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Biomedical subjects

D Lorke

Publications and source records attributed to D Lorke.

At least 19 recordsLinked to original sources

[The supinator fat line--its visualization and validity].

Based on 259 lateral x-ray films of the elbows of healthy subjects, the typical forms of the fat plane overlying the supinator muscle were determined. The forms of this plane in 121 patients who had suffered bony lesions in the elbow joint region were juxtaposed to these x-ray images. Measurements of the proximal distance between the fat plane and the extended tangent of the anterior humeral cortex layer revealed that distances of more than 13 mm in children and of more than 18 mm in adults are highly suspicious of a fracture. The good visualisation of the fat plane by means of various imaging methods is appropriately demonstrated.

Adipose Tissue↗

[The biomechanical significance of the periosteum for the epiphyseal groove].

In a study of 72 rabbits, four, eight, twelve and 16 weeks old, the mechanical resistance of the distal radius and ulna epiphyseal plate against shear strength has been examined. On one side the extremity has been freed of all soft-tissue attachments except the periosteum, on the other side the periosteum of the epiphyseal plate additional has been removed. The mechanical strength of the epiphyseal cartilage increases with age. A decrease of the resistance during sexual maturation has not been observed. In all age groups the stability of the epi-metaphyseal junction is significantly higher with the periosteum. In younger animals it is more marked than in older ones. The biomechanical behaviour of the periosteum can be explained with the principle of a "traction strap": the fibrous periosteum, firmly attached at the perichondrial ring, is stretched from epiphysis to epiphysis and fixes the epiphysis to the metaphysis. The periosteum and its continous tension takes not only part in regulating the longitudinal growth but also increases the resistance of the growth cartilage against shear strength. The dominated influence of the periosteum on the integrity of the epiphyseal cartilage is also supported by corresponding results dealing with the occurrence of Salter and Harris-type I or II fractures in absence or presence of the periosteum.

Age Factors↗

[Periosteal bone resorption in the area of the metaphysis of growing bone as a precursor of epiphyseal injuries. A polarization optical and scanning electron microscopy study].

Macerated epiphyses of the growing infant bone exhibit an irregular surface which can already be observed at the macroscopic level. Polarizing microscopy demonstrates extended zones of bone resorption on the cortical surface, deductable from numerous lacunae of Howship. Ensuing experimentally induced epiphysiolyses, cortical bone fragments adhering to the inner surface of the periosteum are demonstrable by scanning electron microscopy. Having been torn out of the bone together with the periosteum, these cortical fragments leave corresponding defects on the bone surface. Due to the remodelling of the bone, involving the readjustment of the shape of the extremity, the attachment of the periosteum is relatively poor in the metaphyseal region of the growing bone. The influence of pathological forces can therefore easily cause a detaching of the periosteum in this region. The latter results in a significant weakening of the epiphyseal fastening in the zone between the epiphyseal plate and the metaphysis. The patterns of injury in the region of the growth plate are therefore essentially determined by the varying attachment of the periosteum to the metaphysis.

Adolescent↗

The early appearance of fibronectin in the course of metastatic tumor growth in lymph nodes.

In order to study structural changes in the lymph node architecture in the course of metastatic involvement by carcinoma, 70 axillary lymph nodes of 45 female patients affected by breast carcinoma were examined. The following growth pattern of the metastasis was observed: (1) Involvement of vasa afferentia and (marginal) sinuses; (2) lysis of sinus wall and infiltration, causing replacement and lysis of reticulin fibres; (3) appearance of fibrillary fibronectin (FN) as the first noticeable sign of tumor stroma; (4) immigration of fibroblasts along these fibres, appearance of argyrophilic fibres codistributed with fibrillary FN; (5) formation of the complete tumor stroma, neovessels included. The appearance of FN is thus the first step of stroma formation and is interpreted as an "in situ" precipitation of soluble plasma FN.

Adenocarcinoma, Mucinous↗

A new approach to practical acute toxicity testing.

A method for the investigation of the acute toxicity of an unknown chemical substance, with an estimation on the LD50, is described. Using this, it is possible to obtain with 13 experimental animals adequate information on the acute toxicity and on the LD50. This method has no limitations and applies to drugs, agricultural and industrial chemicals. It can be used for every route of administration.

Animals↗

The effect of cyclohexylamine on the embryo following oral administration to mice and rats.

The possible embryotoxic effects of cyclohexylamine hydrochloride doses (expressed as free base) of 10, 30 and 100 mg/kg of body weight per day administered orally in water to mice and rats from the 6th to 15th day post-coitum were investigated. Treatment with daily doses of up to 100 mg/kg of body weight to mice and of up to 30 mg/kg to rats had no adverse effect on the mothers and the embryos. In the rat the dose of 100 mg/kg led to decreased weight gain in the mothers during the treatment period. In parallel, a non-specific retardation of the embryo was found, since the weight of the foetus and of the placenta were significantly reduced. Cyclohexylamine had neither a teratogenic effect nor a primary toxic effect on the embryo in either of the animal species. The tolerated dose without any harm for the development of the embryo was 100 mg/kg/day in mice and 30 mg/kg/day in rats.

Administration, Oral↗

Quantitative aspects of chemical carcinogenesis and tumor promotion in liver.

Chronic exposure of rodents to high dose levels of drugs, food additives and environmental chemicals frequently results in liver enlargement. Several of these compounds have been found to enhance the incidence of liver tumors in animals briefly exposed previously to hepatocarcinogens. Accordingly, it has been advanced that these agents act as tumor promoters. This contention has remained subject of controversy following reports that these substances may also cause liver tumors in noncarcinogen-treated rodents, particularly in those characterized by a relatively high incidence of "spontaneous" liver tumors. Since many of these chemicals are in common use, a crucial question would seem to be whether such effects are due to facilitation of the expression of pre-existing oncogenic potential, i.e., to tumor promotion, or to the synergistic action of weakly carcinogenic agents. As a result of mechanistic differences tumor promotion and syn-carcinogenesis must exhibit different dose-time-response characteristics, and, accordingly, it should be possible, in principle, to discriminate between these phenomena. However, since tumor manifestation periods in low-dose groups frequently exceed the animals average lifespan, this approach may not always yield conclusive data, unless a sensitive early marker of carcinogenic activity can be employed. There is evidence that enzyme-deficient preneoplastic areas in liver can be used for this purpose. A strong quantitative correlation between carcinogen dose, the extent of ATPase deficient areas, and the subsequent appearance of tumors has now been established for a number of hepatocarcinogens. Experimental data are consistent with the concept that two critical events (hits) are required for induction of ATPase deficiency in hepatocytes. The first hit is carcinogen-dependent, whereas the second hit would seem to be due to time-dependent event(s). Tumor-promoters, such as phenobarbital, were found to accelerate and increase formation of preneoplastic islets. This evidence, together with data indicating that the compound is devoid of carcinogenic potential, suggests that phenobarbital may be operative at relatively early stages of hepatocarcinogenesis by increasing the probability of the occurrence of the time-dependent second hit. Such effects are dose-dependent and appear to be related to the induction of liver enlargement. The changes in hepatocellular ploidy status and atypical nuclear figures observed during phenobarbital treatment and cessation thereof, suggest that this compound might induce abnormal redistributions of genetic material. It is postulated that these cytological changes may result in phenotypical manifestation of recessive oncogenic information.

Adenosine Triphosphatases↗

Mutagenicity studies with praziquantel, a new anthelmintic drug, in mammalian systems.

Praziquantel, a new anthelmintic drug with antischistosomal and anticestodal properties, was tested in comparison with a placebo control and a 'positive control' with cyclophosphamide in mammalian test system in vivo for potential mutagenic effects. The test systems used and the tested doses of Praziquantel were: (1) Dominant lethal test on male NMRI mice, 12 mating periods of 4 days each, 1 X 1200 mg/kg BW by mouth; (2) Dominant lethal test on female NMRI mice, treatment during pre-estrus, 1 X 1200 mg/kg BW by mouth; (3) Micronucleus test on male and female NMRI mice, two doses with a 24-h interval and preparation of the femoral marrow 6 h after the second dose, 2 X 300 mg/kg and 2 X 600 mg/kg BW by mouth; (4) Spermatogonial test on the Chinese hamster, two doses with a 24-h interval and preparation of the spermatogonia 48 h after the second dose, 2 X 600 mg/kg BW by mouth. The 1200 mg/kg BW dose corresponded to approximately 1/2 of the LD50 after oral application in the mouse and about 40 times the therapeutic dose (1 X 30 mg/kg BW). The cyclophosphamide doses in the test systems were 1 X 200 mg/kg or 2 X 200 mg/kg BW by mouth. No indication was found of any mutagenic potency of Praziquantel. This agrees with the results of point-mutation tests done by other authors.

Animals↗

Mutagenicity testing in industry.

The aims of authorities, university and industrial scientists are outlined. The prime feature remains: How important are the achieved results for estimating the mutagenic risk to humans? The various methods available for the testing of chemical substances for mutagenicity are compared. Their usefulness to estimate the mutagenic risk are considered and the disadvantages and advantages of such methods are discussed. The industrial toxicologist must apply those methods which permit the most accurate conclusions to be made. Further, the toxicologist has to develop new methods which, based on his own experience are more suitable for making more accurate statements. The results of methods carried out on the germ cell of living mammals permit more accurate statements to be made than investigations on isolated cell cultures and somatic cells. Thus, the dominant lethal test on male and female mice and the spermatogenial test on Chinese hamsters are considered suitable methods for estimating the possible dangers to man.

Animals↗

Semichronic oral toxicity of cadmium. I. Studies on rats.

Cadmium (in the form of CdCl2) was fed to groups of 20 male and 20 female rats each over a period of 3 months in concentrations of 0, 1, 3, 10 and 30 ppm. Appearance, behaviour, food consumption, growth and mortality of the treated rats of all groups were not affected during the 3-month period. The cadmium concentrations did not cause blood, liver or kidney damage. The systolic blood pressure of the treated animals was not increased. Autopsies and histopathological investigation of the animals showed no sign of any alterations. Cadmium accumulated dose-dependently in the kerated by rats over a period of 3 months without harm.

Animals↗

Semichronic oral toxicity of cadmium. 2. Studies on dogs.

Cadmium in the form of CdCl2 was administered with the feed in concentrations of 0, 1, 3, 10 and 30 ppm over a period of 3 months to groups of 2 male and 2 female beagle dogs each. The appearance, behaviour food consumption, growth and mortality of the treated dogs in all groups was not affected. In the groups up to 30 ppm cadmium caused no detectable harm to blood, liver or kidneys. The systolic and diastolic blood pressure of the treated animals of all groups up to 30 ppm was within the normal range. The autopsies and histopathological investigations revealed no evidence of any damage. Cadmium accumulated dose-dependently above all in the kidneys and liver. The dogs tolerated concentrations of up to 30 ppm cadmium in their feed over a period of 3 months without harm.

Animals↗

Evaluation of the mutagenic potential of cyclohexylamine on spermatogonia of the Chinese hamster.

In a cytogenetic study on the spermatogonia of Chinese hamster, cyclohexylamine (neutral sulphate) was evaluated for mutagenic effects in comparison with an untreated control group and a group treated with the mutagenic compound cyclophosphamide, by assessing spermatogonial metaphases of treated Chinese hamster for chromosomal structural changes. Each test group comprised 8 male hamsters selected at random. Approximately 100 metaphases from each animal were assessed. The doses were 5 X 150 mg cyclohexylamine sulphate (approx. 5 X 102 mg base) per kg body-weight orally, and 5 X 100 mg cyclophosphamide per kg body-weight orally. The individual doses were administered at intervals of 24 h. Preparations were made 24 h after the final treatment, essentially by the method of Hoo and Bowles [10]. Gaps, breaks, fragments, deletions and translocations were assessed as structural changes; frequencies were determined of the metaphases (a) with aberration(s) including gaps, (b)with aberration(s) less gaps and (c)with translocation(s). Aberrations occurred in the untreated negative control group (1.24% incl. gaps, 0.25% without gaps). Translocations were not seen in the untreated group. In the cyclochexylamine group, the frequencies of the aberrant metaphases were sometimes less than in the control group (0.87% including gaps, 0.37% without gaps). Statistically, the results were not significantly different from the control data. No translocations were seen after administration of cyclohexylamine. The positive cyclophosphamide control group clearly differed from the untreated control and from the cyclohexylamine group in the parameters (a) to (c); mainly, the results were highly significantly different from those obtained in the untreated control group. The frequencies of the aberrant metaphases were 3.41% including gaps and 1.99% without gaps. The frequency of the translocations was 0.71% (5 out of 704). Cyclohexylamine sulphate, administered 5 times at 150 mg/kg body-weight orally, had no mutagenic effect, whereas cyclophosphamide, adminstered 5 times at 100 mg/kg body-weight orally, had a chromosome-damaging effect on Chinese hamster spermatogonia.

Animals↗