Some effects of mazindol, an anorectic drug, on rat brain monoaminergic systems. Mazindol was devoid of effect both on rat brain steady state levels of 5-HT, 5-HIAA and tryptophan and on the rate of synthesis of 5-HT in the rat brain. Mazindol had no effect on rat brain 5-HT uptake in vivo as determined by the effect of drug pretreatment on the ability of p-chloroamphetamine to lower central 5-HT levels. A large dose of mazindol caused a slight transient decrease in rat brain levels of NA and DA. Blockade of rat brain catecholamine uptake was quantified by studying drug effects on the ability of intraventricularly administered 6-hydroxydopamine to lower brain NA and DA content. Mazindol was an extremely potent inhibitor of rat brain NA uptake in vivo, being 4-5 times more potent than desipramine. Mazindol also blocked rat brain DA uptake. Doses of mazindol needed to release alpha-methyl-m-tyramine from the rat striatum were appreciably greater than the corresponding doses of d-amphetamine. The neurochemical profile of mazindol bears a much closer resemblance to that of d-amphetamine than to that of fenfluramine.


Peptide antagonists of angiotensin-induced adrenal catecholamine release. The effect of analogs of angiotensin (modified with an Ile-substituted for Phe) was studied in the isolated, retrogradely perfused adrenal of the cat. Continuous differential analysis of norepinephrine and epinephrine output was quantified with an automated trihydroxyindole procedure. [Ile8]-angiotensin I and [Ile7]-angiotensin III exhibited negligible secretory activity, in contrast to the stimulatory effects of [Ile8]-angiotensin II (10-20% activity relative to angiotensin II). [Ile8]-angiotensin I blocked angiotensin II-induced catecholamine secretion and a pA2 value of 8.50 was obtained. [Ile7]-angiotensin III was an especially potent antagonist of angiotensin II and a pA2 value of 10.4 was calculated for this heptapeptide analog. The pA2 value for [Ile8]-angiotensin II, a partial agonist in the adrenal medulla was 9.33. These three analogs were equally effective against secretion induced by the corresponding unsubstituted homologs (Ang I and Ang III). These data suggest that all these angiotensin peptides interact with a common receptor. [Ile8]-angiotensin I and [Ile7]-angiotensin III had no effect on adrenal medullary responses induced by KCl, nicotine and bradykinin. These structural analogs of angiotensin are pure competitive antagonists of angiotensin in the cat adrenal chromaffin cell.


Effects of several tricyclic antidepressants on the hemodynamics and myocardial contractility of the anesthetized dogs. Cardiovascular effects of several imipramine analogs were investigated in the anesthetized mongrel dogs. Significant reduction in the cardiac output produced by lower doses (2.5 mg/kg, i.v.) of imipramine and 2-OH-DMI was not due to a depression of myocardial contractility. In contrast, 2-OH-imipramine (1.25 mg/kg) and DMI (2.5 mg/kg) significantly reduced contractility within 10 min after i.v. administration; however, significant decrease in the cardiac output did not occur until after 60 min. Higher doses (5 mg/kg) of imipramine, DMI and 2-OH-DMI significantly attenuated cardiac rate, contractility and output within 5 min after i.v. administration. 2-OH-imipramine, 2.5 mg/kg, i.v., depressed contractility and cardiac output to a degree equivalent to that produced by 5 mg/kg of imipramine, DMI and 2-OH-DMI. 3-Chloro-imipramine (5 mg/kg, i.v.) induced decrease in the cardiac output was essentially due to a significant reduction in the heart rate since the effects of this compound on the contractility were transient in nature. 3-Cl-8-OH-metabolite of this compound had no significant effects on the cardiovascular system. The results of this investigation demonstrated that the complex cardiovascular effects of tricyclic antidepressants observed in these studies were perhaps due to a direct and/or autonomically mediated effects on the heart and vasculature. Further, the data support the conclusions that the activity of the parent compounds together with that of the metabolites contributes to overall changes observed. While all the agents are capable of reducing cardiac output, 2-OH-metabolite of imipramine appears to be most toxic on the myocardium and 3-Cl-imipramine possessed only transient effects on the contractile properties.


Mossy and climbing fiber inputs from cutaneous mechanoreceptors to cerebellar Purkynĕ cells in unanesthetized cats. 1. Mossy and climbing fiber inputs from cutaneous mechanoreceptors to Purkynĕ cells of vermis and pars intermedia of the cerebellar anterior lobe were studied in locally anesthetized, paralyzed cats prepared for painless recording sessions. In this preparation the mossy fiber and climbing fiber pathways remain fully functional. Simple spikes and climbing fiber discharges were recorded simultaneously through extracellular glass micro-electrodes and thereafter filtered off from each other for separate, computer-assisted analysis. Controlled mechanical stimulation (air jets, taps, pressure) was performed on the foot pads of all four limbs and on the hairy skin of the limbs and the body. 2. Long term recording of the spontaneous activity of 110 Purkynĕ cells revealed a simple spike activity of 85 imp./s +/- 49 imp./s (mean +/- S.D.) and 1.00+/-0.78 climbing fiber responses per second. 3. Taps to foot pads and air jets to hairy skin revealed that most of the short latency responses via mossy fibers resulted from activation of the receptors of the ipsilateral forefoot. With the same stimuli climbing fiber discharges from the ipsilateral feet were more frequently evoked than from the contralateral feet. Both via mossy and climbing fibers the contralateral hindlimb gave the smallest contribution. 4. Simple spike responses were evoked more commonly by pad stimulation (tap stimuli) than by hair stimulation (air jets). For both types of stimuli excitatory responses were more frequent (3:1) than inhibitory ones. Similarly, pad stimulation was more effective than hair stimulation in inducing climbing fiber responses. Ipsilateral stimuli were much more effective than contralateral ones in evoking both simple spike and climbing fiber responses. 5. Steady pressure stimuli modify the Purkynĕ cell discharges via mossy and climbing fiber pathways. Excitatory and inhibitory effects often of very long duration have been observed via both pathways. Again the ipsilateral forelimb was more effective than the other limbs. Mossy fiber responses were at least three times as common as climbing fiber responses and excitatory responses were more frequent than inhibitory ones. 6. There is no apparent relation between the spontaneous discharge rates of the Purkynĕ cells and the response magnitudes of the mossy fiber and climbing fiber induced excitatory and inhibitory changes inthe impulse pattern of Purkynĕ cells during steady pressure stimuli.


Somatotopic studies on the vermal cortex of the cerebellar anterior lobe of unanaesthetized cats. 1. In unanaesthetized cats with intact neuraxis the relation between the cutaneous receptive fields of Purkynĕ cells and the position of these cells in the vermis of the cerebellar anterior lobe was studied with the specific question whether this cerebellar area exhibits any kind of somatotopy in the absence of central anaesthesia. To establish the receptive fields the skin of all four limbs and of the trunk was probed with mechanical stimuli (taps, air-jets, pressure). The recording sites in the vermis were determined histologically. 2. In regard to the mossy fiber transmitted input none of the four limbs showed a dominant representation in one or more of the lobules rostral of the fissura prima or in a parasagittal section. For the ipsilateral limbs there is a greater mossy fiber input to lobule V from the forelimb than from the hindlimb (84:59%), and a reversed preponderance for lobule II (45:80%) but this indication of a somatotopic arrangement is not unequivocally paralleled by the other mossy fiber inputs. 3. Also in regard to the climbing fiber input no distinct somatotopical arrangement has been detected. Again it has been noted that the ipsilateral inputs have a somewhat greater input to lobule V from the forelimb than from the hindlimb (35:22%), and the reverse finding holds true for lobule II (10:45%). 4. The overall results did not change appreciably when the  responses were grouped according to their latencies or when the Purkynĕ cells were classified according to the patterns of convergence of their receptive fields. 5. The absence of a distinct somatotopic organization in the vermis is a direct consequence of the considerable convergence from the cutaneous mechanoreceptors of the limbs onto the individual Purkynĕ cells which occurs via the mossy and the climbing fiber pathways. It is suggested that this convergence indicates that the vermal Purkynĕ cells are particularly involved in coordinating the motor activity of forelimbs and hindlimbs.


Role of Ia afferents in the soleus motoneurones. Inhibition during a tibialis anterior voluntary contraction in man. Variations of the soleus H-reflex were studied during voluntary isometric or anisometric contractions of the tibialis anterior in man. At the onset of isometric contractions there was a weak inhibition of the soleus H-reflex, which was not related to the force of the tibialis anterior contraction. 110 msec after the onset of the EMG activity, the inhibition became secondarily more marked and was then related to the force of the contraction. This secondary potentiation of the H-reflex inhibition is brought about by group I fibres activity, since it was markedly reduced during ischemia of the leg. It persisted during local muscular fatigue, this indicating that Ib fibres from tibialis anterior are not involved and that, by the process of elimination, group Ia fibres must be responsible for the supplementary secondary inhibition. It is concluded that the early inhibition is only due to suprasegmental activity, whereas during the secondary part of the inhibition there is a supplementary inhibitory action brought about by Ia fibres from tibialis anterior. The secondary potentiation of the inhibition is therefore likely to be produced via the gamma loop.


[Effect of azabutyrone and its analogs on catecholamine metabolism in the brains of rats]. The action of the neuroleptic azabutyrone and its analogues on the accumulation and disappearance of 3H-norepinephrine and 3H-dopamine was studied in test on rats by using 3H-thyrosine, a tagged precursor of catecholamines. Azabutyrone is shown to be capable to speed up the dopamine circulation rate, as well as that of norepinephrine in the brain of rats. By comparison with azabutyrone the diazabicyclodekanyl derivative produces a more marked effect on the criculation of amines. A further "weighting" of the diazabicyclic radical and also substitution of chlorine for the fluorine atom in the para-position of the phenyl ring of butyrophenone leads to weakening of this effect.


[Molecular profile of the aminopherases of rat heart cytostructures induced by toxic doses of thyroxine]. The development of thyrotoxin intoxication is attended by a sharply increased activity of aminopherases localized in the nuclei, mitochondria and hyaloplasm. The molecular pattern of the study enzymes undergoes a substantial change and is supplemented with new isoforms in the cathod portion of the spectrum embracing the alanine-aminotranspherase of the nuclei and hyaloplasm, and that of the aspartate-aminotranspherase of the nuclei and mitochondria. Actinomycin D, an inhibitor of transcription, abolishes the effect of thyrotoxin stimulating the aminopherase activity and induction of the hormones of new molecular forms of the aminopherases.


[Effect of vitamin E on the functional state of rat liver mitochondria following bilateral subdiaphragmatic vagotomy]. On the basis of a proven protective effect of vitamin "E" in regard to cellular metabolism in hypoxia and presuming that it is exactly the chronic hypoxia that forms the main pathogenetic link in the development of "deneravation changes" the effect of vitamin "E" on the function of hepatic metachondria in rats was studied polarographically and by using tetracycline, as a fluorescent probe, at different dates following bilateral subphrenic vagotomy. The available data prompted an inference of a marked stabilizing influence of the agent on the state of mitochondria in 7 and more days after vagotomy.


[Synthesis of 2,3-diazaphenothiazine. XI. 2- and 3-arylderivatives of 10-methyl-2,3-dihydropyridazine /4,5-b/ / 1,4/ benzothiazin-1,4(10H)-dione]. The synthesis of 3-phenyl-10-methyl-2,3-dihydropyridazine[4,5-b] [1,4]benzothiazin-1,4(10H)-dione (I) and the 2 phenyl siomer-(II) is described. The compounds were prepared by the reaction of 2-methylaminothiophenol with 1,2-dihydro-20phenyl-4,5-dibromopyridazin-3,6-dione in an alkaline aqueous/alcoholic medium. The structure of the two isomers was demonstrated by transformation of (I) into 3-phenyl-10-methyl-3H-pyridazino[4,5-b] [1,4]benzothiazin-4(10H)-one (IV) reported in the literature.


[Effect of psychotropic substances on the physical work capacity of animals under high and low temperature conditions]. By way of comparison the influence of psychostimulators -- benzedrine, caffein and sydnocarb -- on the physical performance capacity of rats exposed to heat and cold was studied. It was ascertained that psychostimulators are capable of heightening the performance capacity of the animals, viz. benzedrine in cooling -- in a dose of 1 mg/kg; caffein -- in overheating -- in a dose of 30 mg/kg; sydrocarb -- in overheating -- in a dose of 5 mg/kg. In the case of benzedrine the increase of performance capacity reaches 29.4, in that of caffein -- 21.0 and in sydnocarb -- 42.1 per cent above the initial level.


[Effect of reserpine, isobarin and dopegit on the resistance of cerebral vessels]. In tests staged on anesthetized cats the effects of reserpine, isobarine and dopegit upon the resistance of cerebral vessels were studied resistographically. In 60--120 minutes after their introduction these drugs raise the resistance of intracranial vessels, inhibiting their reaction to electric stimulation of sympathic nerves and bringing down at the same time the total arterial pressure. An inference is drawn to the effect that the mounting perfusion pressure in the cerebral vessels following the action of reserpine and isobarine occurs as a result of their alpha-adrenoreceptors stimulation with norepinephrine that is intensively secreted from the nerve endings. Dopegit exerts an analogous action through formation of alpha-methyl-norepinephrine, which produces, like norepinephrine, an effect on the cerebral vessels.


[Comparative effects of pentagastrin and caerulein on the insulin secretion in the anesthesized dog]. The insulin-secretory effect of pentagastrin (5-G) and caerulein (CRL) was studied comparatively in the anesthesized dog. Both peptides, infused into the femoral vein for 30 minutes in doses of 0.20 microng/kg/min and 0.035 microng/kg/min respectively, caused a significant increase in plasma IRI without simultaneously modifying blood glucose. The insulin-secretory activity is however transitory for both, being a little more prolonged for CRL. On a molar basis the latter is almost 50 times more active than 5-G. The mechanism of the beta-cytotropic action of CRL and the different behaviour of the two peptides is discussed.


[Oxidation of a naphthenic hydrocarbon, dodecylcyclohexane, in the rat]. Naphthenic hydrocarbons, mainly of fossil origin, are widespread in our environment, and contaminate the food chains; they are also used as food additives. Their fate in mammals is unknown, except for the fact that they are absorbed and accumulate in tissues. Only a few microorganisms have been shown capable or oxidising n-alkyl substituted cycloparaffins. In this study, dodecylcylohexane has been chosen as a typical monocycloparaffin, and has been administered orally to rats. The GLC and GLC-MS analysis of the methylesters of body and hepatic fatty acids led to the identification of cyclohexyldodecanoic and its decanoïc and octanoïc homologs. The alkyl chain undergoes a terminal oxidation followed by the classical beta-oxidation process. After administration of one 200 mg dose, or incorporation of 0.1% of the cycloparaffin in the diet for 2 months, these acids were found at low levels in neutral lipids and phospholipids. Their subsequent metabolic pathway and their possible interaction with the biochemical mechanisms involving phospholipids are under investigation.


[Effect of sea buckthorn, dog rose and sperm oils, preparation "Spedian-2M" on several indices of carbohydrate metabolism and concentration of electrolytes in the tissues of rats and guinea pigs]. A specific lactate-reducing effect of fatty vegetable oils (sea-buckthorn and rose), of the sperm oil and the "Spedian-2M" preparation, of a permanent nature, or sporadically, in tests on rats, and markedly, as well as persistently--in experiments with guinea pigs was revealed. The phenomenon was most distinctly pronounced in the liver. The oils also produce a glycogen-mobilizing effect, since there could be noted a relative stability in the content of glucose in the tissues, and this despite an increased carbohydrate decomposition. The study oils, even in elevated doses, are not toxic, do not intensify the oxidative metabolism of carbohydrates, thus creating all the necessary conditions for stimulation and proteinic synthesis.


The international distribution of biomedical publications. An investigation of the U.S. role in international biomedical publication is reported, based on counts of articles, notes and reviews in 975 biomedical journals covered by the Science Citation Index in 1973. U.S. scientists authored 42% of these biomedical papers, the U.K. 10%, West Germany and France 7% and 6%, and the U.S.S.R. 4%, a sharp change from earlier in this century when Germany and France had much more prominent roles. Overall, 94% of the papers are from OECD and Eastern European countries; only 4% are from underdeveloped regions. U.S. and U.K. papers are far more heavily cited than are papers from other countries; U.S.S.R. papers are particularly under-cited. Biomedical publication rates are shown to be highly correlated (r = 0.9) with both national wealth (GNP) and national affluence (GNP/capita). National publication rates also correlate with Nobel Prize recipients. - Frame, J. D., and F. Narin. The international distribution of biomedical publications.


Structural studies on Halobacterium halobium bacteriorhodopsin. Bacteriorhodopsin, isolated from Halobacterium halobium, is an intrinsic membrane protein containing covalently attached retinal and driven by a cyclic light-driven protonmotive force. In order to extend three-dimensional analyses already in progress and to define the covalent features of such proteins, the determination of the primary structure of bacteriorhodopsin has been initiated, using techniques that can be applied to the sequence analyses of other intrinsic membrane proteins as well. The amino acid composition of bacteriorhodopsin prepared by new procedures compares well to that previously published. Various delipidation procedures have been examined for their effectiveness in yielding protein in a physical state that is susceptible to fragmentation by a number of chemical and proteolytic agents. Organic extraction, particularly in acetone:ammonium hydroxide, has proved most useful. Detergent extraction was effective in delipidating but rendered the protein inert to attack by various cleavage reagents. Sequence information was obtained from fragments isolated from several hydrolytic preparations of low percent cleavage. The most complete fragmentation was obtained from hydrolysis of bacteriorhodopsin previously modified with succinic or maleic anhydride. Both solubility and fragmentation susceptibility were enhanced by these reactions and several other derivatives of bacteriorhodopsin are currently being investigated. The behavior of bacteriorhodopsin under the conditions examined, as well as the sequence information obtained, suggest that bacteriorhodopsin is mostly contained within the lipid milieu of the membrane and may represent a class of membrane proteins that do not contain appreciable hydrophilic domains.


[Effect of quaterone on mitochondrial monoamine oxidase activity in different zones of the stomach in neurodystrophy of its wall]. New data have been made available which confirm the existence of differing quateron sensitivity of tissular monaminoxidases possessing dissimilar substrate specificity. An experimental neurogenic dystrophy of the stomach is attended on the whole by an activated deamidization of monamines, but there could be seen marked differences in the ability to intensify oxidation depending upon the localization of the mitochondrial monaminoxidases in various parts of the stomach. When introduced to intact animals in a dose of 5 mg/kg quateron tends to lower the activity of mitochondrial monaminoxidases in individual receptor areas of the stomach with respect to norepinephrine and, especially, serotonin. In such instances preliminary introduction of quateron prevents an activated oxidation of norepinephrine and serotonin, observed 24 hours after inflicting an injury. In the mechanisms governing deposition of catecholamines and serotonin in the gastric wall occurring under the effect of quateron a definite role plays also the inhibition of the mitochondrial monaminoxidases.


[Effect of x-ray contrast materials on erythrocyte hemolysis]. The effect of roentgen-contrast media on the hemolytic resistance of erythrocytes in conditions of a "hypotonic shock" and on the peroxidation of the erythrocytes lipids membranes was studied. It is shown that all the contrast media potentiate the erythrocytes hemolysis, but do not affect the rate of the lipids peroxidation. Preliminary introduction of pipolphen in a therapeutic dose in a erythrocytes suspension increases the resistance of membranes to the action of the roentgen-contrast media.


The impact of contamination by organochlorine insecticides on poultry nutrition and feeding. Nutrient interactions with organochlorine insecticides have been described primarily for vitamin A and protein. Storage of liver vitamin A is reduced by DDT and dieldrin. Low protein diets protect rats from heptachlor toxicity, whereas the toxicity of DDT, dieldrin and lindane is reduced by increasing the quantity and quality of diet protein intake. Biological performance of poultry is adversely affected by 50 to 500 ppm of most of these compounds. Hatchability of eggs and survival of chicks from hens fed insecticides are usually the most sensitive parameters of toxicity. Higher levels of DDT decrease thyroid activity. While several insecticides reduce egg shell thickness in wild birds, such changes are not observed in poultry. Extensive low level contamination of poultry tissues and eggs results from the organochlorine insecticides, with the exception of methoxychlor where tissue residues are not a problem. Tissue and egg accumulation of residues is related to dose but quantitatively different for each organochlorine compound. Tissue withdrawal and excretion takes place slowly and most of the compounds are metabolized by liver hydroxylating enzymes to various derivatives that are also stored in the body. In one case (heptachlor epoxide), the oxidation product is more toxic than the body. In one case (heptachlor epoxide), the oxidation product is more toxic than the parent compound.


[Pharmacology of uridine and cytidine].

[Pharmacology of uridine and cytidine]. It was established that with intraperitoneal introduction of uridine and cytidine their DL50 for mice equals 5100 and 2700 mg/kg, respectively. In doses of 1/27 and 1/50 of DL50 cytidine reduces by 50 per cent the edema of the rat's paw in a dextran-and formaldehyde-induced inflammation, brings down the body temperature by 1.0--1.2 degrees and cuts down the death-rate among the animals in hyperthermia produced by 2,4-dinitrophenol. Uridine does not affect significantly the course of aseptic inflammation. In adrenalectomized rats the antiexudative action of cytidine does not manifest itself. Both nuclesides fail to exercise any significant influence on the cardiac activity and respiration in cats.


Isolated hypogonadotropic hypogonadism: induction of ovulation with exogenous gonadotropins. Six patients with all of the clinical and laboratory characteristics of isolated hypogonadotropic hypogonadism (bihormonal gonadotropin deficiency) were treated with human menopausal gonadotropins (hMG, Pergonal) and human chorionic gonadotropin (hCG). Of a total of 37 courses of treatment administered, there was evidence of ovulation in 32 (29%). The first four subjects had a total of six pregnancies in 13 treatment cycles. In the remaining two subjects, there were abnormalities in the seminal fluid of both husbands and, as a consequence, only one patient conceived. The average dose and duration of hMG therapy was 3310 IU (44 ampules), administered for 13 days. A wide range of hCG dosage was used to induce ovulation, but three subjects conceived following 5000 IU of hCG on 2 successive days. None of our subjects developed any evidence of the hyperstimulation syndrome, and there was only one instance of twin birth. Serial determinations of hLH performed during hMG therapy were lower than those noted during the normal follicular phase. In contrast, hFSH levels were in the normal follicular phase range. the high success rate in these subjects indicates that the prognosis for inducing ovulation in patients with hypogonadotropic hypogonadism is good.


[Relationship between the structure and biological activity of a series of N-arylbutenyl derivatives of piperidine]. A total of 74 compounds were synthetized and their biological activity studied on 3888 animals and on 347 strains of various microorganisms and fungi. The drugs have a moderate toxicity. The compounds containing an ester grouping of the alkyl radical with an odd number of carbon atoms are less toxic than are those with their even number. Most toxic are drugs that carry a chlorine atom in the orthoposition of the benzene nucleus and are less so the ones containing the bromine atom in this position. The toxicity of bis-quaternary salts diminishes with the rising molecular weight of the radical, this not being found to happen in the series of monoquaternary compounds. Most drugs display a locally anesthetizing and marked antimicrobial and antifungal properties. The antimicrobial activity appears with R-CH3, gradually increasing and becoming maximal with R-C10H21.


Gamete interactions in vitro.

Gamete interactions in vitro. A method was devised that allowed observation of individual sperm in vitro in the presence or absence of unfertilized eggs. Sperm traversing microcapillary tubes in the absence of eggs moved in linear tranjectories. Sperm in the environs of unfertilized eggs moved in erratic paths, owing to repeated adherence of the sperm head to the wall of the microcapillary tube. However, translational velocity was unaltered. Increased adhesiveness was not noted when sperm were exposed to unfertilized eggs following removal of the cumulus oophorus with hyaluronidase. Gamete interactions in vitro were also studied at varying sperm to egg ratios. When gametes were mixed at high sperm to egg ratios (approximately 10(6):1) the cumulus oophorus was rapidly dissolved, and sperm became adherent to the zona pellucida. At low ratios (approximately 10(2):1), the cumulus oophorus remained intact. Binding of sperm to individual cumulus cells was noted. A hypothesis is presented that cumulus oophorus plays a role in fertilization by selectively trapping mature sperm within the perimeter of the egg and, in so doing, extending the duration of time in which gametes remain within close proximity, thus increasing the likelihood of egg contact by capacitated sperm.


Comparison of serum progesterone and endometrial biopsy for confirmation of ovulation and evaluation of luteal function. An endometrial biopsy and a blood sample for progesterone determination obtained simultaneously in the midluteal phase of the cycles of 55 infertile women were compared for reliability for confirmation of presumptive ovulation and evaluation of luteal function. Progesterone levels of 3 ng/ml or greater were found in 90.5% of the cycles. Secretory endometrium was identified in 81% of the cycles. Thirty-three cycles yielded sufficient information to compare the two methods for evaluation of luteal function. Histology and progesterone levels were consistent with each other and the presumed time of ovulation in only 11 cycles. Histology was inconsistent with the presumed time of ovulation in 20 cycles, while progesterone was inconsistent in only two cycles. Additional samples for progesterone determinations were obtained during the biopsy cycles of 15 patients who presented adequate data for evaluation of luteal function. A single, well-timed progesterone determination appeared adequately to reflect the data obtained from serial samples in the same cycle. These results support the thesis that a single, well-timed serum progesterone determination is superior to a single endometrial biopsy as a screening method for confirmation of presumptive ovulation and for evaluation of luteal function.


The effect of intrauterine progesterone treatment on the endometrial prostaglandin F content in the rabbit. The effect on rabbit endometrial prostaglandin F caused by progesterone delivered directly to the uterus was investigated. Four groups of animals were used in the experiment: (1) no treatment (control); (2) an empty Silastic capsule (as an intrauterine device [IUD]) was inserted in one horn and the other horn was sham-operated; (3) a Silastic capsule releasing 150 microng of progesterone/day was placed in one horn and the other horn was sham-operated; (4) a Silastic capsule releasing progesterone was placed in one horn and the opposite horn received an empty Silastic capsule. In group 1, which received no treatment, no difference was noted. In group 2, the prostaglandin content of the horn containing an empty IUD was significantly higher than that of the sham-operated horn. In group 3, the same significant difference was noted between the prostaglandin content of the IUD-containing, progesterone-treated horn and the sham-operated horn. In group 4, no significant difference was observed between the horn containing an inert IUD and that containing a progesterone-releasing device. The addition of progesterone to an IUD does not significantly affect the elevated prostaglandin content of the endometrium caused by an inert IUD.


Effect of excess dietary methionine on rat pregnancy: influence on ovarian delta5-3beta-hydroxysteroid dehydrogenase activity. The addition of 4% dl-methionine to a diet of 18% or 12% casein reduced pregnancy maintenance in the rat from 100% to 48% and 5%, respectively. Fetal weight was subnormal. The major influence of methionine was not due to reduced food intake as determined by pair-fed controls but was related to reduced ovarian function. Thus, administration of estrone (0.5 microng) and progesterone (4 mg) on each of days 3 to 20 restored pregnancy to 100% in methionine-fed rats, but fetal weight remained subnormal. Further ovarian delta5-3beta-hydroxysteroid dehydrogenase activity was subnormal in litter-resorbed, methionine-fed rats. Since adequate amounts of ovarian steroids are required for placenta formation, it is possible that placental development was impaired and served as the cause of fetal wastage in animals consuming excess methionine.


Dermal melanocytosis. Report of an unusual case. A 32-year-old Portugese woman presented with a bluish spot on the right hand. It had appeared at the age of 11 years. The histologic examination revealed typical dermal melanocytes. Although clinically this lesion was typical of an aberrant and persistent Mongolian spot, it exhibited, both histologically and ultrastructurally, also some features of the common blue nevus. Dermal melanocytosis of the macular type, as observed in our patient, is very rare.


Annular erythemas in infants associated with autoimmune disorders in their mothers. Report on three cases. Three infant boys with a centrifugal annular erythema mainly consistent with erythema annulare centrifugum, developing a few weeks after birth, are described. The lesions disappeared before the age of 6 months, without atrophy, and during this period the infants were otherwise healthy. This group is considered to belong to one of three types of reactivity in infants associated with or expressed as a connective tissue disease, especially lupus erythematosus, in the mother and child or in either. In type 1, signs and symptoms of systemic lupus erythematosus are or will be present in the mother and the child displays discoid lupus erythematosus lesions at birth or soon after. In type 2, the mother has the same signs and symptoms as in type 1 but the child develops a centrifugal annular erythema 3-6 weeks after birth. In type 3, discoid lupus erythematosus is present at an early stage in the infant, while the mother is healthy. This type may represent an early onset of lupus erythematosus in the infants.


A study on leukocytes phospholipid composition in mycosis fugoides. Leucocyte phospholipids composition was determined in 16 patients with mycosis fungoides and 20 healthy controls. Statistically significant differences namely, an increase in phosphatidylcholine and diphosphatidylglycerol and a decrease in phosphatidylserine and phosphatidylinositol concentrations between patients and healthy subjects were observed.


An electron microscopic study of sebaceous epithelioma. A case report with two new observations on lipid droplet formation. A lesion presenting a typical histopathological picture of sebaceous epithelioma comprised three kinds of cells; immature, transitional, and mature cells corresponding to the components of the normal sebaceous gland. Melanocytes and melanosomes were absent. These findings clearly distinguished the tumor from basal cell epithelioma, and it was concluded that sebaceous epithelioma represents a primary neoplasm of the sebaceous gland. New observations on lipid droplet formation are made with regard to the glycogen-containing cytolysome - tentatively designated a Liposome - and membrane structures around the lipid droplet found in mature cells.


Atypical sweat duct hyperplasia accompanying keratoacanthoma. 25 cases of atypical sweat duct proliferation in association with cutaneous tumors are described. 20 of these were keratoacanthomas. The compression of the duct either in its dermal or intraepidermal portion is considered to be the etiology. Similar changes are seen with decubitus ulcer and stasis dermatitis. Atypical sweat duct hyperplasia may be useful as an extra aid in the differentiation of keratoacanthoma from well-differentiated squamous cell carcinoma.


[Normolipemic xanthomatoses. a case of xanthoma disseminatum (author's transl)]. A short summary of normolipemic xanthomatoses is exposed. A case of xanthoma disseminatum is reported. The typical clinical picture is described and numerous investigations are recorded. No association with any systemic disorder neither diabetes insipidus nor rheumatoid arthritis could be found. Histologically the granulomas consist of many multinuclear giant cells embedded in an infiltration of histiocytic cells and lymphocytes. Fat staining demonstrates lipid accumulation as a secondary phenomenon. Systemic corticosteroid therapy was effective in preventing the regrowth of the granulomas after their surgical removal.


Binding of the partially purified glucocorticoid receptor of rat liver to chromatin and DNA. The binding of the glucocorticoid receptor of rat liver to chromatin and DNA has been studied with crude and partially purified preparations of cytosol receptor labelled with [3H]-triamcinolone acetonide in vitro. The use of crude preparations of receptor and increasing protein concentrations leads to an apparent saturation of chromatin and DNA, suggesting a limited number of high affinity nuclear acceptor sites for the receptor. Appropriate controls indicate that the observed saturability of chromatin acceptor sites is due to the presence in crude receptor preparations of heat-stable protein factors which interfere with the binding of the receptor to the genome; whereas the apparent saturation of DNA is due to contamination with deoxyribonucleases. If the activated complex of receptor and triamcinolone acetonide (R-TA) is partially purified to a step where it is free from nucleases and inhibitors, its binding to both chromatin and DNA is linearly dependent on the concentration of free (R-TA) in the incubation medium. There is no absolute specificity with respect to the source of DNA or chromatin, although liver chromatin has considerably higher receptor binding capacity than chromatin from avian erythrocytes. The rate kinetics of association and dissociation for the binding of (R-TA) to DNA and chromatin are very similar, but DNA exhibits a 10-fold higher receptor binding capacity than chromatin. These data, in conjunction with the effect of poly-(D)-lysine and and NaCl on the binding of (R-TA) to chromatin and DNA, suggest that most of the receptor molecules bound to chromatin in vitro interact with the "accessible" DNA stretches. Although a small population of receptor molecules may bind specifically to target tissue genome, the detection of these specific sites against the background of unspecific binding is not possible with unfractionated chromatin or DNA preparations.


A test of the hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses in man. The hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses was tested in five subjects following one hour of sustained hyperglycemia. Despite a rapidly falling blood glucose concentration, no increase in plasma growth hormone, cortisol, glucagon, or catecholamines occurred as long as the blood glucose concentration remained above fasting levels. Plasma growth hormone, cortisol, and catecholamines were not released until the mean blood glucose reached 28 mg./100 ml., 39 mg./100 ml., and 39 mg./100 ml., respectively, below the fasting level. Plasma glucagon was suppressed during the period of hyperglycemia. As the blood glucose concentration fell below basal levels, a progressive increase in glucagon occurred. Plasma glucagon returned to fasting values when the nadir in blood glucose was attained. During the period of rapidly falling blood glucose, only plasma insulin showed any change; its response lagged behind the decline in blood glucose. By the time the fasting glucose level was attained, the plasma insulin was still almost three times the basal level. We concluded that under our experimental conditions the rate of fall in blood glucose and the degree of hypoglycemia achieved is primarily determined by the plasma insulin concentration.


Serum insulin response to slow-rise glucose infusion in "genetic prediabetics" (offspring of two diabetic parents). The insulin response to a programed slow-rise glucose infusion designed to mimic the postprandial rise in glucose was studied in five offspring of two diabetic parents (ODP) and seven normal subjects. The ODP had higher mean blood glucose levels towards the end of the infusion and during the postinfusion period. The rates of glucose disappearance calculate during the postinfusion period were comparable in the two groups. Despite the apparent similarity of serum insulin levels of ODP and normal subjects, the amount of insulin secreted per unit of glycemic stimulus was lower in the ODP group. When the glucose infusion test was preceded by an acute load of glucose, similar findings in the insulin secretory dynamics were found in the ODP group. These data suggest that an impairment in insulin secretion exists in ODP when they are challenged by the slow rise of blood glucose achieved by this type of an intravenous glucose infusion.


Mechanism of hypoglycemia observed in a patient with insulin autoimmune syndrome. A 21-year-old female patient complaining of frequent hypoglycemic attacks in the presence of a large amount of circulating insulin-binding antibodies without previous known immunization is described. In order to clarify the possible mechanism of the hypoglycemic attacks occurring in this new syndrome, changes in plasma glucose, plasma total and free immunoreactive insulin (IRI), and C peptide immunoreactivity (CPR) levels were investigated in the patient before, during, and after a three-hour glucose infusion. The character of her antibodies were also examined. An abrupt discontinuation of the glucose infusion caused a sharp decline in the plasma glucose level, reaching a nadir of 30 mg./100 nk, at 270 minutes; then she became unconscious. A huge amount of total IRI of 2,834 micron U./ml. was registered at 180 minutes, while the peak value of free IRI of 208 micronU./ml. was observed 45 minutes after the cessation of the glucose infusion. Plasma CPR was increased from high basal level, 19.6 ng./ml., to the maximum level of 29.2 ng./ml. The maximum insulin-binding capacity of IgG in the patient's serum was 6.25 mU./ml. The antibody-combining site was homogeneous, showing one high-affinity site (K: 1.1 X 10(9)M-1). Neither the prolonged fasting nor the administration of tolbutamide induced the hypoglycemic attack in the patient. The hypoglycemia may be explained by an unduly excessive amount of insulin liberated from a large pool of bound insulin irrespective of blood sugar level. The cause of the antibody production is also discussed.


Effect of food ingestion on intestinal glucagon-like immunoreactivity (GLI) secretion in normal and gastrectomized subjects. This work was undertaken to compare the intestinal GLI responses to oral glucose (1.75 g/kg, 25% sol.), to a carbohydrate-rich meal (carbohydrate content about 1.75 g/kg) and to a protein meal (250-400 g grilled lean beef) in normal (n = 6) and gastrectomized (n = 6) subjects. As expected, after glucose administration the elevation of plasma GLI was more pronounced in the gastrectomy group (approximately 500% above baseline) than in the controls (approximately 75% above baseline). However, the gastrectomized patients responded to the carbohydrate meal with a very slight elevation of circulating GLI (approximately 45% above baseline), similar to that found in the controls (approximately 70% above baseline). After the protein meal, a small increase of GLI was also observed in both groups. In conclusion, in gastrectomized subjects the ingestion of natural foodstuffs is followed by a normal elevation of plasma GLI, thereby suggesting the exclusion of this factor from involvement in the constellation of postgastrectomy syndrome. In these patients, the exaggerated rise in GLI after oral glucose is not representative of increments after physiological stimuli.


A long-term diabetic autonomic nervous abnormality. Reduced variations in resting heart rate measured by a simple and sensitive method. Three types of variation in resting pulse rate were measured, using simple and reproducible methods, in 44 young juvenile diabetics and 11 controls. Diabetics with few years duration of the disease showed normal values of both long-term and cyclic fluctuations, as well as of non-systematic, random variation from beat-to-beat. All three types of variation were reduced in long-term diabetics, and the reduction was in all cases correlated with the duration of diabetes. The decrease in non-systematic, beat-to-beat variation attained statistical significance after 5 to 10 years duration of diabetes. It is concluded that reduced variation in resting pulse rate is a long-term diabetic manifestation and that the decrease of non-systematic, beat-to-beat variations in diabetics is a useful indicator of functional abnormalities of the autonomic nervous system.


Extraction, gel filtration pattern, and receptor binding of porcine gastrointestinal glucagon-like immunoreactivity. Different techniques for the extraction and initial purification of porcine gastrointestinal glucagon-like immunoreactivity (GLI) were compared with reference to yield, and preservation of number and pattern of GLI components. The conventional acid-ethanol technique combined with ethanol-ether purification gave high yields and a reproducible pattern of components. Large amounts of tissue were more easily extracted using another technique, based on extraction by boiling, extraction and precipitation with acetone, and--if necessary--salting out. By means of the latter two techniques mucosal tissue from all of the porcine gastrointestinal tract was extracted and subjected to gel filtration. Glucagon-like peptides were searched for using: 1. a radioimmunoassay which quantifies gut type glucagon (GTG), as well as pancreatic type glucagon (PTG), 2. a radioimmunoassay highly specific for pancreatic type glucagon (PTG), and 3. a radioreceptor assay based on binding of glucagon to porcine liver cell membranes. The oesophageal, the fundic, and the antro-pyloric parts of the gastric mucosa contained very small amounts of GLI. The cardiac gland region contained small amounts of a peptide indistinguishable from "true" glucagon. The duodenal mucosa contained small amounts of "true" glucagon and may be a smaller, glucagon-like peptide. The mucosa of the small intestine contained large amounts of both high and low molecular weight GTG and, in addition, PTG of high molecular weight and "true" glucagon. The colon also contained these components with "true" glucagon in high concentrations. Only small GTG and "true" glucagon were receptor-active, the former with less than its immunometric potency.


Effect of ethynodiol diacetate and a combination-type oral contraceptive compound on carbohydrate metabolism. II. One year intravenous glucose tolerance study. Blood glucose and plasma insulin levels were measured in two groups of women, following one year of oral contraceptive therapy of different types. There were no significant differences from pretreatment glucose and insulin values in the first group of women (on ethynodiol diacetate). In the second group (on norethynodrel and mestranol), there was a significant elevation of mean blood glucose levels in the fasting state and at all times of an i.v. glucose tolerance test. Furthermore, a statistically significant alteration in plasma insulin was observed at all times of the test (except at 120 min). Patients participating in this study will continue this treatment, and results of carbohydrate metabolism monitoring will be reported after 2 years of therapy.


Glucose control of basal insulin secretion in diabetes. The plasma insulin response to both a small increase and decrease in the plasma glucose has been studied in normal and diabetic, non-obese subjects. In a second investigation the plasma insulin concentrations were measured during a gradual reduction of the raised fasting plasma glucose of diabetes to normal levels. In both studies, diabetic patients were found to have a markedly impaired response of the fasting plasma insulin to small changes in plasma glucose. These results do not support the suggestion that stimulated and not basal insulin secretion is impaired in diabetes. Both modes of secretion are probably via the same B-cell release mechanism, which is deficient in diabetes. There was a gradation of response between maturity onset and juvenile onset diabetics.


[Clinical aspects of myocardial infarction in elderly people. Statistical study of 203 cases (author's transl)]. A statistical study was done on two groups of patients. The first group included 128 subjects of less than 65 years of age. The second group comprised 75 subjects aged 65 years or older. The purpose of the study was to identify the most relevant clinical aspects of myocardial infarction in older aged patients. The following variables were taken into consideration: sexual distribution, predisposing factors, causative factors, initial symptoms, site of infarction, physical and instrumental indications, cardiac and extracardiac complications, immobilization time, recovery time, residual aspects at patient discharge, mortality and tyme and type of death. The analysis was performed using both non parametric X2 test and correlating some variables with age independently of the subdivision of cases in groups, according to the method of multiple step-wise and simple regression. In the older age group the most significant statistical data was: the major incidence of infarcts was in women; the prevalence of predisposing factors such as hypertension and diabetes; the most frequent presentation of initial atypical symptoms; the most elevated incidence of hemodynamic complications and the highest mortality.


[Hereditary occurrence of the mesotelesystolic click syndrome: a study of 9 families (author's transl)]. Nine families affected by the mid-systolic click syndrome were studied. Of the one hundred and forty-four first-degree relatives, 117 of whom were living, eighty-four were examined. Thirty-five were found to be affected by the syndrome. Twenty-six were females and nine were males. Auscultatory and phonocardiographic findings consisted either of isolated mis-systolic clicks or systolic murmurs or a combination of the two. Electrocardiograms revealed changes of various types, most commonly of the ST-T segment. About seventy per cent of the patients were symptomatic. Nine members, not examined by the authors, had died suddenly; all had a previous history of "cardiopathy". Progressivity of mitral valve disease with age is not confirmed by the present study. It is suggested that the mode of inheritance of the defect might be that of an autosomal dominant form of Mendelian type with delayed expression of the defect. An alternatove hypothesis of a multifactorial inheritance mechanism, which is more stimulating for future studies on the cause of the syndrome, is also taken into consideration.


[Replacement of cardiac valves with Björk-Shiley and Cooley-Cutter prostheses: a comparative study (author's transl)]. Björk-Shiley and Cooley-Cutter prostheses are the most satisfactory cardiac valves in our experience. They were compared in regard to incidence of emboli and mortality by long-term follow up. Among the 1904 patients who had received a Bjök-Shiley valve between 1969 and 1975 late follow-up could be obtained in 1565 patients. Among the 1329 patients with a Cooley-Cutter valve implanted between 1971 and 1975, late follow-up was obtained in 779. In the mitral valve replacement series, Cooley-Cutter / Björk-Shiley early mortality was 9.9/12.8 (%), late mortality 6.8/12.8 (%), early emboli 5.4/8.1 (%), late emboli 3.7/5.1 (%). In the aortic valve replacement series, Cooley-Cutter/Björk Shiley early mortality was 6.6/8.4 (%), late mortality 2.9/5.1 (%), early emboli 2.7/3.3 (%), late emboli 1.1/2.7 (%). Both early and late mortality and emboli were more favorable in the Cooley-Cutter sample as compared to the Björk-Shiley group. Therefore the Cooley-Cutter prostheses are preferred in both the aortic and mitral positions.


[Reliability of premature atrial stimulation in the study of sinoatrial conduction time (author's transl)]. Premature atrial stimulation was carried out in 32 patients, and for each stimulus the basic cycle (A1A1), test cycle (A1A2), and the return cycle (A2A3) were analyzed. When A2A3 was plotted as the function of A1A2, a biphasic pattern, characterized by a slope phase followed by a "plateau", was observed in 25 subjects. Sinoatrial conduction time (SACT) was calculated using the Strauss method, which assumes that in the plateau A2A3 = A1A1 + SACT. Sinus arrhythmia was also determined in order to evaluate its importance in altering the results of premature atrial stimulation: it should be pointed out that when arrhythmia was marked it was impossible to calculate sinoatrial conduction time. An inverse correlation between A1A1 and the calculated SACT and between A1A1 and A2A3/A1A1 in the plateau was also demonstrated. The reliability of SACT obtained by premature atrial stimulation is discussed in relation to the results obtained and the data found in the literature.


[Acute coronary occlusion of non bacterial thrombotic endocarditis (author's transl)]. A case of acute myocardial infarct caused by a nonbacterial thrombotic endocarditis is reported. It was followed by irreversible shock. The left coronary artery, which was in an abnormal position, was occluded by a verrucous peduncular elongation originating from the anterior left leaflet of the aortic valve.


[Hypoplasia of the right ventricular myocardium (Uhl's disease). Report of a case with review of the literature (author's transl)]. A rare case of congenital hypoplasia of the right ventricular myocardium ("Parchment Right Ventricle" or Uhl's disease) diagnosed by angiocardiography is presented. The predominant clinical feature was recurrent paroxysms of severe arrhythmias which could be controlled only by electric shock. Right heart failure was also present. After a follow-up period of 8 years, the patient, now 27 years old, on diuretic and antiarrhythmic treatment, is well. The literature on Uhl's disease is reviewed and classified into two clinical types; a fatal infantile type in which extreme hypoplasia is present, and a milder adult type in which the anatomical lesion is usually more limited. In the infantile type intractable heart failure was invariably present; in the adult type severe arrhythmias often constituted the major clinical problem. Some of the difficulties in diagnosis and treatment are emphasized.


[Evolution of ventricular depolarization in the acute phase of inferior and posteroinferior myocardial infarction (author's transl)]. Twenty-five patients, hospitalized within 24 hours from the beginning of the precordiaglia due to acute diaphragmatic infarction, with or without a posterior extension, underwent the ECG and VCG recordings for the first consecutive twenty days and on the fortieth day, in order to study the development of ventricular depolarization. To diagnose an infarction of the diaphragmatic and posterior walls the usual ECG and VCG paramaters were used; the ECG was found to be less useful above all for the difficulty of measuring the variations, in the loss of the electrical forces. The electrodes were always placed in the same points suitably signed. Several evolutive modalities of the diaphragmatic infarction were observed; in 52% of the cases the loss of the inferior electrical forces reaches its maximum expression quickly, then it remains almost constant. In 12% of the cases the necrosis increases very clearly, tardily, between the ninth and fourteenth day. In 24% a precocious reduction of the electrical extension of the infarction on the eighth-twelfth day is observed. In 12% of the cases there are irregular oscillations during the whole acute phase. In all cases more or less stressed daily or cyclic oscillations were present. In nine cases an extension of the infarction to the posterior wall was evident; among these in five, two peaks are present; in two an initial increase, in the other two an initial decrease of the electrical extension of the necrosis; then, more or less stressed daily or cyclic oscillations. In another nine cases a single reading of the tracings do not let us diagnose a posterior extension; this is possible only through an "in series" reading. The clinical course and the humoral data do not give any contribution to the interpretation of the founded evolutive variabilities. The necrosis, therefore, must not be considered a zone of homogeneous and global stuffing, but composed of cellular groups in several and variable anatomo-metabolic situations conditioning the observed electrical instabilities.


[Identification of subjects at high coronary risk in the Roman Project of Coronary Heart Disease Prevention (author's transl)]. In the Roman Project of Coronary Heart Disease Prevention two different techniques were employed for the identification of individuals at high coronary risk within the treatment groups of the Project. The "risk score" is a simple additive system developed by the working groups of WHO, while the "multiple logistic function" is a complex mathematical model of multivariate analysis. Both of them consider 5 risk factors (age, systolic blood pressure, serum cholesterol, smoking habits and physical activity at work) and are applied for the identification of individuals belonging to the upper 20% of a risk rank list. The two techniques apparently provide similar predictive performances when applied to epidemiological prospective material collected in other studies where the morbid events are already known. When employed in the study population groups they identify, as high risk individuals, different subgroups of population, which overlap only partially. On the basis of theoretical and practical considerations, it has been decided to employ both techniques and to extend, as a consequence, the proportion of high risk individual, eligible for individual treatment, from 20% to about 30% of the total.


[Correlations between hemodynamic parameters and "a" wave in the right apicocardiogram in patients with arterial pulmonary hypertension (author's transl)]. In a group of patients with arterial pulmonary hypertension of various origin, the relationship between the relative magnitude of the "a" wave of the right apex-cardiogram (ACG) to the total deflection of the ACG ("a/H ratio") to both the right atrial "a" wave and the right ventricular end-diastolic pressure was studied. Both correlations were statistically significant. The results obtained confirm the ACG value in the non invasive study of the right ventricular function.


[Origin of the left circumflex coronary artery from the right Valsalva sinus. Two cases with clinical and instrumental signs of coronary insufficiency (author's transl)]. Two cases of isolated anomalous origin of the left circumflex coronary artery from the right Valsalva sinus are described. In contrast with all the cases reported in the literature, both our female patients had typical angina; in one case, moreover, in coincidence with the precordial pain there were significant alterations of the repolarization, also caused by stress testing with the bicycle ergometer. On the basis of these findings, the authors believe that in patients with this anomaly the angina might be produced through a sharp decrease in the circumflex coronary artery blood flow correlated with caliber changes of the aorta.


[Uhl's anomaly: case description with hemodynamic study and autoptic report (author's transl)]. A 3 month's old baby with Uhl's disease is reported. The diagnosis was made by cardiac catheterization and angiographic evaluation of right atrial and ventricular chambers and was confirmed by autopsy and histopathological examination. The particular features which allow angiographic differentiation from Ebstein's anomaly are considered. On the grounds of anatomical, clinical, and prognostic aspects, it is proposed that the definition of Uhl's anomaly be reserved for cases in infancy only, using the term Osler's disease for adult cases.


Age changes of the pattern of F1 histone subfractions in rat liver and spleen chromatin. The polyacrylamide gel electrophoresis of total histone extracted from young (3 months) and old (26-27 months) rat tissues does not show age-related differences in the pattern of the main five histones. However, when the lysine-rich F1 histone was extracted from chromatin separately by perchloric acid and purified by Biogel P-60 column chromatography from chromatin of rat liver and spleen, the polyacrylamide gel electrophoresis did show obvious age changes in the distribution of F1, F1o, and F1(00) subfractions. In liver chromatin the increase of rat-specific methionine-containing subfraction (F1met.) was also found.


Predicting mortality after elective abdominal aortic aneurysmectomy in the elderly. 40 non-emergency cases of abdominal aortic aneurysmectomy were reviewed. Of the 20 cases who died during the follow-up period, a significant number had more evidence of pre-existing multiple diseases than had the survivors. The results of the study suggest that there is an association between the amount of coincident disease, length of survival, and mortality following elective abdominal aortic aneurysmectomy.


Effect of fundic distension on gastric acid secretion in man. The effect of distension of the fundus and body of the stomach on gastric acid secretion was studied in 26 patients with duodenal ulcer and six healthy subjects. Graded distension produced by inflating a rubber balloon to volumes of 150, 300, and 600 ml resulted in significant sequential increments of acid output. The secretory response outlasted stimulation by at least one hour. In both groups of subjects, the highest acid output obtainable with fundic distension amounted to just above 50% of the maximum secretory response evoked by intravenous infusion of pentagastrin. A significant correlation was found between the peak secretory rates observed during fundic distension and after pentagastrin stimulation. It is concluded that distension of the oxyntic gland area in man is a potent stimulus for gastric secretion of acid and that patients with duodenal ulcer are no more sensitive to this stimulus than healthy subjects.


Effects of oral calcium gluconate on gastric acid secretion and serum gastrin concentration in man. A single oral dose of 4-46 mmol calcium gluconate at pH 5-6 was administered intragastrically to 15 male volunteers without gastrointestinal disease. There was a significant rise in acid output from 30-90 minutes after the calcium was given compared with the basal hourly collection. The serum gastrin level 30 minutes after calcium administration was significantly raised, but no correlation could be demonstrated between the acid and gastrin responses. Serum calcium levels were unchanged throughout. An equimolar dose of magnesium sulphate had no such effects. This study suggests that the intragastric administration of calcium results in independent release of gastric acid and gastrin from the gastric mucosa.


Crohn's disease of the duodenum.

Crohn's disease of the duodenum. Crohn's disease of the duodenum is uncommon, occurring in approximately 2% of patients with Crohn's disease. Approximately 165 cases have been reported in small series in the literature. Our report includes 36 patients, most of whom had symptoms of duodenal disease coincident with or after obvious disease elsewhere in the gastrointestinal tract, although occasionally duodenal disease developed first and rarely disease was confined to the duodenum. Upper abdominal pain and symptoms of gastroduodenal obstruction are the commonest patterns of presentation. Significant weight loss is common, and occasionally major upper gastrointestinal bleeding occurs. The commonest pattern of involvement was contiguous disease of the proximal duodenum and distal stomach. Endoscopically, diffuse granularity, nodularity, and ulceration are seen accompanied by lack of distensibility of the involved area. Granulomas are rarely found in endoscopic biopsies. A bypass procedure was carried out on 18 patients, 15 of whom continue to be free of symptoms with an average follow-up of 6-6 years. When symptoms of obstruction dictate, operative bypass is accompanied by favourable long-term results in the large majority of patients.


Lowering of fasting and food stimulated serum immunoreactive gastric inhibitory polypeptide (GIP) by glucagon. The effect of intravenous glucagon infusion on serum levels of immunoreactive GIP (IR-GIP), insulin (IRI), gastrin (IRG), and on blood glucose has been investigated in six healthy volunteers in the fasting state and during ingestion of a mixed standard meal. Glucagon (500 ng/kg/min) lowered significantly serum levels of IR-GIP and IRG below the fasting values and increased the levels of IRI and blood glucose. Glucagon (50 ng/kg/min) infused 30 minutes before and continued 90 minutes after ingestion of a test meal abolished the IR-GIP response, suppressed significantly the IRG response, and left the IRI response unchanged. The same glucagon dose infused 60 minutes after ingestion of the test meal decreased significantly the raised levels of IR-GIP and IRG to fasting levels without changing IRI values. It is concluded that exogenous glucagon inhibits Gip release at the level of the GIP-producing cells.


Relationship between changes in intraluminal pressure and transmural potential difference in the human and canine jejunum in vivo. Recordings of transmural potential difference (PD) across the jejunum of conscious man in situ are characterised by spontaneous fluctuations of up to 10 mV. In 25 of 31 subjects (comprising seven normal controls and 24 patients under investigation for malabsorption, six of whom had coeliac disease) we observed a clear association between these fluctuations and changes in intraluminal pressure recorded at the same site. The most frequent PD changes were associated with type III pressure waves. These consisted predominantly of large waver (3-1 +/- 0-1 mV; mean +/- SEM, n = 317) which reached maximal amplitude approximately 45 seconds after the pressure peak and had a duration of 120 +/- 3 s, but also included less frequent spikes (0-5 +/- 0-1 mV; n = 110) concurrent with the pressure wave with a duration of 5 +/- 1 s. Although by recording at two sites in the jejunum 10 cm apart we were able to demonstrate that type III pressure waves appeared to be propagated aborally at a median rate of 60 cm per minute, the apparent rates of propagation of the corresponding PD waves were much more variable. The largest PD changes (7-8 +/- 0-4 mV; n = 19), lasting several minutes, were found in association with runs of type I waves (basic rhythm) superimposed on a type III wave. Both pressure and PD activities were suppressed by intramuscular propantheline bromide. Intraluminal pilocarpine caused a transient rise in PD not always accompanied by a change in pressure. Distention of the jejunum by rapid injection of a bolus of isotonic sodium chloride produced a delayed rise in the PD which could be prevented by prior administration of propantheline bromide. Experiments using Thirty-Vella loops of proximal jejunum in conscious dogs confirmed the effect of jejunal distension on the PD and also demonstrated that spontaneous retching is preceded by an increase in the PD. Consideration of these results in conjunction with data from other workers suggests the hypothesis that the larger spontaneous fluctuations in transmural PD in the jejunum of conscious man are caused by changes in electrogenic secretion associated with intestinal motility and mediated by cholinergic mechanisms. The possible association of increased secretory activity with motility may have functions of lubrication as well as diluting and mixing the chyme for easier digestion and absorption.


Plasma levels and intestinal absorption of 25-hydroxyvitamin D in patients with small bowel resection. Plasma levels of 25-hydroxyvitamin D (25-OHD) were found to be significantly reduced in a group of patients with small bowel resection when compared with normal controls. Plasma levels of 25-OHD after an oral dose of 25-hydroxyvitamin D3 (25-ohd3) were also reduced in the patient group. Dietary intake of vitamin D tended to be low in many patients, but seasonal variation of plasma 25-OHD levels indicated normal exposure to sunlight in most of the patients studied. It is suggested that these studies provide some evidence for malabsorption of 25-OHD after small bowel resection, which, it is postulated, may be due to interruption of the enterohepatic circulation of bile acids and of 25-OHD. These factors may contribute towards the low plasma levels of 25-OHD found in the patient group.


Mechanism of malabsorption in giardiasis: a study of bacterial flora and bile salt deconjugation in upper jejunum. Sixty-three unselected cases of giardiasis, with no evidence of other systemic disease, were screened for evidence of steatorrhoea. No patient had any evidence of protein-energy malnutrition. Seventeen (27%) of the cases had steatorrhoea; three (17-8%) of the 17 patients having steatorrhoea also had D-xylose malabsorption. Vitamin B12 absorption was normal in all. Bacterial culture and qualitative analysis of bile salt in jejunal fluid was carried out in all the 17 cases having steatorrhoea as well as 13 cases with normal absorptive parameters (eight cases of irritable bowel syndrome and five cases of giardia infection) who served as controls. All the patients showing bacterial overgrowth had free bile acids in their duodenal aspirate. Free bile acids could also be detected in jejunal aspirates of five of the seven patients having no bacterial overgrowth. Two control cases of giardia infection with normal small bowel function and sterile duodenal aspirate showed evidence of bile salt deconjugation. The significance of these findings is discussed in relation to the pathogenesis of steatorrhoea in patients with giardiasis. The possible role of giardia in bile salt deconjugation is suggested.


Effect of aspirin on intestinal absorption of glucose, sodium, and water in man. The effect of aspirin on small intestinal function in six healthy volunteers was examined using a segmental perfusion technique, with a test solution of 40 mM D-glucose, 140 mM NaCl, and 0-5% polyethylene glycol. Jejunal glucose, sodium, and water absorption rates were inhibited by 50% after oral administration of 2-6 g aspirin. Adenosine triphosphate (ATP) concentration was assayed in jejunal mucosal biopsies before and after aspirin. There was an almost 50% decrease in mucosal ATP levels after aspirin. This effect may be mediated through cellular injury and impairment of mitochondrial energy metabolism. These data suggest that aspirin may significantly alter small intestinal function. It appears possible that the inhibitory effect of aspirin on glucose absorption may account, at least in part, for the lower blood sugar levels observed with the use of the drug.


Chronic pancreatitis: a cause of cholestasis. The bile ducts were visualised using endoscopic retrograde cholangiopancreatography (ERCP), percutaneous or intravenous cholangiography in 38 patients with non-gallstone chronic pancreatitis. Stenosis of the intrapancreatic portion of the distal common bile duct was demonstrated in 11 patients. Ten of the 11 developed transient cholestasis during exacerbations of their chronic pancreatitis. In six cholestasis eventually persisted requiring surgical relief. Secondary biliary cirrhosis was present in one patient. No evidence of pancreatic carcinoma was found in the patients explored surgically. Ten of the patients are alive more than one year after diagnosis. Chronic pancreatitis was of alcoholic aetiology in 10 of the patients with biliary stenosis. Cholestasis and biliary stricture are common but poorly recognised complications of non-gallstone chronic pancreatitis, especially when pancreatitis is severe and due to alcohol.


Models of gastric emptying.

Models of gastric emptying. Some empirical and theoretical models of the emptying behaviour of the stomach are presented. The laws of Laplace, Hooke, and Poisseuille are used to derive a new model of gastric emptying. Published data on humans are used to test the model and evaluate empirical constants. It is shown that for meals with an initial volume of larger than or equal to 300 ml, the reciprocal of the cube root of the volume of meal remaining is proportional to the time the meal is in the stomach. For meals of initial volume of less than 300 ml the equation has to be corrected for the fact that the 'resting volume' of gastric contents is about 28 ml. The more exact formula is given in the text. As this model invokes no neural or hormonal factors, it is suggested that the gastric emptying response to the volume of a meal does not depend on these factors. The gastric emptying response to the composition of the meal does depend on such factors and a recent model of this process is used to evaluate an empirical constant.


Gastric gland metaplasia in the small and large intestine. Fifty-six surgical specimens with various ulcerative intestinal disorders were microscopically investigated for evidence of gastric gland metaplasia. Thiry-one specimens (55-4%) showed pyloric gland metaplasia. Among the 31 patients with pyloric gland metaplasia, five showed true gastric metaplasia, consisting of parietal cells, chief cells, and mucous neck cells. The percentage of true gastric metaplasia among pyloric gland metaplasia was as high as 16%, an overall frequency of 9% among various ulcerative intestinal disorders. The mechanism of pyloric gland metaplasia and true gastric metaplasia is not understood, but may occur secondary to submucosal response to ulcer healing and subsequent alteration of the intraluminal condition in the intestine.


Glucosamine synthetase activity of the colonic mucosa in membranous colitis. Glucosamine synthetase, the first enzyme in glycoprotein synthesis, has been measured in serial rectal biopsies in four patients with membranous colitis. In two of the patients the levels of the enzyme were very high initially and in the other two patients the enzyme levels rose to a peak above the normal range after a delay of up to 10 days. These high levels may be related to the mucus hypersecretion which is a feature of membranous colitis but it seems more likely that they represent the healing of the mucosa.


Ileorectal anastomosis in patients with Crohn's disease of the colon. Thirty-seven patients were studied who had an ileorectal anastomosis performed for Crohn's disease of the colon. Twenty-nine were done as a primary procedure and in eight the anastomosis was made after previous total or segmental colectomy. Three patients developed anastomotic leaks and all three patients died. No patient who had a diverting loop ileostomy performed at the time of ileorectal anastomosis developed anastomotic leaks before or after the ileostomy was closed. Of the 37 patients, three died postoperatively and another five have had less than a one year follow-up. Of the remaining 29 patients, 12 (41%) had recurrences in either the rectum or ileum. Half of the recurrences took place five or more years after surgery. Seven of the 12 patients with recurrences have had their anastomoses taken down. When this recurrence rate of 41% is compared with the recurrence of ileitis in patients after total colectomy and ileostomy for Crohn's disease of the colon, the incidence of recurrence is, as shown in many reports, not markedly dissimilar. Of the patients who develop a recurrence after ileorectal anastomosis, only about half will have to have their anastomoses taken down. In our study, 59% of the patients had no recurrence and another 20-5% had a recurrence but did not require 'take down' of the anastomosis. Thus, almost 80% of our patients at the time of this report have been able to lead a life unencumbered by an ileostomy, making ileorectal anastomosis for this disease a desirable procedure to consider in selected patients.


Incidence and immunochemical features of serum cryoglobulin in chronic liver disease. Essential cryoglobulinaemia was detected in 44 out of 150 patients (29%) screened on the basis of histological confirmation of chronic inflammatory liver disease (chronic persistent or aggressive hepatitis, or cirrhosis). Cryoglobulinemia prevailed in the patients whose hepatic tissue showed more features of active inflammation; also, a female prevalence was observed. There were no correlations between cryoglobulinaemia and either HBsAg positivity or alcoholic liver disease. Mixed cryoglobulins made of heterogeneous immunoglobulins without monotypic components were mostly associated with established cirrhosis, whereas monotypic cryoglobulins were exclusively found in patients with either persistent or aggressive chronic hepatitis. Mixed cryoglobulins with a monotypic component were associated with all histological grades of liver damage. This study affords an objective evaluation of both the frequency and immunochemical features of cryoglobulins associated with chronic inflammatory liver disease.


Immune responses to the hepatitis B surface antigen and liver-specific lipoprotein in acute type B hepatitis. A serial prospective study of cellular immunity to HBsAg and liver-specific membrane lipoprotein was undertaken in 21 adults with acute hepatitis type B. Cellular immunity to HBsAg as determined by leucocyte migration inhibition with partially purified HBsAg as antigen was detected in all the patients during the recovery phase of the illness and was already detectable at the time of admission in 13 (62%) of the cases. In five of the remaining eight the titre of HBsAg in the serum at this time was high and in the whole series there was an inverse correlation between the degree of migration inhibition on admission and the peak HBsAg titre suggesting that antigen or possibly antigen/antibody complexes might be interfering with the demonstration of cellular immunity in vitro. Using a combination of minimum migration index recorded during the recovery period peak HBsAg titre, it was possible to compute the peak aspartate aminotransferase level with reasonable accuracy, a finding consistent with the hypothesis that the severity of the illness is related to both the number of infected hepatocytes and the vigour of the immune response to HBsAg. Evidence of an immune response to the liver-specific hepatocyte membrane lipoprotein was present in 50% of the patients tested at the time of admission, but was transient, having disappeared in every case by four weeks. The minimum migration index recorded with HBsAg as antigen was significantly lower in those with detectable sensitisation to the lipoprotein and it is possible that this autoimmune reaction is also generated by the interaction of T cells with viral antigenic determinants on the liver cell surface.


Contribution to the pathology of strobilocercosis (Strobilocercus fasciolaris) in the liver of man and some animals. Tissue reactions with liver strobilocercosis were studied in man, pheasant and muskrat on the basis of histological examination. Microscopical changes in the liver induced by completely developed and still quite vital strobilocerci are very similar in all these hosts and in all cysts the parasite was enveloped by a fibrous capsule consisting of two layers. The development of regressive changes and the character of tissue reaction during the death of the parasite are discussed. Strobilocercus fasciolaris was found for the first time in man, in a solitary cyst in the liver. The possibility of massive infestation of man liver is pointed out.


Effectiveness of fenitrothion for area control of ticks Ixodes ricinus (L.). Susceptibility to fenitrothion in all stages of unfed ticks Ixodes ricinus increases with their age and this fact is reflected in the effectiveness of various dosages of insecticides applied for area control. The following minimum, but fully effective dosages of the dust Metation P-5 and the spray Metation E-50 (both preparations contain fenitrothion) for application in separate seasons have been ascertained: In September and October 1 kg of fenitrothion per ha of treated area ensures complete control of unfed ticks until the winter of current year. In Aril 3 kg of fenitrothion per ha is necessary, if tick control is to be ensured until the appearance of the new generation, i.e. until the end of August. In May the control of unfed ticks is ensured by 1 kg of fenitrothion per ha, in June to August by 0.3 kg per ha is fully efficacious.


To the knowledge of ticks of domestic animals in Afghanistan. Thirteen species and subspecies of ixodid ticks were found on cattle, zebu, buffaloes, goats, sheep and camels examined mainly at the abattoir of Kabul between September 21 and October 1, 1974. All of them are already known from the territory of Afghanistan.


[Indication for pregnancy interruption in patients with heart diseases]. The early diagnosis of heart disease during or better before pregnancy is one of the most important problems, as cardiac diseases are the most common cause for maternal deaths throughout the world. The knowledge of hemodynamic alterations in circulatory and respiratory physiology during pregnancy complicated by heart disease is a prerequisite for their management. The following indications for therapeutic abortion of pregnancy complicated by heart disease can be concluded according to our own observations: 1. history of significant heart failure (more than grade IV according to the classification of the New York Heart Association), frequent attacks of angina pectoris and longstanding cyanosis: 2. in spite of the most careful heart treatment with digitalis, diuretics and salftree diet cardiac-thorax-rate of more than 55% in congenital heart disease, cardiac-thorax-rate of more than 60% in acquired heart disease, significant signs of heart failure, namely more severe than grade III, tachycardic atrial fibrillation, pulse deficit of more than 30/min, active inflammatory processes of the heart (rheumatic fever, subacute bacterial endocarditis, Takayasu's disease); 3. especially severe metabolic disorders, i.e. diabetes mellitus, malignant hypertension, kidney diseases; 4. primiparae of an age of more than 35 years with any heart disease. Commissurotomy can be accomplished during pregnancy if it is too late for therapeutic abortion. Pregnancy in case of artificial valves is not recommended in general because of impending hemorrhagic diathesis.


[Management of labor in fetal cardiac sound changes after paracervical block]. A pain free period during the first stage of labor is made possible by paracervical block anaesthesia. The extent of risks for the fetus using this method of anaesthesia is measured by different means. Changes of the fetal heart rate after paracervical block must be regarded as a complication. During the period of ten years paracervical block anaesthesia was performed in 10.041 cases in our hospital (Landesfraunklinik Wuppertal). The analysis of all cardiotocograms taken shows changes of the fetal heart rate after paracervical block in 11,3%. Carbostesin with adrenalin (0.5%) was used, 5 ml were injected on each side. Motility disturbances of the uterus and the vena cava-syndrome are clinically evident because of the various reasons for bradycardy. ECG analysis detects a suppression of the sinus-atrial node as a stimulator. During the period of bradycardy after paracervical block Caesarian section is not indicated. A conservative attitude is justified with the patient in a lateral position. Disturbances of uterine motility and long periods of bradycardy call for intrauterine resuscitation with the application of Partusisten (Th 1165) under constant control of maternal circulation. If there are other reasons for a Caesarian section an improvement of the fetal heart rate--as shown in the cardiotocogram--should be achieved in any case.


[Determination of urobilinoide concentration in the urine. New rapid method for clinical determination of urinary-urobilinoids using the Ehrlich-reaction]. A rapid method for quantitative determination of concentration of urobilinoids of fresh urine was developed. The method is based upon extraction of urinary urobilinoids using a mixture of acetic acid and ether and followed by the extraction of the ethereal phase with Ehrlich reagent and a solution of sodium acetate. Readings of absorbance from the absorption band of reaction products from urobilinoids and Ehrlich reagent are done.  Performance of the rapid method: 2 ml urine + 10 ml ether + 2 ml acetic acid were thoroughly mixed for about 15 seconds. The ethereal extract was shaken after addition of 12 ml Ehrlich-reagent for 1 minute and 15 ml half-saturated sodium acetate solution were added. 0-3 minutes afterwards reading of absorption at 560 nm respectively filter Hg 578 nm. Photometer:mg/dl=29 X A578 nm, 1 cm -0,4. Spectrophotometer:mg/dl urobilinoids=13,7 X A560 nm X 1/d -0,22 (d=optical pathway). Photometrical determination of concentration of urobilinoid can also be done using table 1. Accuracy, reproducibility and specificity are fully satisfying for clinical use of the method.


[Cytologic findings in young women with reference to sex behavior]. In a prospective study the interrelations between the sexual history of young women and the results of cervix smears were investigated. The main interest was focused on females bearing a high risk of developing a carcinoma of the cervix due to their sexual behaviour. 569 volunteers up to the age of 25 underwent vaginal examination and subsequently ecto- and endocervical smears were performed. Information about the sexual life was obtained using a questionnaire. These data as well as the results of the smears were stored and analyzed by a computer. The results were compared with references in the literature. They reveal some new aspects of sexuality in young people. The median age of the menarche in this investigation was 12,7 years in correspondence with the literature. The age of the first coitus was found to be in the range reported by other authors. Another point of interest was the use of oral contraceptives in respect to possible epithelial changes of the cervix. Practising oral contraception, the relation between contraceptives of the combined type and the sequential type was 10:1. Most young females discontinue the use of oral contraceptives at least once a year usually for a period of 2 months. The majority of young women had coital experiences with only one partner. A tendency toward promiscuity was not discernible. Inspite of coital experience, a substantial number (15,1%) did not practice any kind of contraception. Besides the use of oral contraceptives (81%), temporary experience with physical (37,2%) and chemical methods (19,8%) were reported. Nearly half of the pregnancies stated in the questionnaires were interrupted. The incidence of contamination with trichomonas and candida was reduced in comparison with the literature. According to results reported by other authors, a higher frequency of positive smears was expected. Among 569 samples, only one smear Pap. III D was found in a 20 year old girl with inconspicious sexual history. Women under the age of 25 years belonging to the risk group should be included in routine check-up with cervical smears.


The death of children following negligence: social aspects. Although the figure of unreported cases of neglected children is much higher than that of physical ill-treatment of children, neglect has rarely received attention, in most cases only when traces of physical ill-treatment were proven at the same time. Symptomatic are in the first place intense emaciation as well as dry puckered, scaly and extremely dirty skin, lack of subcutaneous fatty tissue and of Bichat's fat pad, matted hair, aged face, sunken eyes, and eczema from urine with ulcerations in the buttock and thigh regions. In addition one finds signs of localized hypothermia or rickets. My own observations cover 54 cases in which neglect and malnutrition have caused the death of the children involved. All the children had been living in extremely bad social conditions. The backgrounds of the children's mothers were also socially poor. Most of the mothers were too young to fulfill their duties. The fathers, where known, were alcoholics, unwilling to work and seldom cared for their family. They too were often too young to cope with their role as father. In this day and age, which has provided us with a much better understanding of the importance of the early development of the child for its later social attitude, mothers with all their problems and difficulties should not be left on their own. Motherlike behaviour is not necessarily programmed with the birth of a child. Mother duties must be learned as early as possible. This process should begin during pregnancy at the latest. A few proposals will be made.


[Treatment of anemia in pregnancy].

[Treatment of anemia in pregnancy]. In a therapeutic comparative study two trial-groups (1 and 2) of 30 pregnant women each suffering from iron deficiency anemia of light degree received randomly selected a combination of ferrous succinate and multivitamins (Multibionta-Eisen) or a combination of ferrous sulfate and folic acid (preparations ES). By both medications the decrease of hemoglobin, red blood count and hematocrit could be stopped and a re-increase of these values was seen afterwards. There was no significant differences in response between Multibionta-Eisen and ES. A significant increase of Hb, RBC and Hc as compared prior to treatment was limited to group 2. Possible causes for the non-significant results of group 1 are discussed. The results of the study are demonstrating a certain superiority of preparation ME. This combination showed at least equal efficiency as preparation ES in spite of a smaller iron dosage and was well tolerated without exception. Subjective complaints may be better improved by Multibionta-Eisen.


Post-mortem digoxin levels--two unusual case reports. Digoxin levels in post-mortem specimens are reported for two unusual cases. The blood level of digoxin in one of these cases was five times greater than any previously reported. The other case involved specimens from an embalmed body.


[Printing procedure in scanning electron microscopy and its special application in the field of dermatology]. A method is described by which replicas of skin surfaces for scanning electron microscopic investigations can be made without damage to the skin. The possibility of repeated replication of the same surface area allows to follow in electron microscopy the time dependent changes of morphological aspects of the surfaces.


[Morphology and monocytopoesis of mycosis fungoides]. Nature and nosology of mycosis fungoides have to be reconsidered because there is now evidence of the t-cell nature of the atypical lymphoid cells within the mycoside infiltrate. Therefore the concept of the reticulum cells in the pathogenesis of mycosis fungoides must be corrected. On the ground of morphological and immunological reasons these cells do not exist in the dermis at all. These new findings are the basis of our morphological study in patients with mycosis fungoides. Concentrating on the polymorphous lymphohistiocytic cells, which cannot be classified further by the method of paraffin-thin sections, light microscopically, the exact differentiation is only possible with semi-thin-sections. With this technique there can be made visible the typical features of nuclei of mycosis fungoides cells. The mycosis fungoides cells are characterized by a large nucleus with hyperconvoluted nuclear membranes, prominent nucleoli, irregular distribution of heterochromatin and sparse cytoplasma. The monocytopoiesis, scheduled by the relative number and the 3H-thymidine labeling indices of promonocytes and the activity of naphthol-AS-D-chloroacetate esterase in blood monocytes was markedly increased. These findings are of special interest, because macrophages are not only able to phagocyte but also play a crucial role in immunology. The elevated monocytopoiesis in all stages of mycosis fungoides points to a stimulation of the immunologic system. This supports the hypothesis of a persistent antigen, which stimulates by means of the functional intact monocyte-macrophage system the lymphocyte system leading to a permanent transformation with augmentation of these immunoblasts (mycosis fungoides cells).


[The morphogenesis and functional control of sebaceous glands with reference to free sebaceous glands]. Not very much was known until now about the physiology of sebaceous glands--especially about the regulation of their function. The author divides primary stimuli for the function of sebaceous glands during lifetime from secondary stimuli for the common supply of sebum. Other primary stimuli are a hypophysial sebotropic factor and other hormones of the gonads and adrenal glands. Capillary attraction and the autonomous system (in a low degree) belong to the secondary stimuli. Following the opinion of renowned authors sebaceous glands and production of sebum are just a special secretoric function of the epidermis. The author voices the hypothesis that androgens can stimulate epidermal basal cells to form sebaceous glands and to produce sebum. This is only possible under certain circumstances, above all only in non-keratinised epidermis.


[Clinical picture and therapy of cerebral apoplexy]. The clinical syndrome of "stroke" at first calls for a differentiation between the prognostic more unfavorable massive hemorrhage and the syndromes of cerebral hypoxia or ischemia. The ratio of hemorrhage to ischemia is about 1 to 5. Conclusions may already be drawn on the nature of the apoplectic insult from the clinical symptomatology. For example, the hemorrhagic insult in general begins with severe manifestations of neurological dysfunction such as hemiplegia and coma, while the symptoms of the ischemic insult frequently do not develop all of a sudden but in the course of hours, rarely from 1-2 days. Digitalisation in combination with dextran infusions is the method of choice in treating intermittent ischemias, particularly those provoked by hypertension. Rehabilitation, i.e. passive and active physical exercise, should be started as early as possible. In addition, particular importance must be attributed to prevention and especially to the early recognition of hypertension and of cardiac diseases as a socio-medical problem.


[Pharmacokinetics of cardiac glycosides and clinical consequences]. The purpose of pharmacokinetics of cardiac glycosides is to study the time courses of glycosides in biological fluids, tissues and excreta. The extent of accumulation of a given dose at uniform time intervals depends only from the overall elimination rate constant. By knowing the elimination rate constant the extent to which a cardiac glycoside would accumulate in the body following a fixed dosing regimen can be calculated. The higher accumulation in the central nervous system requires a much longer time. Therefore it may be assumed that the brain is a deep compartment for cardiac glycosides and this compartment cannot be detected by analysis of plasma glycoside concentrations. Central side effects of cardiac glycosides may occur at therapeutic plasma levels. In renal disease a lower maintenance dose of digoxin and methyldigoxin should be administered or the same dose less frequently. Digitoxin does not accumulate in patients with renal failure or in anuria since the extrarenal elimination of digitoxin is much higher compared to digoxin and methyldigoxin.


[New views on gastrointestinal hormones]. In addition to established gastrointestinal hormones--secretin, cholecystokinin-pancreozymin (CCK-PZ), gastrin, and glucagon---some 30 polypeptides with gastrointestinal actions can be listed. New aspects of these substances include the following: Gastrin and vasoactive intestinal peptide (VIP) can be also encountered in the central nervous system and may act as transmitters. CCK-PZ-serum concentrations are found markedly elevated in patients with exocrine pancreatic insufficiency; this may provide the opportunity  to establish a realtively simple screening test. Moreover, there is evidence that serum-CCK-PZ levels serve as satiety signal. Secretin secretion is said to be enhanced in hunger and then to act as a lipolytic hormone. In addition to enteroglucagon, a gastrintestinal peptide identical to pancreatic glucagon has been detected. Gastric inhibitory polypeptide (GIP) inhibits gastric secretion and motility (enterogastrone activity) and together with glucose it stimulates insulin release (incretin activity). Motilin increases lower esophageal sphincter pressure, enhances gastric pepsin secretion and slows down gastric evacuation. Serum levels of pancreatic polypeptide may be found elevated as a diagnostic index in patients with endocrine peptide tumors of the pancreas. Recently, the potential importance of local (paracrine) actions of gastrointestinal polypeptides has been amphasized. Predominantly paracrine activity is exhibited by some prototype hormones, e.g. somatostatin, substance P, bombesian, and the non-polypeptide compounds, prostaglandins.


[Surgical treatment of radiation injuries of the intestinal tract after radiotherapy of malignant tumors]. From 1962-1975 in our hospital 44 patients were operated because of complications of the bowel after irradiation of malignant tumors. 3 patients were operated in the region of subsequent irradiation. While at the small intestine stenoses were the most frequent complication, at the great gut fistula of rectum, colon sigmoideum or vagina besides stenoses were frequent. The time between irradiation and operation differed between 5 weeks and 22 years. The peak of frequency in the region of the great gut was seen about the first year after termination of irradiation, in the region of the small intestine about the second year. Among the operations of the small intestine resection predominates, at the great gut colostomy. Half of the patients were without complications in the postoperative course. 10 patients died postoperatively, 4 of them of peritonitis. In 3 cases suture insufficiency was verified, in 2 further cases this was doubtful. 36 of 44 patients were without carcinoma at the time of operation or control examination. 16 patients survived 5 years or more.


[Juvenile depressive syndromes].

[Juvenile depressive syndromes]. Depressive states can appear in different phases of life. They differ in their phenomenology according to type, dynamics and power of the etiologic factors, as well as to the moment of their appearance in a child's life. Therefore, depressive syndromes during infancy and childhood are very diverse. Depression in childhood is psychopathologically more complex than it is in adulthood, because it occurs in a developing organism. A differential typologic order according to nosologic aspects is difficult to establish. A division into psychogen-reactive, neurotic, organic, structural and endogenous-psychotic depression is only an attempt toward a rough orientation. Contrary to depressive illnesses in adulthood, anaclitic, reactive and neurotic depressions are most frequent in childhood. They are always due to inconvenient relations to and identification with the significant other of the child. There are dynamic interrelations between the different depressive states in childhood. Already in the early phases of development, the foundations are laid for the possible later development in melancholia.