Macrophage LRP1 contributes to the clearance of von Willebrand factor

The relationship between low-density lipoprotein receptor-related protein-1 (LRP1) and von Willebrand factor (VWF) has remained elusive for years. Indeed, despite a reported absence of interaction between both proteins, liver-specific deletion of LRP1 results in increased VWF levels. To investigate this discrepancy, we used mice with a macrophage-specific deficiency of LRP1 (macLRP1(-)) because we previously found that macrophages dominate VWF clearance. Basal VWF levels were increased in macLRP1(-) mice compared with control mice (1.6 ± 0.4 vs 1.0 ± 0.4 U/mL). Clearance experiments revealed that half-life of human VWF was significantly increased in macLRP1(-) mice. Ubiquitous blocking of LRP1 or additional lipoprotein receptors by overexpressing receptor-associated protein in macLRP1(-) mice did not result in further rise of VWF levels (0.1 ± 0.2 U/mL), in contrast to macLRP1(+) mice (rise in VWF, 0.8 ± 0.4 U/mL). This points to macLRP1 being the only lipoprotein receptor regulating VWF levels. When testing the mechanism(s) involved, we observed that VWF-coated beads adhered efficiently to LRP1 but only when exposed to shear forces exceeding 2.5 dyne/cm(2), implying the existence of shear stress-dependent interactions. Furthermore, a mechanism involving β2-integrins that binds both VWF and LRP1 also is implicated because inhibition of β2-integrins led to increased VWF levels in control (rise, 0.19 ± 0.16 U/mL) but not in macLRP1(-) mice (0.08 ± 0.15 U/mL).     

A naturalistic study on the criteria of choice of second-generation antidepressants: A comparison of venlafaxine and SSRIs in depressed inpatients

INTRODUCTION: The objective of this study was to compare, in a naturalistic setting, the efficacy and tolerability of selective serotonin reuptake inhibitors (paroxetine, sertraline, citalopram) and venlafaxine, in 120 depressed inpatients. This paper attempts to review which variables may influence a physician's choice of a specific antidepressant for a specific patient. METHOD: Patients were assessed using the Hamilton Psychiatric Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), the Clinical Global Impression (CGI) and the Symptoms Check List (SCL-90). The two groups under assessment were comparable in all socio-demographic characteristics. We used logistic regression analyses to identify variables that differentiate the two groups at baseline. This, in turn, would represent those variables with the potential to influence a physician's selection of an antidepressant. RESULTS: Venlafaxine patients reported significantly worse scores on MADRS at baseline, but any difference was no longer present at discharge. We found no significant variation in the efficacy of the antidepressants under study and there were no differences in the incidence and profiles of adverse events between the groups of patients. CONCLUSION: The degree of severity of the actual depressive picture appears to influence choice in favour of venlafaxine. However, it appears that the choice of SSRIs is more closely linked to patients who present a previous history of non-mood psychiatric symptoms.     

Family History of Suicide and Personality

The objective of this study was to analyze the impact of family history of suicidal behaviour on psychopathlogical features of inmates. A sample of 1,179 prisoners had a psychiatric interview including the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA). Prisoners completed the Barratt Impulsivity Scale (BIS), Buss-Durkee Hostility Inventory (BDHI), and Eysenck Personality Questionnaire (EPQ). Prisoners with a family history of suicide were compared with prisoners without a family history of suicide on clinical and personality variables. Seventy of the 1,179 prisoners (5.9%) had a family history of suicide. Significantly more FHS positive prisoners had attempted suicide compared with FHS negative prisoners (36% vs. 12%, P < 0.0001). Significantly more FHS positive prisoners had a previous history of convictions, a history of juvenile convictions, and had exhibited aggressive behavior in jail. FHS positive prisoners had significantly higher aggression scores on the BGLHA, higher hostility scores on the BDHI, higher impulsivity scores on the BIS, and higher neuroticism scores on the EPQ. A family history of suicide may be a useful clinical indicator that a prisoner is at increased risk for suicidal behaviour and may have problems with impulsive-aggression.     

Diagnosis, assessment and management of delusional jealousy in Parkinson’s disease with and without dementia

Patients with Parkinson’s disease (PD) may present delusional jealousy (DJ). In a previous cross-sectional prevalence study we identified 15 cognitively preserved and five demented PD patients with DJ. The current study aimed at evaluating their clinical (motor and non-motor) characteristics and the pharmacological treatments associated with DJ, and its subsequent pharmacological management. Patients were assessed by neurologists and psychiatrists using the Hoehn and Yahr scale, the Unified Parkinson’s Disease Rating Scale, the Brief Psychiatric Rating Scale, the Beck Depression Inventory, the Hamilton Anxiety Scale and the Neuropsychiatric Inventory. Efficacy of DJ management was evaluated in follow-up visits. All patients were in therapy with dopamine agonists. A subgroup of five cognitively preserved patients developed DJ after a short period of treatment of therapy with dopamine agonists, while other patients developed DJ after a longer period of dopaminergic treatment. Psychiatric comorbidities were common in cognitively preserved and in demented patients. The pharmacological management included the interruption of dopamine agonists in two patients and the reduction of dopamine agonist dose plus the use of antipsychotics in other patients. These clinical data suggest that the management of medicated PD patients should include investigation for the presence of DJ and the evaluation of clinical characteristics potentially relevant to the prevention or the early recognition of delusions.     

Axial deformation during coronary stenting: an extreme case

We describe a case of longitudinal stent compression induced by withdrawal of a "buddy wire," which we managed by crushing the retracted struts using another stent. To the best of our knowledge, this is one of the first reports of this complication induced by wire manipulation.     

Polycythemia as rare secondary direct manifestation of acromegaly: management and single-centre epidemiological data

Polycythemia associated with acromegaly is usually caused by the systemic manifestations of the disease, such as sleep-apnea or concomitant erythropoietin-secreting kidney tumors. The recognition of underlying pathologies requires a thorough diagnostic process. We report a unique case of acromegaly with polycythemia, not caused by commonly described manifestations of the disease, and receding with octreotide therapy. The medical history of 141 acromegalic patients followed by the Endocrinology Unit of the San Martino University Hospital in Genoa has been also reviewed, together with the literature evidence for similar cases. The diagnostic workflow and 2-years follow-up of a 43-years old acromegalic, polycythemic man with a history of past smoking, moderate hypertension, and mental retardation are described. The hematological parameters of our cohort was retrospectively compared with those of a healthy, age/gender-related control group as well. Therapy with octreotide LAR, 20?mg i.m. q28d was begun soon after diagnosis of acromegaly in the polycythemic patient. Haematocrit level, hormonal setting, as well as pituitary tumor size and visual perimetry during treatment were recorded. Octreotide LAR treatment normalized hormonal alterations, as well as hematological parameters. Polycythemia has not recurred after 2?years of therapy. The median hemoglobin and hematocrit levels of the retrospectively analyzed cohort of acromegalic were significantly lower than normal ranges of a healthy, age/sex- related control population. In conclusions, polycythemia can be a direct, albeit rare, secondary manifestation of acromegaly, that must be considered during the diagnostic work-up of acromegalic patients presenting with such disorder.