[In vitro study of erythroid precursors in Vaquez' disease (polycythemia vera). Evidence supporting 2 populations of erythroid stem cells in the bone marrow]. In vitro studies using the plasma clot culture system have been performed in order to compare the red cell pregenitors able to rise to erythrocytic colonies in 7 days (CFUE) in the bone marrow of polycythemia vera (PV), secondary polycythemias and normal subjects. In PV but never in normal individuals or secondary polycythemias, the bone marrow cells producing erythroid colonies without addition of erythropoietin were found. The erythropoietin dose response curves in PV is biphasic with a plateau up to a concentration of erythropoietin of 0.02--0.05 i.U./ml followed by a near normal response to erythropoietin at higher doses. Thus our results demonstrate that two populations of erythroid stem cells coexist in PV, one being abnormally sensitive to (or independent of) erythropoietin, the other normally responding to erythropoietin. After remission induced by P32 treatment, the abnormal population can disappear but the prognostic significance of this disappearance is uncertain. In the whole these results are in agreement with those of others laboratories using the plasma clot culture system. The reasons of the disagreement with the data published using the methylcellulose technic of culture are discussed.


[Disseminated intravascular coagulation (D.I.C.) and fibrinolysis in patients with acute leukemia (author's transl)]. Biological symptoms of D.I.C. were investigated in 43 patients with acute leukemia. Ten of them were found to be positive either at the onset or at the relapse of the disease and in some cases D.I.C. was triggered by chemotherapy. Among the ten positive cases 3 patients had an acute promyelocytic leukemia, 4 had an acute lymphoblastic leukemia, 2 a myeloblastic and 1 a monoblastic leukemia. D.I.C. was found either in patients with an hypercellular form of the disease or in patients with a normal or low white cell count. Symptoms of D.I.C. in acute leukemia must be systematically sought at the onset and during treatment by chemotherapy and treated with heparin and platelet transfusions as it is now admitted for acute promyelocytic leukemia.


[Distribution of HLA antigens among the population of Finistère (France) (author's transl)]. We have studied by using HLA system, 200 people, without filiation but having the same geographic origine (Finistère). The results have been compared with those measured for Parisian and Basque population. A significantly decrease of antigen A29, B18 and BW16 frequency have been observed in the population from Finistere. But, antigen B8 and B27 seems to be more frequent than in population from Paris. A linkage desequilibrium is described for A1-B8 and A3-B7 haplotypes as in population from Paris, but the desequilibrium for A11-B5 seens to be characteristic of population from Finistere.


Hydergine and vincamine derivative LD 4298 exhibit no anti-sickling properties in vitro. Amongst the treatments proposed for Sickle Cell disease Ergot derivatives and extracts from Pervinca have been proposed. We have studied in vitro the effect of Hydergine and LD 4298 on Sickle Cells and Sickle Hemoglobin according to the following four parameters : percentage of sickling, potassium leak, minimum gelation concentration and speed of gelation. In these studies no anti-sickling effect was detected. Moreover Hydergine at 50 microgram/ml increased spontaneous potassium loss without any anti-sickling effect. One can conclude that these two drugs have no effect on sickling.


Electroencephalogram with sphenoidal needles in sleepwalkers. The etiology of sleepwalking is controversial, the theory that sleepwalking is an epilepsy-like symptom is mostly discounted. Electroencephalogram records, obtained by using sphenoidal needles, are presented as a useful technique and aid to etiological and topical diagnosis. A temporal focus of waves of 4-6 cps was recorded which was not found in the routine EEG procedures. The question is thus raised as to whether sleepwalking may be a result of a paroxysmal disorder in the temporal lobe.


The diagnostic potential of rheoencephalography in psychiatry. A 33 electrode monopolar rheoencephalograph was employed to produce a 15 min record of electrical impedance plethysmographic pulse-volume waves in 139 healthy sujects and 782 patients belonging to 15 psychiatric syndromes. Parameters of amplitude, percent rise time and average inflow angle were hand-measured and their means obtained for 30 waveforms throughout each record. Results obtained depended significantly upon chronological age and in some cases on gender. Mental health was found clearly distinguishable from psychiatric disability, but psychiatric syndromes could not be differentiated from one another. A low percent rise time coupled with a high average inflow angle were typical of youth and mental health.


Verbal characteristics of male and female transsexuals. Slater's Selective Vocabulary Test was given to a group of 56 male and a group of 14 female transsexuals and the results were compared with those of 15-year-old boys and girls, and a group of normal male adults. It was found that whereas normal males and females have a ratio of gender appropriate words to cross gender words of approximately 2 to 1, in both male and female transsexuals that ratio is more like 1 to 1. The way in which this abnormal vocabulary acquisition may come about is briefly discussed. The factors related to this abnormal learning are not known.


A thin 4 pi beta-counter operating by negative high voltage for the 4 pi beta-gamma coincidence measurement. --Operating characteristics. A thin 4 pi beta-counter with five anode wires was operated by supplying negative high voltage to the inner wall and showed good plateau characteristics in the case of using only the center anode to take out signals in the previous experiments. This counter, as the 4 pi beta-counter and both 2 pi beta-counters, showed good plateau characteristics in these detailed experiments and no dependency on the disintegration rates examined up to 6000 dps. Then a 4 pi beta-gamma coincidence equipment was set up using this 4 pi beta-counter and one NaI(T1) scintillation detector with size of 76 mmphi x 76 mm. The radioactivities that were measured for beta-gamma and electron capture-gamma decay nuclides by this coincidence equipment were coincided with those measured by the other one. The improvement of the gamma-ray detection efficiency to aim was achieved by that the efficiency obtained by this system was the same as one by the other system having two NaI(T1) detectors with the same size.


[Production of 67Ga, 68Ga by bombardment of natural zinc target with alpha and 3He particles (author's transl)]. In order to determine the optimum irradiation condition for the production of 67Ga and 68Ga, used in nuclear medicine, excitation function and thick-target yield curves were obtained for alpha and helium-3 reactions of natural zinc. With the initial alpha energy of 25 MeV, the thick-target yield of 67Ga was found to be 165 muCi/muA.hr at the end of bombardment and the 66Ga contamination could be reduced to less than 1% after about 3 days of cooling. 68Ga could be obtained by milking from 68Ge. With the alpha energy range of 17-40 MeV, the thick-target yield of 68Ga was 1.2 muCi/muA.hr at the end of bombardment.


[Production of 61Cu, 62Zn by alpha and 3He particle bombardment of natural nickel (author's transl)]. The optimum irradiation conditions were investigated for the production of 61Cu and 62Zn by alpha and 3He particle bombardment of natural nickel. Formation cross sections and thick-target yields were obtained for reaction products in the energy range of 10 to 40 MeV. For the production of 61Cu and 62Zn, the alpha particle bombardment was found superior to the 3He particle bombardment in so far as the yield was concerned. When the incident alpha energy of 21 MeV was chosen, after 2.4 hours of cooling, 2.1 mCi/muA.h of 61Cu could be produced with less than 1% of 60Cu contamination. For the production of 62Zn, when the incident alpha energy of 35 MeV and the target thickness of 57 mg /cm2 were chosen, 97.5 muCi/muA.h of 62Zn could be produced. Radiochemical purity of 62Zn was the highest at 12 hours after the end of bombardment.


Studies in neutron mutagenesis in maize. --Effects of dose fractionation and cell moisture status on mutation induction. Pollen grains of Bz strain of maize were exposed to 14 MeV neutrons with single or fractioated treatments, and pollinated on the recessive stock. Mutation frequency from Bz to bz was observed after harvest of F1 seeds. No clear difference in the mutation frequencies between single and fractionation series was observed. To investigate the effects of water content upon mutation frequency of neutron and gamma-rays, seeds heterozygous for the Yg2-gene were used. Moisture-stabilized (13%) seeds and seeds steeped in water for 24 hrs were exposed to neutrons or to gamma-rays, and mutation from Yg2 to yg2 was detected as color change green to yellow-green in the seedlings. In the gamma-ray treatments, the mutation frequency of wet seeds was about 1.5 times higher than that of corresponding lot of dry seeds. In the neutron treatment, on the other hand, no clear difference in frequency between wet and dry seeds was observed. It may be concluded that no change or no recovery in neutron-induced mutationwas observed not only in the fractionation treatment but also in the dry and wet seeds treatments.


[The upper gastrointestinal imaging and the gastrogram using 99mTc-pertechnetate (author's transl)]. 99mTc-pertechnetate was used for the diagnoses of the upper gastrointestinal tract. Oral administration was useful for the detection of the stenosis and obstruction on the esophagus and the pylorus to the poor risk patients. Mucosal imaging of the stomach was clearly revealed by intravenous administration, and the scintigram of the patient with stomach cancer showed a cold region. Taking the gastric scintiphoto, temporal radioactivity in the stomach region was recorded (gastrogram). This seems to be a new and prospective approach to the clinical gastroenterology.


Environmental radioactivity in Greenland in 1977. Measurements of fallout radioactivity in Greenland in 1977 are reported. Strontium-90 (and Cesium-137 in most cases) was determined in samples of precipitation, sea water, vegetation, animals, and drinking water. Estimates are given of the mean contents of 90Sr and 137Cs in the human diet in Greenland in 1977.


[Progressive supranuclear palsy: description of a case of early occurrence associated with muscular atrophies (author's transl)]. A case of Progressive Supranuclear Palsy (P.S.P.) of early onset (38 years) is described, with somewhat atypical features: the patient was oligophrenic, had no pseudobulbar signs, but there was some muscular atrophy, particularly of the shoulders girdle. On examination there was a slight cortical and cerebellar atrophy on the air encephalogram. Electromyography showed signs of damage to the lower motor neurone which was confirmed by muscular biopsy. In the literature a muscular atrophy in association with P.S.P. is rarely reported clinically although in some cases studied histologically there was degeneration in the nuclei of the cranial and spinal motor nerves. The present case may be an example of such widespread degeneration.


Uptake of metabolites by germinating blastospores of Histoplasma capsulatum. The uptake of radioactive L-leucine, L-glutamic acid, and guanine was monitored during blastospore germination of Histoplasma capsulatum. Blastospores of H. capsulatum, grown in Salvin's medium at 37 degrees C for 48 h and shifted to 23 degrees C, germinated within 24 h. Metabolite uptake was faster in mycelial cells at 23 degrees C than it was in yeast cells at 37 degrees C. During the yeast to mold transition, the initial rate of uptake was first markedly depressed and then increased and achieved a level characteristic of the mycelial phase of growth. Estimates of macromolecular synthesis occurring during transitional morphological events might be influenced by these differences in the rate of uptake.


[Aromatic and branched chain amino acids after porto-caval anastomosis: plasma and brain regional levels in the rat (author's transl)]. Automated analysis of aromatic and branched chain amino acids was performed in plasma and in four cerebral regions of rats submitted to chronic porto-caval shunt. Compared to controls, plasma of the operated animals exhibited a significant diminution of valine, leucine, isoleucine, a net increase of phenylalanine and tyrosine, with unchanged tryptophan levels. Brain valine, leucine and isoleucine were either increased or unchanged, whereas an enormous increase of aromatic amino acids, uniform in the four cerebral regions, was observed. The lack of correlation between plasmatic and cerebral levels of these essential amino acids leads to the hypothesis that cerebral permeability to amino acids is modified after experimental portocaval anatomosis: we recent confirmed that blood-brain mediated transport of the neutral amino acids is increased in this condition. A slower cerebral turnover of these metabolites could also contribute to elevate their cerebral concentrations after portocaval shunt.


[Thymus gland scan in myasthenia gravis: experience in 52 patients]. A firm relationship has been established between thymus gland pathology and myasthenia gravis. The most frequent changes observed in this gland consist in simple hyperplasia of germinal centers or thymoma. In order to detect these alterations it is necessary to have a suitable reliable technique, beside routine radiological exams: thymus scan has been proposed as an useful tool. Since 1968 we submitted 52 patients to this procedure; we used as a tracer 75Se-Seleniomethionine in most cases, 57Co-bleomycin and 67Ga-citrate in a few cases. The scan was found positive in 22 cases (42%) showing either localized or diffuse uptake in the region of the sternum. Thymus changes were subsequently examined in 26 cases: 22 cases after thymectomy in 4 cases at autopsy. We found a good correlation between positive scan and pathological changes of the gland such as thymoma or germinal center hyperplasia. However in 4 patients with negative scan that previously received radiation therapy or immunosuppressive therapy such pathology was missed: 3 cases of hyperplasia and 1 residual thymoma. We conclude that thymic scan an useful and highly specific diagnostic procedure and should be done before any kind of treatment which affects thymus.


Histoplasma capsulatum: chemical variability of the yeast cell wall. Four strains of Histoplasma capsulatum were analyzed to observe any variations in their cell wall composition. Strain G-184B produced the same amount of sugars reported by Domer (2) although qualitative analyses agreed with Kanetsuna's report (4) as far as the presence of glucose, galactose, and mannose was concerned. Our results agree with previous reports in classifying H. capsulatum into chemotypes I and II, the latter having more alpha-glucan in its cell wall. A decrease in the amount of fraction 2 (alpha-glucan) of strain G-184B was observed when the strain was subcultured in vitro for many years, an effect similar to that reported for Paracoccidioides brasiliensis (12, 13).


[Cerebral mucormycosis in the cat caused by Mucor pusillus]. The pathologic examination of the brain of a pet cat, suspected of rabies, showed lesions of mucormycosis. The causal fungus, Mucor (Rhizomucor) pusillus was isolated and identified. The authors describe the lesions produced, the experimental pathogenicity for the rabbit and the morphologic and physiologic characteristics of the isolate.


Two forms of bacteriolytic endo-N-acetylmuramidase in Acanthamoeba castellanii. Two different molecular forms of bacteriolytic endo-N-acetylmuramidase (EC 3.2.1.17) were found in the Acanthamoeba castellanii culture. The enzymes were separated by column chromatography on DEAE-Sephadex or by polyacrylamide-gel electrophoresis. In young cultures only one molecular form of the enzyme was selectively secreted by amoeba cells to the environment. The second, more basic enzyme protein was preferentially synthesized by aging Acanthamoeba castellanii cells, and was also liberated to the medium. In amoeba cells the bulk of forms A and B of endo-N-acetylmuramidase are associated with subcellular organelles--lysosomes.


Purification, crystallization and properties of triosephosphate isomerase from human skeletal muscle. 1. Triosephosphate isomerase (D-glyceraldehyde-3-phosphate ketoisomerase, EC 5.3.1.1) from human skeletal muscle was purified to homogeneity and crystallized. The crystalline enzyme preparation was resolved on polyacrylamide-gel electrophoresis into three isoenzymes. 2. The molecular weight of the enzyme estimated by gel filtration method was found to be 57,400 +/- 3000. Molecular weight determination under dissociation conditions indicated a dimeric subunit structure of the enzyme. 3. The apparent Km for D-glyceraldehyde-3-phosphate as substrate is 0.34 mM, and for dihydroxyacetone phosphate, 0.61 mM. Vmax of the reaction is, respectively, 7200 and 660 units/mg protein at 25 degrees C and pH 7.5. 4. Molecular and kinetic properties of triosephosphate isomerase from human skeletal muscle are very similar to those of rabbit muscle enzyme.


Changes in cellular concentration of DNA-dependent RNA polymerases A and B during regeneration of rat liver. 1. DNA-dependent RNA polymerases A and B were solubilized from rat liver nuclei at different intervals after partial hepatectomy, and chromatographed on DEAE-Sephadex A-25. Activity of the solubilized RNA polymerases remained unchanged till 6 h after hepatectomy, then started to increase reaching a maximum (350% and 150% of control for the A and B enzyme, respectively) at the 18th hour of regeneration, and was still high at the 36th hour of regeneration. 2. RNA polymerases A and B were extracted and extensively purified from the nuclei of normal and regenerating rat liver. No marked differences in the specific activities between the analogous purified enzymes from normal and regenerating liver were observed, thus the increase in RNA polymerase activities (especially marked in the case of enzyme A) observed after partial hepatectomy is probably due to a real increase in the quantities of enzymes. 3. Concentration of RNA polymerase A in hepatocyte increases from 1.3 x 10(4) (normal liver) to 7.5 x 10(4) (18 h after hepatectomy) molecules per haploid genome. The concentration of polymerase B increases from 3.4 x 10(4) to 5.5 x 10(4) molecules per haploid genome, respectively.


Comparison of susceptibility to staphylococcal nuclease and behaviour in metrizamide gradients of normal and 5-bromodeoxyuridine-substituted chromatin from Physarum polycephalum. Replacement of 20--30% of thymine by 5-bromodeoxyuridine in chromatin DNA of Physarum polycephalum does not cause any visible change in a typical, regular pattern of DNA products obtained upon digestion of chromatin with staphylococcal nuclease. The time course of digestion is similar for normal and substituted chromatin even under conditions when the nuclease cleaves preferentially the dAT regions in DNA. 5-Bromodeoxyuridine label does not significantly affect the DNA/protein ratio in chromatin; this is reflected by similar behaviour of normal and substituted chromatin in metrizamide-density gradients.


Temporal changes in sequential quantitative thallium-201 imaging following myocardial infarction in dogs: comparison of four- and twenty-four-hour infarct images. Thallium-201 ((201)T1) myocardial perfusion imaging allows definition of zones of myocardial infarction and ischemia. The temporal changes in sequential quantitative (201)T1 infarct imaging was studied 4 and 24 hours in dogs subjected to closed-chest anterior wall myocardial infarction. A temporal decrease in (201)T1 imaged infarct areas was noted in 10 of 13 animals. In no animal did the infarct area increase. The imaged infarct area decreased by an average of 30% from 12.9 ± 6.2 cm(2) at 4 hours to 9.1 ± 5.1 cm(2) at 24 hours (p < 0.001), and involved 34 ± 16% of the total (201)T1 left ventricular distribution at 4 hours and 22 ± 14% at 24 hours (p < 0.001). The magnitude of temporal change in imaged infarct area was not predicted by initial image defect or final histopathologic infarct size. Thus, the results of (201)T1 infarct imaging in the early period of infarction are clearly dependent upon the time at which the procedure is performed.


[Inhibition of aminopeptidase activity of rat small intestine by the tripeptide H-Thr-(O-tert. butyl)-Phe-Pro-OH]. The hydrolysis of L-leucine-beta-naphthylamide and L-leucinamide by leucinaminopeptidase (E.C. 3.4.11.1) from bovine eye lens is inhibited by H-Thr (O-tert. butyl)-Phe-Pro-OH. The inhibitor constants are Ki = 1.5 . 10(-5) M and 0.8 . 10(-5) M, respectively. Both brush border peptidases, leucinarylamidase (E.C. 3.4.11.2) AND TRIPEPTIDASE (E.C. 3.4.11.4), are inhibited to a smaller extent (Ki = 0.8 . 10(-3) M). Mn++-ions activate the cytosolic leucinaminopeptidase but not the hydrolysis of leucinamide by the brush border arylamidase. The inhibition of the cytosolic leucinamidase by the peptide (Ki = 3.5 . 10(-4)) is twice as that of the brush border arylamidase.


On the growth metabolism in chick skeletal muscle. A study on the alterations in proteins, glycogen and nucleic acid levels. Biochemical estimations of proteins, carbohydrates and nucleic acids have been made at eleven stages during the post-embryonic growth of six skeletal muscles in chick. Stimulation of protein synthesis by carbohydrates if confirmed in our study on glycogen and NaOH-extractable acidic protein levels. The role of nucleic acids, RNA and DNA, in protein synthesis has been discussed in the light of nucleic acid inhibition by HCl-extractable basic proteins.


Primum utilis esse: the primacy of usefulness in medicine. The famous and oft-quoted maxim "Do no harm" should not be thought of as the first principle of medical ethics. The documents of the Hippocratic tradition and clinical experience indicate that a more appropriate and helpful first principle would be "Above all, be useful." The concept of usefulness implicitly rests at the very heart of medicine itself and the physician-patient relationship. The failure to adhere to this concept undermines the physician-patient relationship, dissolves the distinction between quacks and physicians, and destroys the integrity of the medical profession. The determination of useful medical treatment belongs to both physicians and patients. Any decision to initiate, continue, or discontinue diagnostic or therapeutic action has both a medical and a personal value component; the former properly belongs to physicians and the latter to patients. Practicing medicine with the intent of producing benefit and being useful to the patient is far more fundamental than practicing medicine to avoid harm.


[Use of ferritin conjugates of a lectin from mistletoe (Viscum album L.) for the electron microscopic localization of cell surface receptors]. Ferritin conjugates of a lectin from mistletoe (Viscum album L.) were used for the electron-microscopic demonstration of carbohydrate receptors on the cell surface of human erythrocytes and murine tumor cells. Human A1 erythrocytes showed only a slight focal binding of ferritin. Cells of the mouse ascites tumor strain L 1210 were labelled very tightly on their surface and incorporate the ferritin by pinocytosis. Furthermore they showed cytotoxic changes in their ultrastructure. In the presence of galactose the labelling on the surface, the incorporation of the conjugate within the cell as well as the cytotoxicity were inhibited.


Interrelations between plasma renin activity, aldosterone, and sympathetic nervous system activity in essential hypertension. Interrelations were investigated between plasma renin activity (PRA), dopamine-beta-hydroxylase activity (DBH), plasma aldosterone (PA), plasma cortisol (PC) and plasma sodium concentration (PNa) in renal vein blood of essential hypertension patients in recumbent position. The patients were divided in compliance with the WHO classification into two groups of stage I and stage II of essential hypertension. In stage I a negative correlation was found in all samples of blood between PA and PNa. This means that in recumbent position in stage I the mechanism of regulation sodium -- aldosterone is maintained. In stage II there were very significant correlations between DBH and PRA in the samples from both renal veins. The left renal vein blood gives the best information about secretion of the left adrenal gland. In stage II in samples from the left renal vein a negative correlation was proved between PA and PRA, and also two very similar negative correlations PA -- DBH and PC -- DBH were demonstrated. The results indicate that in recumbent position in stage II the renin secretion is mainly under the control of the sympathetic nervous system, even if the activity of the latter is depressed, normal or enhanced. The possible negative relation between sympathetic activity and corticosteroid secretion in stage II of essential hypertension is discussed.


On the quantitative characterization of human body sway in experiments with long-term performance. Two different conditions of standing were examined in young male subjects with an intact vestibular system by means of stabilography. Low-frequency sways were eliminated by means of a digital high-pass filter. The parameters of the histograms of amplitudes, the autocorrelation functions, and the power-spectral density were estimated. The quantitative parameters of the stabilograms are compared for the two standing positions, both for the frontal and sagittal planes. Quotients of estimates of variance components calculated on the basis of analysis of variance are stated as measures of reliability for the parameters of histograms of amplitudes and power-spectral density in defined frequency bands. The reliability of the standard deviations of amplitudes was much better than the reliability of skewness and excess. The reliability of spectral density differed for frequency ranges investigated. Generally, the quotients of estimates of variance components were higher for the spectral density in the frequency bands of sagittal stabilograms than in those of frontal ones. Performance significantly affected several parameters of histograms and the distributions of power-spectral density. Standard deviation of amplitudes and power-spectral density proved to be suitable for the quantitative characterization of stabilograms.


[Influence of hypoxia and hyperoxia on the 2,3-diphosphoglycerate concentration in rat red blood cells]. The influence of hypoxia (pO2 = 85 mmHg) lasting 5 h, a strong single bleeding of the animals, and the effect of hyperoxia (pO2 = 745 and 1520 mmHg) lasting 24 and 5 h, respectively, on the 2.3-DPG concentration of red cells from rat has been studied. A distinct increase in 2.3-DPG concentration at hypoxia and bleedig, but no reliable alteration in hyperoxia were found. When bled and anemic animals are exposed to hyperoxia (24 h, pO2 = 745 mmHg, normal air pressure) there is also observed a rise of 2.3-DPG concentration, which is much less than in normoxia. A non-linear relationship was established between the change of 2.3-DPG concentration and the percentage of deoxyhemoglobin in the centralvenous blood.


[Changes in lipid metabolism of Wistar rats by changing a high fat to a low fat diet and vice versa]. Wistar rats, 24 weeks of age, with alimentary obesity after fat feeding (50% fat in the diet) for 19 weeks were restricted to fat (3% fat in the diet) for 4 weeks in order to compare the alterations of body and organ weights as well as those of lipid concentrations in epididymal adipose tissue, liver and serum with earlier results [1], obtained before food changing. On these conditions decreases of body weight by about 20%, of the relative mass of epididymal adipose tissue and of the triglyceride content per fat cell were observed. In liver a decline of triglycerides and cholesterylesters (by about 2/3 and 1/3, respectively) and in serum a drop of free fatty acids, but increases of phospholipids, and of free and esterified cholesterol were found. In another series, animals of the same age that had been fed the low fat diet for 19 weeks were administered the high fat diet for 4 weeks and also compared with the state before. Thereby the body weight (by about 20%) and the relative mass of the epididymal adipose tissue gained, but lipid concentrations in this tissue were not affected. In liver the concentrations of triglycerides and cholesteryl esters increased threefold and tenfold, respectively; in serum augmented contents of triglycerides and phospholipids were observed. Besides the changes in adipose tissue, reasons for the forced accumulation of cholesteryl esters in the liver during fat feeding and their retarded removal out of the liver after fat restriction are especially discussed in comparison with that of the triglycerides.


Effect of single and repeated carbon monoxide intoxications on urinary catecholamine excretion in rats. In preliminary experiments it had been shown that the total catecholamines in the urine of rats collected during 5 hrs after stimulation of diuresis with 50 ml tap water/kg body weight per os were not changed significantly following a 3-week training in individual metabolic cages, a short pressing of the animals against the laboratory table, a single i. p. injection of 2 ml sodium chloride solution (145 mmol/l)/kg body weight, or a single s. c. injection of 40 ml air per animal. The excretion was increased after puncture of the retroorbital plexus and after exposure to cold (+5 degrees C) during the 5 hrs. Carbon monoxide poisoning produces an inhibition of diuresis. Therefore, to study the effect of carbon monoxide intoxications on urinary catecholamine excretion we administered 25 ml tap water/kg additionally. Single s. c. injection of 7.2 mmol CO/kg body weight (53% COHb) induced a significant increase of urinary catecholamines. Due to repeated injections of the same CO dose a gradual disappearance of this effect was seen. After 4 weeks the differences to controls are negligible.


[Influence of mediators on plasminogen activator release]. The influence of substances known as low molecular weight mediators such as biogenic amines, peptides and prostaglandins on the plasminogen activator release was studied in the isolated perfused pig ear. Among the substances tested, histamine and the plasma kinins bradykinin and kallidin were found to possess a dose-dependent activator-releasing effect, which in case of histamine can be suppressed by an antihistamine (promethazine). Serotonin and the prostaglandins at concentrations up to 10(-5)M possess no significant activator-releasing effect. Compared with the biogenic peptides angiotensin, oxytocin, vasopressin, and eledoisin, only the latter was found to release plasminogen activator. Studies on the influence of the substances tested on the capillary permeability showed that enhanced permeability is caused only by those mediators which cause also increased activator release.


[Action of LSD and 5-methoxy-N,N-dimethyltryptamine on the high affinity uptake of [3H]-serotonin by isolated rat brain synaptosomes]. LSD (10(-7)M--10(-11)M) and 5-methoxy-N,N-dimethyltyptamine (10(-7)--10(-9)M) inhibited the high affinity uptake of [3H]-5HT into synaptosomes. These results suggest that the inhibition of the high affinity uptake is involved in the psychotomimetic action of LSD and 5MeODMT.


[Effect of progesterone and phenylbutazone on bile flow and bile acid excretion in male Wistar rats]. Bile flow and excretion of monohydroxy-, dihydroxy- and trihydroxy bile acids (MBA, DBA and TBA) were estimated after acute and subacute progesterone and phenylbutazone pretreatment in adult male Wistar rats in three one-hour periods. Different pretreatment with sunflower oil did not influence bile flow and excretion of DBA and TBA. MBA were not detected. Different administration of progesterone and phenylbutazone did not significantly change the TBA/DBA ratio. Progesterone administration (50 mg/kg b. w. i. p.) 2 hours before bile sampling increased bile flow and bile acid excretion in the third one-hour period. After 3 days of pretreatment with progesterone (3 X 50 mg/kg b. w. i. p.) bile flow and TBA-excretion were diminished. Phenylbutazone (100 mg/kg b. w. i. p.) increased bile flow and TBA-excretion both after acute and subacute administration.


Active fragments of native streptokinase obtained by partial tryptic degradation. By partial tryptic digestion of streptokinase, degradation products of the molecular weight range 27 000--42 000 were obtained. Among these, fibrinolysis activating components could be demonstrated.


[Evaluation of thyroid function in non-thyroid diseases]. The, in non-thyroidal illnesses, frequently occurring changes in the serum concentrations of peripheral thyroid hormones, are shown in patients with acute myocardial infarction, compensated and decompensated cirrhosis of the liver, renal insufficiency and in rheumatoid arthritis. The observed changes, (pathological) low total triiodothyronine, low or normal total thyroxine, and normal thyrotrophine), can make the diagnosis of hyperthyroidism impossible. Only in control measurements, after cessation of the simultaneous non-thyroidal illness, the peripheral thyroid hormone concentrations are found to be in the hyperthyroid range. The only way to establish the diagnosis, (or confirm the clinical suspicion), is to prove non-responsiveness of the pituitary to a TRH-stimulus. TRH-tests have, however, no diagnostic value in illnesses that affect pituitary function directly, such as terminal renal insufficiency. The diagnosis of hypothyroidism can be established by measurement of the basal thyrotrophine serum concentration (elevated) or by measurement of the serum concentrations of 3,3'5'-triiodothyronine (reverse T3), which is, according to a recent report, observed to be significantly decreased.


[Testing the dilatation capacity of the hepatic artery with parathyroid hormone]. In portosystemic shunt surgery, there still is a lack of correlation between various preoperative hemodynamic measurements and the postoperative clinical course of patients. The magnitude of post-shunt increment in hepatic arterial flow was found to be directly related to long term prognosis. To predict the arterial response for selecting patients for shunting, we tried to use a new non invasive method: Arterial and portal components of total liver blood flow were determined quantitatively by "Sequential hepato-splenic scintigraphy". Dilatation capability of the hepatic artery, was tested by means of the hemodynamic action of Parathyroid hormone (PH). PH has been found to induce a large and exclusive augmentation of hepatic arterial blood flow. We were able to document a statistically highly significant increase in hepatic arterial flow following i. v. applications of PH. The extent of arterial increment appears to be dependent upon the degree of entrapment of the hepatic arterioles by the fibrous tissues of cirrhosis.


[Biguanides: reasons for withdrawal of drugs and remaining indications]. The pharmacological properties and the mode of action of biguanides is presented. In Austria, the association of lactic acidosis with biguanide therapy has led to a cancellation of the registration of buformin and phenformin. Only, if all contraindications for biguanide therapy are strictly observed, metformin can be prescribed for the treatment of obese patients with type II diabetes.


[Blood lactate and biguanide therapy: comparison between phenformin, metformin and buformin in 408 senile diabetics]. In our series of patients, blood lactate is investigated in type II-diabetics under sulfonylurea or sulfonylureabiguanid treatment. Under biguanides a statistically significant increase of blood lactate is found dose-dependent, but independent of the type of biguanides used.


[Effect of biguanide therapy on lactate metabolism during graded submaximal ergometric testing]. Diabetic patients were subjected to exercise testing before and after a short antidiabetic therapy with phenformin, buformin or metformin. Primarily, changes of lactate and of the acid base balance, were analyzed. After therapy with biguanides all 24 patients had increased lactate levels before and after physical strain. Phenformin showed the greatest influence on the lactate metabolism. Metformin the least.


[Ergospirometric studies on patients with diabetes mellitus and the effect of biguanides on physical performance]. 24 diabetic patients had submaximal exercise testing before, and 4 days after, biguanide treatment. Biguanide treatment resulted in a significantly decreased exercise capacity. This is explained by increased anaerobic energy production, which results in a decrease of the performance of an individual.


[Hypophyseal dysfunction and chronic hemodialysis]. 65 chronic hemodialysed patients showed a mean elevation of serum prolactin up to 35.5 ng/ml and a mean HGH level of 4.2 ng/ml, whereas TSH was within normal range. The response of the prolactin secretion to TRH was poor in patients with a high basal prolactin level. Patients with amenorrhea showed significantly higher prolactin values than menstruating women. It is assumed, that chronic stress caused the elevation of prolactin and HGH.


Role of calcium in the mechanism of action of the prostaglandins E1 and F2 alpha as well as of their antagonist polyphloretin phosphate (PPP). The contractile effect of PGE1 on guinea-pig ileum is not changed either by increase (to 4 mM) or by decrease (to 1 mM) of the Ca++ content in Krebs solution. The decrease of Ca++ in the medium intensifies the contractile effect of PGE2 alpha. Reduction of Ca++ weakens the antagonistic effect of PPP (100 micrograms/ml) against PGF2 alpha. PPP has a marked aftereffect with respect to the effects of PGF2 alpha--in cases of normal Ca++ content in the Krebs solution this aftereffect appears upon longer (10 min) contact of PPP with the intestinal segment, while in cases of changed Ca++ content it appears already after 2-min PPP action. It is concluded that in order to induce contractions in the guinea-pig ileum, PGE1 and PGF2 alpha utilize the internal Ca++. It is assumed that PGF2 alpha increases the reactivity of the anionic sites of the smooth-muscle membrane for Ca++. As a result of this, the complex compounds of Ca++ at its higher concentration make more difficult the realization of the contractile process. It is assumed that Ca++ is needed for the maximum manifestation of the antagonistic effect of PPP.


Background neuronal activity in cat somatosensory cortex before and after VPL damage. Histogram and taxonomic analysis. Two groups of cats under barbiturate anaesthesia are used to study the effect of electrolytic coagulation in the VPL of the thalamus on the extracellular unit activity in the somatosensory cortex (the focus of maximum activity (FMA) of this part of the nucleus affected by the lesion). In the first group of animals a comparison is made between the unit activity before and immediately after coagulation, while in the second group of animals the activity of the neurones, recorded in FMA of the intact VPL is compared with that of the neurones in the homologous symmetrical point in the hemisphere, ipsilateral to the VPL coagulate 10-14 days before the acute experiment. The activity of 246 neurones is studied. Histogram, statistical and taxonomic analyses are performed. It is found that lesion in VPL modifies to a certain extent the pattern of neuronal discharges, although even after the damage rhythmic groups of action potentials simultaneous with the spindle-like EEG waves are recorded in the primary somatosensory cortex (FMA). Evidently, the relay VPL nucleus is not the only pacemaker of spindle activity in its projection cortical area, which is in contradiction with some views expressed in the literature.


Studies on the dense-core vesicles in the ontogenesis of locus coeruleus. I. Localization, type and density of the dense-core vesicles in locus coeruleus during rat ontogenesis. In an attempt to clarify the function of dense-core vesicles quantitative estimation is made of their density and localization in the perikarya, axonal boutons and neuropil of rat locus coeruleus during different ontogenetic stages. The results obtained, compared with the fluorescence- and electronmicroscopic data, suggest participation of the dense-core vesicles in the neuronal development and differentiation: presence in the earliest embryonal periods, statistically significant increase in the density in the period of most intensified growth and maturing of the neuropil and axonal boutons, and change in the density of the perikarya in connection with intensified axonal transport. Quantitative data are also presented about the participation of the dense-core vesicles in synaptic transmission.


Perceived orientation of dot patterns.

Perceived orientation of dot patterns. Fifty subjects were asked to assign orientation to different configurations of bright dots by means of an adjustable long line. Their performance of the task clearly demonstrates that the assigned orientation of each configuration coincides with the orientation of a line drawn through the dot pattern so that the sum of the squared distances between each dot and this line is minimum. Such a line remains invariant in respect to rotation of the set of dots. It is concluded that perceived orientation of dot patterns in the plane is an invariant characteristic of this kind of visual stimulus.


Scaling of light and dark time intervals. Scaling of light and dark time intervals of 0.1 to 1.1 s is performed by the mehtod of magnitude estimation with respect to a given standard. The standards differ in duration and type (light and dark). The light intervals are subjectively estimated as longer than the dark ones. The relation between the mean interval estimations and their magnitude is linear for both light and dark intervals.


Consultant report: Incomplete abortions treated at Jahanshah Saleh Hospital in Tehran, Iran from May 14, 1973 to April 30, 1974. In the period from May, 1973 to April, 1974, one hundred patients were treated for incomplete abortion at the Jahanshah Saleh Hospital in Tehran, Iran. Patients admitted to the hospital were from 4 to 28 weeks' gestation and were routinely administered analgestics before the abortion was completed by D & C. The D & C took about 10 minutes and the patient was usually able to go home that same day. Twenty-four women (24.0%) experienced complication(s) including blood loss, fever requiring antibiotic treatment, and pelvic infection.


Passive cutaneous anaphylaxis: improvement of quantitative analysis by radioactively labelled antigen. Experiments were performed to improve the quantitative analysis of passive cutaneous anaphylaxis (PCA) by labelling the antigen with radioactive iodine. After intradermal injection of antibodies and intravenous administration of labelled antigen in rats a close correlation was found between the radioactivity measured in skin biopsies and the amount of antigen as well as the amount of antibodies. This direct dependence makes it possible to improve quantitatively the reading of PCA test results. A quantitative correlation was also found when radioactivity is measured over the skin by scanning procedures. Therefore it is not necessary to cut out skin biopsies. Thus the same test animal can be used several times, which minimizes biological variations.


Activity of the epipodophyllotoxin VP-16 in the treatment of combination chemotherapy-resistant non-Hodgkin lymphoma. Twenty patients with several histologic subtypes of non-Hodgkin lymphoma who had become resistant to combination chemotherapy were treated with a five-day course of the epipodophyllotixin VP-16. Of 19 evaluable patients, 8 (42%) responded to treatment with 1 complete response and 7 partial responses. The median duration of response was 5.5 months. Seven of the responders had a diffuse lymphoma and 1 had a nodular lymphoma. Of the responders who had diffuse histiocytic lymphoma (DHL), diffuse mixed lymphoma (DML), and diffuse undifferentiated lymphoma (DUL)--the more aggressive histologies in the Rappaport classification--6 of 13 (46%) evaluable patients responded to therapy. Responses were seen in node-dominant, skin-dominant, and marrow-dominant disease. Toxicity was mainly hematopoietic, 53% of patients experiencing leukopenia ( less than 2,000 cells per cu mm) and 68% of patients experiencing thrombocytopenian 2,000 cells per cu mm) and 68% of patients experiencing thrombocytopenia ( less than 100,000 platelets per cu mm). There were two deaths attributable to profound leukopenia with sepsis. The activity of VP-16 in patients who have previously been extensively treated with multiple drugs including vincristine supports its activity in the lymphomas and suggests its lack of cross-resistance with vincristine. The inclusion of VP-16 in primary treatment protocols in the diffuse lymphomas should be considered.


[Incomplete antigens derived from milk proteins in the serum of infants allergic to milk]. 1. Sera of 22 children with cow's milk clinical hypersensitivity were studied to demonstrate the presence of substances immunologically related with milk. They were compared with 23 controls. The infants of both groups were feed with bovine milk. The immunogenic capacity of cow's milk and their major proteins were experimentally investigated. 2. Specific rabbit antisera were obtained by injection of antigens with incomplete Freund adjuvant. Double difussion gel, passive hemagglutination and ultramicromethod for the determination of antigen antibody precipitated were performed. 3. Immunogenicity was proved by precipitation and hemagglutination methods. by precipitation cow's milk antigens were present in 5 of 22 sera of antigenic patients, in 3 of them ALA antigens were present and in only 1 of them, caseina were present. By hemagglutination, 12 of 22 allergic infants showed ALA and BLG and 11 caseine (C). In 2 of 7 controls, beta lactoglobuline (BLG) was present and in an other one C. It was possible to detect incomplete antigens related with ALA, BLG, and C in allergic infants as well as controls. A significative difference was found for BLG (P less than 0.01) and it was highest (P less than 0.003) in infants with protein calorie malnutrition. 4. It is concluded that sensitization depends not only on stimulation of incomplete or complete antigens, as were observed in this study but on the host's capacity to form citrotropic antibody in humoral hypersensitivity or to stimulate lymphocytes in cellular immunity field.


Effect of a single ingestion of alcohol on iron absorption. The effect of alcohol on inorganic and organic iron absorption was studied in 70 subjects, using a whole-body counter technique. The mean iron absorption of a test dose was 24.44%, while in the presence of whisky, absorption fell to 9.73% (P less than 0.0001). Absorption of a test dose in the presence of whisky without alcohol was 10.14% (P less than 0.0001). The alcohol in whisky, therefore, was not responsible for the diminished iron absorption (P greater than 0.20). The absorption of the iron contained in wine with alcohol was 73.31 microgram and wine without alcohol was 67.50 microgram. The difference was not statistically significant (P greater than 0.20). The absorption of inorganic iron contained in a test meal was 165.55 microgram and was not changed in the presence of ethanol (151.35 microgram) (P greater than 0.10). However, the presence of ethanol affected the absorption of heme iron: 538.68 microgram compared with 442.41 microgram with ethanol (P less than 0.0001). These studies show that the acute ingestion of ethanol does not influence the absorption of inorganic iron, while it does diminish the absorption of the organic form.


A new chromosome abnormality in idiopathic sideroblastic anemia: 46,XY,del11q23. A new marker chromosome, deletion 11q23, was observed with the Giemsa banding technique in the bone marrow of a patient with idiopathic sideroblastic anemia. The abnormality was not detectable in the peripheral blood or with nonbanded chromosome studies. Nineteen of 40 cases of this disorder studied and reported to date had chromosomal aberrations, although the majority had only nonbanded karyotypes performed. This apparently high incidence of chromosomal defects and the finding in the present case indicate that more banded-karyotype analyses are needed to assess the presence of possible nonrandom cytogenetic changes in idiopathic sideroblastic anemia.


The significance of bronchial and nasal provocation tests in making the diagnosis of allergy in children. The relationship between positive skin tests and positive provocation tests at the affected organ level was studied in children with rhinitis and bronchial asthma. Of 357 positive skin reactions against pollens only 49% were positive in rhinometry, while of non pollen allergens only 31% of 59 challenges were positive. Of 778 challenges with pollens 40% gave a positive bronchial response, while only 27% of 848 challenges with non pollens were positive. More detailed information is given on single allergens and the consequences for hyposensitation therapy are discussed.


IgE and complement in allergic children. The following measurements were made using radial immunodiffusion with commercial M-Partigen plaques (Behringwerke, Marburg): Global-IgE in the serum of 29 children (17 atopic asthmas, 3 non atopic asthmas and 9 acute urticarias); C3 and C4 complement fractions in 56 patients (27 atopic asthmas, 11 non atopic asthmas and 18 acute urticarias); C3PA complement fraction in 41 patients (18 atopic asthmas, 9 non atopic asthmas and 14 acute urticarias). High IgE serum levels were observed chiefly in the cases of atopic asthma with polysensitization and in urticarias. The anomaly of the complement system most often found in children was an increase of C4 (23,2% of the cases), not related to the clinical form or duration of the disease. An increase of the C3 fraction (14,6% of the cases) was also observed together with an increase of these two fractions in all the cases where an increase of C3PA was observed. Only in 11,1% of atopic asthmas was a decrease of the serum concentration values of C3 observed.


Spontaneous resolution of severe aplastic anemia associated with viral hepatitis A in a 6-year-old child. Recovery from acquired aplastic anemia associated with hepatitis is rare. This case of a 6-year-old boy with severe aplastic anemia is the first reported association of this disease with a hepatitis A infection. Antibody to hepatitis A (anti-HA) was not detected on admission, but was detected three weeks later. Infection with hepatitis B virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were excluded. The peak titer of anti-HA was higher than would be expected for passive transfer of antibody resulting from transfusions. The persistence of antibody for more than 20 months after the last transfusion was not consistent with passive antibody, which would be expected to disappear over that time. This child had indications for allogeneic marrow transplant and a sibling donor who was histocompatible. However, the transplant was postponed because the prognosis was considered to be poor in the presence of active hepatitis. There was a spontaneous remission without the necessity of the transplantation procedure.


Corneal edema with contact lenses under closed-eye conditions. Subjects wore PMMA, CAB, and thin hydrogel contact lenses with their eyes closed for periods of 6 hr. The corneal edema that developed was evaluated by observing the amount of central circular clouding and by measuring the increase in central corneal thickness with a slit-lamp biomicroscope and pachometer. Central circular clouding was greater with the PMMA and CAB lenses than with the thin hydrogel lenses. Corneal thickness increased by different amounts for the three subjects, but the three lens types caused about the same increase in corneal thickness for a given subject.


Red-cell hypoplasia and increased bone marrow reticulin in systemic lupus erythematosus: reversal with corticosteroid therapy. A 29-year-old Chinese male developed severe aregenerative anemia. The bone marrow was diffusely hypercellular with increased marrow reticulin and a persistent failure of erythroid differentiation beyond the pronormoblast stage. Although he did not manifest classic features of systemic lupus erythematosus, multiple serologic studies were in accord with this diagnosis. The patient's defect in erythropoiesis was studied by an in vitro technique for the growth of erythroid colonies. Despite the severe erythroid hypoplasia, the patient's marrow yielded abundant large erythroid colonies. Serum erythropoietin activity was high as judged by use of this in vitro assay. Although the patient's native serum did not affect colony formation, a separated IgG fraction was markedly inhibitory to colony growth. This suggests that the erythroid hypoplasia may have resulted from a unique autoantibody. The patient's hematologic abnormalities completely reversed following treatment with corticosteroids.


Population study of fixation disparity, heterophoria, and vergence. Data on phorias, vergences, and fixation disparities were gathered for distant and near viewing conditions from a nonclinical, young adult population. Normative values were computed from the data for analysis and comparison. Our study revealed slightly less exophoria at far and near than Morgan's study, together with large base-out vergence readings. We found proportionately more esophores with exo fixation disparity who require base-in prism to neutralize the fixation disparity than Ogle's studies found.


Basic principles of lens fracture testing. An analysis of different tests used or proposed for evaluation of the resistance of ophthalmic lenses to breakage is presented. The tests considered subject the lenses to different strain rates, areas under stress, and energy losses. The analysis examines effects of these variables as well as effects of differences in lens-failure stress and lens thickness on test results.


Matrix optics of catadioptric systems.

Matrix optics of catadioptric systems. Analysis of an optical system that contains a combination of reflecting and refracting elements may be very cumbersome by conventional vergence methods, especially if the system contains a large number of elements. This paper presents an algorithm that permits simple and rapid analysis of the paraxial optics of such systems and presents examples of optometric interest.


Cellophane maculopathy: a case report.

Cellophane maculopathy: a case report. Cellophane maculopathy is a fairly common entity frequently overlooked as a possible explanation for decreased visual acuity. A case report is presented to show how this entity presents itself clinically and what procedures are performed to establish the diagnosis.


A duration effect in reaction time to the offset of brief auditory stimuli. A previous study reported no difference in reaction time to the offset of brief bursts of noise as a function of stimulus duration. However, in that study a fixed foreperiod preceded stimulus onset, and the stimulus duration remained constant within blocks of trials. In the present study it was found that when foreperiods and durations are selected randomly from trial to trial, reaction time does vary significantly as a function of stimulus duration.


Effects of orienting tasks on recognition of chess positions. Two experiments using a levels-of-processing paradigm were performed to demonstrate the existence and usefulness of a semantic component in chess knowledge. Experiment I compared forced-choice recognition of chess positions after a structural task (piece counting) as opposed to a semantic task (choosing a move). Recognition accuracy, confidence, and familiarity ratings all showed a facilitation effect in the semantic condition. By including an orienting task that did not encourage semantic processing but still allowed pattern-matching operations to occur (copying a board), Experiment II demonstrated that this task effect was a genuine enhancement of memory due to meaningful processing. One again, the processing of meaningful relations in the semantic task (positional evaluation) produced a higher level of recognition performance than did the more structural processing. These results suggest that aspects of meaning have some input into the processes that generate the memory representation of a chess position.


Effect of thirst and change of thirst on bar-pressing to escape bright light. Female albino rats trained to press a bar to turn off a bright light while water-satiated performed better than rats trained while thirsty. It is suggested that thirst elicits responses such as increased activity which compete with stationary behavior required for bar-pressing. Since the proposed competing responses may facilitate locomotor behavior, this hypothesis might also explain the general finding that hunger or thirst facilitates performance on tasks where escape or avoidance requires locomotion. Switching satiated subjects to the thirsty condition caused decreased performance, while the opposite shift apparently failed to improve performance above the level of a control group.


Developmental trends in the processing of multidimensional stimuli. The ability to process variations in two dimensions of a visual stimulus as efficiently as variations in one dimension was examined in a choice--reaction-time paradigm. Kindergarten children (N = 23), second graders (N = 37), fourth graders (N = 36), and college students (N = 29) were asked to determine which of three simultaneously presented geometric stimuli was different from the other two. The number of dimensions on which the different stimulus was unlike the other two was varied. Sets of trials were also either homogeneous or heterogeneous with respect to the type of dimensional variation presented in the set. The results indicated a developmental change, which is essentially complete by ten years of age, from serial to parallel processing of dimensions.


[Toxic pathology of the hepatocyte in histiotype culture. I. The experimental model. Ultrastructural and cytochemical study]. Principle of the method. Description of the techniques used to obtain the cultures, light and electron microscopic study, biochemical determination of proteins, of DNA, of the incorporation of H3-thymidine, of total and lysosomal acid phosphatase activity. Detailed description of hepatocytes developed in unicellular layer: shape and distribution of the cells, junctions, cellular apparatuses and organelles, cytoplasmic inclusions. Comparison of the hepatocyte in vitro and in vivo. The most obvious differences are related to experimental conditions of geometry and nutrition. Particular note should be taken of the microvillous appendices of the free surface and the underlying explasmic layer. Specific physiological activities are evident, including glycogenogenesis. Discussion of multiplication, growth and cellular differentiation phenomena. Vitality tests. In culture, there may develop a tendency to hypertrophy of the mitochondria, of the dictyosomes, to hyperplasia of the granular or smooth endoplasmic reticulum and above all to increased autophagia.


[Angioimmunoblastic lymphadenopathy (AIL) rich in epithelioid cells presenting a Gougerot-Sjögren syndrome. Nosological relationship between Sjörgen "pseudolymphomas" and AIL (a case with a fatal course)]. The authors report the case of a 62-year-old woman in whom, 18 months following the development of bilateral parotid hypertrophy followed by a dry syndrome, there was the onset of an angioimmunoblastic lymphadenopathy (AIL) which consisted of the association of a multiple lymphadenopathy with a characteristic histological appearance, although poor in plasmocytes, and a febrile syndrome, but in the absence of a complete syndrom from a laboratory standpoint. This fact, incombination with the richness of the nodes in epitheloid cells, is such that this case resembles the type II "dysimmune and pseudo-lymphomatous lymphadenopathies" (DPLL) of Delsol et al. Although the term AIL has never been used before in the title of previous publications of pseudo-lymphomas occuring during Sjögren's syndrome, it would seem possible, as has already been suggested by Diebold et al. (3) with regard to several cases, that certain of these pseudo-lymphomas are true AIL. The rapidly fatal course with visceral spread shown at autopsy and above all the presence of exclusively immunoblastic plaques in several mode areas led, on the basis of the criteria of Nathwani et al. (22), to acceptance of the coexistence of an immunoblastic sarcoma.


[Aleukemic chloroma. review of literature and diagnostic problems: 1 case]. The authors report the case of a 30-year-old man with granulocytic sarcoma of the chest wall presenting as a swelling with axillary lymphadenopathy followed by pleuropericardial effusions. The myeloblastic nature of the tumor cells was confirmed on the adenogram by the detection of granulations, rare Auer bodies and myeloperoxydase activity. It was confirmed by the presence of numerous granulations by electron microscopy and by that of a chloracetate esterase activity detected using Leder's protocol (9) on sections of material mounted in paraffin wax after formol fixation. Four marrow biopsies form different sites were normal. The course was fatal in six months, despite multiple chemotherapy, with massive invasion of the thorax by the tumor without the presence of myeloblasts in the circulating blood. The autopsy confirmed the preponderance of thoracic involvement (greenish in colour) and the presence of diffuse marrow myeloblastosis. In the light of this case, the rare instances (of the order of 10) of aleukaemic chloroma recorded in the literature are reviewed, emphasising the difficulties of diagnosis of these tumours and the ways in which they may be overcome.


[Macroscopic pathologic anatomy technicians. Function and recrutment in the Hospital Center]. The authors lay out 7 years of activity in the Anatomy-Pathology laboratories of a non university hospital center organized with the aim of carrying out an autopsy for more than 50 p. 100 deaths occuring in this hospital. They introduce the concept and title, Technician of Anatomy and Macroscopic Pathology.


[Operative model in psychiatry].

[Operative model in psychiatry]. This model is intended for an objective and dynamic study of mental disorders. It is specified in its various aspects: definition, cultural and historical origins, formation modus, conditions of validity, clinical, methodological, and epistemological effects. Its study shows that psychiatry can change rationality level, while including and extending the data of the previous trends. A new psychiatry better adapted to the contemporary scientific orientation can be considered.


[Psychological treatment of transsexualism and sexual identity disorders some recent attempts]. Psychological treatments of transsexualism and sex gender Dysphoria syndroms. Recent data. There are generally two types of patients requesting sex change operations: one type is the classical but rare transsexual, the others belong to the larger more vague group of sex gender Dysphoria. These syndroms have been felt to be unresponsive to psychotherapy. We review here some recent attempts of psychological treatments which claim to improve satisfaction with biological sex gender identity and result in renonciation of the request of sex reassignment surgery (S.R.S.). These psychotherapies use various methods: Behavior therapy, psychoanalytically-oriented psychotherapy, religious exorcism and conversion. The reports reviewed suggest that sex gender identity may be more malleable than previously thought in transsexual syndrom, at least in relatively youthful subjects. Cases of recent onset of the syndrom which result from a crisis cases underline the necessity for careful evaluation and attempted psychological treatment before undertaking irreversible surgical procedures.


Blunt traumatic rupture of the diaphragm. Blunt traumatic rupture of the diaphragm must be suspected in all patients with massive trauma and especially in those whose chest roentgenogram reveals an abnormal or obscured diaphragmatic shadow. Regular reevaluation is most important. A diagnostic pneumoperitoneum is the most accurate preoperative test available. Transthoracic approach is the operation of choice.


Acute traumatic hemothorax.

Acute traumatic hemothorax. Over the past 5 years, 107 patients have been evaluated for acute traumatic hemothorax at the University of Kentucky Medical Center. Immediate tube thoracostomy was performed on 90 patients for evacuation of blood and air. Only 2 patients died. Thoracotomy was performed as part of the initial therapy in 9 patients. Thoracotomy for continued hemorrhage from a pulmonary parenchymal injury was required in 3 patients from the entire group. Thoracentesis or observation was the initial therapy for limited hemothorax in 8 stable patients. Three of these patients subsequently required tube thoracostomy 2 to 23 days following injury due to expanding effusions, and 1 patient required multiple thoracotomies for sepsis, fibrothorax, and empyema. These observations indicate that early evacuation of blood by means of a tube thoracostomy is essential to minimize morbidity in acute traumatic hemothorax. If continuing hemorrhage after tube thoracostomy occurs, there is a higher association of injury to additional vital structures.


Late sequelae of perioperative myocardial infarction. The late suquelae of myocardial injury occurring at the time of direct myocardial revascularization are unknown. Fifty of 500 consecutive patients undergoing aortocoronary bypass grafting developed both electrocardiographic and enzymatic evidence of myocardial injury. They were matched with 50 patients of similar age, sex, history of previous infarction, severity of angina, degree of coronary arteriosclerosis, and level of ventricular function as determined by preoperative angiographic studies. The conduct of the operation was identical in each group except for prolongation of total cross-clamp time in those patients with myocardial injury. The total number of vessels grafted, the conduit used, and the operative mean graft flow were similar. Results of treadmill stress testing at 24 to 36 months were not significantly different between groups. Angina status, long-term survival, graft patency, and ventricular function were not adversely affected by intraoperative myocardial injury. However, postoperative ventricular function and stress test performance were related to graft patency.


Improved technique of intraaortic balloon insertion. Routine insertion of an intraaortic balloon through the femoral artery may be difficult in the face of obstructive aortoiliac atherosclerosis. Perioperatively, the balloon catheter may be guided through diseased vessels by transabdominal palpation.


Transverse femoral arteriotomy for intraaortic balloon insertion. A technique for intraaortic balloon placement employing a transverse femoral arteriotomy is described. After balloon removal, the arteriotomy can be closed primarily. Avoidance of retained graft material or use of a vein patch reduces the likelihood of vascular complications.


A simple method for exposing the external jugular vein for placement of a permanent transvenous pacing catheter electode. A method is presented for cannulating the external jugular vein and implanting a pacemaker through one incision. No increase in morbidity over the conventional methods has been demonstrated. This technique is an attractive alternative to the standard emthods in use.


Carcinoma of the esophagus.

Carcinoma of the esophagus. Carcinoma of the esophagus continues to have a low 5-year cure rate despite advances in radical surgery and super-voltage radiation. Neither patient education nor newer diagnostic techniques have improved survival. The reported operative mortality is 4 to 30% for esophagogastrostomy and 10 to 44%  for colon interposition. Average survival time with surgery is 11 to 28 months and 5 to 11 months with irradiation. Local recurrence is high (33 to 76%) with irradiation. The reported 5-year survival rate with preoperative irradiation followed by surgery is higher (14 to 25%). Recent reports have concentrated on improving functional rehabilitation rather than improving cure rates. Palliative surgery is more acceptable because of lowered operative morbidity and mortality and the high complication rate with radiation therapy for far advanced disease. New approaches of interest include fundoplication added to esophagogastrostomy, substernal gastric bypass with anastomosis in the neck, reversed gastric tube (Heimlich operation), the addition of postoperative rather than preoperative irradiation in patients with potentially curable lesions, the use of preoperative hyperalimentation, and the potential application of immunotherapy.


Antibody responses to influenza vaccines containing A/New Jersey/8/76. Studies were undertaken with whole virus, subunit and adsorbed subunit influenza vaccines containing the A/New Jersey/8/76 strain to compare the antibody response induced by immunization with these vaccines. There were no significant differences in the haemagglutination-inhibiton (HI) antibody responses to A/New Jersey/8/76 induced by these vaccines in the adult groups under study. Vaccinees over 23 years of age produced good HI antibody responses to one dose of vaccine. Neuraminidase antibody and complement-fixing (CF) antibody responses were determined for the A/Victoria/3/75 component of bivalent vaccines. There were significant increases in neuraminidase inhibiting (NI) antibody titres but no increase in the complement-fixing antibody titres after vaccination.


The mucosa-associated microflora of the rat intestine: a study of normal distribution and magnesium sulphate induced diarrhoea. Specimens of intestinal mucosa of rats were examined closely to determine the distribution of the mucosa-associated microbial flora. Six distinct zones were found along the length of the intestinal tract. The first zone, in the small intestine 50 cm or more from the ileocaecal junction, had no associated flora: however, each of the five other zones had different populations of microorganisms associated with the mucosa. Some of these organisms have not been reposted previously. Treatment of rats with oral doses of the purgative magnesium sulphate resulted in dramatic changes in the distribution of these mucosa-associated microorganisms. The normal flora of ileal and caecal crypts disappeared, while the organisms in colonic crypts were unchanged. Large numbers of mucosa-associated bacteria appeared in the stools of treated animals.


Separation of mouse bone marrow cells using wheat germ agglutinin affinity chromatographyy. Mouse bone marrow cells were fractionated on columns of wheat germ agglutinin-Sepharose 6MB (WGA-Sepharose) and conditions established for specific binding and cell enrichment in the eluted fractions. A small proportion (7%) of the cells applied did not bind to the column and 60% of these were lymphocyte-like cells. Twice as many cells were eluted from the WGA-Sepharose column using N-acetyl-D-glucosamine (GlcNAc), and 80% of these cells were polymorphonuclear granulocytes and metamyelocytes. These cells were only released from the matrix in the presence of GlcNAc at high buffer flow rates (greater than 4 ml/min). Approximately 3 x 10(8) bone marrow cells bound to 1 ml of WGA-Sepharose. At least 5 min were required for 90% binding of the cells and elution of the cells with GlcNAc required nearly 20 min at 24 degrees. At 37 degrees the elution of cells with ClcNAc was much faster (less than 5 min) and a much larger percentage of cells (40-50%) was specifically eluted. Sodium azide (0.02%, w/v) did not prevent cells binding to WGA-Separose or alter the distribution of cells eluted by GlcNAc, but did slightly increase cell yields. Elution of cells with different concentrations of GlcNAc gave fractions enriched in different cell types. Analysis of cell fraction with a fluorescence-activated cell sorter showed that the lymphocyte subpopulation which failed to bind to WGA-Sepharose had been depleted of cells with a high density of immunoglobulin on their surface. The lymphocytes with a high density of surface immunoglobulin were recovered in the cells released from WGA-Sepharose using mechanical agitation.


In vitro degradation of mouse, rabbit and dog antibodies to Vibrio cholerae by succus entericus. Purified antibodies to Vibrio cholerae from mouse, rabbit and dog were digested in vitro by homologous intestinal secretions. When assessed with regard to their complement-dependent vibriocidal activity, IgG antibodies were generally more susceptible to degradation than IgM antibodies, High levels of tryptic inhibitors were required to inhibit this digestion. Rabbit IgG was unusual in being quite resistant to digestion. Gel filtration studies demonstrated that secretory IgA, isolated from mouse intestinal secretions, was resistant to proteolysis. Similar studies on dog IgG and mouse IgM demonstrated production of F(ab') 2-like fragments. Digestss of these antibodies, while devoid of Fc-mediated vibriocidal activity, retained significant protective activity for baby mice.


The source of IgM and IgG in the dog intestine. The source of IgM and IgG2a,b in the dog intestine was investigated, using labelled dog immunoglobulins and chronic Thiry-Vella loops of dog small intestine. Clearancess of IgM and IgG2a,b from serum into intestinal secretions were similar, reflecting transfer of a greater mass of IgG2a,b than of IgM. Only 20% of the intestinal IgM derived from serum, irrespective of the marker used. About one third of the total intestinal IgG, of all sub-classes and accrued from all sources, was serum-derived IgG2a,b. This indicates that serum is a major contributor to dog intestinal IgG2a,b.


Total protein patterns in human amniotic fluid. Total protein patterns of amniotic fluid samples of different age groups, following polyacrylamide disc gel electrophoresis, showed a wide range of variation in early pregnancy, but no two cases had identical banding, indenticating their genetic variability. An assessment has been made here of the total protein, albumin and transferrin patterns from normal fluids of different age groups by gel electrophoresis, in order to observe the genetic variations and relationship with foetal age, if any.


Acquired immunity to the trematode Fasciola hepatica in rats. Following a primary infection of 5 metacercariae (mc) of Fasciola hepatica, rats became immune to challenge with 30 mc. Immunity was less consistently demonstrated following challenge infection with 5 mc. The levels of precipitating and miracidial immobilizing antibodies, and antibodies detected by an indirect fluorescent antibody test, were monitored during the course of a primary infection of 5 mc and challenge infection of 30 mc. Following primary infection, peaks in the antibody response were associated with the invasion and migration of juvenile flukes in the liver parenchyma. Antibody titres fell when flukes entered the bile duct. There was a slight elevation in the titre of all antibodies following challenge, but, apart from those detected by the fluorescent antibody test, this elevation was not as marked as in control animals. It is suggested that flukes become isolated from, or have diminished contact with, the immune system once they enter the bile duct. This might explain why adult flukes survive in immune hosts whereas challenge metacercariae are destroyed.


Incest hoax: false accusations, false denials. Expertise  in investigating incest accusations is essential for psychiatrists because the law requires the reporting of sexual abuse of children. In such cases persistent and methodical investigation tends to yield a consensually credible view of what really happened without resort to special forensic techniques of truth-finding. In order to make a diagnosis of incest hoax, the investigator must thoroughly understand the mechanics of the hoax and the  psychodynamics of the perpetrator. Failure to recognizing a delusional hoax can delay treatment for the perpetrator of the hoax. Failure to recognize a child's fabrication can subject the family to unnecessary legal action and unwittingly support the use of a similar manipulative technique by other susceptible children. Failure to recognize the false retraction of an incest accusation may leave the victim in danger of further sexual abuse or of physical punishment for having revealed the secret.


Sexaully motivated burglaries.

Sexaully motivated burglaries. Overt or covert sexual motivation was found in several repetitive, compulsive burglars. Voyeuristic impulses, transvetism, confused sexual identity, and hatred of mother transferred to women in general are common findings. The possibility of eventual serious attacks on women should be considered in those who in addition to burglaries, particularly committed in bizarre circumstances and alone, have a history of minor attacks on women and mistreatment of animals. The cat appears to symbolize a woman, so mistreatment of cats in combination with sexually motivated burglaries should be considered an important prognostic sign.


Sadism and masochism: sociological perspectives. This paper represents an initial attempt to provide theoretical structure for the sociological study of sadomasochism. Sadomasochistic behavior, like human behavior in general, is most fully understood within a social context. To understand "what is going on" within an S&M episode, one must know something about the culture of the group and how it defines and categorized people and behavior. This is where frame analysis is helpful. Frames are central components of the culture of the group, through which its members interpret the world. To a great extent the frame itself is structured by the language of the groups, which serves to explain to its members what is happening and to justify their desires, motives, and behavior. Frames tell people what is and what is not proper, acceptable, and possible with their world. They define and categorize for their members situations, settings, scenes, identities, roles, and relationships. When people join sadomasochistic groups, or any other kind of group, they are taught not only frames, but also the conceptual tools or "keys" for defining, applying, transforming, and limiting them. Frame analysis helps make sense of findings that might otherwise be difficult to explain. For example, the apparently puzzling existence in the S&M subculture of "dominant" women and "submissive" men when the larger society to which these individuals also belong prescribes aggressiveness for males and passivity for females may be explained in terms of makebelieve, fantasy, and the theatrical frame. Lack of generalization into the larger world of roles and relationships developed within the sadomasochistic subworld is explained in terms of how behavior is "keyed". A number of areas that have not been fully developed here could be profitably explored. For example, although we have attended to the structuring and limiting of S&M frames, we have not explored misframings, miskeyings, breaking frame, and other errors and their consequences for interactants. Hollander, for instance, provides an example in which an S&M episode was miskeyed with disastrous results. Another issue for further exploration involves the ways in which the language of S&M structures the relations between participants in the world by building in notions of activity and passivity and tying these to particular roles in the interaction. The specific identities of people as "dominant" or "submissive", the ways in which they arrive at a recognition of these self-identities, and the stability of these orientations await investigation.


Ammoniagenesis in kidney cortex mitochondria of the rat: role of the mitochondrial dicarboxylate anion transporter. Since glutamine enters rat kidney mitochondria without exchange for an anion, the exit of its carbon skeleton must involve the dicarboxylate anion transporter (malate - inorganic phosphate) for ammoniagenesis to proceed. Therefore, this important mitochondrial anion transporter was studied in isolated renal cortex mitochondria. The phosphate concentration required for half-maximal rates of malate exit from renal mitochondria of normal rats was 1.0 mM. This value was not decreased in renal cortex mitochondria from rats with chronic metabolic acidosis. The maximum velocity of the dicarboxylate transporter was not increased in renal cortex mitochondria from these acidotic rats. These kinetic parameters were similar in liver mitochondria. There was no acute activation of the dicarboxylate carrier when the incubation medium pH lowered. Thus, there is no demonstrable activation of the dicarboxylate anion transporter in kidney cortex mitochondria of the rat with chronic metabolic acidosis. The significance of these results with respect to the regulation of renal ammoniagenesis is discussed.


A study of cell surface constituents restricting Salmonella minnesota R form glycopid mR595 fixation to normal rat embryo fibroblasts. The nature of the cell surface constituent(s) containing sialic acid that block fixation of bacterial glycolipid mR595 to normal rat fibroblasts was explored. Indirect evidence suggests that a trypsin-sensitive, high molecular weight glycoprotein, present in larger amounts on the surface of normal cells (as compared with transformed rat fibroblasts), may be involved as a blocking agent.


Studies on the use of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline for the synthesis of acylamino acid anilides and p-nitroanilides. The use of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) for coupling acyl-L-amino acids with aniline and p-nitroaniline has been investigated. Optically pure anlides are obtained in good yield but partial racemization occurred in one case. p-Nitroanlides cannot be obtained under similar conditions but if the reaction solvent is removed and the residue left for several days, coupling occurs giving a racemic product in moderate yields. Reaction mechanisms are proposed on the basis of isolated and characterized intermediates. It has been found that N-benzoylamino acid anilides and p-nitroanilides are cleaved within a few minutes by hydrogen bromide in acetic acid to give the N-benzoylamino acid and the amine.


Purification and properties of beta-xylosidase from Penicillium wortmanni. A purification method for an extracellular beta-D-xyloside xylohydrolase, EC 3.2.1.37) induced in Penicillium wortmanni is described. It includes diafiltration, acetone precipitation, and hydroxylapatite chromatography. The enzyme has a molecular weight of about 100,000. Its pH optimum is at pH 3.3--4.0 and it is most stable at pH 5.0-6.0. Its isoelectric point is at pH 5.0. Sulfhydryl and histidine reagents are not inhibitory. The influence of added cations and anions is negligible. N-Bromosuccinimide oxidation of two to three tryptophan residues per molecule entails rapid inactivation. Glycon-specificity studies indicate strict requirements at C-2, C-3, C-4, and C-5, although alpha-L-arabinopyranosides are substrates. As the enzyme seems to hydrolyse xylooligosaccharides endwise, with retention of configuration in the reaction product, the enzyme is a true glycosidase, probably operating by a double-inversion mechanism.


A critical analysis of renal blood flow distribution during hemorrhage in dogs. Renal blood flow (RBF) and its distribution were measured before and during hemorrhage by utilizing: 1) and electromagnetic flowmeter, 2) radioactive microspheres, 3) 85Kr washout and 4) a freeze-dissection 85Kr disappearance technique. Before hemorrhage, total RBF was 3.48 and 3.56 ml/g.min measured with microspheres and flowmeter. Outer cortical flow was 6.65 and 7.56 ml/g.min measured with microspheres and freeze-dissection respectively while inner cortical flow was 5.15 and 4.38 ml/g.min. After hemorrhage, total flow as measured with either method was 2.3 ml/g.min. Outer and inner cortical flow (3.85 and 3.08 ml/g.min respectively) measured with microspheres was higher than that measured by freeze-dissection (1.54 and 1.60 ml/g.min). The data suggest that preglomerular renal blood flow distribution may be different than cortical capillary flow distribution, especially during hemorrhage. The freeze-dissection technique provides flow rates for the outer medulla that are closet to component II (outer medullary flow) of any of the components of the externally monitored inert gas washout. Components I and II of the externally monitored washout may represent whole cortex and subcortical outer medulla respectively.


Effect of mild hypovolemia and fluid replacement on regional oxygenation, flow, and small vessel blood content in the rabbit heart. A study was conducted on the effects of mild hemorrhage-induced hypovolemia and subsequent fluid replacement with lactated Ringer's or dextran solution on the hearts of 61 pentobarbital anethetized open-chest New Zealand white rabbits. After a blood loss equivalent to 1.25% of body weight, blood flow in the subepicardial and subendocardial regions of the left ventricular free wall was unaffected, relative tissue PO2 fell, and small vessel blood content, a measure of open capillary density, increased. No regional differences were seen after one hour. With fluid replacement, small vessel blood content returned toward control; coronary blood flow and myocardial relative tissue PO2 were unaltered. These results are best explained by an increased myocardial metabolism and a loss of blood oxygenation in hypovolemia and a return of metabolism toward control with fluid replacement. The lack of regional effects indicated that the subendocardium was no more adversely affected than the subepicardium during the experimentally induced mild hypovolemia.


Stimulatory effect of adenosine on hepatic adenine nucleotide and energy charge levels in shocked rats. In hemorrhagic shocked rats, the hepatic energy charge (ATP+1/2ADP)/(ATP+ADP+AMP) fell rapidly from 0.857 to 0.542 within 2 hours and was rapidly restored to normal levels after completing the reinfusion of shed blood. The total adenine nucleotide levels decreased slowly from 3.83 to 2.57 mumoles per g wet liver 2 hours after shock, and increased to normal levels 2 hours after reinfusion of shed blood. The intraperitoneal injection of 2 mg adenosine/100g body weight, 85 mg glucose/100 g body weight and 3.3 units insulin/100 g body weight, simultaneously with the reinfusion of shed blood, enhanced the recovery of energy charge and adenine nucleotide levels. The injection of 2 mg adenosine alone was ineffective in restoring the energy charge. However, administration of more than 6.7 mg adenosine/100 g body weight enhanced recovery of energy charge and adenine nucleotide levels, whether insulin was added or not.


Vagal stabilization of the ischemic canine ventricle. To determine whether vagal activity during myocardial ischemia functions to stabilize the heart, the left anterior descending coronary artery in dogs was occluded for periods of 3 1/2 minutes with and without concurrent vagal stimulation. Bipolar electrograms were measured from the surface of the canine left ventricle within and outside the regions of intended ischemia. Ischemia in the absence of vagal stimulation depressed both the electrogram amplitude and the upstroke velocity of the electrogram signal. Vagal stimulation significantly decreased the absolute magnitude of the ischemia-induced decrease of the electrogram signal, which indicates that it tended to stabilize the insulted heart. This stabilizing influence however, was seen only in the presence of adrenergic blockade with practolol. The vagal response was only partially blocked by atropine, whereas it was abolished by lidocaine. These results suggest that a vagally mediated stabilization of the ischemic canine ventricle can occur and is unmasked only in the absence of sympathetic neural activity.


Surgical mortality among the elderly. An analysis of 4,050 operations (1970-1974). The overall surgical mortality rate of 3.4 percent in 32,308 operations (22,288 patients) between 1970 and 1974 was essentially the same as the 3.7 percent recorded for 30,241 operations (22,967 patients) during the preceding 5 years. The surgical mortality rate among patients 70 years or older fell significantly (p less than 0.005) from 6.8 percent of 3,754 procedures (2,766 patients) during the 1965--1969 period to 4.8 percent of 4,050 procedures (2, 783 patients) between 1970 and 1974. There was a 50 percent increase in operative mortality from all causes among the elderly when compared to the rates of 4.7 percent of patients and 3.2 percent of procedures observed in patients under the age of 70. If the patients in whom the surgical procedure seemed incidental to their death from other causes are excluded, the mortality rate among the elderly was a more realistic 2.8 percent of procedures (114 patients) between 1970 and 1974. The 30-day mortality rate from all causes noted in this group was 3.7 percent of procedures, or 5.4 percent of patients. These results appear to justify the philosophy that age alone is no contraindication to potentially curative cancer surgery, and demonstrate that such surgery can be performed with acceptable mortality rates.


Alkaline phosphatase isoenzymes.

Alkaline phosphatase isoenzymes. At the time of admission, 4 to 8% of all hospital admissions have a elevation of alkaline phosphatase. This high incidence of alkaline phosphatasemia has resulted in not only a need to identify the source of the elevated alkaline phosphatase; it has also led to a marked proliferation in laboratory procedures aimed at identifying the various isoenzymes of alkaline phosphatase. These various techniques are reviewed and their relative merits are discussed. No single technique adequately delineates all of the alkaline phosphatase isoenzymes, but the combination of heat fractionation, electrophoresis, and the measurement of an additional hepatobiliary enzyme has been shown to be able to identify the source of origin of more than 95% of all cases of alkaline phosphatasemia. The individual isoenzymes of alkaline phosphatase are discussed in detail, and the underlying pathophysiology is reviewed so that physiologic elevations of alkaline phosphatase are not confused with pathologic increases in alkaline phosphatase.


Autologous blood transfusion.

Autologous blood transfusion. Autologous blood transfusion is a procedure in which blood is removed from a donor and returned to his circulation at some later time. Autologous transfusion can be performed in three ways: (1) preoperative blood collection, storage, and retransfusion during surgery; (2) immediate preoperative phlebotomy with subsequent artificial hemodilution and later return of the phlebotomized blood; and (3) intraoperative blood salvage and retransfusion. All three methods of autologous transfusion offer a potentially superior method of blood transfusion which eliminates many of the problems and complications associated with the banking and administration of homologous donor blood.


Erythropoietin assay: present status of methods, pitfalls, and results in polycythemic disorders. Mammalian erythropoiesis is regulated primarily by the hormone erythropoietin (ESP). Studies of ESF have provided information about its biochemistry and its role in regulating hemoglobin synthesis. Such studies rely on assays for erythropoietic activity in biological fluid. The assay which has proven most valuable and is used most widely is based upon the incorporation of radioactive iron into newly-formed red cells of polycythemic mice. While this assay has gained wide acceptance, it is expensive, cumbersome, imprecise, and insensitive, capable of reliably detecting no less than 50 milliunits of erythropoietin. Improvements in assay techniques will require new methodology relying primarily on immunologic recognition for the determination of hormone activity. Currently under development and in experimental use are radioimmunoassays and a hemagglutination inhibition assay. While work has progressed in these areas, these assays are not of proven value at present and meaningful physiological correlations have not emerged from their use. Alternatively, assays for hormone activity using suspensions of hematopoietic cells and the measurement of incorporation of radioactive isotopes into hemoglobin have provided both improvement in sensitivity and precision. The disadvantage of these types of assays is that they are sensitive to factors other than ESF and may give misleading information, depending on whether the factors present stimulate or inhibit cellular proliferation and hemoglobin synthesis. While such techniques may provide a temporary solution to some problems associated with assaying ESF for purification or physiological studies, they are not the best answer to the overall problem of hormone detection and characterization. The most important contribution to this field will be the availability of large amounts of highly purified and well-characterized ESF.


Alteration of human serum ribonuclease activity in malignancy. A review of the literature and current biochemical studies is presented which provides significant evidence of alteration in the level of the enzyme ribonuclease activity in cancer. Current studies reveal that 80% of all cancer patients have alteration in ribonuclease activity and that individuals known to be at high risk for the development of cancer also demonstrate significant alteration of ribonuclease activity. It is noted that while elevation of serum ribonuclease exists within the cancer state and appears to be independent of clinical status (relapse, remission, or cured), diminished activity is found within the tumor itself. Animal models are reviewed which demonstrate that ribonuclease activity becomes elevated in the murine species subsequent to the transplantation of tumor and following the infection of the host with oncogenic virus. The occurrence of elevated ribonuclease activity in high tumor incidence strain mice long before the development of overt tumor is alos discussed. To date it is not possible to assign a specific function to the changes in the level of ribonuclease in connection with the cancer state. However, evidence indicating that tumor chemotherapy is generally associated with early elevation of ribonuclease activity within the tumor cell suggests that increased ribonuclease activity may play a role in the process by which the host restricts neoplastic transformation. The potential of this enzyme as a biochemical marker in cancer is discussed.


The use of mixtures of topical corticosteroids as a mechanism for improving total drug bioavailability: a preliminary report. The feasibility of using mixtures of corticosteroids as a mechanism for enhancing total percutaneous absorption of drug has been investigated. The results of this study indicate that under certain conditions, mixtures of corticosteroids exhibit independent solubility, partitioning and diffusion behavior. Mixtures of three 21-esters of fluocinolone acetonide were found to penetrate excised human skin independently. The mixture flux rate was demonstrated to greatly exceed that attained with any of the component steroid esters at an equal concentration. A mixture composition containing a total steroid concentration of 0.015% was shown to produce significantly greater in vivo human vasoconstriction than any of the individual steroids at comparable concentrations. These results strongly support the potential clinical utility of certain topical corticosteroid mixture compositions.


Design of chemical structure for optimal dermal delivery. The process of dermal absorption can be most conveniently divided into four independent steps, each of which is subject to its own structure-deliverability relationship. These are: (1) the process of release of the active agent molecules from the neat state to the dermal; (2) the process of permeation through the barrier layer; (3) the process of release of the drug from the epidermal barrier phase to the immediate subbarrier layer, (4) the micropharmacokinetics of the drug and its metabolite in the dermal compartment. The rate-controlling process can, in most instances, be identified with one of the first three processes. These in turn are largely subject to the physical chemical, thermodynamic characteristics of the transported species. Although the first process has been essentially ignored by earlier workers, it is in most instances of major concern in designing percutaneously available drug species.


Hydration and percutaneous absorption.

Hydration and percutaneous absorption. The state of hydration of the normal stratum corneum ranks next to the nature of the penetrating molecule as the most important factor in the rate of percutaneous passage of any substance. If the stratum corneum is removed, the barrier to gain or loss of water vapor is lost. Diseased skin in which the process of keratinization is disturbed becomes more susceptible to transepidermal water loss. Diffusion through the stratum corneum is a passive process, affected only by physical factors, chiefly the water vapor pressure gradient. The low diffusion constant and high activation energy suggest that extensive hydration does not drastically affect the 'barrier' function of the stratum corneum. Below 100% ambient relative humidity, water transfers outward and a gradient in water concentration exists within the stratum corneum. The horny layer swells continuously on immersion in water, absorbing as much as ten times the dry weight. The water is bound within the intracellular keratin. Permeability increases rapidly initially and then slows down to a steady state diffusion. Regardless of the increase in permeability, the highly hydrated stratum corneum remains quite water impermeable, with a diffusional resistance ca. 10(4) times greater than an equivalent layer of water. The diffusion process is determined mainly by the intrinsically low diffusivity and the ultrastructure of the intracellular keratin.