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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 613 records · Page 34Linked to original sources

Hepatic arterial streptozocin: a clinical pharmacologic study in patients with liver tumors.

Hepatic arterial infusions of streptozocin (STZ) were compared with peripheral venous infusions administered for 3 h at a dose rate of 0.5 or 1.0 g/m2 . h in five patients with liver-predominant neoplastic disease. Peripheral venous plasma STZ levels were measured during and for 3 h after completion of all infusions. Steady-state was achieved at 2 h and the elimination half-life was 35-40 min, the total body clearance was 400 ml/min, and the volume of distribution of STZ was 20-22 liters in these patients. Comparison of steady-state drug levels demonstrated minimal hepatic extraction (mean 5%). Assuming a hepatic arterial blood flow of 100-200 ml/min with a total body clearance of 400 ml/min, hepatic arterial administration of STZ can be expected to result in a three- to sixfold greater exposure of tumor in the liver compared with the intravenous route. Toxicity was minimal and two patients had evidence of response.

Adult↗

A versatile hydraulically operated respiratory servo system for ventilation and lung function testing.

A description is given of the design and performance of a microcomputer-controlled respiratory servo system that incorporates the characteristics of a mechanical ventilator and also allows the performance of a multitude of test procedures required for assessment of pulmonary function in paralyzed animals. The device consists of a hydraulically operated cylinder-piston assembly and solenoid valves that direct inspiratory and expiratory gas flow and also enable switching to different test gas sources. The system operates as a volume-flow-preset ventilator but may be switched to other operational cycling modes. Gas flow rates may be constant or variable. The system operates as an assister-controller and, combined with a gas analyzer, can function as a "demand" ventilator allowing for set-point control of end-tidal PCO2 and PO2. Complex breathing maneuvers for a variety of single- and multiple-breath lung function tests are automatically performed. Because of the flexibility in selection and timing of respiratory parameters, the system is particularly suitable for respiratory gas studies.

Lung Volume Measurements↗

Gas mixing in the airways of dog lungs during high-frequency ventilation.

Washout of insoluble inert test gases of different diffusivity (He and SF6 or He and Ar) from dog lungs was studied during high-frequency ventilation (HFV). Test gas equilibrium and subsequent washout were performed with HFV, succeeding measurements being performed at different stroke volumes (1.5-2.5 ml/kg body wt), oscillation frequencies (10-30 Hz), and with different lung volumes (32-74 ml X kg-1). Test gas concentrations were continuously measured by a mass spectrometer. The time course of washout could be described as the sum of two exponentials. There were no consistent differences in the time courses of washout between He and SF6 or between He and Ar. It is concluded that gas mixing in the airways during HFV is not significantly limited by diffusion, and this is suggested to apply during HFV to steady-state transport of respiratory gases (e.g., O2 and CO2) as well as to the transient state of inert gas washout.

Animals↗

Gas mixing in dog lungs studied by single-breath washout of He and SF6.

Simultaneously measured helium (He) and sulfur hexafluoride (SF6) single-breath washout was studied in 16 anesthetized paralyzed dogs ventilated with a special hydraulically operated ventilatory servo system. After equilibration of lung gas with 1% He and 1% SF6, the maneuver consisting of inspiration of a test gas-free mixture at constant rate (VI), a variable time of breath holding, and an expiration at constant rate (VE), was performed. Fractional concentrations of He and SF6, recorded against expired volume, were analyzed in terms of slope of the alveolar plateau (S) and series (Fowler) dead space (VD). In control conditions (VI = 0.5 l/s, VE = 0.1 l/s) S was about 10% of alveolar-to-inspired concentration difference per liter expirate both for He and SF6. Both SHe and SSF6 were inversely related to VI and VE, the relative changes being more pronounced with varying VE. SHe/SSF6 was higher or lower than unity depending on VI and VE. Both SHe and SSF6 decreased with increasing preinspiratory lung volume. Breath holding up to 10 s slightly decreased SHe and SSF6 while SHe/SSF6 was unchanged. The contribution of continuing gas exchange to S assessed from comparative measurements using the reversed (single breath washin) technique ranged from 6 to 23% in the various conditions. The VDHe/VDSF6 ratio was 0.84 and was little affected in the various settings. Results indicate that the substantial alveolar gas inhomogeneity in the dog lung and the mechanism accounting for S are little diffusion dependent. By exclusion sequential filling and emptying of lung units is believed to constitute the most important mechanism responsible for the sloping alveolar plateau.

Animals↗

Progressive change in cerebral blood flow during the first three weeks after subarachnoid hemorrhage.

Cerebral blood flow (CBF) was estimated from each cerebral hemisphere by the 133Xe inhalation method. Daily estimates were made during the first 3 weeks after subarachnoid hemorrhage (1265 studies in 116 patients). Some of the patients were taking adrenergic blocking drugs (propranolol and phentolamine), others were taking tranexamic acid, and the rest were taking no drugs. CBF was also studied in 67 normal subjects. The resting CBF was related inversely to age not only for normal subjects but also for patients after subarachnoid hemorrhage (SAH). The CBF fell progressively during the first 2 weeks after SAH and was abnormally low throughout the 3 weeks after hemorrhage. For any 1 day after SAH, those patients who were fully alert had the smallest reduction in CBF. The progressive changes in CBF occurred whether or not an aneurysm was present on angiograms. For aneurysms situated to one side of the midline, the changes in CBF affected both sides of the brain. The progressive decline in CBF was least in those patients who subsequently made the best clinical recovery. Arterial pCO2 seemed to influence CBF throughout the 3 weeks after SAH. During the 2nd week, CBF was especially low in SAH patients treated with tranexamic acid. The serial changes in CBF are discussed in relation to current views concerning the timing of operation for ruptured aneurysms.

Adult↗

Isolation and structural elucidation of naphthomycins B and C.

Two new ansamycin antibiotics, the naphthomycins B and C, were isolated from two different strains of Streptomyces. The structures were determined by comparison of the spectra (UV, 1H NMR, 13C NMR) with those of the known naphthomycin A, by spin decoupling experiments (300 MHz) and in one case by a two dimensional NMR analysis. Naphthomycin B (II) is 30-chloronaphthomycin C. Strikingly, naphthomycin A (I) differs from B and C not only by the presence of an additional methyl group at C (2), but also in the configuration of some of the double bonds. A fourth ansamycin antibiotic of the naphthomycin subgroup, actamycin, is 30-hydroxynaphthomycin C.

Anti-Bacterial Agents↗

Phase I study of human leukocyte interferon in patients with advanced cancer.

Seventeen patients with disseminated cancer were treated with a human leukocyte interferon preparation in doses ranging from 3 X 10(6) to 50 X 10(6) IU daily for 30 days. Doses above 18 X 10(6) IU were considered intolerable in this schedule of administration due to severe fatigue and weight loss. Serum concentrations of interferon were lower than those achieved with either partially pure native or recombinant leukocyte interferon. Three of 17 patients in this study showed minimal evidence of tumor regression. Two patients treated at doses of 18 X 10(6), 36 X 10(6), and 50 X 10(6) IU also received a 5 X 10(6)-IU dose of a second human leukocyte interferon preparation. The latter resulted in less toxicity but similar serum levels. These results suggest that human leukocyte interferons prepared in the same manner may differ significantly in their in vivo biologic properties.

Adult↗

Differences in morphology and protein pattern of human blood platelets during irreversible and diamide mediated reversible aggregation.

Morphological alterations of platelets during reversible aggregation mediated by diamide are compared with those observed during irreversible aggregation. Diamide prevents cell fusion and the formation of loop-like structures which probably arise from fusing plasma membranes. Differences in the protein pattern of platelets after reversible and irreversible aggregation suggest a specific involvement of SH-proteins in irreversible platelet aggregation. The diamide mediated alterations of platelet aggregation behaviour are transitory, i.e. reversibly aggregated platelets respond normally to a new addition of aggregation inducers without and with diamide, respectively.

Arachidonic Acid↗

[Inverted polypoid hamartoma of the rectum in children].

Rectal tumors are rare in childhood. The description of both hamartomatous inverted polyps of the rectum and polymalformative syndrome in the same adolescent, gives the opportunity to remind the manifestations of this unusual tumor and to bring an additional argument to the Schannon Allen's malformative theory.

Child↗

A preliminary trial of vaccinia oncolysates in the treatment of recurrent melanoma with serologic responses to the treatment.

A preliminary trial was designed as a toxicity/feasibility study using a fixed dose of vaccinia melanoma oncolysates (VMO) to treat recurrent stage II and stage III (skin, subcutaneous, and nodal metastases only) melanoma. There were no adverse consequences of the therapy, and 4 of the 12 patients treated seemed to have responded to the treatment by the criteria of the study. Sera from the six patients with the longest survival showed immunoreactivity to human melanoma lines in a Staphylococcus protein A assay (SpA) after 3 months of therapy. While the specificity of this immunoreactivity remains to be determined, the discovery of posttreatment serologic activity in a SpA assay permits investigation of the degree of VMO immunostimulation at different dose levels of the biologic. This assay may provide the means to quantitate optimal biologic dose for future melanoma oncolysate trials. The Southeastern Cancer Study Group is now conducting a phase I/II trial with these vaccinia melanoma oncolysates using the SpA assay to monitor this trial.

Antibodies, Neoplasm↗

Effects of diltiazem on vulnerability to atrial and ventricular reentrant arrhythmias in the normal and ischemic heart.

In experiments on 20 artificially ventilated anaesthetized dogs, the effects of the new calcium antagonist diltiazem on the stimulation thresholds to repetitive extrasystoles and fibrillation of the atria and the ventricles, respectively, and on ventricular dysrhythmias 6-24 h after acute coronary occlusion were investigated. The electrophysiological studies were performed using different methods of programmed stimulation of the heart. The results show that therapeutic doses of diltiazem provide no protection against stimulus-induced supraventricular reentrant arrhythmias with the AV-node not involved in the reentrant circus, and have no antifibrillatory efficacy in electrically induced ventricular arrhythmias in the non-ischemic heart. In acute myocardial infarction there is no antiarrhythmic effect either. Our results can be explained by the fact that diltiazem is a specific calcium antagonist and that the slow response plays only a minor role in the arrhythmias investigated.

Animals↗

Subarachnoid haemorrhage: older patients have low cerebral blood flow.

Daily estimations of hemispheral cerebral blood flow using the xenon-133 inhalation technique was made in 116 patients during the first three weeks after subarachnoid haemorrhage. The patients' cerebral perfusion on average remained less than the normal perfusion expected for their age (based on a single estimation of cerebral blood flow in 67 volunteers). On each separate day after subarachnoid haemorrhage cerebral blood flow was inversely related to the patient's age. Older patients seem especially at risk of developing cerebral ischaemia after subarachnoid haemorrhage. The clinical outcome was more often unfavourable in older patients--that is, in those who tended to have the lowest cerebral blood flow. Present results support the view that episodes of low cerebral blood flow lead to a poor outcome after subarachnoid haemorrhage. Because of the risk of inducing cerebral ischaemia great care should be exercised by physicians administering hypotensive drugs to older patients after subarachnoid haemorrhage.

Adult↗