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Biomedical subjects

R Becker

Publications and source records attributed to R Becker.

At least 181 records · Page 10Linked to original sources

Effects of Hoe 065, a compound structurally related to inhibitors of angiotensin converting enzyme, on acetylcholine metabolism in rat brain.

Hoe 065, a compound structurally related to inhibitors of angiotensin converting enzyme, caused a fall in the content of acetylcholine (ACh) in different brain areas of the rat following i.p. administration in the range 0.03-30 mg/kg. This effect occurred 0.5 h after a single injection and lasted for at least 6 h. Simultaneous administration of the choline uptake inhibitor hemicholinium-3 (HC-3) with Hoe 065 potentiated the decrease in ACh content induced by HC-3. In the same dose range Hoe 065 acutely enhanced the activity of the enzyme choline acetyltransferase as well as the capacity of the high-affinity choline uptake system which is considered as the rate-limiting step in the synthesis of ACh. Cholinesterase activity in vivo was not altered by the compound. Hoe 065 produced a concurrent elevation of brain cyclic GMP content. Taken together, these results suggest that Hoe 065 acutely increases cholinergic activity within its physiological range, probably by means of an enhanced release of ACh.

Acetylcholine↗

Radioimmunoscintigraphy of ovarian cancer with 131-iodine labeled OC-125 antibody fragments.

Radioimmunoscintigraphy (RIS) with 131I labeled OC-125 F(ab')2 monoclonal antibody fragments was prospectively studied in 43 women for primary diagnosis and follow up of ovarian cancer. Total body planar photoscans with a scintillation camera were performed one to seven days after antibody application and results were compared with operation and or CT examination. By the region of interest technique the tumor to non tumor tissue ratio (T/N) was calculated in vivo. Sensitivity in primary diagnosis was 100% (10/10), specificity 33% (1/3). For local recurrency, sensitivity was 86% (19/22), for metastatic loci 80% (17/21). Specificity was 75% and 50%. T/N ratio was in the rage from 1.3 to 2.8. Sensitivity for ovarian cancer is high in primary diagnosis and follow up. By the region of interest technique it is possible to detect small recurrencies and to presume peritoneal carcinosis. Antibody accumulations in diseases different from ovarian cancer however diminish specificity.

Adult↗

Differential effects of anti-arthritic agents on subnormal plasma iron levels in adjuvant arthritic rats.

Nonsteroidal anti-inflammatory drugs (NSAID's) and other antirheumatic compounds such as disease modifying antirheumatic drugs (DMARD's), immunosuppressives and glucocorticoids were tested to determine if daily medication for two weeks could elevate subnormal levels of plasma iron in adjuvant-arthritic (AA) rats. Aspirin, indomethacin, ibuprofen and phenylbutazone were chosen as representative carboxylic acids and pyrazole NSAID's. Although NSAID's at all doses significantly reduced noninjected paw swelling, no NSAID significantly enhanced subnormal plasma iron levels in AA rats. In contrast, the standard DMARD's auranofin and gold sodium thiomalate, as well as the glucocorticoid, dexamethasone and the immunosuppressives, methotrexate and cyclosporin-A all significantly restored plasma iron levels 28 to 100 percent. Plasma iron depression, a parameter of the acute phase response probably under regulation by pro-inflammatory cytokines, is not reversed by NSAID treatment. This appears to be a useful method for distinguishing NSAID's from other anti-arthritic compounds.

Animals↗

[Experiences with transcervical chorionic villi biopsy in 274 studies].

In the years 1985-1987, 274 transcervical chorionic villi biopsy samples were taken at the Klinikum Steglitz Medical Center of the Free University of Berlin. We have information on the outcome of 264 pregnancies (96.3%). 229 cases (83.6%) yielded diagnostically usable results. Multiple biopsy samples were taken in 59 (21.5%) cases. Abnormal results were found in 14 patients. Pregnancy was terminated in 6 cases (2.2%) for proven chromosomal aberrations. In two others, spontaneous abortion occurred before the intended induced abortion. In 4 cases of mosaics, amniocentesis was performed subsequently in the 16th week of pregnancy; three of those pregnancies were carried to full term, and the children are healthy. In one case, we saw a spontaneous abortion in the 26th week of pregnancy. In two cases, we found balanced translocations. Miscarriage was observed in 16 CVS patients (5.8%). Abortion was febrile in two cases, septic in two others.

Chorionic Villi Sampling↗

Predicting falls among patients in a rehabilitation hospital.

A retrospective case-control study within a cohort was carried out to identify factors associated with falling by patients in a rehabilitation hospital. The cohort comprised all patients admitted during a 2-year period from 1984 to 1986. Cases were those who fell one or more times during their hospitalization. For each case, one control matched on sex and date of admission, was chosen. Material from the first year of the cohort (201 cases and 201 controls) was used to define a model to estimate the risk of falling. Of the more than 100 variables considered in the conditional logistic regression models, stroke, incontinence, anticonvulsant medications, and topical eye preparations were significantly associated with the risk of falling. Analyses carried out on the second year of the cohort (155 cases and 155 controls) confirmed the predictive ability of these four variables. By combining the material from both subcohorts we were able to determine that a program to reduce falls directed towards stroke patients and incontinent patients alone could, theoretically, prevent 44% of first falls.

Accidental Falls↗

Destinations of stroke patients discharged from the Montreal area acute-care hospitals.

The destinations of stroke patients after discharge from acute-care hospitals were studied to ascertain the current use of health care resources. The 1984-1985 acute-care hospital discharge listings for the province of Quebec were consulted to identify 3,045 adults of the Montreal area who were discharged, deceased or alive, with a primary or secondary diagnosis of stroke. The relation between the length of stay (i.e., the time to death or discharge to long-term care, rehabilitation, or home) and the explanatory variables (age, sex, neighborhood socioeconomic status, type of stroke, and university affiliation of the discharging hospital) was assessed using Cox's proportional hazards models. Older patients and those with hemorrhagic strokes had the highest risk of death. However, patients with hemorrhagic strokes were more likely to survive if admitted to a university teaching hospital. Older patients, those with nonhemorrhagic strokes, and those admitted to university teaching hospitals were more likely to be discharged to long-term care. A greater proportion of patients discharged to rehabilitation centers were young, lived in a high-socioeconomic-status neighborhood, and had suffered a nonhemorrhagic stroke. Patients had a significantly higher probability of going home if they were young, had had a nonhemorrhagic stroke, had been admitted to a university teaching hospital, or were male.

Age Factors↗

Calibrated double split cast simulations for orthognathic surgery.

A cephalometric prediction tracing serves as a guideline for orthognathic surgery. Transfer of information from prediction tracings to cast simulation (model surgery) is part of treatment planning for surgical correction of dentofacial deformities. Articulated mounting with calibrated double split casts adds precision to the process and makes the final cast operation more effective. Systematic errors in the transfer of information are appraised critically.

Audiovisual Aids↗

Motor and functional recovery after stroke: accuracy of physical therapists' predictions.

The degree to which physical therapists correctly predicted motor and functional outcome for stroke patients was investigated. Therapists used an adapted form of the physical therapy portion of the Patient Evaluation Conference System (PECSc)--a 14-item assessment measured on an 8-point scale. At admission to a rehabilitation hospital, therapists performed initial assessments of seven motor and functional items on 204 patients and assigned goal scores; before discharge the patients were reevaluated and their final scores determined. The accuracy by which therapists correctly predicted the final score ranged from 53% to 67%; therapists were accurate to within one score for 80% to 83% of patients. The only determinant of accuracy was initial score; neither patient characteristics (age, side of lesion) nor staff experience were found to be associated with correctly predicting final score. Sensitivity and specificity of the goals for predicting independence were examined for three items: lying to sitting, ambulation, and stairs. The sensitivity of a goal of independence was high (96% to 100%), indicating that those patients who were independent at discharge were correctly identified by therapists at admission. The predictive value of a goal of dependence was also very high (91% to 100%), indicating that patients predicted to remain dependent did so. These results suggest that therapists' predictions could prove useful in screening patients for rehabilitation and in planning treatment strategies.

Aged↗

Present progress and future development in the therapy for Alzheimer's disease.

The following is a review of the present progress and future development in the experimental therapy of Alzheimer disease (AD). Four different approaches are considered, first a molecular genetic one, second neuropeptide delivery, third trophic factors administration and fourth a cholinergic approach. Advantages and disadvantages of presently applied therapeutical experiments are analyzed and discussed together with the author's own experience and results.

Alzheimer Disease↗

The inheritance of Alzheimer's disease: a new interpretation.

Ninety-one families of Alzheimer patients were studied to determine the proportion of familial cases, to obtain pedigrees for the analysis of the mode of inheritance, and to look for clinical differences between the familial and the nonfamilial cases. The diagnosis was confirmed by autopsy in 26 cases. Thirty-nine cases (43%) were familial, which is defined as more than one case in the family. Our interpretation of the pedigree data is that Alzheimer's disease is etiologically heterogeneous: it may be genetic or sporadic. In the familial type we think that the disease is inherited as an autosomal dominant, with a wide range of age of onset within a family. In one-third of these families the gene is not expressed until over age 70. No clinical differences were found between the familial and the sporadic groups.

Age Factors↗

Evidence for a distinct Ca2+ antagonist receptor for the novel benzothiazinone compound HOE 166.

The pharmacological and binding properties of the novel enantiomerically pure benzothiazinone (R)-(+)-3,4-dihydro-2-isopropyl-4-methyl-2-[2-[4-[4-[2-(3,4,5-tri- methoxyphenyl)-ethyl]-piperazinyl]-butoxyl-phenyl]-2H-1,4- benzothiazine-3-one dihydrochloride (HOE 166), are described. HOE 166 stereoselectively inhibited KCl-but not noradrenaline-induced contractions of guinea-pig pulmonary arteries, rabbit aorta, rat mesenteric artery preparations and k-strophantin-induced enhancement of guinea-pig papillary muscle contraction in a dose-dependent manner. KCl-induced smooth muscle contraction was inhibited by HOE 166 with IC50-values of approximately 70 nM (5-11 times less potent than nifedipine, 2-16 times more potent than verapamil), the respective S-(-)-enantiomer being approximately 10-fold less potent. HOE 166 decreased the upstroke velocity of the slow action potential in partially depolarized guinea-pig papillary muscle at similar concentrations than nifedipine. To investigate possible interactions with the calcium channel, HOE 166 and its S-(-)-enantiomer were characterized by radioligand binding studies in heart, brain and skeletal muscle transverse-tubule membranes. HOE 166 was a 4-15 times more potent inhibitor of reversible (+)-[3H]PN200-110, (-)-[3H]desmethoxyverapamil and d-cis [3H]diltiazem binding compared to its pharmacologically less active (S)-(-)-enantiomer, with IC50 values in the low nanomolar range. Extensive equilibrium and kinetic studies suggest that HOE 166 exerts its Ca2+-antagonistic effect by binding to a Ca2+-channel-associated drug receptor which is distinct from the 1,4-dihydropyridine, phenylalkylamine or benzothiazepine-selective domain. This HOE 166-selective site is, however, allosterically linked to the other sites of the Ca2+ antagonist receptor complex. We conclude that HOE 166 is a novel calcium antagonist.

Action Potentials↗

Semisynthetic human insulin: pharmacokinetics and biological potency in healthy subjects in comparison with highly purified porcine insulin.

Pharmacokinetics and the biological activity of a new semisynthetic human insulin (VEB Berlin-Chemie) were investigated in 5 healthy men. Following an overnight fast, 0.2 IU per kg body weight of human and pork insulins (SNC insulin; VEB Berlin-Chemie) were injected subcutaneously into thigh of each individual at a time interval of 8 days. To assess biological potency of both insulins all subjects were twice connected to the BIOSTATOR. A very similar pattern of serum insulin levels (IRI) was observed following subcutaneous injection of human and pork insulin, marked by a sharp initial increase and maximum values reached after 2.5 hours. 8 hours after the insulin administration the original fasting concentrations were nearly attained. According to C-peptide levels, both insulins inhibited endogenous insulin secretion. Evaluation of insulin action was determined by euglycemic clamp technique, provided by the BIOSTATOR, whose function was transformed into a glucose-controlled dextrose infusion system. The amount of glucose delivered by the system in order to keep the blood glucose steady state concentrations at the fasting level was utilized as the measure of biological activity of the injected insulin on glucose metabolism. Maximum values of glucose infusion were achieved between 3 and 4 hr after injection of human and pork insulins. At the end of the study (8 hr) the glucose administration did not return to its initial rate. After administration of both the human and porcine insulins, a marked but similar decrease of FFA concentrations was observed. This indicated a clear-cut inhibition of lipolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Potential pharmacotherapy of Alzheimer disease. A comparison of various forms of physostigmine administration.

This paper reviews clinical trials with physostigmine administered to Alzheimer patients using three different routes of administration: oral, i.v. and intracerebroventricular (i.c.v.). It compares results obtained with three different routes by the authors as well as by other authors. Particular emphasis is given to a novel type of physostigmine administration, the i.c.v. route. Advantages and disadvantages, as well as side effects of each route are presented and discussed.

Administration, Oral↗

Response time of stroke patients to a visual stimulus.

We used a computer program to test response time among stroke patients in a clinical setting. Visual stimuli were presented to 82 hospitalized stroke patients, to 21 hospitalized controls, and to 76 nonhospitalized controls. Stroke patients had longer mean response times than controls. Patients with right hemispheric lesions had longer response times than those with left hemispheric lesions when the stimuli were presented on the left. The corresponding phenomenon of longer response times in patients with left hemispheric lesions to stimuli presented on the right was not observed. Patients with right hemispheric lesions with visual hemineglect had a longer mean response time than those without visual hemineglect when the stimuli were presented on the left or centrally, whereas the patients with right hemispheric lesions without neglect had a mean response time similar to that of patients with left hemispheric lesions.

Cerebrovascular Disorders↗

MRI demonstrates descending transtentorial herniation.

Descending cerebral transtentorial herniation (DTH) is a serious and often fatal complication of intracranial mass lesions. The condition can be inferred from clinical neurologic signs, but has not been visualized during life. Using midsagittal magnetic resonance images (MRIs), we compared vertical brainstem position on 50 images from normals and 21 images from 15 clinically stable patients with large supratentorial tumors. The length of Twining's line (T), the perpendicular distance from T to the pontomesencephalic junction (T-PMJ), and from T to the apex of the midbrain aqueduct (T-A) were measured. We also measured lateral shifts of the diencephalon and midbrain on axial images. T-PMJ decreased from 2.04 +/- 0.06 mm in normals to 0.94 +/- 0.2 mm in patients with large cerebral tumors (p less than 0.0001). Similarly, T-A decreased from 6.35 +/- 0.13 mm in normals to 4.83 +/- 0.35 mm in patients (p = 0.001). Lateral diencephalic-midbrain shifts often accompanied DTH but to an unpredictable degree. Either lateral or downward brainstem shift could occur alone and did not necessarily produce specific neurologic signs or an altered state of consciousness. Anatomic DTH occurs in life, it can be quantified with MRI, and in slowly developing cerebral mass lesions the process can precede the appearance of neurologic signs and symptoms that indicate lower-diencephalic or midbrain dysfunction.

Brain Diseases↗

Nutritional evaluation of grain amaranth for growing chickens.

The nutritional value of raw and autoclaved grain amaranth, its milling fractions (perisperm and bran), fat-free flour, and of popped amaranth was evaluated for growing chickens. The control diet, which was composed primarily of corn and soybean meal, contained 3.06 kcal apparent ME (AME)/g and 23.6% CP. Test diets contained about the same AME and CP levels, and the following levels of the test samples: whole grain amaranth flour, 61.46%; fat-free flour, 62.10%; perisperm, 49.50%; bran, 35.30%; and popped amaranth, 61.10%. Two groups of six unsexed broiler chicks each, 2-day old when received, were used per diet. Chickens fed diets containing autoclaved grain amaranth or its fractions over 17 or 18 days grew as well as those fed the control diet. Feeding of popped amaranth resulted in poorer performance. On a dry matter basis, AME values of raw grain amaranth flour, fat-free flour, perisperm, bran, and popped amaranth were found to be 3.21, 3.09, 3.68, 3.06, and 2.98 kcal/g, respectively. Respective AME values for the first four autoclaved samples were 3.04, 2.94, 3.10, and 3.17 kcal/g. Autoclaved grain amaranth and its perisperm fraction replaced corn in the diets of growing chickens with similar performance results.

Animal Feed↗

[The tongue as a factor in craniofacial growth. 4. Results of animal experiments].

Post-natal craniofacial growth in the miniature pig MIN-LEWE is influenced by the tongue in various ways. Periodic and locally differentiated intensive craniofacial growth explains why the tongue has a measurable effect on jaw growth only at certain times. This is the situation in animals glossectomized at an age of 12 weeks. Shortening of the tongue in miniature pigs aged six weeks resulted in no measurable changes in the jaw after a prolonged post-surgical interval (23 weeks), which indicates that the capacity of the orofacial system during post-natal development is considerable.

Animals↗