[Diagnostics and treatment of suicidality; a matter of customization]. / Diagnostiek en behandeling van suïcidaliteit; een kwestie van maatwerk.

This article illustrates the importance of conducting a comprehensive analysis of suicidality through the case study of an adolescent patient dealing with both depressive disorder and obsessive-compulsive disorder. The aim of treating suicidality is to address the underlying psychiatric conditions and factors contributing to the disorder. This necessitates a thorough evaluation of the treatment environment, the establishment of continuous care, and ensuring safety. By utilizing a new model to distinguish various forms of suicidal behavior and examining suicidality as a distinct phenomenon, it becomes possible to create individualized diagnostic and treatment approaches, along with effective risk assessments. In the presented patient, intrusive thoughts significantly impacted her suicidality. The treatment approach for patient A involved employing eye movement dual task (EMDT), exposure therapy and strategies to enhance autonomy. This approach aims to reduce suicidality, facilitate recovery, and alleviate the fear of losing control.

High cumulative JC virus seroconversion rate during long-term use of natalizumab.

BACKGROUND AND PURPOSE: John Cunningham virus (JCV) seropositivity is a risk factor for the development of natalizumab-associated progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients. When JCV seronegative patients seroconvert, their risk of developing PML increases. Limited longitudinal data exist about the seroconversion rate amongst natalizumab-treated relapsing-remitting MS (RRMS) patients. Our objective was to evaluate the seroconversion rate in a large Dutch cohort of natalizumab-treated RRMS patients. Seroconversion was defined as at least two consecutive seropositive serum samples (or cessation of therapy after a single seropositive sample because of seropositivity) after initial seronegative testing. METHODS AND RESULTS: In our study of 179 patients for whom longitudinal blood samples were available over a long period (median 4.2 years), anti-JCV antibody indices were measured in 933 available samples. Eighty-six patients (48.0%) tested seronegative initially. Of these 86 seronegative patients, 23 patients (26.7%) seroconverted during follow-up. The annualized seroconversion rate was 7.1%. Seroconversion occurred between 9 and 90 months (median 43 months) of treatment. The rate of seroconversion was independent of follow-up duration. No significant increase was seen in the anti-JCV antibody index in the non-converting patients during the follow-up. CONCLUSION: The annualized seroconversion rate of 7.1% in patients using natalizumab, cumulatively leading to more than 25% of seronegative patients becoming seropositive in 4 years, is of clinical relevance and should be taken into account in the risk assessment when considering the start of natalizumab therapy.

Enhanced axonal metabolism during early natalizumab treatment in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: The considerable clinical effect of natalizumab in patients with relapsing-remitting multiple sclerosis might be explained by its possible beneficial effect on axonal functioning. In this longitudinal study, the effect of natalizumab on absolute concentrations of total N-acetylaspartate, a marker for neuronal integrity, and other brain metabolites is investigated in patients with relapsing-remitting multiple sclerosis by using MR spectroscopic imaging. MATERIALS AND METHODS: In this explorative observational study, 25 patients with relapsing-remitting multiple sclerosis initiating natalizumab treatment were included and scanned every 6 months for 18 months. Additionally 18 matched patients with relapsing-remitting multiple sclerosis continuing treatment with interferon-ß or glatiramer acetate were included along with 12 healthy controls. Imaging included short TE 2D-MR spectroscopic imaging with absolute metabolite quantification of total N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds, myo-inositol, and glutamate. Concentrations were determined for lesional white matter, normal-appearing white matter, and gray matter. RESULTS: At baseline in both patient groups, lower concentrations of total N-acetylaspartate and creatine and phosphocreatine were found in lesional white matter compared with normal-appearing white matter and additionally lower glutamate in lesional white matter of patients receiving natalizumab. In those patients, a significant yearly metabolite increase was found for lesional white matter total N-acetylaspartate (7%, P < .001), creatine and phosphocreatine (6%, P = .042), and glutamate (10%, P = .028), while lesion volumes did not change. In patients receiving interferon-ß/glatiramer acetate, no significant change was measured in lesional white matter for any metabolite, while whole-brain normalized lesion volumes increased. CONCLUSIONS: Patients treated with natalizumab showed an increase in total N-acetylaspartate, creatine and phosphocreatine, and glutamate in lesional white matter. These increasing metabolite concentrations might be a sign of enhanced axonal metabolism.

C-reactive protein in the very early phase of acute ischemic stroke: association with poor outcome and death.

Acute ischemic stroke may trigger an inflammatory response that leads to increased levels of C-reactive protein (CRP). High levels of CRP may be associated with poor outcome because they reflect either an inflammatory reaction or tissue damage. We evaluated the prognostic value of CRP within 12 h of onset of ischemic stroke. Levels of CRP were routinely obtained within 12 h of symptom onset in 561 patients with ischemic stroke. CRP values were dichotomized as <7 or ≥7 mg/L. The full range of CRP values was used to detect a possible level-risk relationship. We studied the relation between CRP values and poor outcome (modified Rankin Scale score >2) or death at 3 months. A multiple logistic regression model was applied to adjust for age, sex, NIHSS score, current cigarette smoking, diabetes mellitus, hypertension, statin use, and stroke subtype. After adjustment for potential confounders, patients with CRP levels ≥7 mg/L had a significantly increased risk of poor outcome (adjusted OR 1.6, 95% CI 1.1­2.4) or death (adjusted OR 1.7, 95% CI 1.0­2.9) at 3 months. In addition, the risk of poor outcome or death at 3 months increased with higher levels of CRP. CRP within 12 h of ischemic stroke is an independent prognostic factor of poor outcome at 3 months.

Inflammation in deep vein thrombosis and the development of post-thrombotic syndrome: a prospective study.

BACKGROUND: The aim of this study was to investigate whether inflammatory markers (interleukin-6 [IL-6] and C-reactive protein [CRP]) in the acute phase of deep vein thrombosis (DVT) are associated with elevated venous outflow resistance (VOR), thrombosis score (TS), reflux and the development of clinical post-thrombotic syndrome (PTS). METHODS: In 110 patients with a first DVT, plasma concentrations of IL-6 and CRP were determined on the day of admission. VOR, TS and reflux were measured 7 days, 1 and 3 months after diagnosis. After 1 year patients were evaluated for PTS using the Clinical, Etiologic, Anatomic and Pathophysiologic (CEAP) classification and Villalta scale. RESULTS: Median levels of IL-6 and CRP were 7 pg mL(-1) and 21 mg L(-1), respectively. After 3 months, VOR was elevated in 33 patients (30%), TS in 33 (30%) and reflux in 57 (52%). Incidence of PTS was 36.7% using CEAP>or=3 and 35.4% using Villalta-scale>or=5. Elevated levels of IL-6 and CRP were related to higher outcomes of VOR after 3 months [relative risks (RR) 2.4 (95% CI 1.5-3.9) and 1.4 (1.1-3.3), respectively] and for IL-6 to TS [1.5 (1.1-2.1)]. For reflux no relation was found. After 90 days, elevated outcomes of VOR, TS and reflux were related to PTS after 1 year. The association of IL-6 and CRP with PTS was weak using the CEAP classification with a RR of 1.2 (0.7-2.2) and 1.8 (0.9-3.3) and absent according to the Villalta scale 0.6 (0.2-1.4) and 1.2 (0.6-2.5), respectively. CONCLUSION: The results of this study suggest that inflammation might play a role in incomplete thrombus clearance, venous outflow obstruction and the development of PTS after 1 year.

Multilayer compression bandaging in the acute phase of deep-vein thrombosis has no effect on the development of the post-thrombotic syndrome.

OBJECTIVE: The purpose of this randomized study was to evaluate the influence of immediate multilayer compression bandages before application of elastic stockings in the acute phase of deep-vein thrombosis (DVT) on development of the post-thrombotic syndrome (PTS). METHODS: Sixty-nine patients with acute symptomatic DVT were randomized to immediate bandaging (n = 34) or no bandaging (n = 35). After reduction of edema sized-to-fit elastic stockings were applied in all patients after 7-14 days. Follow-up visits and non-invasive examinations were planned after 7, 30 and 90 days and 1 year. Venous outflow resistance (VOR) was measured by strain gauge plethysmography. Thrombosis score (TS) and reflux were measured by duplex scanning. After one year patients were evaluated for clinical PTS using both the clinical scale of the CEAP classification and the Villalta score. RESULTS: Improvement of clinical symptoms and decrease of leg circumference was better on day 7 in the bandaging group, but after 1 and 3 months clinical symptoms had improved equally in both groups. In 7 patients in the no-bandaging group a bandage was applied after all because of persistent edema after 10 days. There were no differences in VOR, TS and reflux. Using the CEAP classification the incidence of PTS was 39% in patients with bandages and 42% in patients without bandages (RR 0.91, 95% CI 0.50-1.66). Using the Villalta score the incidence of PTS was resp. 29 and 33% (RR 0.87, 95% CI 0.41-1.8). There was no difference in severity of PTS. CONCLUSION: Immediate multilayer compression bandaging in the acute phase of DVT is effective in reducing edema and complaints in the first week, but has no effect on thrombus regression, valve incompetence and the development of clinical PTS after 1 year.

Psychotropic drug use in a group of Dutch nursing home patients with dementia: many users, long-term use, but low doses.

The aim of this study was to describe the use of psychotropic drugs in a psychogeriatric nursing home, "Joachim en Anna", in Nijmegen, the Netherlands. To this end the medical records of 890 nursing home patients with dementia, admitted between 1980 and 1989, were analysed retrospectively. Each time pattern of psychotropic drug use was registered. Drugs were coded by means of the Anatomical Therapeutic Chemical classification system. The daily dose was expressed as the ratio of the mean prescribed daily dose and the defined daily dose. Side-effects and changes in prescription patterns throughout the years patients were admitted were analysed. A total of 3,090 time patterns of exposure to psychotropics were registered. Neuroleptics, benzodiazepines, and antidepressants accounted for 58, 32, and 9 percent of the time patterns, respectively. For almost every drug prescription the prescribed daily dose was lower than the defined daily dose. More than 75 percent of these nursing home patients had at least one prescription for a psychotropic drug during institutionalization. One or more side-effects were observed in 50 percent of the patients who used a neuroleptic. The total number of patients receiving psychotropics did not change throughout the study. Psychotropics were prescribed for long-term use, but in a low dose. Side-effects were frequently observed while the correct individual dose was being determined.

[Use of psychotropic drugs in a group of nursing home patients with dementia: many users, long-term use but low dosages]. / Psychofarmacagebruik bij een groep dementerende verpleeghuispatiënten: veel gebruikers, langdurig gebruik, maar lage doses.

Of 890 nursing home patients with dementia, admitted between 1980 en 1989 to Dutch nursing home 'Joachim en Anna' in Nijmegen, each episode of psychotropic drug use was retrospectively registered. Drugs were coded by means of the Anatomical Therapeutic Chemical (ATC)-classification system and the daily dose was expressed as the ratio of the prescribed daily dose and the internationally agreed defined daily dose. Side effects were analysed as were changes in prescription patterns throughout the years of patient admittance. A total of 3090 episodes were registered. Neuroleptics, benzodiazepines and antidepressants accounted for 58, 32 and 9% of the prescriptions. In almost every drug-prescription the prescribed daily dose was lower than the defined daily dose. More than 75% of the patients had at least one prescription for a psychotropic drug during institutionalization. Half of those patients who used a neuroleptic showed one or more side effects. Neither the total amount of patients with psychotropics nor the duration of usage changed throughout the years of patient admittance. It is concluded that a majority of these nursing home patients got at least one prescription of a psychotropic drug during institutionalization. Psychotropics were prescribed for long-term usage, but in low doses. Side effects were frequently observed in determining the right dose.

Sub-50 oral contraceptives affect folate kinetics.

The effects of long-term use of oral contraceptives containing less than 50 micrograms of estrogen (sub-50 OCs) on the kinetics of folic acid monoglutamate, vitamin B12 levels, and iron status have been studied in 29 OC users (Marvelon) and in 13 women without OC use serving as controls. At 210 min after oral folate loading the median serum folate concentration was significantly lower in OC users when compared to the control group. OC users showed significantly higher total iron binding capacity and significantly lower serum vitamin B12 concentrations. This data demonstrates that sub-50 OCs significantly affect folate kinetics and vitamin B12 levels. However, the folate and vitamin B12 status does not seem to be at risk.

Interaction of legume lectins with the cellular metabolism of differentiated Caco-2 cells.

The binding of the legume lectins Phaseolus vulgaris E4 and L4, Glycine max agglutinin, Vicia faba agglutinin, and Pisum sativum agglutinin to intact differentiated Caco-2 cells and to brush border membranes of differentiated Caco-2 cells was investigated, and their impact on the cellular metabolism and the microvilli of these cells was assessed. P. vulgaris isolectin E4 showed the most intense staining after binding of fluorescein isothiocyanate-labeled lectin to intact Caco-2 cells. P. sativum agglutinin showed the weakest staining intensity. The dissociation constant for P. vulgaris isolectin E4 and P. sativum agglutinin binding was 0.11 x 10(-5) and 1.69 x 10(-5) mol/L, respectively. The values of the dissociation constants for P. vulgaris isolectin L4, G. max agglutinin, and V. faba agglutinin were situated in between these extremes. Stimulation of thymidine, glucosamine, and fucose incorporation was observed after exposure to P. vulgaris isolectins and soybean agglutinin. V. faba agglutinin had an inhibitory effect, whereas P. sativum agglutinin showed little or no effect. Compared with control cells and P. vulgaris isolectin L4- and P. sativum agglutinin-incubated cells, the microvilli of P. vulgaris isolectin E4-, soybean agglutinin-, and V. faba agglutinin-incubated cells were shortened significantly. The data provide evidence that a correlation exists, not only between the dissociation constants of the lectins and the fluorescent staining intensity, but also between the dissociation constants of the lectins and the extent of the legume lectin-induced changes in the cellular metabolism.

The methyl-5 alpha-dihydrotestosterones mesterolone and drostanolone; gas chromatographic/mass spectrometric characterization of the urinary metabolites.

Before including the detection of the methyl-5 alpha-dihydrotestosterones mesterolone (1 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) and drostanolone (2 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) in doping control procedures, their urinary metabolites were characterized by gas chromatography/mass spectrometry. Several metabolites were found after enzymatic hydrolysis and conversion of the respective metabolites to their trimethylsilyl-enol-trimethylsilyl ether derivatives. The major metabolites of mesterolone and drostanolone were identified as 1 alpha-methyl-androsterone and 2 alpha-methyl-androsterone, respectively. The parent compounds and the intermediate 3 alpha,17 beta-dihydroxysteroid metabolites were detected as well. The reduction into the corresponding 3 beta-hydroxysteroids was a minor metabolic pathway. All metabolites were found to be conjugated to glucuronic acid.

Dysfunctional presynaptic alpha 2-adrenoceptors expose facilitatory beta 2-adrenoceptors in the vasculature of spontaneously hypertensive rats.

Previous studies on spontaneously hypertensive rats (SHR) have yielded inconsistent information about functional aberrations of the presynaptic alpha 2- and beta 2-adrenoceptor-mediated modulation of sympathetic neurotransmitter release. In the present investigation we studied the capacity of presynaptic beta 2-adrenoceptors that enhance noradrenaline (NA) release in the portal vein of freely moving, unanesthetized SHR and normotensive Wistar rats (WR) using the beta 2-selective agonist fenoterol. The results show that the presynaptic beta 2-adrenoceptor population in SHR responds to significantly lower dosages of fenoterol than that in WR. The reason for this enhanced action, however, could not be attributed to the beta 2-adrenoceptor itself, nor to a diminished neuronal uptake of NA, but to a diminished responsiveness of the presynaptic alpha 2-adrenoceptor. Stimulation of presynaptic alpha 2-adrenoceptors with oxymetazoline (45 micrograms/min) decreased basal NA levels by 46% in WR and by 3% in SHR. Blockade of alpha 2-adrenoceptors, using 0.5 mg/kg yohimbine, induced a 4.86-fold rise in the basal NA level in WR but only a 1.89-fold rise in SHR. A subsequent dose of fenoterol, however, resulted in a further 2.5- and 2.6-fold rise in WR and SHR, respectively, indicating that there is a normal presynaptic beta 2-adrenoceptor population in the vasculature of SHR.

Social inhibition and motor skill performance in first, third and fifth grade children.

A systematic literature search over a period of 7 years yielded 28 articles about social inhibition with few of them addressing the relationship between social and motor functioning. Two sets of empirical data are reported. Firstly, a replication of the study performed by Zimmer in 1981 on the relationship between social inhibition and motor skill performance has been carried out with first, third and fifth grade children. Contrary to Zimmer's (1981) earlier findings with pre-school children, no relationship was found between motor skills test and social inhibition at any of the three age levels studied. Secondly, a group of children who attended extra physical education classes because of delay in motor performance (called "motoric remedial teaching") was found to score significantly lower on the motor skills test and higher on the social inhibition scale than a matched group of classmates. These findings indicate that although social inhibition appears not to be related to motor skill performance in the normal population, a significant relationship is present in a special sample of motorically delayed children.

Chaos and illusion.

Pharmacology is the study of the interaction of drugs with living organisms, especially humans. The body is a very complicated system, which suggests that the 'effect' induced by a drug is not a single entity but a change in several variables at the same time, all of which are interrelated in a nonlinear fashion. Research on nonlinear systems in other fields of science--commonly known as chaos theory--may therefore be of use in understanding pharmacology, as explained here by J. M. van Rossum and J. E. G. M. de Bie. They argue that in the study of drug effects, several variables should be measured simultaneously. Many pharmacologists prefer to construct an illusion of reality, studying just one of the essential variables and averaging data in a population of subjects, thus losing the opportunity to understand what a drug really does to a patient.

Pharmacokinetic study of extradural and intrathecal sufentanil anaesthesia for major surgery.

We have studied the plasma concentrations (Cp) and pharmacokinetics of sufentanil injected i.v. (IVS), intradurally (IS) or extradurally (ES) under general anaesthesia in 31 patients undergoing major abdominal surgery. Sufentanil appeared in plasma very rapidly and Cpmax was also attained rapidly after both extradural and intrathecal injection. Apart from the first 2 min after injection, Cp after ES and IVS were comparable until the end of the study. Cp after ES was greater than after IS up to 0.25 h. Cp after IS was significantly greater than that after ES at 1 h and 2.5 h, and was also greater than that after IVS at 3 h. At tracheal extubation there was no difference in Cp between groups. Peak Cp values were significantly different between ES and IS, but the times taken to reach Cpmax were comparable. Plasma pharmacokinetics after ES and IS were similar. The plasma mean residence time and volume of distribution of sufentanil at steady state after ES and IS were significantly different in comparison with those after IVS.

Rapid and sensitive gas-chromatographic determination of caffeine in blood plasma, saliva, and xanthine beverages.

A gas chromatographic procedure is reported for the determination of caffeine in plasma, saliva, and xanthine beverages. Using a 75 cm column packed with OV-17, nitrogen-sensitive detection, and 1 ml samples, a suitable limit of analysis (coefficient of variation (CV) = 10.2%) of 50 ng/ml was obtained in plasma. Within-day CVs at caffeine concentrations of 0.1-0.5-2.0-7.5-15.0 micrograms/ml in plasma were 7.7-5.6-4.8-3.8-3.4%, respectively. The limit of detection, defined as the injected quantity of caffeine giving rise to a signal to noise ratio of 2, is 40 pg, corresponding to a plasma concentration of 1 ng/ml. The procedure involves addition of the internal standard 7-pentyl theophylline and alkaline extraction of the sample with dichloromethane. The method described rivals any gaschromatographic assay published so far in rapidness and accuracy. Plasma and saliva caffeine concentrations were determined in a healthy male volunteer after swallowing 400 ml of coffee. The calculated pharmacokinetic parameters, assuming complete absorption of caffeine from the G.I. tract, agree well with previously published values.

Doping control of testosterone and human chorionic gonadotrophin: a case study.

Doping control for testosterone and human Chorionic Gonadotrophin (hCG) requires special attention as a difference must be made between the endogenous and exogenous origin of both substances. The detection of exogenous testosterone is based on the ratio of testosterone- to epitestosterone-glucuronide (T/E) in urine. The problems with this ratio are discussed. For hCG analysis in urine the utilization of sandwich-type hCG specific assays instead of hCG/hCG beta competitive assays is recommended. A case study in which an athlete self-administered testosterone and hCG before a competition is described. The T/E ratio and hCG concentration in urine were followed during this period of self-administration. The results demonstrate the relevance of the T/E ratio and of the selected hCG assay. The ratio of testosterone to human Luteinizing Hormone (T/hLH) in serum also indicated the use of hormones. Although the athlete's urine was negative for exogenous testosterone directly after competition, he would have been found positive for hCG.

Oxidation-reduction (redox) potentiometry in blood in geriatric conditions: a pilot study.

Oxidation-reduction (redox) potentials in blood were measured potentiometrically in 36 elderly people: 26 long-stay patients in a nursing home and 10 healthy elderly people (controls). The geriatric patients were obviously more affected by various chronic geriatric conditions, clearly used more medications, and had much higher quantitative invalidity scores (help index) compared to the control group. The average redox potential (Eh) in the geriatric patients was significantly (p less than 0.001) higher (300 mV +/- 24) than that in the control group (269 mV +/- 19). Repeated measurements showed some intraindividual variability of Eh. The pH in blood and a number of haematological and anthropometrical parameters did not differ significantly, except for the haemoglobin content, which was somewhat lower in the geriatric group (p less than 0.02). Eh did not correlate with the haemoglobin content. In addition, no effects of age or sex on the value of Eh were found. It was concluded that the general physical condition of the geriatric patients could be responsible for an increase of Eh, although drug effects and nutritional factors could not be excluded. Eh can be regarded as a measure for the balance of oxidant and reductant component in tissue fluids. Comparison between the Eh of younger and healthy elderly people indicates that this balance is apparently unaltered in healthy elderly persons, although elderly people may be more susceptible to disturbance by disease conditions, possibly as a result of a decreased homeostatic capacity of the redox balance. As many redox components play a role in the biochemistry of oxy-radicals, one may speculate on the possible value of Eh in relation to oxy-radical tissue damage.