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Biomedical subjects

P Gerhardt

Publications and source records attributed to P Gerhardt.

At least 37 records · Page 2Linked to original sources

[Volumetry of abdominal tumors. Problems--feasibility].

If multimodal tumor therapy in the abdomen is to be effective, exact staging is required for which one needs precise planimetric and volumetric data. The most important indication for clinically reliable volumetric determination of tumor size in the abdominal region is monitoring liver metastases during chemotherapy. Determination of volume can be effectively realized using 3D reconstruction. Therefore, the primary data set must be complete and contiguous. The mass should be depicted strongly enhanced and free of artifacts. At present, this prerequisite can only be complied with using thin-slice spiral CT. Phantom studies have proven that a semiautomatic reconstruction algorithm is recommendable. The basic difficulties involved in volumetric determination of tumor size are the problems in differentiating active malignant mass and changes in the surrounding tissue, as well as the lack of histomorphological correlation. Possible indications for volumetry of gastrointestinal masses in the assessment of neoadjuvant therapeutic concepts are under scientific evaluation.

Abdominal Neoplasms↗

Comparison of neurokinin substance P with morphine in effects on food-reinforced operant behavior and feeding.

In the present study, substance P (SP) was injected intraperitoneally (IP), and its effects on operant behavior were assessed in rats, which had been trained to bar press for food reward on a fixed-ratio (FR) 20 schedule. These effects were compared with IP injection of morphine sulfate, which had previously been shown to strongly suppress operant responding on FR schedules. The IP injection of SP resulted in a dose-related decrement in response rates. SP in a dose range of 250-500 micrograms/kg decreased operant responding, whereas SP in a dose range of 5-50 micrograms/kg did not influence response rates. The IP injection of morphine (10 mg/kg) markedly suppressed operant responding. However, in contrast to the rate-decreasing effects of SP, this suppression was not selective for the reinforced lever as responding on the nonreinforced lever, used as a control, was also decreased. Furthermore, both injection of 10 mg/kg morphine and SP in a dose range of 250-500 micrograms/kg was found to reduce food intake when the animals had free access to food subsequent to the operant conditioning session. The present results provide the first evidence that systemically administered neurokinin SP can affect operant responding for food reward. The suppressive effects on operant behavior and feeding obtained with systemic SP or morphine are discussed with respect to recent findings showing that both drugs can modulate mesolimbic dopamine activity after systemic drug injection.

Animals↗

Evidence for mnemotropic action of cholecystokinin fragments Boc-CCK-4 and CCK-8S.

Memory-modulating and reinforcing effects of the cholecystokinin (CCK) fragments, CCK-8S and Boc-CCK-4, after systemic application in rats were investigated. Habituation to the novelty of environmental stimuli was used to test for mnemonic effects using two different tasks (rearing behavior in an open field; head-dips in a hole-board). Immediate posttrial administration of CCK-8S and Boc-CCK-4 resulted in a reduction of rearing and head-dip behavior during testing, indicative of enhanced habituation and, thus, facilitation of memory. In contrast, administration of CCK-8S and Boc-CCK-4 with a delay of 2.5 or 5 h after training or pretrial injection of CCK-8S did not enhance habituation. No evidence for reinforcing or aversive properties of CCK-8S and Boc-CCK-4 was observed in a conditioned place preference task. In summary, the results indicate memory-enhancing effects of peripherally, posttrial-administered CCK-8S and Boc-CCK-4.

Amino Acid Sequence↗

[Role of i.v. cholangiography and ultrasonography in preoperative diagnosis before laparoscopic cholecystectomy].

In a prospective clinical study the relevance of i.v. cholangiography and ultrasonography for preoperative diagnosis before laparoscopic cholecystectomy was assessed. Imaging of the common bile duct was realized successfully via i.v. cholangiography in 96.3% of all patients. Compared with ERCP, i.v. cholangiography diagnosis proved correct in 91.6% of all cases with pathological depiction of the common bile duct. Ultrasonography offered a sensitivity of 97.8% for assessing the common bile duct diameter. However, the distinction between intraductal concrements and artifacts caused by air superposition may be difficult. I.v. cholangiography is the most sensitive and easy to realize diagnostic technique to identify concrements in the common bile duct. The results of this study indicate that a combined strategy of i.v. cholangiography and ultrasonography may replace ERCP for preoperative diagnosis before laparoscopic cholecystectomy, if there is a sufficient depiction of the common bile duct and without concrements in it.

Adolescent↗

Microscopic and thermal characterization of hydrogen peroxide killing and lysis of spores and protection by transition metal ions, chelators, and antioxidants.

Killing of bacterial spores by H(2)O(2) at elevated but sublethal temperatures and neutral pH occurred without lysis. However, with prolonged exposure or higher concentrations of the agent, secondary lytic processes caused major damage successively to the coat, cortex, and protoplast, as evidenced by electron and phase contrast microscopy. These processes were also reflected in changes in differential scanning calorimetric profiles for H(2)O(2)-treated spores. Endothermic transitions in the profiles occurred at lower temperatures than usual as a result of H(2)O(2) damage. Thus, H(2)O(2) sensitized the cells to heat damage. Longer exposure to H(2)O(2) resulted in total disappearance of the transitions, indicative of major disruptions of cell structure. Spores but not vegetative cells were protected against the lethal action of H(2)O(2) by the transition metal cations Cu, Cu, Co, Co, Fe, Fe, Mn, Ti, and Ti. The metal chelator EDTA was also somewhat protective, while o-phenanthroline, citrate, deferoxamine, and ethanehydroxydiphosphonate were only marginally so. Superoxide dismutase and a variety of other free-radical scavengers were not protective. In contrast, reducing agents such as sulfhydryl compounds and ascorbate at concentrations of 20 to 50 mM were highly protective. Decoating or demineralization of the spores had only minor effects. The marked dependence of H(2)O(2) sporicidal activity on moderately elevated temperature and the known low reactivity of H(2)O(2) itself suggest that radicals are involved in its killing action. However, the protective effects of a variety of oxidized or reduced transition metal ions indicate that H(2)O(2) killing of spores is markedly different from that of vegetative cells.

Journal Article↗

[Pancreatic carcinoma--preoperative diagnosis and indications for surgery].

Symptomatic pancreas tumors are diagnosed in general by ERCP, transabdominal ultrasonography, and computed tomography. Endoscopic ultrasonography, angiography (facultative) and video laparoscopy in combination with laparoscopic sonography and peritoneal lavage are providing preoperatively important additional information about the spreading of the tumor. Preoperative diagnostic procedures should allow the surgeon to exclude patients with an unresectable tumor from extended resection. In most of these patients satisfactory palliation can be achieved endoscopically. The indication for surgical treatment of resectable pancreatic tumors is based on the mortality of pancreaticoduodenectomy far beyond 5% in experienced centers. Improved surgical techniques and improved perioperative management together with the implementation of accurate preoperative analysis of risk factors allow resection of primary pancreatic tumors with a low morbidity and mortality.

Chronic Disease↗

Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine activity.

There is ample evidence that the neurokinin substance P (SP) can have neurotrophic as well as memory-promoting effects. This paper outlines a recent series of experiments dealing with the effects of SP and its N- and C-terminal fragments on memory, reinforcement, and brain monoamine metabolism. It was shown that SP, when applied peripherally (IP), promotes memory (inhibitory avoidance learning) and is reinforcing (place preference task) at the same dose of 37 nmol/kg. Most important, however, is the finding that these effects seemed to be encoded by different SP sequences, since the N-terminal SP1-7 (185 nmol/kg) enhanced memory, whereas C-terminal hepta- and hexapeptide sequences of SP proved to be reinforcing in a dose equimolar to SP. These differential behavioral effects were paralleled by selective and site-specific changes in dopamine (DA) activity, as both SP and its C-, but not N-terminus, increased extracellular DA in the nucleus accumbens (NAc), but not in the neostriatum. The neurochemical changes lasted at least 2 h after injection. These results show that the reinforcing action of peripheral administered SP may be mediated by its C-terminal sequence, and that this effect could be related to DA activity in the NAc. Direct application of SP (0.74 pmol) into the region of the nucleus basalis magnocellularis (NBM) was also memory-promoting and reinforcing, and again, these effects were differentially produced by the N-terminus and C-terminus, supporting the proposed structure-activity relationship for SP's effects on memory and reinfrocement. These results may provide a hypothetical link between the memory-modulating and reinforcing effects of SP and the impairment in associative functioning accompanying certain neurodegenerative processes.

Amino Acid Sequence↗

Mnemogenic effects of injecting RA-octil, a CE-inhibitor derivate, systemically or into the basal forebrain.

The aim of this study was to investigate the effects of systemically or intracerebrally administered RA-octil, a derivative of the angiotensin converting enzyme (CE)-inhibitor ramipril, on memory and reinforcement and to compare its effectiveness with that of the neurokinin substance P (SP). In the first experiment systemic post-trial application of RA-octil and SP in the rat enhanced habituation, a learning task which does not require motivational treatments. Unlike SP, injection of RA-octil did not have reinforcing effects as measured with a conditioned place preference task. In the second experiment, a facilitation of inhibitory avoidance learning was obtained by injection of RA-octil or SP unilaterally into the basal forebrain immediately after the learning trial. In contrast, a 5 h delayed injection of RA-octil had no effects on learning. The results demonstrate memory-enhancing effects of RA-octil after systemic application as well as after injection into the basal forebrain. Furthermore, the mnemogenic effects of SP after central and peripheral administration were confirmed. Since RA-octil, although being structurally closely related to CE-inhibitors, does not affect plasma CE, yet exhibits mnemogenic effects, it is possible that "cognition-enhancing" actions of CE-inhibitors are dissociable from their action within the renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗

[Color-coded three-dimensional reconstruction from spiral CT data sets: physical viewpoint for improvement of the method].

This paper demonstrates the possibility of improving the spatial depth impression of colour-coded three-dimensional reconstructions by modulation of colour saturation. Patients were observed with spiral computed tomography (slice thickness 10 mm, table feed 10 mm/s, reconstruction of overlapping axial images at 2 mm increment). Interesting anatomical and pathological objects (vessels, organs, tumours, metastases) were segmented, colour-coded, and reconstructed three-dimensionally. Spatial depth impression of the coloured objects could be improved by modulating not only the brightness, but also the colour saturation.

Aorta, Abdominal↗

[A comparison of plain film, axial CT, 2D and 3D reconstructions in unstable spinal injuries following surgery].

During a period of 18 months about 70 patients suffering from an unstable spinal injury were operated in the surgical department of our clinic. In 50 of these patients it was possible to correlate the results of preoperative radiography and CT with the operative findings. Several cases of distraction instability in the dorsal column had not been recognised in the preoperative radiologic evaluation. Therefore the rationale of this study was the question as to whether modern CT technology can help to avoid such wrong diagnoses. For that purpose radiographs, axial CT-scans of 2 mm thickness or less, sagittal and coronal 2D and (in 35 cases) 3D reconstructions were re-evaluated step by step by a specifically trained radiologist without knowing the operative findings. 15 additional lesions out of 28 were demonstrated and specifically classified as distraction instabilities of the dorsal column using the improved CT technology.

Adult↗

Intravascular ultrasound in tumor staging.

Our preliminary results show that intravascular ultrasound scanning yielded the correct diagnosis in each patient who underwent surgery. We therefore conclude that this method is a potent adjunct to diagnostic procedures in pretherapeutic tumor staging when applied directly to the questionable region of the vessels. In contrast, evaluation of suspected tumor infiltration of the portal vein by positioning the catheter in the inferior vena cava or aorta was generally impossible due to technical problems. We hope that these problems will be solved as technology progresses.

Adult↗

Positively reinforcing effects of the neurokinin substance P in the basal forebrain: mediation by its C-terminal sequence.

The conditioned corral preference paradigm was used to assess reinforcing effects of substance P (SP) and its N- and C-terminal fragments injected unilaterally into the region of the nucleus basalis magnocellularis (NBM) in rats. Behavioral testing was carried out in a circular open field, consisting of 4 quadrants equally preferred by the animals prior to conditioning. A single conditioning trial was performed. Rats received one microinjection (0.5 microliter) of SP (0.74 pmol), of the N-terminal fragment SP (1-7) and the C-terminal fragment analog DiMe-C7 (each at doses of 0.074, 0.74, and 74 pmol), or vehicle (phosphate-buffered saline; PBS). After injection the rats were placed into the open field with the four quadrants being separated by Plexiglas barriers (closed corral). During the test for conditioned corral preference, when provided a choice between the four quadrants, only those rats injected with SP and the equimolar dose of DiMe-C7 (0.74 pmol) spent more time in the treatment corral, indicative of a positively reinforcing action. None of the other doses of DiMe-C7 and of SP(1-7) influenced the preference behavior. For rats injected with 0.74 pmol SP, SP (1-7), and DiMe-C7, a behavioral analysis was performed for the 15 min conditioning trial. SP and DiMe-C7 reduced rearing and grooming behavior, whereas DiMe-C7 and SP(1-7) increased locomotor activity. However, the acute behavioral effects of SP and its fragments were not correlated with the subsequent place preference behavior during the test trial. The results are discussed in the framework of a structure/activity relationship for the positively reinforcing properties of SP in the region of the NBM. Furthermore, neuropathological implications of the present data are considered, since the homologous nucleus basalis of Meynert in man is known to degenerate in Alzheimer's disease, which is characterized behaviorally by a progressive deterioration in associative functioning.

Animals↗

Enhanced learning produced by injection of neurokinin substance P into the region of the nucleus basalis magnocellularis: mediation by the N-terminal sequence.

The effect of unilateral injection of the neurokinin substance P (SP) and of certain N- or C-terminal SP-fragments into the region of the nucleus basalis magnocellularis (NBM) on inhibitory avoidance learning was investigated. Rats with chronically implanted cannulae were tested on a one-trial uphill avoidance task. Immediately after the training trial, rats were injected with 0.74 pmol SP or equimolar dosed SP(1-7), DIME-C7, or SP(7-11). Control groups included vehicle-injected rats and a group given an injection of SP(1-7) 5-h after the trial. When tested 24 h later, rats treated with SP or SP(1-7), but not with DIME-C7 or SP(7-11), exhibited longer step-up latencies than vehicle-treated controls. The retention latencies for rats in the SP(1-7) 5-h delay group did not differ from those of vehicle-injected animals, ruling out proactive effects of SP(1-7) on performance. The results show that SP facilitates retention of an inhibitory avoidance response when injected into the NBM. Furthermore, the amino acid sequence that encodes this effect may be located in the N-terminal part of the SP-molecule.

Animals↗