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Biomedical subjects

P Klinger

Publications and source records attributed to P Klinger.

8 recordsLinked to original sources

Reflux-induced apoptosis of the esophageal mucosa is inhibited in Barrett's epithelium.

BACKGROUND: Apoptosis maintains cell homeostasis. Altered apoptosis is involved in carcinogenesis. It was our aim to investigate whether reflux esophagitis may alter apoptosis in the esophageal mucosa and whether antireflux surgery may restore normal apoptosis. METHODS: Apoptosis was studied preoperatively and postoperatively in esophageal biopsies of 39 patients with various grades of reflux esophagitis and in Barrett's mucosa using the TUNEL method. Biopsies were also taken from lesions of the squamous epithelium adjacent to the Barrett's mucosa. RESULTS: Apoptosis increased with the severity of esophagitis. Apoptosis was low in Barrett's epithelium. Squamous epithelium adjacent to Barrett's mucosa showed increased apoptosis. After surgery apoptosis decreased in squamous epithelium, and it remained low in Barrett's epithelium. CONCLUSIONS: Apoptosis in reflux esophagitis may be protective against increased proliferation. Low apoptosis following antireflux surgery indicates that surgery is effective to prevent reflux-induced cell proliferation. Inhibition of apoptosis in Barrett's may promote carcinogenesis. This may not change following surgery.

Apoptosis↗

Laparoscopic partial posterior fundoplication improves poor oesophageal contractility in patients with gastrooesophageal reflux disease.

OBJECTIVE: To investigate the effect of partial posterior fundoplication on oesophageal contractility in patients with gastrooesophageal reflux disease (GORD). DESIGN: Follow-up study with 6 months of survey. SETTING: University hospital, Austria. SUBJECTS: 24 consecutive patients with GORD and poor oesophageal contractility. INTERVENTIONS: Laparoscopic partial posterior fundoplication. Oesophageal contractility was assessed manometrically. MAIN OUTCOME MEASURES: Changes in measurements of mean contraction amplitudes in the distal oesophagus, the number of contractions with amplitudes of less than 30 mmHg, the number of interrupted and simultaneous contractions, and the total number of defective contractions. RESULTS: 16 of the patients (67%) complained of dysphagia preoperatively, and none postoperatively. The mean (SEM) amplitudes in the distal oesophagus improved significantly (level 442.4 mmHg (3.5) compared with 31.8 mmHg (3.3), p = 0.03, and level 5-45.7 mmHg (3.8) compared with 32.6 mmHg (3.7), p = 0.02), the number of contractions with amplitudes below 30 mmHg decreased (18.0% (5.7) compared with 38.3% (6.2), p = 0.02), as did the number of interrupted or defected contractions (11.5% (3.6) compared with 26.3% (5.5), p = 0.03, and 29.5% (6.5) compared with 66.6% (5.1), p < 0.0001 respectively). There was no significant effect on the number of simultaneous waves (p = 0.11). CONCLUSIONS: Partial posterior fundoplication improves poor oesophageal body motility. This results in improvement of preoperative dysphagia.

Adult↗

Prevention and management of related complication due to laparoscopic operation: pneumothorax, pneumomediastinum and subcutaneous emphysema.

Essential prerequisite of laparoscopic operation is establishing and maintaining pneumoperitoneum with a certain pressure. But under certain circumstances CO2-gas insufflating could induce pneumothorax, pneumomediastinum and subcutaneous emphysema during the operation. to probe the mechanism of the above complications. 2 typical cases were reported with attempt to probe the mechanism of the development of such applications. We believe that high intra-abdominal pressure during operation is the primary cause of the complications. The essentials of prevention and management of such complications were proposed.

Adult↗

The production of an amyloidogenic metabolite of the Alzheimer amyloid beta precursor protein (APP) in thyroid cells is stimulated by interleukin 1 beta, but inhibited by interferon gamma.

Thyroid epithelial cells have been shown to have a high APP expression and to produce large amounts of its metabolic derivatives, namely secreted APPs and a potentially amyloidogenic 41-kDa C-terminal fragment. It was the aim of the present study to analyze how APP production and metabolism were regulated in human thyroid cells. The effects of three cytokines, interferon gamma (IFN gamma), interleukin 1beta (IL-1 beta) and transforming growth factor (TGF) beta, were investigated. Cell extracts and supernatants were studied by immunoblotting using specific N- and C-terminal APP antibodies. Quantification was performed by densitometric scanning. We demonstrate that IFN gamma has a strong suppressive effect on the production and metabolism of APP. From a concentration of 30 U/ml upwards it reduces the cellular APP content, decreases the amounts of secreted APPs and inhibits the generation of the 41-kDa amyloidogenic APP fragment. In contrast, IL-1 beta has a stimulatory influence on the generation of the amyloidogenic 41-kDa APP metabolite, but does not affect the cellular holoprotein or APPs. TGFbeta has no significant effect on APP. Our results demonstrate that cytokines can regulate APP production and metabolism in thyroid cells. IFN gamma is the first naturally occurring agent described to inhibit the generation of amyloidogenic APP fragments. It may be of relevance in preventing amyloid deposition during inflammatory processes in the thyroid gland, but may exert a similar protective effect in other non-neuronal and neuronal tissues.

Adult↗

Metabolism of dextromethorphan in human liver microsomes: a rapid HPCL assay to monitor cytochrome P450 2D6 activity.

A new HPLC assay was developed to study dextromethorphan O-demethylation to dextrorphan in vitro using human liver microsomes to investigate the activity of the polymorphic monooxygenase cytochrome P450 2D6 (CYP 2D6). The separation of dextromethorphan and its main metabolite dextrorphan was performed on a polymeric C18 reversed-phase column with UV-detection using levallorphan as an internal standard. Liver samples from ten subjects were screened for dextrorphan formation whereby three groups with different abilities to metabolize dextromethorphan could be found. Seven microsomal preparations from extensive metabolizers showed an average dextrorphan formation rate of 298 +/- 68 pmol/mg protein.min, one sample was classified to belong to an intermediate dextromethorphan metabolizer (79 pmol/mg protein.min), whereas two samples of poor metabolizers exhibited significantly lower rates of dextromethorphan metabolism with values of 11 and 27 pmol/mg protein.min, respectively. This assay permits not only a fast in vitro screening for cytochrome P450 2D6 monooxygenase activity but is also an excellent tool to determine potential drug-drug interactions with this important metabolizing enzyme.

Adult↗

Comparative anterograde amnestic and anticonvulsant effects of two types of NMDA receptor antagonists: MK-801 and HA-966.

The anterograde amnestic effects of non-competitive NMDA antagonists MK-801 and HA-966 on classic fear conditioning in goldfish (Carassius auratus) were examined in a series of experiments. Experiments 1 and 2 contrasted the anterograde amnestic effects of MK-801, (+)HA-966, and (-)HA-966. Experiment 3 examined the effects of MK-801 and (+)HA-966 on the expression of conditioned responses. Experiments 4 and 5 investigated whether the potency of MK-801, (+)HA-966 or (-)HA-966 in blocking NMDA-induced convulsions paralleled their potency in producing amnesia. The results showed that MK-801 was more potent than (+)HA-966 in producing anterograde amnesia and impairing expression, while (-)HA-966 did not produce anterograde amnesia. The anticonvulsant potency of MK-801, (+)HA-966, and (-)HA-966 paralleled their amnestic potency. These findings suggested that MK-801 and (+)HA-966 produced anterograde amnesia by their specific antagonism of the NMDA receptor complex.

Amnesia↗

Protocols for pharmacists' intervention in a 160 bed hospital.

The structure of many hospital pharmacy departments has become decentralized in order to provide pharmacists and other health care professionals with access to patient records. This change in departmental structure decreases the manager's ability to supervise the clinical activities of staff pharmacists. A policy for pharmacist intervention was developed by the pharmacy department. The policy identifies actions to be taken in specific situations, thus serving to standardize care.

Clinical Protocols↗

A computer program for selecting animals for control and experimental groups in biochemical studies.

The standard method for selecting experimental animals for control and experimental groups is by a randomization process in which each animal is placed into one of the groups without looking at any of its individual differences. An alternative, active matching process is proposed by which three to five animals are chosen to form 'experimental units' that are closely matched with respect to average weight and with respect to distribution of weights (standard distribution values). Several such units are then randomly assigned to each control or treatment group and, at the end of the experiment, the animals within each unit are pooled prior to analysis. The merits of this approach and a computer algorithm for making the selections are described.

Algorithms↗