Decorin and suramin inhibit ocular fibroblast collagen production

Background: The process of ocular wound healing with respect to glaucomatous filtering procedures is of current interest. Delaying this response in patients could possibly lead to more favorable surgical results. So far, only highly toxic antimetabolites have come into frequent clinical use. The possible efficacy of other groups of substances such as growth factor inhibitors has not yet been examined in vitro. Methods: We exposed Tenon's capsule fibroblasts in tissue culture to various concentrations of decorin and suramin. The dose responses of type I and type III collagen to these inhibitors were measured using an ELISA-type dot blot assay. Total cellular protein production was assayed by measuring the incorporation of tritiated leucine. Results: At a concentration of 10 g/ml, suramin reduced the collagen production by more than 80%. Decorin, at a concentration of 100 g/ml, reduced type I collagen production by about 50% while type III collagen was reduced by 80%. At these concentrations, the total cellular protein production was not inhibited. Conclusions: Both suramin and decorin, which specifically inhibit the action of growth factors on target cells, reduce the production of collagen synthesis by Tenon's capsule fibroblasts. This is a specific effect, because total protein production is not influenced. This sets these substances apart from antimetabolites. Decorin and suramin may have clinical relevance in that they appear to interfere with ocular wound healing more specifically than the substances so far frequently used.     

Management of fibrous histiocytoma of the corneoscleral limbus: Report of a case and review of the literature

Background: Fibrous histiocytomas of the corneoscleral limbus are rare tumors. We present an additional case and review the treatment approaches in the literature. So far, only light and electron microscopic studies have been performed. We used immunohistochemical stains to further characterize the cellular composition. Methods: The excised lesion was routinely fixed and processed for light microscopy and immunohistochemical studies. For comparison, three dermal fibrous histiocytomas were also examined and processed similarly. Results: The corneolimbal tumor was mainly composed of fibroblasts and histiocytes with a large amount of interstitial collagen, arranged in a storiform pattern. Immunohistochemical stains were positive for histiocytes, fibroblasts, and a marker for mesenchymal cells. The staining pattern of the dermal lesions was similar. Conclusion: Fibrous histiocytomas of the corneolimbal region are morphologically benign, slowly growing and infiltrative tumors. Complete resection, especially of the deep margin, is suggested. The immunohistochemical staining pattern is similar to that of dermal fibrous histiocytomas, which behave in a benign manner.     

Disseminated neuroblastomas under 1 year of age: cell biology and prognosis

Tumor specimens of 203 infants with neuroblastomas of different clinical stages — registered in successive multicenter clinical trials of the German Society of Pediatric Oncology — could be examined for N-myc amplification, chromosome 1-ploidy and — structure, CD₄₄ std. expression (in tumor tissue, and also in patients sera).Eightyseven (= 43%) of these infants had a non-localized, disseminated neuroblastoma, mainly involving sympathetic nerve tissue, lymphnodes, liver, skin, bone marrow and bones (46 patients were classified into the 4_s group, 41 patients in the true 4 group).If the clinical classification between stage 4 and stage 4_swas neglected, then 17 of these infants (= 20%) had N-myc amplification (4—64 copies) with 16 already dead. Seven of 9 examined patients with true stage 4 had chromosome 1p aberrations (with N-myc amplification in 5), and among the dead there were 2 with CD₄₄ negative expression.In another series, serum CD₄₄ std. was measured by ELISA, and the highest (significantly different) Kruskal-Wallis mean rank values (147.8) were found in infants (n = 6) with stage 4_s compared to the low mean-rank-value of 71.9 in patients with stage 4 (n = 65). Stage 1—3 patients (n = 42) had values of 99.8—88.6.Thus, infants with disseminated neuroblastomas, showing non-diploidy, normal chromosome 1p structure, non-N-myc amplification and high CD₄₄ std. expression in tumor tissue, and also high CD₄₄ std. values in serum, will have the highest chance of survival due to tumor-non-progression.On the other hand, N-myc amplification in the tumor cells was found to be characteristic for stage 4_s neuroblastoma patients with tumor progression (n=6). Therefore, 4_s neuroblastoma-patients with N-myc amplified tumors should be aggressively treated like true stage 4 tumor patients!     

Immunohistochemistry of anterior proliferative vitreoretinopathy

Anterior proliferative vitreoretinopathy is characterized by epiretinal proliferation that extends anteriorly over the vitreous base, and may, in addition to the cells usually contributing to proliferative vitreoretinopathy, also contain cells of ocular structures located in that area. We examined 11 complete globes with aPVR that were enucleated after previous severe trauma or perforating injuries (n=8) and complicated retinal detachment (n=3) by a panel of immunohistochemical markers. We found presence of RPE, glial cells, macrophages and fibrocytes, as consistently reported in PVR membranes. In addition, T-cell lymphocytes were present in 6 of the cases, and cells expressing the common leucocyte antigen on 8 cases. Cells staining positive for the intracytoplasmic contractile filament-smooth muscle actin were present in 5 cases and cells staining for desmin in one case. Collagen type IV was part of most of the membranes, and vessels with leakage of plasma factors were present in more than half of the cases.This paper was presented in part at the First Annual Meeting of the European Community Ophthalmic Research Association (ECORA), Bonn, Germany, 6.10.1993.     

Effects of prostaglandin F2α(PGF2α) and prostaglandin I2 (PGI2) on nerve-mediated secretion in guinea-pig colon

We have applied conventional flux-chamber and intracellular recording methods to investigate the effects of the prostaglandins PGF₂ and PGI₂ upon epithelial ion transport and on the electrical behaviour of submucosal neurones in guinea-pig colon. In flux-chamber experiments on segments of colon, both prostaglandins evoked a dose-dependent increase in short-circuit current that was reduced in chloridedepleted Krebs solution and by serosal addition of tetrodotoxin or atropine, but was unaffected by hexamethonium. These results indicate activation of chloride secretion via submucosal neurones. The response to PGF₂ was decreased by piroxicam. Application of PGF₂ or PGI₂ to submucosal neurones evoked depolarization of the membrane potential associated with an enhanced spike discharge. The depolarizing response was tetrodotoxin insensitive, indicating a direct effect of the prostaglandins on the impaled neurones. Membrane depolarization was frequently associated with the occurrence of fast excitatory postsynaptic potentials, suggesting in addition that part of the excitatory effect is mediated by the activation of neural circuits that drive the impaled neurone synaptically. The results of this study indicate that the secretory effects of prostaglandins are mediated in part by submucosal neurones and further suggest that the colonic submucosal plexus may function as an amplifier to enhance the epithelial response to inflammatory mediators.     

Koinzidenz von schizophrener Psychose und Panikstörung mit Agoraphobie

The coincidence between panic disorder and depression is a well known phenomenon. However, only few studies investigated the coincidence of panic disorder with schizophrenia. This may in part be explained by the fact that both positive and negative symptoms of schizophrenia may mask the clinical symptoms of a panic disorder. We report on a female patient suffering both from agoraphobia with panic disorder and paranoid schizophrenia according to ICD-10. The productive psychotic symptoms responded well to treatment with a low dose of zotepine, whereas the panic disorder was effectively treated with a combined therapy with imipramine and cognitive behavioral therapy. Although it has to be questioned whether the coincidence between panic disorder and schizophrenia reflects two different diagnostic entities, the occurrence of symptoms of a panic disorder in schizophrenia deserve further attention because these may be treated efficiently by a specific pharmacotherapy and psychotherapy.     

The significance of hierarchy in postgraduate education

There are structures of hierarchy in the postgraduate education. The postgraduate education is organized as a programme the young doctor has to absolve. The instruction and the control of the implementation of that programme must be carried out by a competent and experienced older physician, who is responsible for the correctness of that, the young doctor has to learn in his postgraduate education. The older physician unequivocally is integrated in the hierarchy above the young doctor legitimated by his knowledge, his experience and his personality. The hierarchy demonstrates itself as an indication of the moral integrity of the community and of each only individual.     

Fluorine-18 fluorodeoxyglucose positron emission tomography in the follow-up of differentiated thyroid cancer

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with¹³¹I) and a negative FDG PET, in four cases¹³¹I-negative lymph node metastases were detectable with PET. Even in the patients with concordant staging, differences between¹³¹I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of¹³¹I-positive/FDG-negative,¹³¹I-negative/FDG-positive and¹³¹I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours¹³¹I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS.     

Influence of sleep deprivation on neuroactive steroids in major depression.

There is evidence from preclinical and clinical studies that concentrations of neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy. However, no data are available concerning the impact of sleep deprivation on the concentrations of neuroactive steroids. A total of 29 drug-free patients (12 men, 17 women) suffering from major depression according to DSM-IV criteria were treated with partial sleep deprivation (PSD). Response to PSD was defined as a reduction of at least 30% according to the six-item version of the Hamilton depression scale (6-HAMD). Plasma samples were taken the day before and after PSD (days 0 and 1) and after one night of recovery sleep (day 2) at 8:00 am. The samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. There was no influence of PSD on the concentrations of neuroactive steroids either in PSD responders (n=20) or in nonresponders (n=9). However, nonresponders showed significantly higher concentrations of 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), 3alpha,5beta-tetrahydroprogesterone (3alpha,5beta-THP), and dehydroepiandrosterone (DHEA) before or after PSD compared to responders. In contrast to antidepressant drugs, which correct the dysequilibrium of neuroactive steroids in major depression within several weeks, PSD does not affect the concentrations of neuroactive steroids either in responders or in nonresponders.     

Effects of alprazolam on cholecystokinin-tetrapeptide-induced panic and hypothalamic-pituitary-adrenal-axis activity: a placebo-controlled study.

Cholecystokinin-tetrapeptide (CCK-4) induces panic attacks both in patients with panic disorder (PD) and healthy volunteers. It has been shown that panic elicited by CCK-4 is improved after treatment with antidepressants. Moreover, a reduction of CCK-4-induced panic has also been demonstrated after treatment with lorazepam in single subjects and after selective GABAergic treatment with vigabatrin. Although benzodiazepines are widely used as anxiolytics, no controlled study on the effects of benzodiazepines on CCK-4-induced panic symptoms is available so far. Therefore, we investigated the effects of alprazolam and placebo on CCK-4-induced panic symptoms in a double-blind, placebo-controlled study. A total of 30 healthy subjects were challenged with 50 microg CCK-4. Out of these 30 subjects, 26 showed a marked panic response to CCK-4. Subjects were rechallenged after a 7-day interval and treated with 1 mg alprazolam or placebo 1 h prior to the second CCK-4 challenge. Panic was assessed using the acute panic inventory (API) and a DSM-IV-derived panic symptom scale (PSS). Moreover, the number of reported symptoms and self-rated anxiety and arousal were recorded. We found a significant reduction of the API and PSS scores and of the number of reported symptoms compared to placebo. Moreover, compared to placebo the CCK-4-induced ACTH and cortisol release were significantly attenuated during the CCK-4 challenge after alprazolam treatment. However, also placebo treatment reduced CCK-4-induced anxiety and HPA-axis activation to a certain extent. In conclusion, our data show that alprazolam reduces CCK-4-induced panic, which supports the hypothesis of a possible interaction between the GABA and the CCK system.