Relationship of brainstem raphe echogenicity and clinical findings in depressive states

Transcranial sonography (TCS) revealed reduced brainstem raphe (BR) echogenicity in major depressive disorder (MDD). Here, it was studied whether BR echogenicity discriminates MDD and adjustment disorder with depressed mood (ADDM), and whether BR echogenicity relates to depression severity or treatment responsivity. For this, 15 patients with single episodes of MDD (MDDs), 22 with recurrent MDD (MDDr), 15 with ADDM, and 50 healthy controls were investigated with TCS. Frequency of reduced BR echogenicity was similar in groups MDDs (53%), MDDr (50%) and ADDM (60%), but significantly lower in the controls (8%). Patients with reduced BR echogenicity had lower scores on the 21-item Hamilton Depression Rating Scale and the Motor Retardation Scale, compared with patients with normal BR echogenicity. BR echogenicity scores were significantly lower in SSRI responders to serotonin reuptake inhibitors (SRI) than in non-responders. Reduced BR echogenicity indicated SSRI responsivity with 70% sensitivity, 88% specificity and a positive predictive value of 88%. No impact of age, gender or antidepressant medication on BR echogenicity was found. These results indicate that reduced BR echogenicity is not related to diagnostic category of depressive state. Reduced BR echogenicity might reflect a pathology predisposing to a certain subtype of depression characterized by less psychomotor retardation and better responsivity to SRI.     

Detection of pulmonary tuberculosis in patients with a normal chest radiograph

OBJECTIVES: To describe the early symptoms of pulmonary tuberculosis (TB) when the chest radiograph (CXR) is normal. SETTING: Centralized, provincial TB control program. SUBJECTS: Twenty-five patients with culture-positive pulmonary TB and a normal CXR were identified from a review of 518 consecutive patients with culture-positive pulmonary TB in the province of Saskatchewan from January 1, 1988 to March 31, 1997. Patients with abnormal CXRs at the time of diagnosis were excluded from the analysis. RESULTS: Twenty-three of the 25 patients (92%) were symptomatic at the time of diagnosis, with cough/sputum (76%) being reported most commonly. Eleven patients were identified because of contact tracing from cases of infectious pulmonary TB, while the other 14 patients were identified because of an investigation of symptoms. Twenty-four patients (96%) exhibited one or more symptoms of cough for > 1 month, fever for > 1 week, or skin-test conversion after contact with infectious TB. The sputum smear of only one patient was positive. Two patients were pregnant at the time of diagnosis, one patient was HIV-positive, and one patient demonstrated isoniazid-resistant organisms on sensitivity testing. Five patients were diagnosed as having primary TB associated with Mantoux skin-test conversion. The incidence of culture-positive pulmonary TB with a normal chest radiograph was < 1% in the period from 1988 to 1989 and steadily increased to 10% in the period from 1996 to 1997. CONCLUSIONS: Culture-positive pulmonary TB with a normal CXR is not uncommon, and the incidence of this presentation is increasing. Patients with this presentation of TB are typically symptomatic and/or are detected by contact tracing to infectious cases of pulmonary TB. The results suggest that patients presenting with a cough for > 1 month, with a fever for > 1 week, or with documented skin-test conversion < 2 years after known exposure to infectious TB should have sputum submitted for a Mycobacterium tuberculosis smear and culture despite a normal CXR.     

Catecholamine synthesis and metabolism in the central nervous system of mice lacking α2-adrenoceptor subtypes

Background and purpose:

This study investigates the role of α₂-adrenoceptor subtypes, α_2A, α_2B and α_2C, on catecholamine synthesis and catabolism in the central nervous system of mice.

Experimental approach:

Activities of the main catecholamine synthetic and catabolic enzymes were determined in whole brains obtained from α_2A-, α_2B- and α_2C-adrenoceptor knockout (KO) and C56Bl\7 wild-type (WT) mice.

Key results:

Although no significant differences were found in tyrosine hydroxylase activity and expression, brain tissue levels of 3,4-dihydroxyphenylalanine were threefold higher in α_2A- and α_2C-adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in α_2A and α_2CKOs compared with WT [WT: 2.8 ± 0.5, 1.1 ± 0.1; α_2AKO: 6.9 ± 0.7, 1.9 ± 0.1; α_2BKO: 2.3 ± 0.2, 1.0 ± 0.1; α_2CKO: 4.6 ± 0.8, 1.5 ± 0.2 nmol·(g tissue)⁻¹, for dopamine and noradrenaline respectively]. Aromatic L-amino acid decarboxylase activity was significantly higher in α_2A and α_2CKO [WT: 40 ± 1; α_2A: 77 ± 2; α_2B: 40 ± 1; α_2C: 50 ± 1, maximum velocity (V_max) in nmol·(mg protein)⁻¹·h⁻¹], but no significant differences were found in dopamine β-hydroxylase. Of the catabolic enzymes, catechol-O-methyltransferase enzyme activity was significantly higher in all three α₂KO mice [WT: 2.0 ± 0.0; α_2A: 2.4 ± 0.1; α_2B: 2.2 ± 0.0; α_2C: 2.2 ± 0.0 nmol·(mg protein)⁻¹·h⁻¹], but no significant differences were found in monoamine oxidase activity between all α₂KOs and WT mice.

Conclusions and implications:

In mouse brain, deletion of α_2A- or α_2C-adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any α₂-adrenoceptor subtypes resulted in increased activity of catechol-O-methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in α_2A and α_2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport.     

Effect of tecarfarin,a novel vitamin K epoxide reductase inhibitor,on coagulation in beagle dogs

Background and purpose:

Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.

Experimental approach:

Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).

Key results:

Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K₁ treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.

Conclusions and implications:

Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients.     

Development of the Manchester framework for the evaluation of emergency department pharmacy services

International Journal of Clinical Pharmacy - Many countries, including the United Kingdom, have established Emergency Department (ED) pharmacy services where some ED pharmacists now work as...     

Impaired transcallosally mediated motor inhibition in adults with attention-deficit/hyperactivity disorder is modulated by methylphenidate

Using transcranial magnetic stimulation (TMS) in children with ADHD, an impaired transcallosally mediated motor inhibition (ipsilateral silent period, iSP) was found, and its restoration was correlated with improvement of hyperactivity under medication with methylphenidate (MPH). Hyperactivity has been reported to decrease during transition into adulthood, although some motor dysfunction might persist. As one underlying neurophysiological process, a development-dependent normalization of motor cortical excitability might be postulated. In order to test this hypothesis, we measured the iSP in 21 adult ADHD patients and twenty-one sex- and age-matched healthy controls. In 16 of these patients, a second TMS was performed under treatment with MPH. Our results indicate a persistence of impaired transcallosally mediated motor cortical inhibition (shortened duration) in ADHD adults, which was correlated with clinical characteristics of hyperactivity and restlessness, and was restored by MPH. In contrast to ADHD in childhood, the iSP latency was not impaired, suggesting a partial development-dependent normalization of motor cortical excitability in ADHD adults. ISP duration appears to be a sensitive parameter for the assessment of disturbed intercortical inhibition in adults with ADHD.     

Intracortical motor inhibition and facilitation in adults with attention deficit/hyperactivity disorder

Using transcranial magnetic stimulation (TMS), disturbed facilitatory and inhibitory motor functions were recently found to correlate with motor hyperactivity in children with ADHD. Since hyperactivity seems to become reduced in ADHD during the transition to adulthood, a normalization of motor cortical excitability might be assumed. Therefore, we investigated the same inhibitory and facilitatory TMS paradigms in ADHD adults as we had previously examined in children. Motor cortical excitability was tested with TMS paired-pulse protocols in 21 ADHD adults and 21 age- and gender-matched healthy controls. In contrast to our results in ADHD children, no group-specific differences in amplitude changes of motor evoked potentials for inhibitory inter-stimulus intervals (ISI) (3, 100, 200 and 300 ms) or for facilitatory ISIs (13, 50 ms) could be detected. In ADHD adults, disturbed facilitatory and inhibitory motor circuits as found in ADHD children could not be shown, probably due to a development-dependent normalization of motor cortical excitability.     

Cutaneous lymphomas showing prominent granulomatous component: clinicopathological features in a series of 16 cases

Background  The presence of a prominent granulomatous tissue reaction in skin biopsies from primary cutaneous or systemic malignant lymphomas with secondary cutaneous involvement is a rare but well-known phenomenon.
Objective  This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component.
Patients and methods  The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30⁺ cutaneous T-cell lymphoma (2 patients), CD4⁺ small/medium pleomorphic cutaneous T-cell lymphoma (1 patient), primary cutaneous B-cell lymphoma (3 patients) and peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement (4 patients) were reviewed.
Results  The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established.
Conclusion  The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.

Conflicts of interest

None declared.