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Biomedical subjects

R Koch

Publications and source records attributed to R Koch.

At least 199 records · Page 11Linked to original sources

DNA haplotype analyses of patients with hyperphenylalaninemia.

Linkage analysis of phenylketonurics has shown a strong association between the DNA haplotype at the phenylalanine hydroxylase (PAH) locus and phenylketonuria (PKU). Similarly, a genetic linkage between less severe forms of hyperphenylalaninemia (HPA) and the PAH locus has been suggested. In the present study we analyzed this linkage in more detail. Haplotypes at the PAH locus were determined for 19 individuals with moderately elevated plasma phenylalanine and normal urinary neopterin/biopterin ratios. Fourteen of these individuals had plasma phenylalanine levels of 4-10 mg/dl (mild HPA), and the other five had plasma phenylalanine levels of 10-19 mg/dl (atypical PKU). Thirteen of the 15 HPA families consisted of an affected child and at least one other sibling. Elevated plasma phenylalanine was seen to genetically segregate with specific PAH alleles in each family. Summation of the LOD scores for both categories of moderate plasma phenylalanine elevation gave a maximum value of 3.556 at theta = 0. At theta = 0 this gives a probability of linkage between the PAH locus and the locus for moderate phenylalanine elevations that is approximately 3,600:1. None of the alleles segregating with either mild HPA or atypical PKU were of haplotype 2 or 3, and 13/20 were of types 1 or 4. This is in agreement with the most deleterious mutations being on haplotypes 2 and 3 and with the less severe mutations being on haplotypes 1 and 4. chi 2 Analyses indicated no statistically significant correlation between HPA and a particular haplotype or restriction-enzyme site.

Alleles↗

[Results of treatment of malignant melanoma--a computer analysis of 772 patients].

The data of 772 patients with malignant melanoma, treated from 1.1.1972 to 30.6.1988 in the Regional Hospital Dresden-Friedrichstadt were analysed by computer. The probability of survival was estimated separately by the method of Kaplan and Meier in dependence on clinical stage in the time of the first treatment, pT and sex. The 10-year survival rate in clinical stage I amounts to pT1 = 100%; pT2 = 82.9% +/- 4.0%; pT3 = 67.1 +/- 4.3% and pT4 = 58.0 +/- 4.7%. There are significantly differences between women and men with melanomas of the category pT2 and pT3 in favour of women (pT2: 88.6%:70.0%; pT3: 75.8%: 53.4%). In the cases of pT4 melanoma there are no differences (61%:53%). The average time of survival from these patients who have died from melanoma shows also marked differences according to pT (pT2 = 46.6 month, pT3 = 36.6 month, pT4 = 30.2 month).

Female↗

[Type A behavior--a uniform construct?].

Single dimensions of the Type-A-behaviour pattern and their contributions to the etiology and pathogenesis of cardiovascular and psychosomatic diseases are very often discussed. Our studies are concerned with the analysis of 40 blue collar workers and patients (40 patients with hyperuricemia, 36 psychotherapy patients) in definite groups of age. By item analysis and multivariate statistical procedures (variance, factor and discriminant analysis) we found an overlapping effect of psychosocial factors of work and on the other hand the influence of neurotic symptoms and behaviour patterns.

Adult↗

[Patterns of psychosocial stress factors and health criteria].

Derived from the principles of capacity and of need's realization in the load-strain-coping-concept a 5-cluster result with parameters of subjective health and psychosocial factors is demonstrated. These patterns reflect the different connections between health and the person-environment interaction. A high subjective professional load is connected with a poor health state only in a low professional performance and/or deficits of need's realization.

Adaptation, Psychological↗

[Comparative analysis of narcosis and local anesthesia in surgery of malignant melanoma of the skin].

A nonrandomized trial was performed to compare the survival rate attained in patients with malignant melanoma who underwent their operations under general anaesthesia (g.a.) and in those who underwent surgery with only local anaesthesia (l.a.). All stage I patients were treated and followed up in our hospital exclusively. Data recorded in 190 patients operated on under g.a. from 1972 to 1980 and 376 patients operated on with l.a. from 1981 to 1987 were evaluated by computer. The 5-year survival rates calculated by the Kaplan-Meier method were as follows: Breslow's thickness up to 1.50 mm (pT1 and pT2): g.a. 91.4% l.a. 94.5%; 1.51-3.00 mm (pT3a) g.a. 64.1%, l.a. 84.5% (P less than 0.01); over 3.00 mm (pT3b and pT4) g.a. 57.9%, l.a. 62.2% (P greater than 0.05). Women with pT3a melanoma had more benefit from the operation in l.a. (93.1% to 69.7%) than did men (71.6% to 55.2%). The l.a. does not prejudice the prognosis, whether the l.a. improves the prognosis has to be stated. The available evidence that anaesthetic agents influence host defence could be an explanation for the better results with l.a.

Anesthesia, General↗

Clinical trial of 'off diet' older phenylketonurics with a new phenylalanine-free product.

Ten PKU subjects were treated with Product 196 for one year. Product 196 is a special phenylalanine-free dietary supplement consisting primarily of essential amino acids, carbohydrate, Vitamin C and some minerals, made by Scientific Hospital Supplies Limited, Liverpool, England. It is intended for persons with phenylketonuria who are not consuming a phenylalanine-restricted diet. During the year that the 10 subjects were on the product, they remained asymptomatic, maintained their weight and appeared healthy. Subjective behavioural improvement was noted in six but no significant changes in intelligence were noted.

Adolescent↗

Memantine inhibits serotonin-induced rise of cytosolic Ca2+ activity and of cyclic GMP level in a neuronal cell line.

Serotonin (5-HT) evoked a rise of cytosolic Ca2+ activity in neuroblastoma X glioma hybrid cells, most probably due to the entry of extracellular Ca2+; cyclic GMP synthesis was also stimulated. The rise of both cytosolic Ca2+ activity and of cyclic GMP level was blocked by memantine (1-amino-3,5-dimethyladamantane). Memantine inhibited the rise of the cyclic GMP level non-competitively (Ki about 50 microM). Thus, memantine suppresses the effects of 5-HT in the neuronal cell line, most likely by blocking Ca2+-permeable ion channels. This interpretation is in line with the previously reported finding that memantine suppressed the 5-HT-induced depolarizing response in the same cell line.

Amantadine↗

The Zurich Study. VII. Insomnia: symptoms, classification and prevalence.

This study describes sleep behaviour and insomnia in a representative cohort of a Swiss population. Interviews were carried out prospectively from age 20-21 to 27-28 years, starting with 292 males and 299 females. Females usually go to bed earlier and sleep 30 min longer than males. Taking into account length and periodicity of insomnia we can distinguish occasional insomnia (OI), repeated brief insomnia (RBI), and continued insomnia (CI), defined by operational criteria. The prevalence of sleep problems is stable from age 21-28, at 36%-40%. CI (prevalence 8%-10%) and RBI (13%-19%) are both medical problems in terms of treatment by professionals (10%-17%) or self-medication (7%-12%). The majority of insomniacs cope with sleep problems in various other ways. Frequency and patterns of symptoms of insomnia are described.

Adult↗

Experimental radiofrequency (RF) coagulation with computer-based on line monitoring of temperature and power.

The safety and reliability of radiofrequency coagulative techniques are questioned after each coagulation, especially in functional neurosurgery. In spite of the high level of technical development of modern surgical RF generators there is still uncertainty about the character of the coagulative lesion. For the present study, a 500 kHz RF generator was connected through a module for analog/digital conversion and for regulation to a personal computer provided with a software programme for the graphic display in real time of the RF power and of the temperature/time curves. The effects of thermocoagulation were studied in fresh egg white, and monopolar lesions were made in the subcortical white matter of rabbits with a probe with a 0.5 mm diameter and a bare tip of 3 mm in length. The regularity of thermocoagulation depends on the accurate temperature reading at the tip of the electrode. The ideal course of the temperature is a smoothly ascending curve from the level of 37 degrees C to the level present for coagulation, followed by a straight horizontal line. With too slow a response of the probe to temperature changes there is an inherent danger of overheating in the initial phase of the procedure. Additionally the power level has to be adjusted for each probe. On line monitoring with graphic display of the physical parameters provides a direct control of the course of the coagulation. Regular curves of the physical parameters without temperature overshoot correspond to reproducible lesions in vitro and in vivo.

Animals↗

Cryopreservation of human and rabbit oocytes and one-cell embryos: a comparison of DMSO and propanediol.

The aim of this study was to improve the cryopreservation of human oocytes and pronuclear embryos. One-step and multiple-step addition of dimethyl sulphoxide (DMSO) and 1,2-propanediol (PROH) and three different freezing protocols with intermediate temperatures of -35, -70 and -110 degrees C were investigated. This work was performed using rabbit oocytes as well as human oocytes and one-cell embryos from the routine IVF programme. Also, human polyploid pronucleate oocytes were used in controlled prospective studies of morphological intactness and development in vitro. Rabbit oocytes survived best (113/126) when PROH was added in one step and controlled freezing stopped at -110 degrees C. But the development was better (141/187) if DMSO was added in multiple steps and the oocytes were cooled to -70 degrees C before being plunged into liquid nitrogen. The mode of addition of the cryoprotectant influenced development only if slow freezing was stopped at -35 degrees C (51 versus 34%). Using PROH, the development after thawing was also better if cooling was stopped at -35 degrees C (51 versus 37%) and DMSO was superior to PROH when the oocytes were cooled slowly to -110 degrees C (66 versus 37%). In the human, significantly more pronucleated than unfertilized oocytes developed after freezing (92 versus 50%). The best results were achieved with pronuclear embryos using 1.5 M PROH and cooling to -110 degrees C, when 91.7% of the surviving oocytes developed further. This is a marked improvement of the development rate and comparable to embryo freezing.

Animals↗

Comparative results on survival of human and animal eggs using different cryoprotectants and freeze-thawing regimens. I. Mouse and hamster.

The achievement of successful pregnancies and births after in-vitro fertilization and embryo transfer of frozen-thawed human oocytes has stimulated further work on improving the established methodology. The present investigation was conducted on 1837 mouse oocytes, 1785 mouse pronuclear stage embryos, 1400 hamster oocytes and 1024 hamster pronuclear-stage embryos. In an effort to study the advantages and disadvantages of a newly introduced, 1,2-propanediol (1,2-PROH)-based system over the conventionally used dimethylsulphoxide (DMSO)-based methodology, a direct, prospective comparison between the two cryoprotectants was undertaken in a randomized trial. The combination of 1,2-PROH and DMSO potentiates their cryoprotective effect on mouse and hamster eggs. 1,2-PROH seems to improve cryopreservation in the animal system, though not significantly. Four different protocols were used to evaluate the effects of two changing experimental parameters. These were, firstly, the intermediary temperature attained before placing the cells into liquid nitrogen and, secondly, the modification of the method of adding and removing the cryoprotectant. The morphological survival rate, fertilization rate and developmental rate were significantly better in the low intermediary temperature compared with the high intermediary temperature system of cryopreservation. In addition, the rate of zona pellucida breakdown diminishes considerably in the former compared with the latter system. The 'rapid' sucrose method of cryoprotectant equilibrium and removal showed, in most groups, results which were lower than, or equal to, the traditionally used 'multiple-step', 'slow' method.

Animals↗

Comparative results on survival of human and animal eggs using different cryoprotectants and freeze-thawing regimens. II. Human.

A total of 269 human pronuclear embryos and 84 oocytes were subjected to four different protocols of cryoprotectant equilibration, washing out and freeze-thawing. The morphological survival, rate of development, fertilization in vitro and overall survival rate were estimated in the groups of fresh, aged oocytes, diploid and multipronuclear embryos used. With some restrictions, the conclusion can be drawn that slow, low intermediary temperature 1,2-propanediol (1,2-PROH) and 1,2-PROH/dimethyl sulphoxide (DMSO) systems are superior to the rapid, high intermediary temperature 1,2-PROH and the traditionally used DMSO systems. The best success rates were reached with the combination of cryoprotectants in the low intermediary temperature group. Thirty-three patients had 37 transfers of cryopreserved pronuclear embryos (n = 103), resulting in eight pregnancies (24.2% per transfer) thus doubling the pregnancy rate in the stimulation cycles for the same period (21% per transfer). Thawing at a rate of 50 degrees C/min is not incompatible with the survival of slowly frozen human oocytes and pronuclear embryos cooled to an intermediary temperature of -70 degrees C using the DMSO system.

Cell Survival↗

School achievement in treated PKU children.

Phenylketonuric children who were treated early and maintained a pherestricted diet through age 10 were compared with those who discontinued the diet after age 6 on a standardized test of intelligence, school achievement, language and perceptual skills. Mean IQ, reading and spelling test scores improved between ages 6 and 10 for the on-diet children in comparison to those who were off-diet. However, mean scores on arithmetic, language and perceptual skills declined at a uniform rate for both groups. Children with PKU scored significantly lower than did their non-PKU siblings on tests of visual perception and visual-motor skills. Because the school years, particularly, the early teens, pose increased stress in affected PKU individuals, it is recommended that dietary restriction at least through the high school years is prudent for their optimal physical, mental, emotional and educational growth.

Achievement↗

Regulation of prolactin synthesis in vitro by estrogenic and antiestrogenic derivatives of estradiol and estrone.

The estrogenic and antiestrogenic activities of derivatives of estradiol and estrone were determined in vitro using the ability of primary cultures of immature rat pituitary cells to synthesize PRL. Estradiol derivatives were the most potent estrogens in the assay. Large ethinyl substitutions in the 17 alpha position generally caused a decrease in estrogenic potency (up to 1000-fold). The 3 phenolic hydroxyl was important, but not essential, for the estrogenic activity of the estradiol molecule. Estratriene was approximately 1000 times less potent than estradiol. However, significant estrogenic activity was observed with the compound anordin (EC50, 8 x 10(-9) M), which could potentially be converted to a dihydroxylated derivative but without an aromatic A ring. Similarly, the steroid androst-5-ene-3,17-diol was weakly estrogenic (EC50, 3 x 10(-8) M). Steriods with a ketone in the A and D rings were generally inactive as estrogens and antiestrogens. Estradiol derivatives with 17 beta amines were only weak estrogens. Estrone derivatives were less active than the corresponding estradiol derivatives. 4-Nitromethoxyestrone exhibited weak antiestrogenic properties; however, 4-nitroestrone and methoxyestrone were both estrogens. The reason for the antiestrogenic properties of 4-nitromethoxyestrone is obscure, as the compound does not have structural features similar to those of known nonsteroidal antiestrogens. Minor alterations to the estradiol molecule at the 11 beta (OH) or 6 (ketone) position had little effect on estrogenic potency; however, large substitutions at the 11 beta (RU 39,411) or 7 alpha (ICI 164384) position produced antiestrogenic compounds. RU 39,411 was approximately 10 times more active as an antiestrogen than 4-hydroxytamoxifen, whereas ICI 164,384 was approximately 10 times less active than 4-hydroxytamoxifen. A series of hypothetical models is proposed that could explain the antiestrogenic properties of RU 39,411 and ICI 164,384 by an interaction with the estrogen receptor steroid-binding site.

Animals↗

[Occupational disability among teachers and its relation to subjective health status and professional performance].

The aim of this study was to examine the relationship between absenteeism and functional health state, action competence, realization of professional goals and essential needs as well as subjective strain in job and family and type A behaviour pattern. The results of discriminant analyses from a sample of 774 teachers (group 1; no sickness leave days, group 2: sickness leave days greater than 28) are discussed.

Absenteeism↗

[The effect of formalin fixation on several properties of the brain].

Described in this paper are the effects on formalin fixation of 106 human brains autopsied at a large neuropsychiatric hospital. Mass and volume of the brains changed considerably during a 3-week fixation period. On average mass increased by 50 g, volume by 57 ml. Mean brain density decreased during the first week and attained its final value almost at the end of the third week. Most changes seem to happen during the first week. Male and female brains behaved differently. Formulas to predict at autopsy time mass and volume of the brain after 3-week fixation in formalin are presented. Possible interpretations of our findings are discussed and compared with results reported by previous workers on this subject.

Adolescent↗

Nonphenylketonuric hyperphenylalaninemia.

Sixteen subjects with nonphenylketonuric hyperphenylalaninemia were followed up during a period of years. Dietary treatment did not seem to influence the outcome, and no relationship between blood phenylalanine and intellectual outcome was demonstrable.

Adolescent↗