Biomedical subjects

P Schmitz

Publications and source records attributed to P Schmitz.

At least 19 recordsLinked to original sources

PubMed2002

Effects of beta-endorphin on nasal allergic inflammation.

BACKGROUND: Beta-endorphin is a derivative of pro-opiomelanocortin. Cells of the immune system can also synthesize and secrete beta-endorphin. Its concentration is increased during the allergic reaction and during stress. Increased reactivity during psychological stress of allergic subjects is also well known. OBJECTIVE: Is beta-endorphin one physiological link between stress and an exacerbation of the allergic reaction? METHODS: First, intranasal beta-endorphin challenges with subsequent lavages to determine histamine and albumin levels and measurements of nasal flow and resistance in dose-response and time course experiments were performed. Secondly, we examined whether beta-endorphin pre-treatment increased the antigen-induced release of histamine and albumin in nasal lavages and the clinical symptoms. RESULTS: Exogenous beta-endorphin (100 pM-10 microM/mL) induced a dose-dependent increase in nasal symptoms in asymptomatic allergic subjects with rhinitis (n = 14) as well as in non-allergic controls (n = 10), but did not release any mediators into nasal secretion. However, comparing the antigen-evoked release of mediators into nasal secretions with that of a beta-endorphin pre-treated antigen challenge we could note a significant enhancement of human serum albumin influx (P < 0.05) and histamine liberation (P < 0.05) 10 min after antigen challenge compared with the allergen challenge alone, with also a correlation with the more pronounced decrease in nasal flow (P < 0.05). CONCLUSION: These results suggest that beta-endorphin-induced increase in nasal congestion is mediated through direct neuroendocrine receptor activation independent of mast cell activation and that during the allergic reaction there is a beta-endorphin/mast cell interaction that enhances the mediator response to nasal allergen challenge.

Administration, Inhalation↗

PubMed1999

Evaluation of a target contouring protocol for 3D conformal radiotherapy in non-small cell lung cancer.

BACKGROUND: A protocol for the contouring of target volumes in lung cancer was implemented. Subsequently, a study was performed in order to determine the intra and inter-clinician variations in contoured volumes. MATERIALS AND METHODS: Six radiation oncologists (RO) contoured the gross tumour volume (GTV) and/or clinical target volume (CTV), and planning target volume (PTV) for three patients with non-small cell lung cancer (NSCLC), on two separate occasions. These were, respectively, a well-circumscribed T1N0M0 lesion, an irregularly shaped T2N0M0 lesion, and a T2N2M0 tumour. Detailed diagnostic radiology reports were provided and contours were entered into a 3D planning system. The target volumes were calculated and beams-eye view (BEV) plots were generated to visualise differences in contouring. A software tool was used to expand the GTV and CTV in three dimensions for an automatically derived PTV. RESULTS: Significant inter-RO variations in contoured target volumes were observed for all patients, and these were greater than intra-RO differences. The ratio of the largest to smallest contoured volume ranged from 1.6 for the GTV in the T1N0 lesion, to 2.0 for the PTV in the T2N2 lesion. The BEV plots revealed significant inter-RO variations in contouring the mediastinal CTV. The PTV's derived using a 3D margin programme were larger than manually contoured PTV's. These variations did not correlate with the experience of ROs. CONCLUSIONS: Despite the use of an institutional contouring protocol, significant interclinician variations persist in contouring target volumes in NSCLC. Additional measures to decrease such variations should be incorporated into clinical trials.

Carcinoma, Non-Small-Cell Lung↗

PubMed1999

Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study.

This open, multicentre, randomized phase II trial was conducted to determine the effect of isolated limb perfusion (ILP) with tumour necrosis factor-alpha (TNFalpha) in combination with melphalan with or without interferon-gamma (IFNgamma) in patients with in-transit metastases of melanoma of the limbs (MD Anderson stage IIIA or IIIAB, AJCC stage III). The 64 patients included were randomized to receive either a two- drug regimen consisting of TNFalpha and melphalan (TM-ILP) or a three-drug regimen consisting of TNFalpha, melphalan and INFgamma (TIM-ILP). Patients randomized to receive IFNgamma were pretreated for 2 days before the ILP with once daily 0.2 mg IFNgamma subcutaneously and also received the same amount of IFNgamma during ILP. A total of 47 complete responses (73%) were reported, 22 (69%) of which occurred in the TM-ILP group and 25 (78%) in the TIM-ILP group; the difference was not significant. The 14 partial responses (22%) were split evenly between the treatment groups. In the TM-ILP group, two cases of stable disease and one case of progressive disease were reported. The overall response rate (complete plus partial responses) was 100% in the TIM-ILP group and 91% in the TM-ILP group, yielding an overall response of 95% for this study. In the historical control data, where 103 patients had received melphalan alone (M-ILP), there were 54 records of complete responses (52%) and 80 of complete or partial responses (78%). The median survival time estimated by the Kaplan-Meier method was 819 days for the TM-ILP group, > 705 days for the TIM-ILP group and 873 days for the combined study population; estimates for time to local progression or recurrence were 327 days, in excess of 498 days and 405 days, respectively. The corresponding figure for the historical controls was 338 days. These data suggest that TNFalpha associated with melphalan may be superior to melphalan alone for ILP.

Adult↗

PubMed1998

[Sclera fixation of posterior chamber lenses in vitrectomized eyes. Perfluorocarbon as an operative aid].

INTRODUCTION: Accurate positioning of transsclerally fixated intraocular lenses in vitrectomized eyes is difficult to achieve because of the lack of stability of the globe. External stabilization with a Flieringa device is widely used. Internal stabilization, however, with liquid perfluorocarbon seems to be more advantageous. METHODS: Endostabilization with perfluorocarbon after pars plana vitrectomy prior to transscleral fixation of a posterior chamber lens was performed in 18 eyes. The intraocular lens floats on the surface of the perfluorocarbon. The level of the liquid can be adjusted to position the lens accurately. Transscleral fixation of the intraocular lens was followed by silicone oil injection in 4 eyes and by BSS injection in 14 eyes. RESULTS AND CONCLUSIONS: Endostabilization of the globe with liquid perfluorocarbon serves as a diaphragm preventing hemorrhage into the vitreous cavity and sliding of the intraocular lens, thus permitting proper positioning. There were no complications either intraoperatively, or postoperatively. Perfluorocarbon is a considerable aid in facilitating the positioning of a transsclerally fixated intraocular lens.

Adult↗

PubMed1997

Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats.

cAMP/cAMP-dependent protein kinase (PKA) signaling pathway has been recently proposed to participate in both the late phase of long term potentiation in the hippocampus and in the late, protein synthesis-dependent phase of memory formation. Here we report that a late memory consolidation phase of an inhibitory avoidance learning is regulated by an hippocampal cAMP signaling pathway that is activated, at least in part, by D1/D5 receptors. Bilateral infusion of SKF 38393 (7.5 microg/side), a D1/D5 receptor agonist, into the CA1 region of the dorsal hippocampus, enhanced retention of a step-down inhibitory avoidance when given 3 or 6 h, but not immediately (0 h) or 9 h, after training. In contrast, full retrograde amnesia was obtained when SCH 23390 (0.5 microg/side), a D1/D5 receptor antagonist, was infused into the hippocampus 3 or 6 h after training. Intrahippocampal infusion of 8Br-cAMP (1.25 microg/side), or forskolin (0.5 microg/side), an activator of adenylyl cyclase, enhanced memory when given 3 or 6 h after training. KT5720 (0.5 microg/side), a specific inhibitor of PKA, hindered memory consolidation when given immediately or 3 or 6 h posttraining. Rats submitted to the avoidance task showed learning-specific increases in hippocampal 3H-SCH 23390 binding and in the endogenous levels of cAMP 3 and 6 h after training. In addition, PKA activity and P-CREB (phosphorylated form of cAMP responsive element binding protein) immunoreactivity increased in the hippocampus immediately and 3 and 6 h after training. Together, these findings suggest that the late phase of memory consolidation of an inhibitory avoidance is modulated cAMP/PKA signaling pathways in the hippocampus.

Animals↗

PubMed1997

[Disruption of the blood-aqueous barrier after implantation of sclera-fixed posterior chamber lenses. Early postoperative phase and long-term outcome].

The implantation of transsclerally sutured posterior chamber lenses (PCL) leads to greater trauma to the eye than endocapsular PCL implantation. Persistent breakdown of the blood-aqueous barrier might impair the postoperative long-term prognosis. Using laser-tyndallometry, we quantified the disorder of the barrier function during the early postoperative phase and in the long-term postoperative course for both surgical procedures. During the first 3 postoperative days, flare values were three times higher in the group with transsclerally sutured PCL than in the conventional PCL group. Cell counts after transscleral suture fixation (27.7 +/- 18.3/0.075 mm3) decreased slightly during the first 5 postoperative days. In contrast, the conventional PCL group regained the preoperative level (2.5 +/- 5.1) after 3 days. After 3 months, no significant differences in flare values and cell counts were seen between the two groups. After implantation of transsclerally sutured posterior chamber lenses, breakdown of the blood-aqueous barrier was initially more pronounced than in conventional PCL implantation. However, the barrier function was re-established equally in both groups in the long term. No signs of a persistent disorder of the barrier were found.

Adult↗

PubMed1997

Somatosensory evoked potentials modified by laser-induced lesions of the rat cortex.

The effect of focal application of laser energy on the modification of somatosensory evoked potentials (SEPs) was studied in sensory cortical fields of the rat. This article describes the methodological set-up for recording of SEPs and for determining location and size of the laser-induced lesion. The results show that both the size of the lesion of the somatosensory cortex, and the suppression and time of recovery of cortical SEPs varied depending on the laser energy dose. It remains to be analyzed by further experiments if the recovery of SEPs is due to a transient dysfunction of the somatosensory cortex or if it reflects cortical plasticity.

Animals↗

PubMed1997

Burnout in psychiatric nursing: a meta-analysis of related variables.

The purpose of this study was to describe the relative strengths of a number of variables on burnout among psychiatric nurses. A meta-analysis of correlations revealed that burnout was negatively associated with job satisfaction, staff support and involvement with the organization and positively associated with role conflict. The results of the meta-analysis were in line with results of other studies in which different populations were investigated. Therefore, the findings as such are not specific to psychiatric nurses. Based on the literature, three typical risk factors of burnout among psychiatric nurses were found: the patient group the nurse works with, such as patients who are aggressive and suicidal; the inequity in the exchange process between nurses and patients; and the unrealistic expectations of nurses of the patients' potential for rehabilitation.

Burnout, Professional↗

PubMed1997

[Spontaneous pregnancy after laparoscopic salpingostomy and electrocoagulation of the ovarian surfaces in a patients with polycystic ovary syndrome].

We report a case of a 25 year-old woman with repeated ovarian stimulation and laparoscopy because of anovulatory and tubal infertility due to polycystic ovarian syndrome (PCOS), who then spontaneously conceived. The complex nature of the multivariate cause of sterility is discussed together with therapeutic possibilities both in terms of the case-history and the literature.

Adult↗

PubMed1996

Hippocampal cGMP and cAMP are differentially involved in memory processing of inhibitory avoidance learning.

Cyclic GMP (cGMP) and cyclic AMP (cAMP) have been proposed to participate in the early and late stages of long-term potentiation (LTP), respectively. Here we report on the effect of post-training intrahippocampal infusion of membrane-permeable analogues of these cyclic nucleotides on the consolidation of inhibitory avoidance learning in rats and on the effect of this task on hippocampal cGMP and cAMP levels. Bilateral intrahippocampal microinjection of 8 Br-cGMP (1.25 micrograms per side) enhanced retention test performance when given immediately (0 min), but not when given 180 min, after training. In marked contrast, intrahippocampal infusion of the same dose of 8 Br-cAMP facilitated memory consolidation when given 180 min, but not 0 min, after training. Rats submitted to an inhibitory avoidance task showed a significant increase in the amount of cGMP in the hippocampus at 0 and 30 min after training, and in the amount of cAMP 30 and 180 min after training. Taken together, these results indicate that cGMP-regulated processes in the hippocampus play an important role in the early stages of memory consolidation and that cAMP signalling pathways are involved in the late post-training memory processing of inhibitory avoidance learning.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

The Rotterdam Daytime Sleepiness Scale: a new daytime sleepiness scale.

A new daytime sleepiness scale was constructed on the basis of interviews with 96 apnea patients (the Rotterdam Daytime Sleepiness Scale) and included three subscales of Global Evaluation, Behavioral Impact, and Affected Life Domains. The scale showed satisfactory convergent and discriminant validity.

Adult↗

PubMed1995

[Efficacy of the tumor necrosis factor-alpha (rTNF-alpha) associated with interferon-gamma and chemotherapy in extracorporeal circulation in the limb in inoperable malignant melanoma, soft tissue sarcoma and epidermoid carcinoma. A 4-year experience].

The authors review their experience of 4 years with isolated limb perfusion for the application of high dose TNF-alpha associated to IFN-gamma and melphalan for the treatment of regionally advanced tumours such as malignant melanoma, soft tissue sarcoma and epidermoid carcinoma. In malignant melanoma, the complete remission rate reaches 91%. In irresectable soft tissue sarcoma, this treatment when used as a neoadjuvant treatment saves the limb from amputation in 87.5% of the cases. Similar results are obtained for epidermoid carcinoma. With the regional application of high doses of TNF-alpha associated to chemotherapy and IFN-gamma, it has been possible to validate the concept of a strategy based on a dual targeting, that is the selective impact of the intratumoral vessels by TNF-alpha and of the tumour cells by chemotherapy. This approach appears to be the treatment of choice for locally advanced tumours of the limbs. However, as a single therapy, this procedure should be considered in melanoma as an induction therapy, and in sarcoma, as a preoperative treatment.

Antineoplastic Agents, Alkylating↗

PubMed1995

Administration of high-dose tumor necrosis factor alpha by isolation perfusion of the limbs. Rationale and results.

Recombinant tumor necrosis factor alpha (rTNF alpha) has potent antitumor activity in experimental studies on human tumor xenografts. However, in humans, the administration of rTNF alpha is hampered by severe systemic side effects. The maximum tolerated dose ranges from 350 to 500 mg/m2, which is at least 10-fold less than the effective dose in animals. Isolated perfusion of the limbs (ILP) allows the delivery of high-dose rTNF alpha in a closed system with acceptable side effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In patients with melanoma-in-transit metastases (stage IIIA or AB), we obtained a 91% complete response rate compared with 52% after ILP with melphalan alone. In unresectable soft tissue sarcomas, this protocol was found to produce a 50% complete response with 87.5% limb salvage, since most tumors became removable. Release of nanograms levels of TNF alpha in the systemic circulation was evident, but control of this leakage and appropriate intensive care resulted in acceptable toxicity. Angiographic, immunohistological, and immunological studies suggest that the efficacy of this protocol is due to a dual targeting: rTNF alpha activates and electively lyses the tumor endothelial cells, while melphalan is mainly cytotoxic to the tumor cells. ILP with rTNF alpha appears to be a useful model for studying the biochemotherapy of cancer in man.

Antineoplastic Agents↗

PubMed1994

Rationale for using TNF alpha and chemotherapy in regional therapy of melanoma.

Recombinant tumor necrosis factor-alpha (rTNF alpha) has potent antitumor activity in experimental studies on human tumor xenografts. However, in humans, the administration of rTNF alpha is hampered by severe systemic side-effects. The maximum tolerated dose ranges from 350 to 500 mg/m2, which is at least 10-fold less than the efficient dose in animals. Isolation perfusion of the limbs (ILP) allows the delivery of high dose rTNF alpha in a closed system with acceptable side-effects. A protocol with triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a 91% complete response, compared with 52% after ILP with melphalan alone. Release of nanograms levels of TNF alpha in the systemic circulation was evident but control of this leakage and appropriate intensive care resulted in acceptable toxicity. Angiographic, immunohistological, and immunological studies suggest that the efficacy of this protocol is due to a dual targeting: rTNF alpha activates and electively lyses the tumor endothelial cells while melphalan is mainly cytotoxic to the tumor cells. ILP with rTNF alpha appears to be a useful model for studying the biochemotherapy of cancer in man.

Animals↗

PubMed1994

Effect of the infusion of the GABA-A receptor agonist, muscimol, on the role of the entorhinal cortex, amygdala, and hippocampus in memory processes.

Rats were bilaterally implanted with cannulae in the entorhinal cortex, amygdala, and hippocampus; after recovery, they were trained in a step-down inhibitory avoidance task and tested for retention 24 h later. Muscimol (0.03 microgram) or D-amino-5-phosphonovalerate (5.0 micrograms) infused in the entorhinal cortex 20 min prior to training inhibited the amnestic effect of the same dose of muscimol infused into this area 100 min after training. Thus, memory-relevant information must be processed by the entorhinal cortex at the time of training in order that this cortex may play a late post-training role in memory processing. Pretraining intraentorhinal muscimol administration did not affect the amnestic effect of the post-training infusion of muscimol into the amygdala and hippocampus, or the inhibition of memory expression induced by a pretest infusion of CNQX into the amygdala and hippocampus or into the entorhinal cortex. Pretest intraentorhinal muscimol also did not influence the effect of pretest intra-amygdala and intrahippocampal CNQX administration. These data indicate that the cells of the entorhinal cortex that are sensitive to pretraining muscimol are not part of the inputs that lead to post-training processing by the amygdala and hippocampus, or to the intervention of the amygdala, hippocampus, and entorhinal cortex in memory expression. The present findings are compatible with the possibility that, instead, the entorhinal cortex may be an output of the amygdala and hippocampus at the time of memory expression.

2-Amino-5-phosphonovalerate↗

PubMed1994

Clinical experience with high-dose tumor necrosis factor alpha in regional therapy of advanced melanoma.

Isolated perfusion of the limbs (ILP) allows the delivery of high dose rTNF alpha in a closed system with acceptable side-effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a 91% complete response compared with 52% after ILP with melphalan alone. Leakage and release of nanograms levels of TNF alpha in the systemic circulation can be abrogated in most patients by low pump flow, continuous leak monitoring, extensive washout, and limb massage. In case of unavoidable leakage, appropriate intensive care results in minimal toxicity. The ILP with rTNF alpha appears to be a useful model for studying the biochemotherapy of cancer in humans.

Animals↗

PubMed1992

[Employment of continuous biotest systems for monitoring the Rhine river].

As a part of the work of the German Commission for the Prevention of Pollution of the River Rhine biological test automats are developed and proved in a research project. The joint project "Development, Testing and Implementation of Biotests for the Monitoring of the River Rhine" sponsored by the Federal Ministry for Research and Technology (BMFT) and the Federal Environmental Agency (UBA), aims to provide a scientific and technical basis for an improved Rhine monitoring system. To realize a biological effect monitoring with functional subjects at the trophic levels of producers, primary and secondary consumers and destruents, the test spectrum includes algae, mussels, daphnia, fishes, and bacteria. Moreover, at the suborganismic level a test system with plant protoplasts is tested. Assessment schemes for the evaluation of measuring data and alarm situations, and limit values for releasing alarms are defined by the Working Group "Biotests for the Monitoring of the River Rhine" (WIR). By means of applicability criteria the most suitable biotests are chosen and recommended for the use on the River Rhine. The first results are presented in this paper.

Animals↗

PubMed1991

[Sclera fixation of posterior chamber lenses. Indications, technique and results].

Over 18 months we implanted posterior chamber lenses in 40 eyes using transscleral suturing. The indication for this technique was the absence of capsular support, in most cases due to previous cataract surgery and/or trauma. A uniform procedure was used. After a medium follow-up of 9 months the major complications were as follows: immediately after the operation transient keratopathia was present in a third of the cases; 6 eyes showed iritis, which persisted in 4 eyes. Other late complications were cystoid macular edema in 2 cases and central vein occlusion, retinal detachment and recurrent iritis in single cases. Despite these complications the functional results were favorable in 32 eyes with a best corrected vision of 6/12 or better. Poor visual outcome could be related to the operative procedure in 2 eyes and to pre-existing pathology in the remaining 6 cases. We conclude that the operative technique should be improved to reduce complications.

Follow-Up Studies↗