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Biomedical subjects

W Bergler

Publications and source records attributed to W Bergler.

At least 55 records · Page 3Linked to original sources
PubMed1995

The influence of an insecticide on the function of the eustachian tube.

Organophosphorus compounds in the form of insecticides are in widespread use and have recently attracted considerable interest as environmentally toxic agents. As little is known about the effect of environmental toxins on the tubal function in the ear, we studied the middle ear pressure necessary to force the eustachian tube to open (POL = pressure opening level) under physiological conditions in laboratory mini pigs and under the influence of an i.v. organophosphorus compound (Paraoxon). The median POL in the untreated animals was 6.4 kPa (n = 8). After intoxication with Paraoxon the median POL increased to 12.0 kPa (n = 8). Tubal instillation of surfactant in intoxicated pigs reduced the POL to a median of 7.3 kPa (n = 8), while in non-intoxicated animals (n = 4) it also lowered the POL, though not significantly. These results suggest that organophosphorus compound interferes with the surfactant-dependent tubal patency.

Animals↗
PubMed1994

[Reconstruction of oral cavity and oropharyngeal defects with a pure muscle-fascia flap].

As a rule carcinomas of the oral cavity and oropharynx are not diagnosed in early stages. Surgical resections of these tumors including margins of safety invariably result in large defects. At present, one-stage flap techniques are preferred for reconstruction, as exemplified by pectoralis major myocutaneous flaps and free revascularized jejunum grafts. The skin island of the myocutaneous flap is underlayed by fat tissue as a sliding surface. Temporary sutures are necessary but have the disadvantage of producing a convex configuration. This shape compromises anatomical reconstruction of the oral cavity and oropharynx. Robertson et al. in 1985 demonstrated an alternative method for a muscle-fascia flap from the pectoralis major muscle. In comparison to the temporalis muscle-fascia flap, the pectoralis muscle-fascia flap is associated with a lesser incidence of complications. Although it is still too early to conclude their definitive use, their application in some cases is now being questioned because of such factors as reduced time of anesthesia.

Carcinoma, Squamous Cell↗
PubMed1990

Cisplatin reduces epidermal growth factor receptors in squamous-cell carcinoma in vitro. Preliminary results.

A radioreceptor assay was used to determine the number and affinity of epidermal growth factor (EGF) receptors in a human squamous carcinoma cell line of the larynx (HLac 79) after exposure to cisplatin (DDP). Cells exposed to high concentrations of cisplatin showed about 30% fewer receptors compared to untreated and low-dose-treated cells. This reduction in the number of receptors might be responsible for the decreased growth when stimulated by EGF. Cisplatin appears to lower the concentration of EGF receptors on carcinoma cells, which might result in additional antiproliferative activity especially in carcinomas with high EGF receptor expression.

Carcinoma, Squamous Cell↗
PubMed1990

P-170 glycoprotein, glutathione and associated enzymes in relation to chemoresistance of primary human renal cell carcinomas.

High intrinsic chemoresistance contributes to the dismal outcome of patients with disseminated renal cell carcinoma (RCC). In experimental cell lines, two defined defence mechanisms, P-170 glycoprotein and glutathione metabolism, have been established in multidrug resistance, a cross-resistance to cytotoxic compounds without functional or structural similarities. In 21 primary human RCCs, P-170 expression was examined, glutathione content and activities of related enzymes determined and the results were correlated to the degree of in vitro chemoresistance. P-170 was found in 10 of 17 resistant tumors but in none of the sensitive cases. The glutathione content was significantly higher and the related enzyme distinctively enhanced in resistant RCCs. Both mechanisms occurred independently and may well explain the multidrug resistance of RCC. Therefore, reversal of one or both systems may have a clinical impact on the chemotherapy of RCCs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

The expression of epidermal growth factor receptors in the oral mucosa of patients with oral cancer.

Representative tumor samples and mucosal samples were taken from three different groups of patients and were stained immunohistochemically for their expressions of epidermal growth factor receptors (EGFR). Patients in group 1 had oral squamous carcinoma, with specimens taken from the tumor as well as from the mucosa without tumor invasion. Patients in group 2 had no evidence of tumor but had heavy drinking and smoking habits. Tumor-free patients who do not drink or smoke served as the control group. The findings in the present study showed that the tumor and mucosal samples from groups 1 and 2 had increased EGFR expression while the control group showed significantly less EGFR. These results suggest that EGFR may play a role in the development of premalignant tissue changes, which are probably influenced by chronic toxic irritation.

Alcoholism↗
PubMed1988

Glutathione content and gamma-glutamyltranspeptidase activity in squamous cell head and neck cancer xenografts.

Drug resistance is a major problem in chemotherapy of squamous cell head and neck cancers (SCHNC). Since glutathione (GSH) plays a crucial role in mediating tumor cell resistance against various toxic insults, GSH metabolism in SCHNC xenografts was investigated. Xenografts from lymph node metastases contained markedly higher GSH concentrations compared with those derived from the corresponding primary lesions. After subcurative chemotherapy with cisplatin (DDP), a significant increase of both GSH levels and gamma-glutamyltranspeptidase activity (gamma-GT) was gained in tumor HT1M. Tumor HT3M showed high concentrations of GSH and gamma-GT, although these latter concentrations did not increase following chemotherapy with DDP. These findings suggest a possible impact of GSH metabolism on both the formation of metastases and the phenomenon of drug resistance in SCHNC.

Animals↗
PubMed1988

[Treatment of zoster oticus].

On the basis of aetiology and pathophysiology a rational concept for the treatment of zoster oticus is attempted. The current literature and own experiences favour the simultaneous application of the virostatic acyclovir and glucocorticosteroids.

Acyclovir↗
PubMedDate not supplied

Dose-dependent inhibition of phospholipase A2 by paraoxon in vitro: preliminary results.

To establish the dose dependency of phospholipase A2 (PLA2) inhibition by the organophosphorus compound (OPC) paraoxon (POX), human platelet membranes were incubated after Ca2+ removal (to inactivate the PLA2) with 0.3, 1 and 3 microg ml(-1) POX for 5, 30 and 60 min each. The PLA2 activity (pmol mg[-1] protein min[-1]) was measured after subsequent enzyme reactivation. The PLA2 activity in native platelets was considered to be 100%; all other measured values are expressed as a percentage thereof. Data were analysed with the Mann-Whitney Wilcoxon rank order test and ANOVA. Statistical significance was assumed for P < or = 0.01. Paraoxon inhibited in a dose-dependent manner the PLA2 activity. Different incubation times of the inactive PLA2 with POX did not have any additional effect on the activity reduction after activation. At the tested POX concentrations the PLA2 activity was 42 +/- 5.4%, 29 +/- 3.4% and 15 +/- 6.6%, respectively. The corresponding butyrylcholine esterase (BChE) activities were <<1% of the baseline activity. Phospholipase A2 is less sensitive to POX inhibition than BChE and, at clinically achievable POX concentrations, shows a clear dose dependency. Further work is needed to elucidate the exact mechanism and time dependency of the phenomenon.

Blood Platelets↗
PubMedDate not supplied

Control of blood pressure, heart rate and haematocrit during high-dose intravenous paraoxon exposure in mini pigs.

A therapeutic regimen was established to keep blood pressure, heart rate and haematocrit within the normal range during high-dose paraoxon (PX) exposure (ca. 150 x LD50) in mini pigs in order to achieve survival. Previous experiments showed that mini pigs exposed to high-dose PX died shortly after PX infusion due to hypertension, tachycardia and increased haematocrit if no antihypertensive and fluid therapy was initiated. Therefore, antihypertensive and fluid therapy with magnesium (MgSO4) and Ringer's solution was established to keep the blood pressure, heart rate and haematocrit within a pre-established normal range. Anaesthesized mini pigs received intravenously PX (54 mg kg(-1) body wt.) dissolved in alcohol. The control group received alcohol in corresponding amounts. When the blood pressure and heart rate increased, MgSO4 was given intravenously until measured values reached the normal range. When the haematocrit increased, fluids were given intravenously until the haematocrit reached the normal range. The measured values in the PX group were compared with the measured values of the control group using the 'rank order test'. As intended, no statistically significant differences between blood pressure, heart rate or haematocrit were found after therapy, but the PX group required statistically significantly more MgSO4 and fluids than the control group to keep the blood pressure, heart rate and haematocrit within the normal range. We assume that the increased need of antihypertensive therapy is due to a phaeochromocytoma-like pattern caused by an excessive release of catecholamines from the adrenal medulla, which is under sympathotonic control and activated by acetylcholine. Paraoxon is known to cause endogenous acetylcholine poisoning. The high fluid requirements in the PX group are most probably caused by extravasation of fluids due to the damage inflicted on biological membranes by organophosphorus compounds. An activation of secretory glands probably also contributes to the increase in haematocrit through consumption of fluids. In conclusion, the survival of mini pigs exposed to high-dose PX can be achieved by tight control of blood pressure, heart rate and haematocrit using MgSO4 and fluids.

Animals↗
PubMedDate not supplied

L-lactate protects in vitro acetylcholinesterase (AChE) from inhibition by paraoxon (E 600).

Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of serine hydrolases, is frequent. Oximes are the only enzyme reactivators clinically available. Recent work has shown that lactate is able to reduce in vitro the POX effects on butyrylcholinesterase (BChE). Most of the acute clinical symptoms, however, are caused by inhibition of acetylcholinesterase (AChE). Effects of lactate on the inhibition of AChE by POX were assessed in vitro in plasma of 12 (six male, six female) healthy human volunteers. The determinations were repeated using different lactate and different POX concentrations. The AChE activity determinations were performed in the following settings: (BL) baseline (untreated plasma); (a) after addition of POX to plasma (pl + POX); (b) after POX and plasma were incubated and then lactate was added (pl + POX/lact); (c) after addition of lactate to plasma (pl + lact); (d) after lactate and plasma were incubated and then POX was added (pl + lact/POX); (e) after lactate and POX were incubated and then added to plasma (lact + POX/pl). In the micro- and millimolar ranges, lactate is able to protect in vitro AChE from inhibition by POX when added to human plasma prior to POX or when incubated with POX prior to addition to plasma. Lactate added to plasma after POX has no protective effect. In a second set of experiments, the effect of lactate on AChE activity was determined. At high millimolar concentrations, lactate itself inhibits AChE non-competitively (mixed inhibition) to an extent comparable to POX (inhibition constant K(I) = 254 mM).

Acetylcholinesterase↗
PubMedDate not supplied

Pralidoxime and l-lactate effects in vitro on the inhibition of acetylcholinesterase by paraoxon: pralidoxime does not confer superior protection.

Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of serine hydrolases, is frequent. Although oximes are the only enzyme reactivators presently available, clinical experience with their use was rather disappointing. Recent work has shown that under certain conditions l-lactate is also able to reduce in vitro the POX inhibition of butyrylcholine- and acetylcholineesterase (BChE and AChE). To assess the practical relevance, if any, of these findings, the protective effects of pralidoxime (PRX) and those of lactate had to be compared in the same in vitro model. Effects of PRX on the inhibition of AChE by POX were assessed in vitro in plasma of 12 (six male and six female) healthy human volunteers. The determinations were repeated using different oxime and different POX concentrations. The AChE activity determinations were performed using the following sampler: sample BL-baseline (or untreated plasma); sample a-after addition of POX to plasma (pl + POX); sample b-after POX and plasma were incubated and then oxime was added (pl + POX/PRX); sample c-after addition of oxime to plasma (pl + PRX); sample d-after oxime and plasma were incubated and then POX was added (pl + PRX/POX); sample e-after oxime and POX were incubated and then added to plasma (PRX + POX/pl). Results were corrected for spurious enzyme 'pseudo-activity' due to interaction between PRX and substrate (acetylthiocholine) in the absence of enzyme. In the micro- and millimolar ranges, PRX is able to protect in vitro AChE from inhibition by POX when added to human plasma prior to POX or when incubated with POX prior to addition to plasma. Adding PRX to plasma after POX has no protective effect. The PRX results were compared statistically with historical lactate data (obtained under identical conditions) using the Wilcoxon matched pairs test, with significance assumed for p = 0.01. No difference between PRX and lactate's protective effect on the AChE inhibition by POX was found in the in vitro model used. We therefore conclude that in vivo testing of lactate as a POX protective agent is warranted.

Acetylcholinesterase↗
PubMedDate not supplied

High-dose intravenous paraoxon exposure does not cause organophosphate-induced delayed neuropathy (OPIDN) in mini pigs.

Organophosphorus compounds are inhibitors of serine hydrolases. Some of these compounds produce, in addition to their high acute toxicity, a more persistent effect: organophosphate-induced delayed neuropathy (OPIDN). The putative molecular entity whose inhibition is thought to be responsible for OPIDN is the neuropathy target esterase (NTE). Although in vitro NTE is resistant to paraoxon (PX), occasional case reports have associated PX with OPIDN. To assess clinically whether or not high-dose i.v. PX causes OPIDN in mini pigs, 14 mini pigs were anaesthesized, intubated and mechanically ventilated. In a first set of experiments eight pigs received 1 mg PX kg(-1) body weight (BW) dissolved in alcohol. Two control animals received alcohol in a corresponding amount. After infusion of PX, survival of the animals during the acute phase of intoxication was achieved by intensive-care support, using appropriate drugs and fluids according to a pre-established protocol. The mini pigs were extubated 1036 +/- 363 min later (mean +/- SD). The pigs were observed prior to PX application and for 6 weeks thereafter for any abnormalities and/or signs of OPIDN, such as leg weakness, ataxia and paralysis. Observations were graded on a scale for three categories (position, motor deficiency, reaction), with a maximal cumulative score of 9. In a second set of experiments (four additional pigs) larger PX doses were used (3, 9, 27 and 81 mg kg(-1) BW). After recovering from general anaesthesia/surgery, within 2 weeks all animals reached the initial score on the scale. It can be concluded that high-dose i.v. PX exposure does not induce OPIDN in mini pigs during the 6-week observation period.

Animals↗
PubMedDate not supplied

Idiopathic chronic hiccup: combination therapy with cisapride, omeprazole, and baclofen.

Idiopathic chronic hiccup (ICH) is defined as recurring hiccup attacks that last for longer than an arbitrary time limit (eg, 1 month) and for which no organic cause can be found. In patients with ICH, therapy is largely empiric. For practical purposes, idiopathic hiccup can be assumed to have its origin either in the viscera (gastrointestinal tract) or in the central nervous system. Cisapride and omeprazole--through reduction of gastric acid production and facilitation of gastric emptying, respectively--are thought to reduce an assumed afferent input from the periphery to a putative supraspinal hiccup center. Baclofen is thought to reduce excitability and depress reflex hiccup activity. Fifteen male patients (mean [+/- SD] age, 68.2 +/- 11.6 years) who had recurring hiccup attacks for a mean duration of 100.8 +/- 134.1 months (range, 12 to 564 months) were treated for ICH with a combination of cisapride, omeprazole, and baclofen (COB). Therapy led to a total disappearance of hiccup in 40% (6 of 15) of the treated patients. An additional 20% (3 of 15) of patients experienced substantial relief. A Mann-Whitney rank order test showed a highly significant reduction in the severity of the hiccup attacks as reflected in the subjective assessment scale scores taken before therapy (8.6 +/- 1.3) compared with those taken after 20 weeks of therapy (4.1 +/- 3.8). Thus we concluded that COB is an effective empiric therapy in at least some patients with ICH.

Adult↗
PubMedDate not supplied

Carbon monoxide and nonquantitative carbon dioxide detection.

INTRODUCTION: The capnometric demonstration of end-tidal carbon dioxide (CO2) is a reliable method of differentiating between a correct endotracheal tube position and an accidental misplacement of the tube into the esophagus. Recently, several CO2 detectors have been introduced for monitoring end-tidal CO2 in the "out-of-hospital" setting, where quantitative capnometry with capnography is not yet available. HYPOTHESIS: These devices are not influenced by carbon monoxide (CO) present in lethal concentration. METHODS: A heated (37 degrees C) 2.3 L reservoir bag filled one-third full with water (representing the stomach in esophageal misintubation) was machine ventilated (tidal volume: 450 ml; frequency: 16/min) with the following mixtures for three minutes each: 1) 95% O2, 5% CO; 2) 45% O2, 5% CO, 50% N2O; and 3) 44% O2, 5% CO, 50% N2O, 1% halothane. The presence of end-tidal CO2 was monitored with each of the following devices: 1) MiniCAP III CO2 Detector; 2) StatCAP CO2 Detector; 3) EasyCAP CO2 Detector; 4) PediCAP CO2 Detector; and 5) Colibri CO2 Detector. RESULTS: In none of the cases was the presence of CO2 signaled by the detector. CONCLUSION: The presence of 5% CO does not interfere with infrared spectrometry detection (MiniCAP and StatCAP) or chemical detection (EasyCAP, PediCAP, and Colibri) of CO2. The devices can be used safely in patients with CO poisoning for monitoring of endotracheal tube position.

Capnography↗
PubMedDate not supplied

Improved antiproliferative effect of cisplatin combined with phorbol ester. An in vitro study.

A combination of cisplatin (DDP) and tumor promoter phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) or nonphorboid tumor promoter mezerein (MEZ) were tested by 5-bromo-deoxyuridine (BrdU) and 3,4,5-dimethylthiazol-2,5-disphenyl-tetrazolium bromide (MTT) assays for their antiproliferative actions. DDP and TPA showed a synergistic effect at concentrations where the single drug did not show any significant action. The BrdU assay seemed to be more sensitive than the MTT assay in measuring these drug effects. Epidermal growth factor (EGF)-receptor number and affinity on treated cells were not altered as showed by 125I-EGF-receptor assay. EGF stimulation experiments suggested an inhibition of receptor-mediated signal transduction by TPA.

Bromodeoxyuridine↗
PubMedDate not supplied

Feasibility of proliferation studies using the BrdU and MTT assays with a head and neck carcinoma cell line.

After the failure of interferon monotherapies for head and neck cancer, an increasing number of combination experiments with chemotherapy and interferons have been carried out to improve the antiproliferative effect. In vitro drug testing requires sensitive assay to detect synergistic effects of tested combinations in order not to get false-negative results. The widely used MTT assay (3,4,5-dimethylthiazol-2,5-diphenyltetrazolium bromide) and the BrdU assay 5-bromo-2-deoxyuridine were compared. It could be shown that the BrdU assay is over 10 times more sensitive and that it reflects the cell proliferation status as shown by flow-cytometric analysis using double staining with BrdU. Labeling with BrdU also allows the estimation of the S phase time. Because of the direct effect of interferons on the cell cycle, the BrdU assay could be appropriate for proliferation studies using interferons.

Bromodeoxyuridine↗