[1st clinical and animal experimental experiences with tricalciumphosphate (TCP)-implantations].
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Biomedical subjects
Publications and source records attributed to G Riess.
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Thirty-nine patients with malignant stenoses of the esophagus (22 adenocarcinomas, 17 squamous cell carcinomas) were treated either with Nd:YAG laser recanalization alone (N = 20) or with laser recanalization and subsequent endoluminal afterloading irradiation with iridium-192 at a dose of 3 x 7 Gy (6 x 7 Gy). Squamous cell carcinoma patients in the afterloading group showed a prolonged dysphagia-free first interval (65 vs. 30 days, p less than 0.03), while patients with an adenocarcinoma did not share this benefit, and had a need for more frequent endoscopic procedures (p less than 0.05). The complication of esophagitis was only seen following afterloading treatment (21%, N = 4). Re-stenosis occurred in all patients. Neither the duration of relative dysphagia nor survival time was prolonged after endoluminal irradiation in adenocarcinoma or squamous cell carcinoma patients. After prior laser recanalization, palliative afterloading treatment with iridium-192 would seem helpful only in cases of squamous cell carcinoma with a high performance status with the aim of prolonging the first dysphagia-free interval.
The present investigation confirms that initially implemented procedure to produce poly(methylidene malonate 2.1.2) (PMM 2.1.2) nanoparticles (Lescure et al. Pharm Res 1994;11:1270-77) lead to products mostly containing plasticizing oligomers which strongly lowered glass-transition temperature (Tg), dramatically reduced nanoparticle consistency and rendered them too sensitive to solubilization when diluted in an aqueous medium. From MALDI-TOF spectroscopy analysis, performed on intact colloids, emerged some structural information about these oligomeric species which could result from an intramolecular cyclization mechanism occurring soon in the course of the polymerization process. Thus, with the objective of overcoming these drawbacks, this contribution deals with the variations of manufacturing specifications such as pH and magnetic stirring speed to try and modulate molecular weight (MW) of nanoparticle constituents and reduce oligomer concentration. Although the analyses performed on these new nanoparticles were rather encouraging, the colloid formation yield became so low that it required the development of other methodologies, excluding a previous emulsion step, and allowing a controlled production of PMM 2.1.2-made nanoparticles having better physico-chemical characteristics while keeping good pharmaceutical capabilities.
Left ventricular infarctions were produced in guinea pigs, and the contractile response to beta-adrenergic and H2-histaminergic stimulation was tested in isolated perfused heart preparations. Adenylate cyclase activity and binding characteristics of sarcolemmal beta 1-, H2-, and muscarinic cholinergic receptors were determined in sarcolemmal membrane preparations of the uninvolved right ventricle of the same hearts. Three days after infarction, the positive inotropic effects of isoproterenol (2.8 X 10(-9) mol/L) and tyramine (5.5 X 10(-5) mol/L) were nearly abolished, while the inotropic effects of impromidine (4.6 X 10(-7) mol/L) and dimaprit (8.5 X 10(-6) mol/L) were not impaired. Stimulation rates of cardiac adenylate cyclase activity by isoproterenol were markedly reduced (-90%) whereas impromidine, dimaprit, and NaF revealed stimulation rates equivalent to the sham-operated control group. beta-Receptor binding studies with [3H]dihydroalprenol revealed 90% loss and nearly 10 times lowered affinity (KD) of the remaining receptors, while specific binding of [3H]tiotidine and [3H]quinuclidinyl-benzylate was unchanged in the same preparations. All of the above alterations could be prevented to a similar extent by treatment with different beta-blocking agents, but differences between the drugs were seen with respect to survival rates and reduction of infarct size. In agreement with previous findings, we conclude that the observed alterations in the nonischemic surviving myocardium are the result of specific damage of sarcolemmal beta-receptors due to excessive exposure to increased catecholamines after infarction. The stimulation of the uninvolved H2-receptors may be of therapeutic value.