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[Selective local hyperthermy of tumor tissue. Homogenized energy supply also to deep-seated tissues by high-performance decametric wave coil section plus dual system raster motion (author's transl)].

Based on results of selective tumor tissue hyperacidification and whole-body hyperthermy the paper deals with the advantages of local hyperthermy and gives a review of the various methods of energy supply for hyperthermy in living tissue. It follows a presentation of physical and biophysical fundamentals on selective local hyperthermy of tumor tissue by radiation, by r. f. rotational magnetic fields and by r. f. capacitor fields. Using a gelatine phantom for measuring the energy supply with the various modes of local hyperthermy it is then shown that it is solely the divergent rotational magnetic field which allows to substantially reduce the inhomogeneity of energy supply also in z-direction (increasing depth in body tissue) by introducing a relative raster motion of the applicator in x-y-direction (plane parallel to body surface). It is only the introduction of the x-y raster principle combined with a described dual system array (CMT Selectotherm System) which permits the high and rather homogeneous supply of thermal energy also to deep-seated tumor tissue in the patient without concomitant critical superheating of tissues near the skin. Finally the paper gives a theoretical derivation of the temperature profile for selective local hyperthermy of tumor tissue. With due consideration of heat dissipation by convection and conduction, this endeavour shows rather promising aspects for the therapeutic efficiency obtainable in each case of treatment.

Animals

Chemosurgery for skin cancer: fixed tissue and fresh tissue techniques.

Complete microscopical control of the excision of cancer of the skin is achieved by removing tissues layer by layer and examining the undersurface of each layer by means of frozen sections. If the cancer is extensive and complicated or if it is of a type readily spread over an excisional surface, the tissues are fixed in situ with zinc chloride prior to excision (chemosurgery, fixed tissue technique). If the cancer is not too extensive or complicated, the tissues are excised in the fresh, unfixed state (chemosurgery, fresh tissue technique). Both techniques are highly reliable; for example, in two consecutive series of basal cell carcinomas treated chemosurgically, the five-year rate of cure was 99.3% for the 9,351 lesions removed by the fixed tissue technique and 97% for the 127 lesions removed by the fresh tissue technique.

Biopsy

[Studies on the number of fat cells and connective tissue cells in white adipose tissue in chronic starvation and after refeeding. II. Investigations on obese and lean C 57 BL/6 J-mice (author's transl)].

UNLABELLED: Former investigations (Rakow et al., 1970, 1971a, b 1974) have demonstrated a constancy of the adipocyte number in white adipose tissue (parepididymal fat pads) of lean NMRI-albino-mice and aurothioglucose-obese NMRI-albino-mice during starvation and subsequent refeeding. In contrast the number of cells of connective tissue showed great variations under the experimental conditions mentioned above. The present paper describes which changes of the different cell populations within the adipose tissue could be demonstrated in lean and obese C57BL/6 J-mice. MATERIAL AND METHODS: The investigations were performed with obese and lean male C57BL/6 J-mice. The control animal groups were fed for six weeks 2.5 g (lean mice) and 2 g (obese mice), respectively, Altromin 1115R daily (starvation phase). After this time some of these animalwere killed (exp. groups H). The remaining animals now were fed Altromin 1115R and additional oat falkes ad libitum. Three (exp. groups HW3) and seven (exp. groups HW 7) days, respectively, after the beginning of the refeeding phase the animals were killed. After sacrifice the epididymal fat pads were weighed and treated with either (fat extraction). The dry mass was hydrolized with PCA (0.5 m, 90 degrees C, 40 min). In the supernatant the DNA (Burton, 1956), RNA (Ceriotti, 1955) and polysaccharide content (Seifter et al., 1950) were measured. The sediment was hydrolized with NaOH (0.5 n, 37 degrees C, 24 hrs). In this solution the protein content (Lowry et al., 1951) was determined. In addition fat cells were isolated according to Rodbell (1964). The fat cell diameters were determined microscopically and the average masses of the fat cells were estimated. From the wet weight of the fat pads and the average fat cell mass and number of fat cells were calculated. The remaining suspension of fat cells and cells of connective tissue were utilized for cell smears. These cell smears were stained with Schiff's reagent (Feulgen et al., 1924; Graumann, 1953). With an integrating microdensitometer (Deeley, 1955) the average relative DNA-content of single cell nuclei was measured and the ploidy patterns were estimated. The DNA-content was measured chemically according to Burton (1956). From the whole DNA-content of the fat pads and the DNA-content of the fat cell population the number of cells of the connective tissue was calculated...

Adipose Tissue

Effect of arrhythmogenic doses of deslanoside on the uptake of monoamines in brain tissue and in cardiac tissue.

The purpose of our study was to determine whether a toxic arrhythmogenic dose of digitalis administered to an in vivo preparation would affect the neuronal uptake of norepinephrine, serotonin and dopamine in brain tissue and norepinephrine in cardiac tissue. This was investigated by intoxicating anesthetized cats with deslanoside, removing cardiac and brain tissue at the onset of ventricular fibrillation, and examining the ability of brain tissue to accumulate [3H]-NE, [3H]-T-HT and [3H]-DA and cardiac tissue to accumulate [3H]-NE. It was found that deslanoside inhibited uptake of [3H]-NE into the left ventricle and [3H]5-HT into the area postrema. These selective effects may reflect greater blood flow to these regions or different sensitivities of the transport mechanisms for these amines. This inhibition of uptake into both left ventricular tissue and area postrema may contribute to some of the cardiovascular and emetic effects seen with digitalis drugs.

Animals

Effects of dietary calcium on blood and tissue lipids, tissue phospholipids, calcium and magnesium levels in rabbits fed diets containing beef tallow.

Levels of lipids, calcium and magnesium in blood and tissue were examined in rabbits to determine the effects of 20% beef tallow diets containing three levels of calcium, less than 0.02, 0.8 or 1.6%. In plasma, the calcium-deficient (less than 0.02%) diet contributed to elevated cholesterol and phospholipid, but had no effect on triglyceride levels. Plasma calcium decreased in the calcium-deficient group and plasma magnesium decreased in the high-calcium (1.6%) group of rabbits. Lipid levels of some tissues varied with the level of dietary calcium. Cholesterol, total phospholipid, sphingomyelin and phosphatidylethanolamine were generally elevated in livers of calcium-deficient rabbits, but the individual phospholipids were decreased in skeletal muscle. Lungs of the calcium-deficient group also had lower phospholipid levels than the high-calcium group. Liver, kidneys, brain and adipose tissue triglyceride levels were highest in the high-calcium group. The calcium level of skeletal muscle was lower in the calcium-deficient group than in the high-calcium group. Calcium in brain and adipose tissue were highest in the calcium-deficient group. Except for adipose tissue, magnesium levels of the tissues studied were not affected by dietary calcium.

Animals

Uptake of (3H)progesterone and (3H)5alpha-dihydroprogesterone by rat tissues in vivo and analysis of accumulated radioactivity: accumulation of 5alpha-dihydroprogesterone by pituitary and hypothalamic tissues.

These in vivo studies explored the possibility that the metabolism of progesterone to 5alpha-dihydroprogesterone (5alpha-DHP) and 3alpha-hydroxy-5alpha-pregnan-20-one in hypothalamus and pituitary may influence gonadotropin release. [3H]progesterone or [3H]5alpha-DHP was injected iv into ovariectomized or ovariectomized-adrenalectomized rats for 10 0r 30 min. 3H content was determined for plasma, anterior pituitary, medial basal hypothalamus (MBH), cerebral cortex, muscle and uterus. Isotopic dilution analyses of the accumulated 3H were made for progesterone, 5alpha-DHP, 3alpha-hydroxy-5alpha-pregnan-20-one, 20alpha-dihydroprogesterone, 20alpha-hydroxy-5alpha-pregnan-3-one, and 5alpha-pregnane-3alpha, 20alpha-diol on samples from the 10 min groups. With progesterone injections, most of the tissue 3H was distributed among progesterone, 5alpha-DHP, and 3alpha-hydroxy-5alpha-pregnan-20-one. Progesterone was the predominant 3H-steroid in uterus, MBH, cerebral cortex and muscle. [3H]5alpha-DHP was the other major 3H-steroid in MBH and the predominant one in pituitary. In terms of tissue/plasma concentration comparisons, no tissue concentration of [3H]progesterone was greater than that in plasma except for MBH in the ovariectomized-adrenalectomized group. In contrast, [3H]5alpha-DHP levels in pituitary, MBH and cerebral cortex were many fold greater than those in plasma and muscle. MBH and pituitary levels were significantly greater than that in cerebral cortex. With 5alpha-DHP injections, most tissue 3H was associated with 5alpha-DHP and/or 3alpha-hydroxy-5alpha-pregnan-20-one. No [3H]progesterone was detected. [3H]5alpha-DHP predominated in pituitary and MBH, while 3alpha-hydroxy-5alpha-pregnan-20-one predominated in the others. In terms of tissue and plasma concentration comparisons, MBH, pituitary and cerebral cortical concentrations of [3H]5alpha-DHP were markedly higher than plasma, muscle, and uterine levels. Pituitary and MBH concentrations were also greater than that in cerebral cortex. Tissue levels of [3H]3alpha-hydroxy-5alpha-pregnan-20-one were not significantly greater than that in plasma. Thus, 10 min after injection of either [3H]progesterone or [3H]5alpha-DHP, high and significant amounts of 5alpha-DHP are accumulated in pituitary and hypothalamus, but not in uterus, which suggests that its presence may be functionally important in governing progesterone-sensitive processes in these feedback tissues.

20-alpha-Dihydroprogesterone

[The distribution of the aldolase isoenzymes in various human tissues and the anomaly in cancerous tissues -especially in gastric cancer- (author's transl)].

Three aldolase isoenzymes; aldolase A, B and C were found in various human tissues including gastric mucosa, by means of substrate specificities (the fuctose-1, 6-diphosphate aldolase/fructose-1-phosphate aldolase activity ratio) and electrophoresis. The basic pattern of aldolase isoenzyme in man consisted of nine active bands, which were designated as I, II, III, IV, V, VI, VII, VIII and IX band from anode side respectively. The I band corresponded to aldolase C, V to aldolase A and IX to aldolase B. The II, III and IV band are hybrid molecules composed of subunit of aldolase A and C, and the VI, VII and VIII of subunit of aldolase A and B. The V band was present in all tissues, while IX was detected in the liver, kidney and stomach. The I, II, III and IV band were found in all tissues except for muscle. These findings were extremely different from those in other species. In normal gastric mucosa, active bands were composed of I, II, III, IV, V, VIII and IX band, while in gastric cancerous tissue, I, II, III, VIII and IX band were absent or markedly decreased in activity. In contrast, the V band increased. In fetal gastric mucosa, they showed the same pattern as cancerous. In extract of cancerous tissues, the FDP/F1P activity ratio was 20.5+/-2.2, as compared with 7.2+/-0.1 in normal gastric mucosa. In serum of patients with gastric cancer, the FDP/F1P activity ratio was 9.7+/-1.2, while it was 2.9+/-0.4 in normal human serum. These results suggest that the elevation in serum of the FDP/F1P ratio in gastric cancer is due to increase in muscle type isoenzyme (aldolase A) which is derived from cancerous tissue. Furthermore, the analysis of serum aldolase isoenzyme will save for cancer diagnosis.

Brain

[Plasma- and tissue concentrations following intramuscular administration of etofenamat. Pharmacokinetics of etofenamat and flufenamic acid in plasma, synovium, and tissues of patients with chronic polyarthritis after administration of an oily solution of etofenamat].

Studies on Plasma and Tissue Concentrations of Etofenamate following Intramuscular Application/Pharmacokinetics of etofenamate and flutenamic acid in plasma, synovia and tissues of patients with chronic polyarthritis after application of oily etofenamat solution Pharmacokinetics of etofenamate (ETO, CAS 30544-47-9; Rheumon i.m.) and flufenamic acid (FLU, CAS 530-78-9) were investigated in plasma, synovial fluid, and tissues after single intramuscular application of etofenamate to patients with rheumatoid arthritis. 62 patients with indicated operative procedure in the knee-joint received a single dose of etofenamate dissolved in oil before operation. At definite times between 1.5 and 48 h post injectionem samples from 6 patients of each time group were collected. Samples of plasma, synovial fluid, synovial membrane, muscle, bone, hyaline cartilage, and fat tissue and in some cases meniscus cartilage were taken. Concentrations of ETO and its active metabolite, FLU, were determined by HPTLC. In all tissues investigated, concentration/time courses of ETO and FLU were observed. ETO and FLU were measured first in all matrices 1.5 h at the latest 3 h post injectionem. Pharmacokinetics in tissues follows that in plasma. Rate-limiting step is the liberation of drug from the oil depot. For a long period pharmacokinetics of ETO and FLU is mainly determined by the constant liberation from the oil depot (zero order kinetics of liberation). Zero order kinetics is deduced from the linear ascent of the cumulated AUC (in percent) vs. time plot. It is directly related to the liberation of drug from the galenical formulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The autoimmune response to male reproductive tissues of rabbits. IV. Induction of autosensitization to central accessory tissue by the intraabdominal release of endogenous secretions.

A study is described in which tissue- and secretion-specific autosensitization was induced in adult male rabbits through intraabdominal cannulation of one or more of their central accessory glands. Both primary and secondary humoral antibodies were elicited by this procedure, as determined by tanned cell hemagglutination and passive hemolysis, i.e., complement fixation. The secondary antibody responses were elicited by (i) cannulation of animals which had been previously stimulated by cryosurgery or combined cryosurgery and injection of pooled accessory tissue extract, and (ii) isoinjection of previously cannulated animals with accessory tissue extract. Primary antibody responses were less in animals castrated at the time of cannulation compared to those in noncastrated animals; but, paradoxically, subsequent challenges with tissue extract induced higher secondary antibody titers in castrated animals. These observations may be explained in castrates by (i) reduced uptake of antibodies--a result of the sparing effect on circulating antibodies in castrated animals because of accessory tissue atrophy, or (ii) increased production of antibodies through postcastration immune enhancement. In noncastrates secondary antibody depression may be related to (i) increased absorption of antibodies by an accessory gland complex which is much larger than that found in castrates, or (ii) tolerance, due to exposure of the antibody-producing system to excess accessory tissue antigen.

Abdomen

Distribution of a major connective tissue protein, fibronectin, in normal human tissues.

Fibronectin is a major surface-associated glycoprotein of cultured fibroblasts and it is also present in human plasma. Antiserum specific for human fibronectin was used to study the distribution of fibronectin in normal adult human tissues. The protein was detected (a) characteristically in various basement membranes including capillary walls: (b) around individual smooth muscle cells and in the sarcolemma of striated muscle fibers; and (c) in the stroma of lymphatic tissue and as thin fibers in loose connective tissue. The distribution of fibronectin was distinct from that of collagen and elastic fibers, but was very similar to reticulin, as demonstrated by conventional histological staining. The results indicate that fibronectin is a major component of connective tissue matrix. The distribution also indicates that most types of adherent cells abut fibronectin-containing structures. This supports the possible role of fibronectin in cell-cell and cell-matrix interactions in tissues.

Basement Membrane

GM3 ganglioside in various tissues of rabbit. Tissue-specific distribution of N-glycolylneuraminic acid-containing GM31.

Molecular species and concentrations of GM3 ganglioside in rabbit tissues, brain, thymus, lung, liver, stomach, intestine, kidney, testis, muscle, and erythrocytes were determined. The highest concentration was found in lung (431.7 nmol/g wet tissue). With the exceptions of brain, thymus, and erythrocytes, GM3 was the dominant ganglioside and comprised more than 50% of the total gangliosides. In brain and thymus, GM3 composed 0.76% and 17.28% of the total gangliosides, respectively. The sialic acid composition of GM3 was determined by mild methanolysis and neuraminidase treatment combined with either permethylation or trimethylsilylation. N-Glycolylneuraminic acid-containing GM3 was found in thymus, lung, kidney, and intestine in addition to N-acetylneuraminic acid-containing GM3, but N-acetylneuraminic acid was the sole sialic acid of GM3 in the other tissues. Sixty-four percent of the thymus GM3 consisted of N-glycolylneuraminic acid. High concentrations of C-20 sphingosine and stearic acid were characteristic for brain GM3 and the major long chain base of the other tissues was C-18 spingosine. The fatty acid composition of GM3 varied in each tissue. The difference in mobility on a thin-layer plate was due to the difference in its molecular constitution, being derived from a combination of fatty acid, long chain base, and sialic acid.

Animals

[Tissue-specific depression of DNA synthesis by calcium salt-free liver and lung extracts that are able to increase the stability of cell linkage in the tissue].

The macromolecular fraction of Ca-free salt extracts (Ca-FSE) removed from lungs and liver of adult rats, mice and fishes inhibits DNA synthesis in the embryonic tissue. The effect of Ca-FSE is tissue-specific rather than species-specific. Ca-FSE was earlier reported to increase with the same specificity the tissue stability to mechanical disruption. A concept is proposed that the tissue-specific adhesive factor may play the role of G1-chalone in epithelial tissue.

Animals

[Obesity and adipose tissue. 2. Hormonal regulation of adipose tissue metabolism].

The effects of hormones on human adipose tissue are reviewed with respect to the pathogenesis, prevention and therapy of obesity. Insulin. The insulin-resistance in the obese is associated with a decrease of the number of insulin receptor sites, which is likely to be secondary to increased insulin levels. Catecholamines. Human adipose tissue contains alpha- and beta-adrenergic receptors. Alterations in the relation of alpha- and beta-adrenergic responsiveness may be important in the pathogenesis of regional forms of obesity. Gastrointestinal hormones. As opposed to adipose tissue of other species lipolytic effects of gastrointestinal hormones were as yet not clearly demonstrated in human fat cells. Prostaglandins were implicated in the pathogenesis of metabolic obesity. However, the effects of these C-20 fatty acids on human adipose tissue remain to be elucidated. Parathyroid hormone has been shown to possess lipolytic activity in vitro. This property may be important under physiological conditions too. Triglyceride storage diseases and lipomatoses are discussed as models for studying impaired hormonal responsiveness in human adipose tissue.

Adipose Tissue

Soft Tissue Volume Augmentation at Single Implant Sites Applying Collagen Matrices or Connective Tissue Grafts: 10-Year Follow-Up of a Randomized Controlled Trial.

AIM: To compare up to 10 years clinical, profilometric and patient-reported outcomes of implant sites previously augmented using a volume-stable collagen matrix (VCMX) or connective tissue graft (SCTG) in the aesthetic zone. METHODS: The original non-inferiority randomized controlled trial (RCT) enrolled 20 patients who received soft tissue volume augmentation with VCMX or SCTG at single implant sites. Clinical assessments and standardized measurements were performed at baseline after crown insertion and at 6 months, 1, 3, 5, 7.5, and 10 years. The primary outcome was mucosal thickness. Secondary outcomes included marginal bone levels (MBL), probing depth (PD), bleeding on probing (BOP), plaque control record, Pink Aesthetic Score (PES), OHIP-14 and buccal profilometric changes. Group comparisons were performed using mixed-effects and generalized estimating equation (GEE) models, which account for within-patient correlations due to repeated measurements and allow inclusion of all available data without requiring imputation for missing observations. RESULTS: Of the 20 originally enrolled patients, 10 (5 in the SCTG group and 5 in the VCMX group) were available for re-examination at 10 years. The adjusted between-group difference in mucosal thickness was -0.02 mm (95% CI -0.99 to 0.96). As the lower bound of the confidence interval remained above the prespecified non-inferiority margin of -1 mm, non-inferiority of VCMX was shown. Buccal contour changes were comparable during the early follow-up, while a trend toward a greater long-term contour decrease was observed in group VCMX (-0.31 mm [95% CI, -0.65 to 0.03]; p = 0.07). Mean PES values were 10.6 in the SCTG group and 9.6 in the VCMX group, with no significant between-group differences (p = 0.45). Both groups revealed high levels of oral health-related quality of life, with low median OHIP-14 scores (SCTG, 0.0; VCMX, 1.0; p = 0.26). CONCLUSION: These preliminary long-term findings showed no clinically relevant differences between SCTG and VCMX in terms of clinical, profilometric and patient-reported outcomes. While SCTG remains the reference standard, VCMX represents a less invasive alternative but with a slight tendency toward greater long-term contour reduction. CLINICAL SIGNIFICANCE: Volume-stable collagen matrices serve as a viable alternative to autogenous connective tissue grafts for peri-implant soft tissue volume augmentation, particularly in patients seeking a reduced morbidity, without compromising long-term clinical or aesthetic outcomes. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017484.

Humans