Neuroleptic-induced parkinsonism is associated with olfactory dysfunction

Objective   There is increasing evidence for olfactory deficits in patients with extrapyramidal disorders, but little is known about their occurrence in patients with drug-induced extrapyramidal symptoms (EPS). The present study was performed to investigate olfactory function in depressed patients with drug-induced parkinsonism under treatment with D2-blocking neuroleptic drugs compared to depressed controls on similar neuroleptic dose without EPS (no-EPS), and neuroleptic-naive depressed controls (no-NL). Methods   A total of 79 depressed patients with (N = 59) and without psychotic features (N = 20) were included in the study. Psychotic patients were treated with D2 blocking neuroleptic drugs. Of the neuroleptic-treated patients, 15 developed EPS. In all patients psychophysical olfactory testing was performed using “Sniffin’ Sticks” which included assessment of odor thresholds for phenylethylalcohol (PEA), odor identification, and odor discrimination. Results   Patients in the EPS group had significantly lower olfactory scores than patients in the no-EPS or no-NL groups. Patients in the no-NL and no-EPS groups were not significantly different from each other in terms of olfactory function. Using partial correlations controlling for the patients’ age, significant correlations were observed for EPS patients between severity of EPS and odor thresholds and odor identification, but not for odor discrimination. This indicated that olfactory function decreased with increasing severity of EPS symptoms. Conclusions   Our data show that olfactory deficits may be drug-induced in patients with primary affective disorder with a sensitivity toward developing EPS.     

Illusory vowels resulting from perceptual continuity: a functional magnetic resonance imaging study

We used functional magnetic resonance imaging to study the neural processing of vowels whose perception depends on the continuity illusion. Participants heard sequences of two-formant vowels under a number of listening conditions. In the "vowel conditions," both formants were always present simultaneously and the stimuli were perceived as speech-like. Contrasted with a range of nonspeech sounds, these vowels elicited activity in the posterior middle temporal gyrus (MTG) and superior temporal sulcus (STS). When the two formants alternated in time, the "speech-likeness" of the sounds was reduced. It could be partially restored by filling the silent gaps in each formant with bands of noise (the "Illusion" condition) because the noise induced an illusion of continuity in each formant region, causing the two formants to be perceived as simultaneous. However, this manipulation was only effective at low formant-to-noise ratios (FNRs). When the FNR was increased, the illusion broke down (the "illusion-break" condition). Activation in vowel-sensitive regions of the MTG was greater in the illusion than in the illusion-break condition, consistent with the perception of Illusion stimuli as vowels. Activity in Heschl's gyri (HG), the approximate location of the primary auditory cortex, showed the opposite pattern, and may depend instead on the number of perceptual onsets in a sound. Our results demonstrate that speech-sensitive regions of the MTG are sensitive not to the physical characteristics of the stimulus but to the perception of the stimulus as speech, and also provide an anatomically distinct, objective physiological correlate of the continuity illusion in human listeners.     

Comparison of a new neuromuscular transmission monitor compressomyograph with mechanomyograph

BACKGROUND: We developed a new neuromuscular transmission monitor, the compressomyograph (CMG, European patent number: EP 06018557.6, US patent number: US 60/824.541). This is the first preliminary report comparing neuromuscular block monitored by CMG and the Relaxometer mechanomyograph (MMG). METHODS: The two monitors were randomly allocated to the left or right hands of 16 patients. T1, first twitch of the train-of-four (TOF) expressed as percentage of control response, and the TOF ratio (T4:t1) were used to evaluate the neuromuscular block produced by rocuronium 0.6 mg kg(-1). RESULTS: The CMG monitor exhibited no pre-relaxation reverse fade (T4>T1) or T1 exceeding 100%. There was no significant difference in mean (SD) onset time, Dur(25) (time to T1 25% recovery), or Dur(0.9) (time to 0.9 TOF ratio recovery) measured by the CMG [2.4 (0.9), 22.6 (4.1), 43.1 (10.3) min, respectively] compared with MMG [2.1 (0.9), 22.9 (3.3), 43.3 (10.0) min, respectively]. According to Bland and Altman analysis, the bias (upper and lower limits of agreement) for T1% was -0.3% (+13.4% and -13.8%) and for TOF ratio was -0.009 (+0.068 and -0.085). CMG showed 100% sensitivity and 75% specificity in indicating full relaxation for tracheal intubation, and 80% sensitivity with 86% specificity in predicting MMG 0.9 TOF ratio. CONCLUSIONS: The CMG could be a reliable clinical monitor in the daily anaesthesia practice that does not require time to set up or rigid support of the arm.     

Large external iliac vein aneurysm in a patient with a post-traumatic femoral arteriovenous fistula

We report about a young patient with a large aneurysm of the left external iliac vein associated with a traumatic arteriovenous fistula between the left superficial femoral artery and the femoral vein after a stab wound 20 years ago. The patient presented with swelling of the left leg, which developed during the past years and worsened after saphenectomy 12 months before hospital admission. The chronically hyperperfused common iliac artery proximal to the arteriovenous fistula was compressing the common iliac vein. The venous outflow obstruction and subsequent venous hypertension render a possible explanation for the formation of the iliac vein aneurysm. Surgical repair of the venous aneurysm by interposition grafting and closure of the arteriovenous fistula was successful. A postoperative computed tomography scan showed a 50% size reduction of the feeding artery, underlining the ability of the arterial system to normalize arterial diameter in response to flow reduction, even after a high flow situation had existed for probably >20 years.     

Analysis and classification of B-cell infiltrates in lupus and ANCA-associated nephritis

Intrarenal B cell infiltrates resembling secondary lymphoid tissue have been found in several forms of inflammatory kidney disease. Their role in renal inflammation is not well defined, perhaps because B cell clusters have been regarded as a single entity while being quite heterogeneous. Therefore we characterized intrarenal lymphoid clusters of 32 patients diagnosed with lupus nephritis and 16 with ANCA associated nephritis. We identified four increasingly organized levels of intrarenal aggregates from scattered B cells to highly compartmentalized B cell clusters with central follicular dendritic cell networks. Most B cells displayed a mature non-antibody producing phenotype with antigen presenting ability. In regions of B cell infiltration, expression of the lymphoid chemokine BCA-1 was found in cells of a dendritic-like morphology and most B cells expressed the corresponding receptor CXCR5. Biopsies containing B cells had significantly higher levels of BCA-1 mRNA expression compared to those without, suggesting a role of BCA-1 and CXCR5 for B cell infiltration into the kidney. Our study proposes a new classification of B cell clusters in lupus and ANCA associated nephritis which might help to study the function of intrarenal B cell clusters in a more differentiated manner.     

Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection

Autoimmune liver diseases, such as autoimmune hepatitis (AIH) and primary biliary cirrhosis, often have severe consequences for the patient. Because of a lack of appropriate animal models, not much is known about their potential viral etiology. Infection by liver-tropic viruses is one possibility for the breakdown of self-tolerance. Therefore, we infected mice with adenovirus Ad5 expressing human cytochrome P450 2D6 (Ad-2D6). Ad-2D6-infected mice developed persistent autoimmune liver disease, apparent by cellular infiltration, hepatic fibrosis, "fused" liver lobules, and necrosis. Similar to type 2 AIH patients, Ad-2D6-infected mice generated type 1 liver kidney microsomal-like antibodies recognizing the immunodominant epitope WDPAQPPRD of cytochrome P450 2D6 (CYP2D6). Interestingly, Ad-2D6-infected wild-type FVB/N mice displayed exacerbated liver damage when compared with transgenic mice expressing the identical human CYP2D6 protein in the liver, indicating the presence of a stronger immunological tolerance in CYP2D6 mice. We demonstrate for the first time that infection with a virus expressing a natural human autoantigen breaks tolerance, resulting in a chronic form of severe, autoimmune liver damage. Our novel model system should be instrumental for studying mechanisms involved in the initiation, propagation, and precipitation of virus-induced autoimmune liver diseases.     

Attention and amygdala activity: an fMRI study with spider pictures in spider phobia

Facilitated detection of threatening visual cues is thought to be adaptive. In theory, detection of threat cues should activate the amygdala independently from allocation of attention. However, previous studies using emotional facial expressions as well as phobic cues yielded contradictory results. We used fMRI to examine whether the allocation of attention to components of superimposed spider and bird displays modulates amygdala activation. Nineteen spider-phobic women were instructed to identify either a moving or a stationary animal in briefly presented double-exposure displays. Amygdala activation followed a dose–response relationship: Compared to congruent neutral displays (two birds), amygdala activation was most pronounced in response to congruent phobic displays (two spiders) and less but still significant in response to mixed displays (spider and bird) when attention was focused on the phobic component. When attention was focused on the neutral component, mixed displays did not result in significant amygdala activation. This was confirmed in a significant parametric graduation of the amygdala activation in the order of congruent phobic displays, mixed displays with attention focus on the spider, mixed displays with focus on the bird and congruent neutral displays. These results challenge the notion that amygdala activation in response to briefly presented phobic cues is independent from attention.

Long‐term remission after cessation of interferon‐α treatment in patients with severe uveitis due to Behçet's disease

Objective

To retrospectively assess the development of visual acuity and the frequency and duration of relapse‐free periods in patients who were treated with interferon‐α (IFNα) for severe uveitis due to Behçet's disease (BD) and who completed a followup period of ≥2 years.

Methods

IFN alfa‐2a was administered at an initial dosage of 6 million IU per day, then tapered to a maintenance dosage of 3 million IU twice per week, and finally discontinued, if possible. In case of a relapse, IFN treatment was repeated. Visual acuity at the end of followup was compared with visual acuity when ocular disease was in remission.

Results

Of 53 patients (96 eyes), 52 (98.1%) responded to IFN. In 47 patients (88.7%), IFN could be discontinued when the disease was in remission. Twenty of these 47 (42.6%) needed a second treatment course during a median followup of 6.0 years (range 2.0–12.6 years). Visual acuity improved or remained unchanged in 91 eyes (94.8%). Ocular disease was still in remission in 50% of the patients 45.9 months after cessation of the first IFN course. The relapse rate tended to be lower in women than in men. The BD activity score decreased significantly during followup, but long‐term remission of nonocular BD manifestations was not achieved. However, since local treatments were sufficient, no systemic treatment was administered.

Conclusion

Our findings indicate that IFNα induces long‐lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis.

     

Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients

Morbidity and mortality caused by invasive Aspergillus infections are increasing. This is because of the higher number of patients with malignancies treated with intensive immunosuppressive therapy regimens as well as their improved survival from formerly fatal bacterial infections, and the rising number of patients undergoing allogeneic haematopoietic stem cell or organ transplantation. Early initiation of effective systemic antifungal treatment is essential for a successful clinical outcome in these patients; however, clinical clues for diagnosis are sparse and early microbiological proof of invasive aspergillosis (IA) is rare. Clinical diagnosis is based on pulmonary CT scan findings and non-culture based diagnostic techniques such as galactomannan or DNA detection in blood or bronchoalveolar lavage samples. Most promising outcomes can be expected in patients at high risk for aspergillosis in whom antifungal treatment has been started pre-emptively, backed up by laboratory and imaging findings. The gold standard of systemic antifungal treatment is voriconazole, which has been proven to be significantly superior to conventional amphotericin B and has led to a profound improvement of survival rates in patients with cerebral aspergillosis. Liposomal amphotericin B at standard dosages appears to be a suitable alternative for primary treatment, while caspofungin, amphotericin B lipid complex or posaconazole have shown partial or complete response in patients who had been refractory to or intolerant of primary antifungal therapy. Combination therapy with two antifungal compounds may be a promising future strategy for first-line treatment. Lung resection helps to prevent fatal haemorrhage in single patients with pulmonary lesions located in close proximity to larger blood vessels, but is primarily considered for reducing the risk of relapse during subsequent periods of severe immunosuppression. Strict reverse isolation appears to reduce the incidence of aspergillosis in allogeneic stem cell transplant recipients and patients with acute myeloid leukaemia undergoing aggressive anticancer therapy. Well designed, prospective randomised studies on infection control measures effective to prevent aspergillosis are lacking. Prophylactic systemic antifungal treatment with posaconazole significantly improves survival and reduces IA in acute myeloid leukaemia patients and reduces aspergillosis incidence rates in patients with intermediate-to-severe graft-versus-host reaction emerging after allogeneic haematopoietic stem cell transplantation. Voriconazole prophylaxis may be suitable for prevention of IA as well; however, the results of large clinical trials are still awaited.