Fast gamma oscillations in areas MT and MST occur during visual stimulation,but not during visually guided manual tracking

We studied the incidence of oscillatory activity in the gamma range (35–110 Hz) in single cell and multi-unit activity recorded from extrastriate areas MT (middle temporal) and MST (superior middle temporal) while rhesus monkeys performed different behavioural tasks. During full field stimulation by coherent motion of random dots, we observed gamma oscillations in approximately 20% of the cells. The average oscillation frequencies differed considerably between both animals (60 Hz vs 100 Hz). In both animals, oscillatory modulation was particularly strong at sites that showed a strong directional bias to visual stimulation. The amount of oscillatory activity was roughly the same whether stimulus movement was presented during fixation or whether the animal had to perform pursuit movements across a stationary visual pattern. If cells were engaged in gamma oscillations during visual stimulation, the amount of oscillatory modulation was dependent on stimulus direction, stimulus velocity and stimulus contrast. During a visually guided manual tracking task no gamma activity was detectable. Cells with clear oscillatory modulation during the full field stimulation failed to show oscillatory activity when the animal was involved in a motor task in which the visual motion information had to be evaluated for the correct movement of the hand. Our results reaffirm the ubiquitous presence of stimulus-induced gamma oscillation in extrastriate areas MT and MST of the awake monkey during various stimulus conditions, but they fail to support the notion that high-frequency gamma oscillations in this area play a specific role during cortical control of a motor response to visual stimulation. Electronic Publication     

Biomaterial implants induce the inflammation marker CRP at the site of implantation

Following implantation of biomaterial patches into the gastrointestinal tract, we analyzed the host's response towards the foreign material. Asymmetric patches of polydioxanone covered Vicryl or poly-3-hydroxybutyrate were sutured onto the rat stomach. Tissue samples were generated at distinct time intervals after surgery, and RNA profiles were compared by Differential Display. RT-PCR analysis of gene candidates that seemed differentially expressed showed that vitamin D binding protein mRNA was induced in stomach tissue after implantation of the biomaterial patches. In parallel, the amount of C-reactive protein mRNA was found to be increased transiently as well. Implants induce a tissue response that is specific for a given material.     

Comparative effectiveness of flupenthixol and risperidone on negative symptoms of schizophrenia

The efficacy of flupentixol and risperidone were compared in a randomized double-blind study in 153 chronic schizophrenic patients. Flupentixol showed to be not inferior to risperidone concerning schizophrenic negative symptoms at week 8, 16 and 24. Positive symptoms and general psychopathology improved comparably, too. There was a trend in favor of flupentixol concerning the improvement of depressive symptoms and a trend in favor of risperidone concerning the improvement of preexisting parkinsonian symptoms. The study data justify to regard flupentixol as a "partial atypical" antipsychotic.     

Genetic perspectives on the serotonin transporter

The serotonin transporter (5-HTT) is most well known as the site of action of the serotonin reuptake inhibitors, which were initially developed as antidepressants, but now are the most widely used agents in the treatment of many additional neuropsychiatric and related disorders. The discovery that the gene that expresses the 5-HTT possesses a functional promoter-region polymorphism, which is associated with temperament and personality traits such as anxiety and negative emotionality as well as some behaviors, led to many studies examining this polymorphism in individuals with different neuropsychiatric disorders. The subsequent development of mice with a targeted disruption of the 5-HTT in our laboratory has provided an experimental model to examine the many consequences of diminished (in +/-, heterozygote mice) or absent (in -/-, homozygote knockout mice) function of the 5-HTT. The 5-HTT-deficient mice were also crossed with other knockout mice, allowing the study of multiple neurobiologic dysfunctions. As multiple genes are probably involved in the expression of complex behaviors such as anxiety, as well as neuropsychiatric disorders, these more genetically complex mice may more closely model disorders with complex etiologies. Thus, the combination of these comparative human and mouse studies may extend the opportunities to examine genetic alterations from a novel "bottom-up" approach [gene knockout or partial gene knockout in a combinational gene x gene x (yet unknown) gene approach], which is complementary to the traditional "top-down" genetic approach based upon studies of individuals with diagnosed neuropsychiatric disorders and their family members.     

Merkel cell carcinoma of the eyelid: histological and immunohistochemical features with special respect to differential diagnosis

· Background: Merkel cell carcinomas (MCC) not infrequently involve the periorbital region and the eyelids. Clinically, they are relatively characteristic but often unsuspected. Histologically, MCC are often misdiagnosed as lymphoma, melanoma, or metastatic small cell carcinoma of the lung (SCCL). · Methods: We present clinical, histological, and immunohistochemical data on six eyelid cases (all females; age 63–102 years; one with concomitant CLL) from our files of 77 MCC with special respect to differential diagnosis. For comparison, 22 SCCL were analyzed. Immunohistochemistry was done with antibodies against pan-cytokeratin (pan-CK), cytokeratin-20 (CK-20), neurofilament protein (NF), neuron-specific enolase (NSE), chromogranin (CHR), and S100 protein (S100). · Results: Morphologically, five of six MCC were prototypic, one was of the small cell variant. Immunohistochemically, dot-like positivities for pan-CK and CK-20 were seen in all six MCC, and for NF in five tumors. None of the 22 SCCL stained positively for CK-20 or NF but 21/22 cases were positive for pan-CK. Only 1/21 SCCL showed dot-like patterns for pan-CK; 20/21 reacted diffusely. All MCC and 13/22 SCCL displayed CHR-positive cells. All MCC and all SCCL were positive for NSE and negative for S100. · Conclusions: Dot-like positivities for CK-20 or NF are important to prove MCC and to exclude SCCL in clinically and morphologically doubtful cases. Dot-like positivities for pan-CK favor MCC, but do not always exclude SCCL. NSE and CHR are of no value for the differential diagnosis of MCC and SCCL. Melanoma and lymphoma are ruled out by negativity for S100 and pan-CK, respectively. Received: 8 July 1997 Revised version received: 10 December 1997 Accepted: 17 December 1997     

The influence of the lower patellar pole in the pathogenesis of chronic patellar tendinopathy

Resection of the lower patellar pole provides good results in the treatment of jumper’s knee. Therefore we hypothesized that the length of the lower patellar pole is increased in patients with chronic patellar tendinopathy. Cohort study, level of evidence 2. Between 2000 and 2005, 25 patients with chronic patellar tendinopathy underwent conservative and surgical treatment in our clinic. All of them had preoperative MRI were three independent examiners measured the Caton Index, the length and the ratio of the articular and non-articular patellar surface, tendon length and thickness and the thickness and length of the hypodens lesions in the patellar tendon. The measurements were compared with 50 MRI of a control group with no clinical patellofemoral disorders or patellar tendinopathy. Significant changes in tendon thickness (9.42 ± 2.87 vs. 4.88 ± 1.13; P < 0.0001), a longer non-articular surface of the patella (10.62 ± 2.86 vs. 7.098 ± 2.53; P < 0.0001) and significant higher ratio between the articular and the non-articular patellar surface (0.32 vs. 0.24; P < 0.0001) were found in the jumper’s knee group. No significant changes were seen in the length of the articular surface or the Caton Index. The development of chronic patellar tendinopathy in athletes might be associated with a longer lower patellar pole as patients with jumper’s knee showed a longer non-articular patellar surface compared with the control group.     

Esophageal stenosis in childhood: dystrophic epidermolysis bullosa without skin blistering due to collagen VII mutations.

We report a 9-year-old girl who experienced recurrent dysphagia since infancy. Crohn's disease was suspected because she had aphthous ulcers of the mouth and anal dermatitis with hematochezia. After bougienages of esophageal stenoses and medication for inflammatory bowel disease proved unsuccessful, interdisciplinary re-examination revealed the cause of the symptoms to be an extracutaneous form of dystrophic epidermolysis bullosa, a genetic skin fragility disorder. Dystrophic epidermolysis bullosa is caused by mutations in the COL7A1 gene encoding collagen VII, a protein of the epidermal attachment complex, and typically manifests with trauma-induced skin blistering, scarring, nail dystrophy, and, in some cases, mucosal involvement. The present proband never developed skin blisters but had nail dystrophy and erosions of the oral, esophageal, and genitoanal mucosa, which healed with slight scarring. Mutation analysis disclosed compound heterozygosity for recessive mutations in the COL7A1 gene. The paternal mutation 425 A-->G caused abnormal splicing resulting in a premature stop codon. The maternal mutation G2775S led to the substitution of a glycine by a serine in the triple helical domain of collagen VII. This case shows that mucosal disease and esophageal strictures in childhood are not always acquired, but can also represent a genetic defect of dermal-epidermal adhesion, even in the absence of skin blistering.     

The effects of (R)-N-(1-methyl-2-phenylethyl) adenosine (L-PIA), a standard A1-selective adenosine agonist on rat acute models of inflammation and neutrophil function

L-PIA, a standard A₁-selective adenosine agonist, was evaluated orally in carrageenan (CRG)- and reverse passive arthus-pleurisy. White blood cell (WBC) and exudate accumulation were assessed four hours after induction of the inflammatory response. L-PIA inhibited WBC accumulation in both models with ID₅₀'s of 4.37 and 4.42 mg/kg, respectively. In contrast, exudate was inhibited by L-PIA only in the CRG pleurisy model (ID₅₀=1.01 mg/kg). In mechanistic studies, L-PIA reversed the drop in circulating neutrophil count which occurred within 15 minutes after CRG injection, suggesting that L-PIA may inhibit adhesion of the cells to the endothelium. The effects of L-PIA on several parameters of rat neutrophil function were determined. Enzyme release, O ₂ ^– , TXB₂, and LTB₄ production were monitored in response to FMLP and opsonized zymosan (SOZ) stimulation. At high concentrations L-PIA had a mild inhibitory effect on O ₂ ^– release in response to FMLP and had a moderate effect on arachidonic acid metabolite production, in response to both stimuli. The other response were unaffected. These results suggest that L-PIA may prevent diapedisis or neutrophil adhesion to the endothelium, but has a minimal effect on enzyme release O ₂ ^– , LTB₄ and TXB₂ production.