic hemarthrosis of the knee. Is routine arthroscopic examination necessary? A study of 320 consecutive patients.

BACKGROUND AND AIMS: Distortions and contusions of the knee are common. Fairly often they will result in hemarthrosis. The purpose of this study was to evaluate the findings in patients with acute traumatic hemarthrosis of the knee and based on these findings estimate the necessity of acute arthroscopic examination. MATERIAL AND METHODS: A total of 320 patients were examined arthroscopically between the years 1994 to 96 in the Turku University Hospital. Patients with other than chondral or osteochondral fractures were excluded. RESULTS: The most common arthroscopic findings were rupture of the ACL (45%), dislocation of the patella (23%) and meniscal tear (21%). In only 113 (35%) cases an immediate therapeutic procedure was performed in addition to the arthroscopic examination. CONCLUSIONS: Based on our findings we believe that routine arthroscopic examination is not necessary in patients with acute traumatic hemarthrosis of the knee. In our opinion the patient should be examined and followed by an orthopedic surgeon and if a lesion requiring operative treatment is diagnosed or suspected, an arthroscopic examination should be scheduled. The timing of the procedure should be such that all possible lesions encountered can be treated in the same operation.

Accelerated up-regulation of L-Sox5, Sox6, and Sox9 by BMP-2 gene transfer during murine fracture healing.

Fracture repair is the best-characterized situation in which activation of chondrogenesis takes place in an adult organism. To better understand the mechanisms that regulate chondrogenic differentiation of mesenchymal progenitor cells during fracture repair, we have investigated the participation of transcription factors L-Sox5, Sox6, and Sox9 in this process. Marked up-regulation of L-Sox5 and Sox9 messenger RNA (mRNA) and smaller changes in Sox6 mRNA levels were observed in RNAse protection assays during early stages of callus formation, followed by up-regulation of type II collagen production. During cartilage expansion, the colocalization of L-Sox5, Sox6, and Sox9 by immunohistochemistry and type II collagen transcripts by in situ hybridization confirmed a close relationship of these transcription factors with the chondrocyte phenotype and cartilage production. On chondrocyte hypertrophy, production of L-Sox5, Sox9 and type II collagen were down-regulated markedly and that of type X collagen was up-regulated. Finally, using adenovirus mediated bone morphogenetic protein 2 (BMP-2) gene transfer into fracture site we showed accelerated up-regulation of the genes for all three Sox proteins and type II collagen in fractures treated with BMP-2 when compared with control fractures. These data suggest that L-Sox5, Sox6, and Sox9 are involved in the activation and maintenance of chondrogenesis during fracture healing and that enhancement of chondrogenesis by BMP-2 is mediated via an L-Sox5/Sox6/Sox9-dependent pathway.

Association between pleural plaques and coronary heart disease.

OBJECTIVE: The aim of this study was to verify a clinical impression that patients with coronary heart disease disproportionately frequently have calcified pleural plaques. METHODS: Chest X-rays were collected from 148 patients referred consecutively to the Helsinki University Central Hospital for coronary angiography and from 100 consecutive lung cancer patients seen at the same hospital. The radiographs were analyzed for the presence of calcified pleural plaques according to the classification the International Labour Office. A generalized linear model with binomial distribution and log link was used to estimate the relative risks and their 95% confidence intervals (95% CI). RESULTS: The prevalence of calcified pleural plaques was 35% for the coronary patients and 19% for the lung cancer patients. Calcified pleural plaques were more common among the men than the women, and the risk increased with age. The relative risk of calcified pleural plaques, adjusted for age and gender, was 2.19 (95% CI 1.44-3.32) for the coronary patients as compared with the lung cancer patients. CONCLUSIONS: Further studies with better information on past exposure to asbestos and other potential risk factors are warranted to confirm the observations and to examine whether the association between coronary heart disease and calcified pleural plaques is related to an etiologic or an individual susceptibility factor common to both of these conditions.

Induction of periosteal callus formation by bone morphogenetic protein-2 employing adenovirus-mediated gene delivery.

Although the chondrogenic response of periosteum is well established in healing fractures, the mechanisms mediating the proliferation and differentiation of periosteal chondroprogenitor cells are poorly understood. In the present study we demonstrate that bone morphogenetic protein-2 (BMP-2), introduced by adenovirus-mediated gene transfer, alone is capable of inducing callus formation at the site of periosteal injection. Both immunohistochemistry and Northern analysis demonstrated activation of type II collagen production between days 4 and 7 after the injection, followed by activation of type X collagen expression. The activation of chondrogenesis was associated with increased expression of L-Sox5 and Sox9, suggesting that the BMP-2 effect is mediated via Sox proteins. This capacity of adenovirus-mediated overproduction of BMP-2 to induce chondrogenesis (and subsequent endochondral ossification) should be useful for tissue engineering of cartilage and bone.

Gender-related differences in response to placebo in benzodiazepine withdrawal: a single-blind pilot study.

RATIONALE: Benzodiazepines have dependency-producing properties, and the majority of patients who are prescribed benzodiazepines and are treated for benzodiazepine dependency are women. Inability to cope with withdrawal symptoms may lead to continued consumption of benzodiazepines, often with the development of tolerance and dose escalation as a consequence. OBJECTIVE: In the present study we analyzed gender-related differences in reactions to placebo injections in a placebo-controlled study of the effects of the benzodiazepine antagonist flumazenil among patients previously treated for benzodiazepine dependency and healthy controls. METHODS: Ten patients and ten controls (five males and five females in each group) received two placebo injections (separated by 15 min) on two separate occasions (1-13 weeks apart). The patients had been benzodiazepine free for 47 (4-266) weeks on the first occasion. Subjective ratings of symptoms, thought to be important during/after withdrawal of benzodiazepines, were made before and after each injection, as well as registrations of blood pressure and heart rate. RESULTS: An overall difference existed between previously benzodiazepine-dependent subjects and healthy controls, with patients scoring higher on negative and somatic aggregates and lower on a positive aggregate. A four-way interaction (group x gender x occasion x time) was found for negative and somatic aggregates, which could mainly be explained by the reactions of female patients. Thus, females had the highest base-line ratings and were the only group that showed a significant reduction in symptom ratings after placebo injections on the first occasion. Gender differences were also found for systolic and diastolic blood pressure. There was no significant response to placebo among male patients or for controls (males or females) for ratings of any variable. CONCLUSIONS: The results suggest that there might be gender-specific differences in reactions to placebo injections, with female patients being more affected. Arguments for and against explanatory factors such as expectation, provider factors, habituation, regression toward the mean, and reduction of anxiety are presented.

Acute tolerance during intravenous infusion of alcohol: comparison of performance during ascending and steady state concentrations--a pilot study.

Although acute tolerance (AT) to alcohol has been demonstrated in many single-dose studies, the existence of AT at steady state concentrations of alcohol has been questioned. In the present study, six subjects were examined as (1) 7.5% alcohol or (2) placebo was administered intravenously (IV). The order of the infusions was randomized. The alcohol infusions were designed to result in similar blood alcohol concentrations at 20, 60, and 140 min (approximately 0. 7 per thousand). At 20 min, the concentrations were rising; the steady state (+/-0.10 per thousand) was reached after 60 min and continued until 140 min. Three reaction time (RT) tests from the automated psychological test system were used (simple RT, two-choice RT, and two-choice RT with auditory inhibition). When the performance of the subjects was compared at rising and steady-state concentrations of alcohol, AT was shown for the most complex task requiring parallel processing, i.e., RT with failed inhibition, test. However, at steady state (i.e., 60 vs. 140 min), AT was not found for any of the tests. Further, the analysis showed that the test results of different individuals were related to their estimated normal alcohol consumption and that these differences presumably influenced the test results in accordance with our earlier findings.

Expression of cathepsins B, H, K, L, and S and matrix metalloproteinases 9 and 13 during chondrocyte hypertrophy and endochondral ossification in mouse fracture callus.

Fracture repair provides an interesting model for chondrogenesis and osteogenesis as it recapitulates in an adult organism the same steps encountered during embryonic skeletal development and growth. The fracture callus is not only a site of rapid production of cartilage and bone, but also a site of extensive degradation of their extracellular matrices. The present study was initiated to increase our understanding of the roles of different proteolytic enzymes, cysteine cathepsins B, H, K, L, and S, and matrix metalloproteinases (MMPs) 9 and 13, during fracture repair, as this aspect of bone repair has previously received little attention. Northern analysis revealed marked upregulation of cathepsin K, MMP-9, and MMP-13 mRNAs during the first and second weeks of healing. The expression profiles of these mRNAs were similar with that of osteoclastic marker enzyme tartrate-resistant alkaline phosphatate (TRAP). The changes in the mRNA levels of cathepsins B, H, L, and S were smaller when compared with those of the other enzymes studied. Immunohistochemistry and in situ hybridization confirmed the predominant localization of cathepsin K and MMP-9 and their mRNA in osteoclasts and chondroclasts at the osteochondral junction. MMP-13 was present in osteoblasts and individual hypertrophic chondrocytes near the cartilage-bone interphase. In cartilaginous callus, the expression of cathepsins B, H, L, and S was mainly related to chondrocyte hypertrophy. During bone remodeling both osteoblasts and osteoclasts contained these cathepsins. The present data demonstrate that degradation and remodeling of extracellular matrices during fracture healing involves activation of MMP-13 production in hypertrophic chondrocytes and osteoblasts, and cathepsin K and MMP-9 production in osteoclasts and chondroclasts.

Comparison of urinary 5-hydroxytryptophol, breath ethanol, and self-report for detection of recent alcohol use during outpatient treatment: a study on methadone patients.

This study compared urinary 5-hydroxytryptophol (5HTOL) with breath-ethanol testing as objective ways to disclose recent drinking by outpatients attending a methadone maintenance treatment clinic. Information about quantity and frequency of alcohol use was obtained by confidential self-reports. Random screening was performed on Mondays-Fridays in connection with routine clinic visits for methadone dosing. An observed urine sample for monitoring of illicit drug use and determination of 5HTOL, expressed as a ratio to 5-hydroxyindole-3-acetic acid (5HIAA), was obtained from 202 patients (59 women and 143 men), 16 of whom refused to complete the self-report and/or do a breath-ethanol test. Patients taking disulfiram or calcium carbimide for alcohol detoxification were excluded. Among the 177 subjects remaining, 47 (26.6%) reported intake of any alcohol on the previous day (range, 10-230 g ethanol; median, 40). Only four of those could be identified by a positive breath-test, while 17 showed a urinary 5HTOL/5HIAA ratio above the cutoff limit. Their alcohol consumption (median, 60 g) was significantly higher compared with those showing ratios within the reference interval (median, 35 g). The sensitivity of 5HTOL/5HIAA testing for detecting self-reported drinking in excess of 50 g ethanol was 77%. An additional nine patients who claimed abstinence still showed abnormal 5HTOL/5HIAA ratios, and so did three of the patients who refused to do a breath-ethanol test and/or complete the self-report. Altogether, 59 of 190 methadone-maintained patients (31.1%) had been drinking any alcohol on the previous day (i.e. Sunday-Thursday) according to self-report and/or urinalysis data, 29 (49.2%) of whom were identified by the urinary 5HTOL/5HIAA ratio and only four (6.8%) by utilizing breathalyzer.

Prediction of single episodes of drinking during the treatment of alcohol-dependent patients.

Drinking episodes during the treatment (relapses or lapses) of alcohol-dependent patients is predicted from clinical ratings of patients and individual background data such as alcohol drinking history and social status. The probability of these relapses (or lapses) is determined up to three days in advance using a logistic regression procedure. The study group consisted of 33 male alcohol-dependent persons, who participated in a treatment program. Clinical ratings were performed three times a week by a trained person during a visit to the clinic. The questionnaire contained 23 different items about irritation, craving for alcohol. sleep disturbances, etc. The relapses were either self-reported or detected by a biochemical marker in a urine sample that was taken daily. The most important factor for a relapse in alcohol drinking was shown to be if the patient already had had one relapse during the treatment. Other important clinical factors were the levels of irritation and autonomic disturbances. None of the variables measuring mood shifts was significant. Family conditions during childhood were the most important background variables. The predictions turned out to have a rather high specificity, but the sensitivity was lower. Half of the relapses were not predicted by an increased probability for relapse. Self-reported relapses were predictable from preceding interviews and were also less frequent compared to those detected objectively by the biochemical markers.

Rated well-being in relation to plasma concentrations of l- and d-methadone in satisfied and dissatisfied patients on methadone maintenance treatment.

RATIONALE: One of the major problems in methadone maintenance treatment is to find optimal individual doses for the patients. OBJECTIVE: The present study investigated whether the use of rating scales together with enantioselective analysis of l-methadone might facilitate dose adjustments in a clinical situation. METHODS: Rating scales were used to evaluate subjective and objective signs of well-being in relation to plasma methadone concentrations in two groups of patients receiving methadone maintenance treatment. The first group (n = 25) was well-adjusted according to clinical observations and were satisfied with their methadone doses (86.2+/-4.3 mg). The second group (n = 25) was in need of the methadone dose adjustment; they complained of low dosing, despite a dose level of 69.2+/-4.0 mg/day. RESULTS: Results indicated a significant correlation between dose and methadone concentration among dissatisfied patients only. The trough levels of d,l-methadone and l-methadone, as well as their elimination rates, were similar in the two groups of patients. There was a variable predominance of l- over d-methadone in plasma (ratio approximate to 1.2; range 0.7-3.6). Illicit use of drugs by the patients was related to the methadone dose and to satisfaction with the dose received. Increased illicit drug use among dissatisfied patients was successfully eliminated by raising the methadone dose. Subjective and objective ratings of the satisfied patients were quite stable throughout the evaluation period, whereas the ratings of the dissatisfied patients were unstable. These patients seemed to be more sensitive to low trough levels of methadone than the satisfied patients. Associations between the subjective and objective ratings and plasma methadone, along with background characteristics, were characterized by multiple regression analyses. The plasma concentrations of l-methadone were one of the most important explanatory variables in these analyses. Associations between well-being and methadone concentrations in plasma were stronger for l-methadone than for d,l-methadone. CONCLUSIONS: Selective measurements of the active isomer and the use of rating scales should be of clinical value when monitoring methadone maintenance treatment patients.

Patient perceptions of psychological and physiological withdrawal symptoms and positive factors associated with gradual withdrawal from methadone maintenance treatment: a prospective study.

Psychological and physiological withdrawal symptoms and some positive factors were studied in 10 methadone maintenance treatment patients during methadone dose reduction. The subjective ratings were made during a period of 10 days around each reduction occasion, 3 days before dose reduction and 7 days after (i.e., within the periods). To permit comparisons of the subjects' ratings between earlier and later stages of the dose reduction process, a division has been made between the first half and the second half of the total reduction occasions (i.e., between the periods). Three of the patients completed the dose reduction, while the others interrupted their withdrawal attempts. The results show that the aggregate psychological symptoms were rated low, but that, as expected, they increased significantly from the first to the second half of the dose reduction. A significant increase of the psychological symptoms also occurred from the days before each reduction to the days after. The aggregate physiological symptoms were rated very low. A significant increase in rated withdrawal intensity is found within the reduction occasions. There were no significant changes with regard to the aggregate positive factors, either within or between the reduction occasions.

Acute alcohol tolerance in social drinkers: changes in subjective effects dependent on the alcohol dose and prior alcohol experience.

Using subjective ratings of the degree of alcohol intoxication, the interaction between the drinking history of the subjects, the alcohol dose, and acute alcohol tolerance were examined in light and moderate alcohol consumers (N = 10). Both groups of subjects were tested with doses of alcohol corresponding to 0.5 and 1.0 g/kg. Dose order was random and tests were carried out with an interval of 1 week. Reports of the subjects' previous experience with these doses of alcohol indicated that the moderate consumers ingested the lower (but not the higher) of the doses quite regularly, whereas light consumers were rather inexperienced with both of the doses. Comparison of blood alcohol concentrations as measured by breath and blood analysis yielded slightly different results, the concentrations being significantly higher as measured by breath analysis. This result was mainly associated with the initial phases, where this difference was greatest. Acute tolerance was assessed by comparing the ratings at equal concentrations of alcohol on the ascending and the descending limbs of the alcohol concentration curve. Due to the lag in the measurements of breath and blood alcohol concentrations, the outcome of the evaluations of acute tolerance was also influenced by whether breath or blood alcohol concentrations were used to obtain similar concentrations in both phases. Results based on the breath alcohol concentrations showed that in light alcohol consumers, acute tolerance was demonstrated for both of the doses. In moderate alcohol consumers only the higher of the doses produced evidence for acute tolerance. However, if comparisons are based on blood alcohol concentrations, moderate alcohol consumers also show an apparent acute tolerance for the lower of the doses tested. The present results clearly demonstrate the complexity of the acute tolerance phenomenon, and emphasize the fact that the results are dependent on the dose of alcohol, the subjects' prior experience with alcohol as well as the procedure used for measuring alcohol concentration.

Effects of flumazenil in the treatment of benzodiazepine withdrawal--a double-blind pilot study.

Flumazenil, a partial benzodiazepine agonist with low intrinsic activity, was tested for potential use in patients experiencing withdrawal symptoms after traditional treatment for benzodiazepine dependency. On two occasions, separated by 1-13 weeks, ten patients treated for benzodiazepine dependency and ten controls received cumulative doses of flumazenil (0.05, 0.10, 0.25, 0.50 and 1.00 mg at 15-min intervals) or placebo, with assessments of withdrawal symptoms and physiological variables after each dose. As expected, there was an overall difference between patients and controls, with patients scoring higher on negative and somatic items and lower on positive psychological items. Flumazenil reduced symptoms thought to be important in withdrawal in patients treated for benzodiazepine dependency. In contrast to the patient group, controls reacted in the opposite direction with increases in negative experience when given flumazenil. Further research may develop flumazenil as a therapeutic option in the treatment of benzodiazepine withdrawal.

Abstinence fear in methadone maintenance withdrawal: a possible obstacle for getting off methadone.

The present study attempts to shed light on methadone maintenance patients expectations regarding withdrawal symptoms during voluntary methadone detoxification. The study includes two groups of subjects; one group who have tried on their own initiative to terminate their methadone maintenance treatment (Group 1) and one group that contains rehabilitated patients who have not tried to quit using methadone (Group 2). Two main results have emerged. Group 1 has negative expectations beforehand about the intensity of withdrawal which significantly exceed the later, actual experience. Group 2 has negative expectations about the intensity of withdrawal that significantly exceed the negative expectations of Group 1. The clinical implications of these results are discussed.

Acute alcohol tolerance in cognitive and psychomotor performance: influence of the alcohol dose and prior alcohol experience.

Using tests for cognitive performance (the Pauli test) and psychomotor coordination (the Pursuit Rotor test), the interaction between the drinking history of the subjects, the alcohol dose, and acute alcohol tolerance were examined in light and moderate alcohol consumers (N = 10). Both groups of subjects were tested with doses of alcohol corresponding to 0.5 and 1.0 g/kg. Dose order was random and tests were carried out at an interval of 1 week. Reports of the subjects' previous experience with alcohol indicated that the moderate consumers ingested alcohol in higher quantities than the light consumers. The light consumers were rather inexperienced with frequent alcohol consumption at the quantities investigated, as were the moderate consumers for the higher of the alcohol doses used. Acute tolerance was assessed by comparing performance at equal concentrations of alcohol on the ascending and the descending limbs of the alcohol concentration curve. In the test for cognitive performance, both doses of alcohol in light alcohol consumers yielded significant differences between the ascending and descending limbs of the alcohol concentration curve, suggesting the existence of acute tolerance. In the moderate alcohol consumers, only a tendency to acute tolerance was observed for the higher of the doses tested. In the test for the psychomotor performance, both of the measures of frequency (of misses) and duration (of time outside the target area) were used. The results showed that in the light consumers, acute tolerance was seen for both of the doses, and to some extent for both of the dependent measures (frequency and duration) investigated. However, in the moderate alcohol consumers, acute tolerance was only observed for the higher of the doses and only for the duration measure. Given the difference in drinking history between the two groups of subjects, the implication would be that when the dose of alcohol exceeds the subjects' prior experience, acute tolerance seems inevitable. The present results clearly demonstrate the complexity of the acute tolerance phenomenon, and emphasize the fact that the results are dependent on the subjects' prior experience with alcohol as well as the dose of alcohol ingested, and consequently suggest the interaction between acute and chronic alcohol tolerance.

Effects of long-term abstinence on psychological functioning: a prospective longitudinal analysis comparing alcohol-dependent patients and healthy volunteers.

Using a prospective longitudinal design, differences between abstinent alcohol-dependent patients (n = 15) and abstinent healthy volunteers (n = 11) were determined with respect to their psychological functioning and alcohol consumption patterns following abstinence. Results showed no differences in alcohol consumption. In 20% of the patients and 9% of the controls more than 10% of protocols indicated alcohol intake, and in 27% of the patients and 27% of the controls less than 10% of protocols indicated alcohol intake. Total abstinence was reported by 53% of the patients and by 64% of the controls. For patients, validation of self-reported alcohol consumption was carried out via biological markers. Patients and controls differed in terms of increased sleep, euphoria, concentration, initiative, anxiety, negative and positive craving, pessimistic thoughts, autonomic disturbances, and humour. A gradual normalization back to baseline levels was observed for some symptoms. These results suggest that affective/mood states may be unstable for alcoholics, and further, that these symptoms may be related to the protracted withdrawal syndrome or may represent residual symptomatology.