Primary intra-articular epithelioid sarcoma of the knee: Unusual presentation of a rare entity.

We report a case of a 60-year-old female with severe and progressive pain of her right knee. Physical therapy, pain medication, and arthroscopic debridement were unsuccessful. Finally, pathological examination revealed an intra-articular epithelioid sarcoma, a rare tumor in an atypical location. Patient died within 5 months after initial admission. Despite this unusual clinical course and presentation, we would like to share the valuable clinical lessons we learned from this case. Introduction of a coordinating physician in combination with a multidisciplinary treatment regarding optimal pain management should optimize treatment results in future patients.

Prevalence and determinants of medication non-adherence in chronic pain patients: a systematic review.

BACKGROUND: Chronic pain is commonly treated with analgesic medication. Non-adherence to prescribed pain medication is very common and may result in sub-optimal treatment outcome. The aim of this review was to investigate the prevalence of medication non-adherence and to present determinants that may help identify patients at risk for non-adherence to analgesic medication. METHODS: A search was performed in PubMed and Embase with systematic approach including PRISMA recommendations. Individual risk of bias was assessed and systematic data extraction was performed. RESULTS: Twenty-five studies were included. Non-adherence rates to pain prescriptions ranged from 8% to 62% with a weighted mean of 40%. Underuse of pain medication was more common than overuse in most studies. Factors that were commonly positively associated with non-adherence were dosing frequency, polymedication, pain intensity, and concerns about pain medication. Factors negatively associated with non-adherence were age, again pain intensity and quality of the patient-caregiver relationship. Underuse was positively associated with active coping strategies and self-medication, and negatively associated with perceived need for analgesic medication. Overuse was positively associated with perceived need, pain intensity, opioid use, number of prescribed analgesics, a history of drug abuse, and smoking. CONCLUSION: Non-adherence to analgesic medication use is very common in the chronic pain population. The choice for pharmacological therapy should not only be based upon pain diagnosis but should also take the risks of non-adherence into account. The value of adherence monitoring or adherence enhancing interventions has to be investigated in future studies.

Mental health among living kidney donors: a prospective comparison with matched controls from the general population.

The impact of living kidney donation on donors' mental health has not been sufficiently nor comprehensively studied. Earlier studies demonstrated that mental health did not change in the majority of donors, however they often lacked a suitable control group and/or had other methodological limitations. Consequently, it remains unclear whether changes in mental health found among a minority of donors reflect normal fluctuations. In this study we matched 135 donors with individuals from the general Dutch population on gender and baseline mental health and compared changes in mental health over time. Mental health was measured using the Brief Symptom Inventory and Mental Health Continuum Short Form. Primary analyses compared baseline and 6 months follow-up. Secondary analyses compared baseline and 9 (controls) or 15 months (donors) follow-up. Primary multilevel regression analyses showed that there was no change in psychological complaints (p = 0.20) and wellbeing (p = 0.10) over time and donors and controls did not differ from one another in changes in psychological complaints (p = 0.48) and wellbeing (p = 0.85). Secondary analyses also revealed no difference in changes between the groups. We concluded that changes in mental health in the short term after donation do not significantly differ from normal fluctuations found in the Dutch general population.

[Neurosyphilis: unexpected reunion with an old acquaintance]. / Neurosyfilis: onverwacht weerzien met een oude bekende.

A 45-year-old man was admitted to a psychiatric hospital with confusion and disorientation; he was suspected of having Korsakoff syndrome. He was known to have a history of alcohol abuse, complicated by epileptic fits, and to have had a recent ischaemic cerebrovascular attack. Unexpectedly, screening for syphilis turned out to be positive. Examination of the cerebrospinal fluid led to the diagnosis of neurosyphilis. Most neurological and psychiatric symptoms disappeared after treatment with antibiotics.

[Myocarditis and cardiomyopathy: underestimated complications resulting from clozapine therapy]. / Myocarditis en cardiomyopathie; ernstige complicaties van clozapinetherapie.

BACKGROUND: Treatment with clozapine can affect the heart, leading to serious complications such as myocarditis and cardiomyopathy. When in their early stages both illnesses are difficult to diagnose; this can have serious consequences. Recent analyses of clozapine data suggest that particularly myocarditis is possibly more common than has been assumed hitherto. AIM: To determine the frequency of these complications and to find out what diagnostic tests are available and whether it is necessary or possible to adjust current guidelines on these complications. METHOD: The relevant literature was consulted via PubMed, Embase Psychiatry and Psycinfo on the basis of the keywords 'clozapine' and 'myocarditis', 'cardiomyopathy' and 'heart failure'. RESULTS: Studies showed that the incidence of myocarditis varied from 0.015 to 1.3%. Cardiomyopathy was the subject of fewer studies, one study reported an incidence of 0.022%. More than 50% of the cases of myocarditis developed during the first few weeks of treatment, the average time being about 15 days. For an early diagnosis it is important to monitor the patient's symptoms carefully, especially during the first four weeks following the start of medication. Monitoring should include laboratory tests and electrocardiography. Echocardiography and MRI can be useful additions to the diagnostic process. CONCLUSIONS: Early diagnosis of myocarditis is important because it is a serious condition. Timely recognition of subclinical myocarditis could possibly prevent later complications such as cardiomyopathy. Clinical guidelines are proposed on the basis of the literature.

[Galactorrhoea and the use of selective serotonin reuptake inhibitors]. / Galactorroe en het gebruik van selectieve serotonineheropnameremmers.

The subject of this case study is a female patient who was treated with a selective serotonin reuptake inhibitor (SSRI), citalopram, because of a depressive episode. She developed symptoms of galactorrhea; there was a time relationship between suspension of the treatment with citalopram and a reduction of the galactorrhea symptoms. The consulting internist assumed that the symptoms were due to hyperprolactinemia arising from under-supplementation of thyroid hormone and resultant hypothyroidism. Psychiatrists usually see galactorrhea in patients who are taking antipsychotics. However, few psychiatrists know that galactorrhea can also be caused by SSRIs. When a patient has symptoms of bilateral galactorrhea and has used an SSRI and when hyperprolactinemia has been found in laboratory tests it is probably advisable to stop the SSRI medication. The article mentions what additional research is needed.

Panic disorder and depression: relationship between psychological and biochemical aspects.

In a group of medication-free out-patients suffering from depression and/or panic disorder we investigated the interdependence between psychological parameters such as aggression and biochemical parameters such as serotonin and tryptophan. We compared the findings in the patient group with a reference group. In the group of patients as a whole negative correlations were observed between the concentration of serotonin in platelets and depression and with hostility and aggression against others. Serotonin in plasma and tryptophan correlated negatively with hostility. The findings support the suggested link between aggression and depression with a low functioning serotonergic system.

Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features.

The aim of this multicenter, randomized, double-blind, 8-week study was to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of hospitalized patients with DSM-IV diagnosis of severe depressive episode with melancholic features. Patients with a baseline score of > or = 25 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to receive treatment with either mirtazapine (N = 78, 15-60 mg/day) or venlafaxine (N = 79, 75-375 mg/day, twice a day) in a rapid up-titration schedule. Efficacy was assessed with the Montgomery-Asberg Depression Rating Scale (MADRS), HAM-D-17, and Clinical Global Impression scale, and quality of life was assessed with the Quality of Life, Enjoyment, and Satisfaction Questionnaire and Quality of Life in Depression Scale. Tolerability was assessed with the Utvalg for Kliniske Undersogelser (UKU) side effect scale and by reporting adverse events. Both drugs were effective in reducing overall symptoms of depression, showing substantial reductions in group mean MADRS scores (-20.1 for mirtazapine and -17.5 for venlafaxine) and HAM-D-17 scores (-17.1 for mirtazapine and -14.6 for venlafaxine) at the end of the treatment. Although not statistically significant, at all assessment times higher percentages of patients treated with mirtazapine were classified as responders (> or =50% reduction) on the HAM-D (at endpoint, 62% vs. 52%) and MADRS (at endpoint: 64% vs. 58%). Likewise were the percentages of remitters (HAM-D score < or =7; MADRS score < or =12) also higher in the mirtazapine group. A statistically significant difference favoring mirtazapine was found on the HAM-D Sleep Disturbance factor at all assessment points (p < or = 0.03). Both treatments were well tolerated. Although slightly more subjects treated with mirtazapine reported at least one adverse event, a statistically significantly higher percentage of patients treated with venlafaxine (15.3%) than mirtazapine (5.1%) dropped out because of adverse events (p = 0.037). Quality of life improved in both treatment groups. In this study, treatment with mirtazapine resulted in a trend toward more responders and remitters than treatment with venlafaxine and in significantly fewer dropouts as a result of adverse events.

Primary repair of patellar tendon rupture without augmentation.

Repair of patellar tendon ruptures has often relied on cerclage augmentation and prolonged immobilization in extension. We are reporting our experience with avulsion injuries as well as midsubstance ruptures, both treated with primary repair without augmentation, allowing early mobilization in the athlete less than 40 years of age. Repairs were performed to allow knee flexion to more than 60 degrees. Rehabilitation was performed with heel slides, allowing flexion to 45 degrees for the first 3 weeks, increasing to 90 degrees at 3 to 6 weeks, and thereafter without restriction. An accelerated weightbearing and muscle strengthening program was adopted. At a mean follow-up of 2.6 years (range, 20 to 61 months), 12 patients had returned to their previous levels of activity. No loss of extension or extensor lag was noted; mean flexion loss was 5 degrees. Patellofemoral symptoms and signs were present in five patients, but activity was limited in only two. Mean peak torque at 60 deg/sec was 92% (range, 73% to 105%). Mean Lysholm score was 94 +/- 2.5 points. Primary repair with immediate, protected range of motion resulted in uniformly excellent results and obviated the need for manipulation or subsequent hardware removal.

[Impact of demographic changes on drug utilization related to diabetes in Aquitaine]. / L'incidence de l'évolution démographique sur la consommation pharmaceutique liée au diabète en Aquitaine.

Diabetes is a chronic disease highly correlated to age. In 1998, the Sickness Find of the Aquitaine region has reimbursed 273 million French Francs for expenditures related to diabetes pharmaceuticals. The amount would increase to 300 million French Francs in 2005, a growth of nearly 10%, whereas the Aquitaine population would increase only 4%, from 2,909,000 in 1998 to 3,024,000 seven years later. The difference comes from population aging, as the calculations are undertaken "other things being equal": the insurance coverage rate, the disease prevalence rate, the consumption of pharmaceuticals per patient are supposed unchanged during the period.

Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group.

OBJECTIVE: To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed inpatients and outpatients. METHOD: Patients with a major depressive episode (DSM-III-R), a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression (HAM-D), and > or=2 on HAM-D Item 1 (depressed mood) were randomly assigned to a 6-week treatment with either mirtazapine (N=66, 15-60 mg/day) or fluoxetine (N=67, 20-40 mg/day). The upper limit of the mirtazapine dose range was above the dose range approved in the United States (15-45 mg/day). Efficacy was evaluated by the HAM-D, Clinical Global Impressions, the Visual Analogue Mood Rating Scale (VAMRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method. RESULTS: Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group. The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period, reaching statistical significance at days 21 and 28. At assessments from day 21 and onward, the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points, the magnitude of difference usually seen between an efficacious antidepressant drug and placebo. Mean dosages at weeks 1-4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine; the respective dosages at weeks 5-6 were 56.3 mg and 35.8 mg. Similar numbers of patients dropped out due to adverse events; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group. CONCLUSION: We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy.

Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum.

In lymphocytes, the expression of early immune response genes is regulated by NF-AT transcription factors which translocate to the nucleus after dephosphorylation by the Ca2+-dependent phosphatase, calcineurin. We report here that mice bearing a disruption in the NF-ATc gene fail to develop normal cardiac valves and septa and die of circulatory failure before day 14.5 of development. NF-ATc is first expressed in the heart at day 7.5, and is restricted to the endocardium, a specialized endothelium that gives rise to the valves and septum. Within the endocardium, specific inductive events appear to activate NF-ATc: it is localized to the nucleus only in endocardial cells that are adjacent to the interface with the cardiac jelly and myocardium, which are thought to give the inductive stimulus to the valve primordia. Treatment of wild-type embryos with FK506, a specific calcineurin inhibitor, prevents nuclear localization of NF-ATc. These data indicate that the Ca2+/calcineurin/NF-ATc signalling pathway is essential for normal cardiac valve and septum morphogenesis; hence, NF-ATc and its regulatory pathways are candidates for genetic defects underlying congenital human heart disease.

Neuropsychiatrie aspects of HIV infection.

Human immuno deficiency virus may cause a broad spectrum of psychiatric sequelae. In this review we discus the possible associations between HIV infection with psychosis, mild neurocognitive disorder and dementia. The cerebral reserve model gives an explanation why HIV infected individuals with low educational level and/or intravenous drug users are more vulnerable to direct and indirect neurotoxic effects of HIV.

Redundant expression but selective utilization of nuclear factor of activated T cells family members.

Nuclear factor of activated T cells (NF-AT) complexes regulate the induction of many early T cell activation molecules. Four related proteins can function as the cytoplasmic subunit of NF-AT, and their overlapping expression patterns and the mild phenotype of the NF-ATp null mice suggest that they may be functionally redundant. We characterized the distribution and activation of cytoplasmic NF-AT proteins in mature lymphocytes and found that NF-ATc, NF-ATp, and NF-AT4/x/c3 are co-expressed and co-regulated in mature T and B cells. Each protein forms independent DNA binding complexes, and at physiologic concentrations, NF-ATc and NF-ATp complexes out-compete NF-AT4/x/c3 for occupancy of NF-AT sites from the IL-2, IL-3/granulocyte-macrophage CSF, IL-4, and CD40 ligand genes. This predicts heavily redundant immune regulatory functions of NF-ATp and NF-ATc, but distinct activities for NF-AT4/x/c3. Additionally, Ab interaction with NF-ATp induces high affinity NF-kappaB site interaction, suggesting that nuclear partners may dramatically vary the specificity of the NF-AT family.

Effects of clomipramine on plasma amino acids and serotonergic parameters in panic disorder and depression.

We examined the effects of long-term (six months) treatment with the serotonin potentiating tricyclic antidepressant clomipramine on several serotonergic parameters in panic disorder and depressive patients. Serotonin (5-HT) levels in blood, platelets and plasma were significantly reduced to 4%, 3% and 28% of their respective baseline values. In addition, the plasma level of tryptophan was also significantly reduced, although the decrease was only 16%. Three months after discontinuation of clomipramine treatment, 5-HT in blood and platelets reached baseline values again, while the plasma 5-HT level was still reduced to 68% of pretreatment values. Unexpectedly, the plasma tryptophan concentration was even lower at this time-point than after six months of treatment. These results show that clomipramine not only has an effect on 5-HT levels in blood, platelets and plasma, but also on plasma tryptophan concentration. We speculate that low plasma tryptophan after treatment may constitute a risk for the recurrence of psychopathology.

Different nuclear signals are activated by the B cell receptor during positive versus negative signaling.

It is not known how immunogenic versus tolerogenic cellular responses are signaled by receptors such as the B cell antigen receptor (BCR). Here we compare BCR signaling in naive cells that respond positively to foreign antigen and self-tolerant cells that respond negatively to self-antigen. In naive cells, foreign antigen triggered a large biphasic calcium response and activated nuclear signals through NF-AT, NF-kappa B, JNK, and ERK/pp90rsk. In tolerant B cells, self-antigen stimulated low calcium oscillations and activated NF-AT and ERK/pp90rsk but not NF-kappa B or JNK. Self-reactive B cells lacking the phosphatase CD45 did not exhibit calcium oscillations or ERK/pp90rsk activation, nor did they repond negatively to self-antigen. These data reveal striking biochemical differences in BCR signaling to the nucleus during positive selection by foreign antigens and negative selection by self-antigens.

The T cell activation factor NF-ATc positively regulates HIV-1 replication and gene expression in T cells.

Clinical deterioration in human immunodeficiency virus type 1 (HIV-1) infection is associated with increased levels of viral replication and burden in the peripheral blood and lymphoid organs. T cell activation and ensuing cellular gene activation can be critical for HIV-1 replication. The hypothesis that the nuclear factor of activated T cells (NF-AT) may influence HIV-1 replication is therefore compelling given the tight correlation of HIV-1 transcriptional induction to T cell activation. We report that certain NF-AT(Rel) family members productively bind the kappaB regulatory elements, synergize with NF-kappaB and Tat in transcriptional activation of HIV-1, and enhance HIV-1 replication in T cells. These results link regulatory factors critical to T cell commitment directly to HIV-1 replication.