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Biomedical subjects

M Beer

Publications and source records attributed to M Beer.

At least 163 records · Page 9Linked to original sources

[Vasoconstrictor effects on isolated vessel segments determined by pressure-volume measurements].

A method for pressure-volume measurement in isolated segments of dog saphenous veins and femoral arteries is described. Its applicability was shown by means of the vasoconstrictor effects of noradrenaline and serotonin. By this method changes in intravascular pressure were measured in dependence upon the in- and outflowing volume of liquid. The pressure-volume diagrams allowed to estimate the intravascular pressure, work, resistance and compliance of the vascular segments. From the diagrams differences in the responses of veins and arteries to the biogenic amines could be demonstrated. The concentration-response relationships of the venous segments for noradrenaline and serotonin corresponded to those obtained in helically cut venous strips.

Animals↗

[Polyneuropathy after cisplatin treatment].

Polyneuropathy developed in 7 of 87 women who had been treated with cis-platinum for ovarian carcinoma. Distal disturbances of sensitivity were clinically prominent, the emphasis being on disturbed vibratory perception and acrognosis. No relevant signs of motor dysfunction were noticed, neither clinically nor neurophysiologically. Sural biopsies taken from two women revealed a primary axonal degeneration, mostly affecting the myelinic fibres of large diameter. In 3 cases mild reversion was seen, and in 4 cases no definite reversion, of the disturbed functions - uncertain gait and clumsiness of the hands - during the follow-up period of 6 to 30 months.

Aged↗

Do vitamin D supplements improve the physical capabilities of elderly hospital patients?

A randomized double-blind controlled trial of the effect of vitamin D supplementation on the abilities of elderly hospital patients to carry out basic activities of daily life is described. Those patients included in the trial had plasma 25-hydroxyvitamin D concentrations which were low or low normal as judged by the normal range in young adults. After 2 to 9 months on the trial there was no significant difference in the performance of the control and treatment groups.

Activities of Daily Living↗

[NMR tomography in urology. Principles--technics--risks--areas of use].

NMR tomography is a new imaging method based on nuclear magnetic resonance. It is possible to obtain sectional views of the human body in all three planes without ionizing radiation. NMR can differentiate soft tissue better than CT, and large blood vessels can be simultaneously evaluated without using contrast medium. The pathological process could be imaged exactly in every examination. Due to the lack of image clarity caused by breathing movement, NMR is not superior to CT when using contrast medium in the epigastrium. Calculation of relaxation times T1 and 2 shows clear differences between tumor and normal tissue. However, contrary to initial expectations. NMR did not permit a type-specific diagnosis to be made. Three-dimensional images improve the process of staging tumors, especially in the retroperitoneal space and in the pelvis. As with CT, metastatic lymph nodes can only be demonstrated when they have reached a size of at least 1 cm. Further studies will be necessary to evaluate the validity of this new imaging method.

Contrast Media↗

[Clinical significance of nuclear magnetic resonance tomography in urology. Initial experiences].

NMR tomography, which is based on nuclear magnetic resonance, enables the production of sectional images of the human body without ionising radiation. In particular, the field of urology places great hopes on this new procedures, since the contrast in soft tissue is considerably better than that of computer tomography. Our first clinical results confirm the advantages of the soft tissue differentiation as well as the possibility to judge the large vessels safely and simultaneously without contrast medium, which is advantageous in the detection of tumours in the retroperitoneum and in the region of the kidneys. An improvement of the preoperative staging of urological tumours can be achieved by means of primary three-dimensional images. Only after several years of experience with NMR tomography and all its variations will it be able to evaluate properly, to what extent clinically relevant diagnostic possibilities are offered by the analysis of relaxation values.

Diagnosis, Differential↗

Histone positions within the nucleosome using platinum labeling and the scanning transmission electron microscope.

An approach to studying the organization of macromolecular complexes using heavy-atom labeling has been developed and applied to the problem of determining the positions of the histone proteins within the nucleosome. The approach is based on the capability of the scanning transmission electron microscope to image heavy atoms. Nucleosomes containing histones labeled with heavy atoms were prepared by lysine modification of selected histones with methyl (methylthio)acetimidate, followed by reconstitution of the modified histones into nucleosomes, and reaction of the reconstituted nucleosomes with chloroglycyl-1-methioninatoplatinum (II). Micrographs of the platinum-labeled nucleosomes were obtained using the scanning transmission electron microscope, and analyzed using both computer and manual techniques. The results of the analysis were 24 A resolution maps of the distribution of high electron scattering density picture elements (representative of platinum atoms) indicating the position of each histone. The significance of those results and the general applicability of the platinum-labeling techniques are discussed. Finally, a description of the histone positions within the nucleosomes is presented and discussed in relation to the current literature on nucleosome structure.

Affinity Labels↗

Discrimination of collagen types by methionine-specific stain.

Chloroglycyl-L-methioninatoplatinum (II) (Pt-GLM) specifically labels methionine residues in collagen. Rat Type I and calf Type III collagen segment long spacing aggregates show differences in Pt-GLM bands, in agreement with known methionine positions. Reconstituted fibers formed from the same two collagens again demonstrate some differences in band pattern, which can be understood in terms of the amino acid sequences and the known packing of molecules in the fiber. Native collagen fibers have been extracted from rat and chick tendon (predominantly Type I collagen). These have been stained with Pt-GLM and studied in the Johns Hopkins STEM and a CTEM. Density profiles along the collagen fibers have been obtained, and those for successive 670-A repeats averaged, by computer programs. The position of peaks in the average density profiles for these various fibers show very good correlation with the known locations of Met residues. The band patterns and density profiles for native and reconstituted Type I fibers are very similar and differ from those of reconstituted Type III fibers.

Amino Acid Sequence↗

Incidence of metabolic bone disease in rheumatoid arthritis and osteoarthritis.

Bone biopsy specimens from the iliac crest were obtained during surgical operations from 45 patients with rheumatoid arthritis (RA) and 41 with osteoarthritis (OA). Control material was obtained from 20 cases of sudden death due to cardiovascular disease. By both conventional histology and image analysis techniques about a quarter of all patients showed some osteoporosis. This was equally common among the OA and RA patients. It was more common among those with transparent skin and those taking corticosteroids. The only case showing mild osteomalacia suffered from OA. No gross differences were apparent between the groups in relation to plasma biochemical studies, diet, or exposure to sunlight. These results are in striking contrast to the high incidence of osteomalacia in RA reported from the west of England; moreover they do not confirm reports of hypercalcaemia among rheumatoid subjects. We conclude that the differences regarding osteomalacia are due to selection of cases. We find no evidence that osteomalacia is specifically associated with RA.

Aged↗

Measurement of plasma group I pepsinogens.

Plasma group I pepsinogen (PG I) concentration is now a readily available non-invasive marker of gastric secretory function, with several potentially useful applications. Ninety-eight percent of control subjects had a plasma PG I below 115 ng/ml while values above this level were seen in 43% of duodenal ulcer patients. Plasma PG I levels below the observed normal lower limit of 30 ng/ml were seen consistently in patients with documented achlorhydria or pernicious anaemia. In 48 patients with a variety of upper gastrointestinal disorders there was a significant correlation between PG I pepsinogens and pentagastrin-stimulated maximal acid output. Changes in plasma PG I promise to be useful in evaluating both operations on the vagus and newer anticholinergic drugs, whilst in epidemiological and family studies these measurements seem well suited to explore duodenal ulcer heterogeneity.

Achlorhydria↗

Concurrent or sequential use of cytotoxic chemotherapy and hormone treatment in advanced breast cancer: report of the Swiss Group for Clinical Cancer Research.

In a trial of combined hormone treatment and cytotoxic chemotherapy 464 patients with advanced breast cancer were randomly allocated to either concurrent or sequential treatment. Cytotoxic drugs were given only if the antitumour activity of the hormone treatment was inadequate. Hormone treatment consisted of oophorectomy for premenopausal and tamoxifen administration for postmenopausal patients. Length of survival was better, though not significantly, in premenopausal patients (p = 0.29) treated concurrently and in postmenopausal women (p = 0.17) treated sequentially; the difference was highly significant (p = 0.003) only for postmenopausal women in the low-risk category. The findings suggest that postmenopausal women with metastatic breast cancer should probably be treated primarily by carefully monitored hormone treatment.

Antineoplastic Agents↗

The evolution of Japanese management: lessons for U.S. managers.

To find the key to the success of Japanese economic performance since World War II, Marsland and Beer explore five main "environmental" factors used by Japanese firms to build a successful human resources management approach: Japanese social values, the structure of private enterprise, the structure of labor markets, the historic development of the Japanese employment system, and the structure of Japanese management. This discussion shows that post-war Japanese management, faced with rapid change, introduced new concepts and techniques that reinforced and maintained certain social values and traditions that fit well with human resources management objectives. This skillful blend of new ideas with traditional values enabled the Japanese to achieve superior economic performance.

Japan↗

A phase II study of cisplatin in advanced gastric cancer.

Twenty patients with recurrent or metastatic gastric adenocarcinoma and prior chemotherapy were treated with cisplatin, 60-120 mg/m2 as a 6-hr infusion repeated every 3 weeks. There were 4 partial responses in 18 evaluable patients. Seven patients had stable disease. Time to progression ranged from 6 to 28 weeks. Median WBC nadir was 3.2 X 10(3)/mm3 (range, 1.5-7.1) and platelet nadir 120 X 10(3)/mm3 (range, 13-220). A transient increase in serum creatinine was observed in 6 cases, and nausea and vomiting in all. We conclude that this drug is active in stomach cancer and that it warrants further trials in combination chemotherapy.

Adult↗

Phase I study of carboplatin given on a five-day intravenous schedule.

Twenty-six adult patients were entered in a phase I trial of carboplatin, a new cisplatin derivative with reduced potential for nephrotoxicity. All patients had solid tumors and the median World Health Organization performance score was 2 (0-3). Twelve patients had not received prior chemotherapy. The drug was administered as a 15-minute IV infusion, without pre- or posthydration, at daily doses of 40-125 mg/m2 for five consecutive days. Antiemetics were given only if needed. Thrombocytopenia and neutropenia were dose related and dose limiting. One patient died from septic shock at the highest dose level. Nonhemolytic anemia was also encountered. Nausea and vomiting were experienced by most patients but gastrointestinal intolerance was severe in only two patients. One patient had hypercreatininemia, which was minor and rapidly reversible. Other toxic effects consisted of negligible fatigue, paresthesia, pruritus, local pain, stomatitis, headache, and alopecia. Although none of the patients achieved a partial or complete response, antitumor effect was strongly suggested in two patients with thyroid and cervix cancer, respectively. Carboplatin is an attractive candidate for phase II trials. In good-risk patients, such trials could be initiated at a daily dose of 100 mg/m2 for five consecutive days every five to six weeks.

Adult↗

[Simultaneous or sequential hormono/chemotherapy and a comparison of various polychemotherapies in the treatment of metastatic breast cancer].

Since in the treatment of advanced breast cancer chemotherapy and the various hormonal manipulations seem recently to have reached a plateau of effectiveness when used alone, it is widely assumed that the combination of both treatment modalities could improve therapeutic results. The outcome is reported of a study encompassing 109 pre- and 297 postmenopausal evaluable cases with previously untreated metastatic breast cancer. The patients were randomized either to a concurrent chemo/hormonotherapy or to the hormonal treatment alone, chemotherapy being delayed until the occurrence of tumor progression. All patients were further randomized to 3 chemotherapy regimens (LMFP, LMP/FVP, LMFP/ADM) representing three different degrees of intensity. Pre-menopausal patients tend to live longer with the concurrent combination of both modalities, whereas postmenopausal patients fare better when chemotherapy is delayed until the occurrence of tumor progression with hormonotherapy alone. However, the differences in survival are statistically significant only in postmenopausal patients with a less aggressive tumor ("low-risk"). The more aggressive cytotoxic combinations elicit higher response rates than "minimal chemotherapy", but the differences translate only marginally into different survivals. These findings are discussed with regard in particular to their importance in establishing widely acceptable therapeutic rules for the treatment of advanced breast cancer.

Adult↗

Pharmacokinetics of VP16-213 given by different administration methods.

Plasma pharmacokinetics of VP16-213 were investigated after a 30-60 min infusion in 14 adult patients and six children. In adult the elimination half-life (T1/2 beta), plasma clearance (Clp) and volume of distribution (Vd) were respectively 7.05 +/- 0.67 h, 26.8 +1- 2.4 ml/min/m2, and 15.7 +1- 1.8 l/m2; in children 3.37 +/- 0.5 h, 39.34 +1- 6.6 ml/min m2, and 9.97 +/- 3.7 l/m2. After repeated daily doses no accumulation of VP16-213 was found in plasma. The unchanged drug found in the 24 h urine after administration amounted to 20-30% of the dose. In eight choriocarcinoma patients plasma levels of VP16-213 were measured after oral capsules and drinkable ampoules. The bioavailability compared to the i.v. route was variable, mean values being 57% for capsules and 91% for ampoules. In one further patient, with abnormal d-Xylose absorption results, VP16-213 was not detectable in plasma after the oral ampoule dose. Steady state levels investigated in three patients after 72 h continuous VP16-213 infusion (100 mg/m2/24h) were around 2-5 micrograms/ml. Levels of VP16-213 were undetectable in CSF after i.v. or oral administration.

Administration, Oral↗

Johns Hopkins University, Baltimore, Maryland.

The STEM can be used in one of three modes: 1) to image individual atoms; 2) to measure mass or molecular weight; 3) to collect electron energy loss spectra or x-ray fluorescence data. Heavy atom imaging is used to identify chemical groups in a molecule or macromolecules in an assembly. Specific labels have been developed for bases in nucleic acids. These permit localization of bound proteins on single strand nucleic acids. Pt(gly-L-met)Cl is a specific label for methionine residues of proteins as shown with the SLS aggregate of collagen. Lysine can be labeled as well if first methyl (methyl-thio-acetimidate) is coupled. This labeling procedure permits the localization of individual histones within a nucleosome. Mass determination can be used to answer crucial questions about biological assemblies. This is demonstrated by examples from muscle structure.

Amino Acids↗

Direct proof of autoreactive T-lymphocytes in experimental allergical encephalomyelitis (EAE).

A microcytotoxicity assay to prove directly against myelin basic protein directed cytotoxic T cells has been developed. Spleen and lymph node cells of myelin basic protein immunized strain 13 guinea pigs were restimulated in vitro with basic protein for 5 days and used as attacking cells. Autologous spleen cells were coated with about 10(7) molecules basic protein by hydrophobic attachment, labelled with 51Cr and used as targets. Concentration dependent lysis (74% corrected lysis) was measured with attackers gained 12 days post immunization. Controls performed using unspecific (PHA) stimulated attackers and non BE coated target showed no lysis. Lysis was shown to be MHC restricted. The test may serve as a tool for the assay of human demyelinating diseases.

Animals↗