Chord length sampling with memory effects for spatially heterogeneous Markov media: Application to the rod model.

In this work we propose a modified Chord Length Sampling (CLS) algorithm, endowed with two layers of "memory effects," aimed at solving particle transport problems in one-dimensional spatially nonhomogeneous Markov media. CLS algorithms are a family of Monte Carlo methods which account for the stochastic nature of the media by sampling on-the-fly the random interfaces between material phases during the particle propagation. The possibility for the particles to remember the last crossed interfaces increases the accuracy of these models with respect to reference solutions obtained by solving the Boltzmann equation on a large number of realizations of the Markov media. In previous investigations, CLS models with memory have been tested exclusively for spatially uniform stochastic media: in this paper we extend this class of Monte Carlo methods to the case of spatially nonhomogeneous configurations. The effectiveness and the robustness of the modified CLS are probed considering several benchmark problems with varying material cross sections and Markov media densities. The obtained results are a stepping stone towards a generalization to three-dimensional models.

A study of the real-world effectiveness of group psychoeducation for bipolar disorders: Is change in illness perception a key mediator of benefit?

BACKGROUND: Findings from efficacy trials of group psychoeducation (PE) for bipolar disorders (BD) led to its inclusion in evidence-based guidelines as a first-line mandatory treatment. However, pragmatic trials and observational studies are needed to determine its real-world effectiveness, impact on outcomes deemed important to patients and to clarify potential mediators of any benefits. METHODS: Individuals with BD were offered the opportunity to participate in 20h of PE and asked to complete pre- and post-intervention ratings of symptoms, knowledge about BD, medication adherence, and illness perception. A priori, two key patient outcomes were identified (social functioning and self-esteem); sample attrition due to dropout or relapse was recorded. RESULTS: Of 156 individuals who completed the pre-PE assessments, 103 completed the program and post-PE assessments. Only 4 of 53 dropouts were associated with BD relapse. Post-intervention, the PE completers demonstrated a statistically significant improvement in social functioning (p = 0.003, Effect Size (ES) = 0.26) and a trend towards improved self-esteem (ES = 0.14). Whilst there were significant changes in medication adherence (p = 0.002, ES = 0.28), knowledge of BD (p < 0.001, ES = 1.20), and illness perception (p < 0.001, ES = -0.37), mediational analysis demonstrated that only change in illness perception was associated to change in functioning (p=0.03) with no contribution from changes in knowledge of BD or medication adherence. CONCLUSIONS: In real-world settings, over 60% individuals completed 10-session course of PE. After controlling for demography and baseline clinical state, change in illness perception, rather than change in knowledge or medication adherence, emerged as a potential mediator of some benefits of PE.

Affect intensity measure in bipolar disorders: a multidimensional approach.

BACKGROUND: Emotional dysregulation, characterized by high levels of both arousal and intensity of emotional responses, is a core feature of bipolar disorders (BDs). In non-clinical populations, the 40-item Affect Intensity Measure (AIM) can be used to assess the different dimensions of emotional reactivity. METHODS: We analyzed the factor structure of the AIM in a sample of 310 euthymic patients with BD using Principal Component Analysis and examined associations between AIM sub-scale scores and demographic and illness characteristics. RESULTS: The French translation of the AIM demonstrated good reliability. A four-factor solution similar to that reported in non-clinical samples (Positive Affectivity, Unpeacefulness [lack of Serenity], Negative Reactivity, Negative Intensity), explained 47% of the total variance. Age and gender were associated with Unpeacefulness and Negative reactivity respectively. 'Unpeacefulness' was also positively associated with psychotic symptoms at onset (p=0.0006), but negatively associated with co-morbid substance misuse (p=0.008). Negative Intensity was positively associated with social phobia (p=0.0005). LIMITATIONS: We cannot definitively exclude a lack of statistical power to classify all AIM items. Euthymia was carefully defined, but a degree of 'contamination' of the self-reported levels of emotion reactivity may occur because of subsyndromal BD symptoms. It was not feasible to control for the possible impact of on-going treatments. CONCLUSIONS: The AIM scale appears to be a useful measure of emotional reactivity and intensity in a clinical sample of patients with BD, suggesting it can be used in addition to other markers of BD characteristics and sub-types.

Duration of untreated bipolar disorder: missed opportunities on the long road to optimal treatment.

OBJECTIVE: Duration of untreated illness represents a potentially modifiable component of any diagnosis-treatment pathway. In bipolar disorder (BD), this concept has rarely been systematically defined or not been applied to large clinically representative samples. METHOD: In a well-characterized sample of 501 patients with BD, we estimated the duration of untreated bipolar disorder (DUB: the interval between the first major mood episode and first treatment with a mood stabilizer). Associations between DUB and clinical onset and the temporal sequence of key clinical milestones were examined. RESULTS: The mean DUB was 9.6 years (SD 9.7; median 6). The median DUB for those with a hypomanic onset (14.5 years) exceeded that for depressive (13 years) and manic onset (8 years). Early onset BD cases have the longest DUB (P < 0.0001). An extended DUB was associated with more mood episodes (P < 0.0001), more suicidal behaviour (P = 0.0003) and a trend towards greater lifetime mood instability (e.g. rapid cycling, possible antidepressant-induced mania). CONCLUSION: Duration of untreated bipolar disorder (DUB) will only be significantly reduced by more aggressive case finding strategies. Reliable diagnosis (especially for BD-II) and/or instigation of recommended treatments is currently delayed by insufficient awareness of the early, polymorphous presentations of BD, lack of systematic screening and/or failure to follow established guidelines.

Clinical features associated with trait-impulsiveness in euthymic bipolar disorder patients.

BACKGROUND: A strong association has been reported between trait-impulsiveness and bipolar disorder (BD). Much attention has been focused on this association, but subgroup analysis has generated conflicting results, raising questions about the role of trait-impulsiveness in suicidal behavior and substance misuse in bipolar patients. METHOD: We compared Barratt Impulsiveness Scale-10 scores between 385 euthymic bipolar patients and 185 healthy controls. We then investigated possible association between impulsiveness scores and the following clinical characteristics: suicide attempt (SA), lifetime alcohol/cannabis misuse, rapid cycling and mixed episodes. RESULTS: Bipolar patients and healthy controls had significantly different BIS-10 total score and subscores (motor, attentional and nonplanning impulsiveness) (all p values <0.0001). No association was observed between BIS-10 total score, personal history of SA, number of SA, age at first SA and history of violent SA. Higher BIS-10 total scores were associated with alcohol misuse (p=0.005), cannabis misuse (p<0.0001), with an additive effect for these two substances (p=0.005). Higher BIS-10 total scores were also associated with rapid cycling (p=0.006) and history of mixed episodes (p=0.002), with an additive effect of these two variables (p=0.0006). LIMITATIONS: We used only one clinical measurement of impulsiveness and did not carry out cognitive assessment. CONCLUSION: This study demonstrates that trait-impulsiveness may be considered as a dimensional feature associated with BD and with a more severe clinical expression of the disease, characterized by a history of substance misuse, rapid cycling and mixed episodes. We found no association between impulsiveness and SA characteristics in bipolar patients, confirming some previous negative results.

Clinical and dimensional characteristics of euthymic bipolar patients with or without suicidal behavior.

BACKGROUND: The clinical and dimensional features associated with suicidal behaviour in bipolar patients during euthymic states are not well characterised. METHODS: In a sample of 652 euthymic bipolar patients, we assessed clinical features with the Diagnostic Interview for Genetics Studies (DIGS) and dimensional characteristics with questionnaires measuring impulsivity/hostility and affective lability/intensity. Bipolar patients with and without suicidal behaviour were compared for these clinical and dimensional variables. RESULTS: Of the 652 subjects, 42.9% had experienced at least one suicide attempt. Lifetime history of suicidal behaviour was associated with being a woman, a history of head injury, tobacco misuse and indicators of severity of bipolar disorder including early age at onset, high number of depressive episodes, positive history of rapid cycling, alcohol misuse and social phobia. Indirect hostility and irritability were dimensional characteristics associated with suicidal behaviour in bipolar patients, whereas impulsivity and affective lability/intensity were not associated with suicidal behaviour. LIMITATIONS: This study had a retrospective design with no replication sample. CONCLUSIONS: Bipolar patients with earlier onset, mood instability (large number of depressive episodes, rapid cycling) and/or particular addictive and anxiety comorbid disorders might be at high risk of suicidal behaviour. In addition, hostility dimensions (indirect hostility and irritability), may be trait components associated with suicidal behaviour in euthymic bipolar patients.

Effect of absorbable and nonabsorbable sugars on intestinal calcium absorption in humans.

The effects of glucose, galactose, and lactitol on intestinal calcium absorption and gastric emptying were studied in 9, 8, and 20 healthy subjects, respectively. Calcium absorption was measured by using a double-isotope technique and the kinetic parameters were obtained by a deconvolution method. The gastric emptying rate was determined with 99mTc-diethylenetriaminepentaacetic acid and was expressed as the half-time of the emptying curve. Each subject was studied under two conditions: (a) with calcium alone and (b) with calcium plus sugar. Glucose and galactose increased the calcium mean transit time and improved the total fractional calcium absorption by 30% (p less than 0.02). Lactitol decreased the mean rate of absorption (p less than 0.001) and reduced the total fractional calcium absorption by 15% (p less than 0.001). The gastric emptying rate did not appear to influence directly the kinetic parameters of calcium absorption. These results show that both glucose and galactose exert the same stimulatory effect as lactose on calcium absorption in subjects with normal lactase whereas lactitol mimics the effects of lactose in lactase-deficient patients. Thus the absorbability of sugars determines their effect on calcium absorption.

Calcium absorption from milk in lactase-deficient subjects.

Intestinal calcium absorption from milk containing lactose (+) and from another containing glucose (-) was studied in eight patients with normal lactase (NL) and seven lactase-deficient (LD) subjects to determine if lactase deficiency is implicated in Ca absorption. The results were compared with data obtained from Ca ingestion in a water solution. Ca absorption was measured by a double-isotope technique and the kinetic indices were obtained by a deconvolution method. With (-), Ca absorption was identical in NL and LD subjects and slightly higher than with water solution (15%, NS). With (+), Ca absorption in NL subjects was identical with that from water solution; in LD subjects it increased (23%, p less than 0.02). These data indicate that: Ca is absorbed equally well from milk as from water solution; (+) favors Ca absorption in LD subjects, which suggests that milk ingestion might be encouraged in LD subjects to avoid Ca deficiency; and (-) should be a valuable alternative for lactose-intolerant patients.

[Influence of chronic renal failure on the D-xylose test in man]. / Influence de l'insuffisance rénale chronique sur le test au D-xylose chez l'homme.

The aim of this study was to investigate the effect of chronic renal insufficiency on absorption, distribution and elimination of D-xylose which was chosen as a "test substance". Pharmacokinetic analysis was based on eighteen D-xylose tests carried out either by the enteral or parenteral route in a randomized fashion on nine patients suffering from chronic renal insufficiency. These results were compared with those obtained in healthy volunteers. The renal clearance was simultaneously measured with the 51Cr-EDTA test. In the experimental conditions the intestinal absorption of D-xylose was not modified qualitatively (absorption rate) nor quantitatively (systemic availability). Inspite of this, the maximal concentration of the D-xylose was higher in these patients and was reached later than in healthy volunteers. This fact should be taken into consideration when interpreting the results of a D-xylose test in patients suffering from chronic renal insufficiency.

A simple method for measurement of intestinal calcium absorption in humans by double-isotope technique.

We describe a method for the fast calculation of total fractional calcium absorption (TFCaA) by the double-isotope technique (45Ca orally and 47Ca intravenously). The gamma- and beta-activities of plasma or urine samples were measured simultaneously. 47Ca activity was obtained by a gamma-ray spectrometer after exclusion of scandium 47. The 45Ca activity was measured directly by subtracting the 47Ca plus 47Sc component from the total beta-activity. In addition, 45Ca activity was determined after 8 weeks, to allow for 47Ca and 47Sc decay. There was good correlation between these two methods of measuring 45Ca activity. TFCaA was calculated both by deconvolution taken as a reference method and from the equilibrium quotient 45Ca/47Ca observed in several blood or urine samples collected at different times. The most convenient sampling time for calculation of this ratio was reappraised, taking into account the type of solution ingested orally (water or milk). The results indicate that simultaneous counting of gamma- and beta-activities of an appropriate plasma or urine sample provides a good and rapid measure of the calcium absorption. This method is considered to be useful as a clinical tool.

Effects of lactose on intestinal calcium absorption in normal and lactase-deficient subjects.

The effect of lactose on intestinal calcium absorption was studied in 12 normal-lactase subjects and 7 lactase-deficient subjects. Calcium absorption was compared by using the double isotope technique with or without the presence of an oral load of 50 g of lactose in each subject. The kinetic parameters were measured by the deconvolution method. In the normal lactase group, the lactose prolonged the duration of absorption at a maximum rate and therefore increased the total fractional calcium absorption from 0.224 +/- 0.039 to 0.356 +/- 0.076 (p less than 0.001). In the lactase-deficient subjects, the lactose decreased the total absorption from 0.255 +/- 0.039 to 0.209 +/- 0.032 (p less than 0.005); this effect resulted in a decrease of the maximum absorption rate. There was no significant difference between the two groups when calcium was ingested alone. These results indicate that the effect of lactose on calcium absorption is dependent on intestinal lactase activity.

[Pharmacokinetic study of a cephalosporin: cefoperazone in patients with a Kehr drain]. / Etude pharmacocinétique d'une céphalosporine: la céfopérazone chez des patients porteurs d'un drain de Kehr.

Cefoperazone is a semi-synthetic cefalosporine for parenteral use which has an excellent activity against a wide range of grampositive and gramnegative bacteria, especially Pseudomonas aeruginosa, Enterobacter, Proteus indole positive and Serratia marcescens. The pharmacokinetics of the new antibiotic have been studied in patients who had undergone cholecystectomy and choledochotomy for lithiasis and who required T-tube drainage of the bile duct. Five patients were anicteric and one was icteric. Mean serum concentration of cefoperazone determined by a microbiological method) measured after a two-hour intravenous perfusion of 2 g cefoperazone was 198.6 microgram/lm; this level is higher than the mean level measured in normal subjects (134 microgram/ml) but lower than the mean level measured in patients with hepatic insufficiency (208 microgram/ml). Apparent half life of elimination was longer (mean 4.1 hours) in the patients than in controls (mean 1.6 hours) and compares with that of patients with hepatic insufficiency (mean 4.3 hours). The distribution volume and renal clearance are similar to that in healthy volunteers and patients with hepatic insufficiency. Extrarenal clearance of cefoperazone was significantly lower in our patients (15.8 ml/min), as it is in patients with hepatic insufficiency (7.3 ml/min), than in the control group (59.4) ml/min). Cefoperazone concentrations in the bile were 10-20 times higher than those in the serum; in the icteric patient the concentrations achieved were still higher than the MIC values for organisms commonly encountered in the bile. These results open the way to the use of cefoperazone to treat infectious biliary diseases, particularly angiocholitis, which need a high biliary antibiotic concentration.

[Excess mortality in out-patients psychiatry: first results of a Geneva study]. / Surmortalité en psychiatrie ambulatoire: premiers résultats d'une étude à Genève.

The project intends to prove an excess of mortality among the out-patients of the official psychiatric center of Geneva. The study is of the follow-up retrospective type. The primary results confirm the hypothesis. They show an increased relative risk of death by suicide and other non natural causes, for both sexes, as well as by natural causes (especially respiratory diseases) but only among women.

[Pharmacokinetic study of a cephalosporin, cefoperazone, in liver failure]. / Etude pharmacocinétique d'une céphalosporine, la céfopérazone, dans l'insuffisance hépatique.

The pharmacokinetics of cefoperazone, a semi-synthetic cephalosporin for parenteral use with a spectrum covering P. aeruginosa, E. cloacae, indole-positive Proteus and S. Marcescens, was studied after a 2-h intravenous infusion of 2 g of the drug in 6 patients with moderate liver function impairment (viral hepatitis in 4 cases, alcoholic fatty liver and cirrhosis in 2 cases). At the end of the infusion, mean serum concentrations (determined by a bioassay) were 208 microgram/ml in the patients and 134 microgram/ml in healthy volunteers. The half-life was 4.3 h in patients and 1.6 h in healthy volunteers. Volume of distribution and renal clearance were similar in the two groups. Extrarenal clearance of cefoperazone was lower in the patients (7.3 ml/min) than in the control group (59.4 mg/min). Urinary excretion of biologically active drug was markedly increased in the patients (79% of the dose) compared with healthy volunteers (24%). This study provides evidence that liver function impairment increases with both the apparent half-life of elimination and the urinary excretion of the drug. The results raise the question of the desirability of cefoperazone dosage adjustment in patients with hepatic diseases.

[Diagnosis of lactase deficiency with the expired hydrogen (H2) test]. / Diagnostic des déficits en lactase par le test de l'hydrogène (H2) expiré.

To determine the sensitivity and specificity of breath hydrogen (H2) in detecting lactase deficiency, breath H2 collected by end-expiratory sampling and capillary blood glucose were measured after ingestion of 50 g of lactose in 36 patients with biopsy-proved isolated lactase deficiency, 42 with normal lactase activity and 6 with lactase deficiency secondary to mucosal lesions. All patients had digestive symptoms clinically compatible with lactose malabsorption. The maximum increase in breath H2 concentration was more than 1.1 mumol/l (25 ppm) in all patients with isolated lactase deficiency, and less than 0.88 mumol/l (20 ppm) in 88% of patients with normal lactase activity; there were 5 false-positive results, attributed in one case to small bowel colonization and in another case to rapid transit after gastric surgery. Secondary lactase deficiency was accurately detected by neither breath H2 nor blood glucose.

Asphyxia caused by laryngeal impaction of an esophageal polyp.

We report a case of asphyxia due to laryngeal obstruction by an esophageal polyp with subsequent cerebral anoxia and death. We review the clinical manifestations and pathological aspects of benign esophageal tumors, with emphasis on the importance of an early diagnosis if a patient has repeated sensations of a regurgitated pharyngeal mass.

[Heparin treatment. Comparison between intravenous and subcutaneous administration]. / Traitement héparinique. comparaison entre les voies d'administration intraveineuse et sous-cutanée.

48 patients with acute deep venous thrombosis of the lower limbs were treated with sodium heparin. In 23 patients heparin was injected subcutaneously (s.c.) twice a day and in 25 patients heparin was given by continuous intravenous perfusion (i.v.). Pain and edema disappeared after 8.7 days (s.c.) and 11.7 days (i.v.) respectively. One non fatal pulmonary embolism occurred in each group. A second venography was performed in 24 patients after 7 days of treatment and revealed no difference between the two groups. As judged by repeated thrombin time determination, anticoagulation was ineffective on at least one day in 39% of patients treated subcutaneously and in 60% of patients treated intravenously. The two pulmonary embolisms occurred in patients with ineffective anticoagulation. It is concluded that heparin may be used either intravenously or subcutaneously in the treatment of acute deep venous thrombosis. Thromboembolic complications occurred with both methods of treatment when anticoagulation was ineffective.