Plasma levels of phenobarbital and phenytoin in epileptic outpatients. In a group of 65 epileptic outpatients the reliability of intake of prescribed medication was evaluated according to two criteria. The following results were obtained: the number of patients with no or irregular intake of antiepileptic drugs in the whole group was 28%; the relationship between dose and observed plasma levels in patients reliable to intake could be verified; physicians were more often aware of unreliable intake by their patients than could be expected by chance.


The role of cerebral perfusion pressure as origin of brain edema in acute arterial hypertension. In a series in 8 cats, cerebral perfusion pressure (CPP) was evaluated over a period of 5 min after production of an acute arterial hypertension. The mean percentual increase of blood pressure, CPP and ICP equalled 100%. the fact, that ICP does not play any role in acute hypertension, indicates that an abrupt elevation of filtration pressure within the capillaries must be the decisive factor leading to edema.


A study of the activity of platelet monoamine oxidase in patients with migraine headaches or with 'cluster headaches'. The results of the study of the activity of platelet monoamine oxidase (MAO) in patients with migraine headaches or with 'cluster headaches' are presented. In both types of headaches, MAO activity is lower than in normal subjects. We suggest that the low MAO activity is due to a primary constitutional defect.


Renal revascularization after splenic artery implantation into the kidney. Consecutive serial angiographic study in the dog. 29 mongrels were subjected to splenic artery implantation into the left kidney. Consecutive angiographies showed that this procedure regularly was followed by an initial thrombus formation in the implanted artery and an early recanalization of this thrombus. After creation of stenosis and eventually occlusion of the left renal artery, newly formed intrarenal vessels could be demonstrated next to the implanted artery. These vessels formed communications between the splenic and intrarenal arteries. At angiography of the implanted splenic artery the constrast medium was seen to pass over to the newly formed vessels and to intrarenal arteries followed by contrast medium opacification of the renal parenchyma and the renal vein and excretion to the pelvis and ureter. The experimental animals survived contralateral nephrectomy and ligature of the ipsilateral renal artery provided that a slowly progressing stenosis of this artery was created.


Profound reflex bradycardia produced by transient hypoxia or hypercapnia in man. A quadraplegic patient was able to breathe adequately for the first 3 days after his cervical spinal cord was transected by a bullet. However, for several days thereafter spontaneous ventilation became inadequate, most likely due to edema of the cord, and mechanical ventilation was required. When the ventilator was disconnected for required tracheal aspiration, before there was any tracheal stimulation, profound bradycardia, hypotension and syncope occurred within a few seconds. The bradycardia could be diminished by atropine and its onset delayed by prior ventilation with oxygen. Because of the rapid onset of the hemodynamic changes and their correlation with relatively small changes in PaO2 and PaCO2, it is suggested that this vagally mediated bradycardia represents the primary cardiac reflex response to peripheral chemoreceptor stimulation, which, although extensively studied in experimental animals, has not before been described in man. Just as in animals, it seems likely that the inability to hyperventilate permitted the primary cardiac reflex to occur rather than the usual response of tachycardia to chemoreceptor stimulation which is prepotent with spontaneous ventilation. An understanding of this reflex was important in the clinical mangement of this patient.


Ex vivo vascular perfusion of the isolated rat small bowel. Importance of the intestinal brush border enzyme-release in basal conditions. The vascular perfusion of the whole isolated intestine of the rat with homologous non-diluted blood is compared with classical in vivo experiments. During a 2 1/2-hour perfusion procedure no significant difference was noted between the two experimental schedules as far as haemodynamic, histological, mechanical and/or electrical activities of the gut are concerned. However, striking changes in the intestinal brush border enzyme output within the lumen appear between ex vivo and in vivo experiments. The early increase of intraluminal intestinal sucrase, already after the 95th min of perfusion indicate clearly the existence of a subcellular damage even not detectable by other tests of viability. Therefore, it is suggested that release of brush border enzymes might represent an interesting criterion of viability of in vitro or ex vivo preparations.


Evaluation of implanted faulty demand pacemakers by magnet waving and electrical chest wall stimulation. A report of clinical experience. 15 different models of implanted demand pacemakers (61% Cordis models) in 156 patients were scrutinized owing to an announcement that had identified 3 faulty Cordis series and, as a consequence, had provoked considerable uncertainty among all pacemaker patients in the community. Malfunctions of the sensing, and reed switch mechanisms as well as changes in pacers' refractory periods were excluded by the electrical chest wall stimulation (ECWS), magnet waving (MW) or a combination of both. That those models suspected of malfunction show merely a drop in rate was verified. Established patterns of early rate drop guided the exchange for new units: no abrupt or complete rate drop occurred and no patient was lost. The application of indirect overdrive revealed that the blocking capacity for rapid rates was in Omni-Ectocor units less reliable than in Ectocor units. The characteristic reactions to MW and ECWS of the 15 demand pacemaker models were determined. Because both methods proved to be as easy to apply as they were beneficial for the follow-up, also in the uncommon situation created by the Cordis announcement, the application of both of these methods on a routine basis in pacemaker clinics is advocated.


Acute coronary events in some Dutch countryside communities. Incidence of, mortality from and fatality of acute myocardial infarction (AMI) and fatal attack of presumed coronary origin (FCA) were registered between July 1970 and March 1974 in a well-defined Dutch countryside population. Patients with a documented previous AMI or aged 70 or older were excluded. AMI (431 cases) and FCA (124 cases) were considered separately. No differences in coronary history profile, age or sex distribution could be demonstrated. However, the period of premonitory symptoms preceding FCA was at a 5% level significantly shorter than in AMI, provided that the unstable angina was the first symptom of IHD. The combined fatality rate of AMI and FCA, counting death during the first 28 days only, was 25% under age 55 and 32% in age group 55-69 yr. None of the 171 cases under age 55 who survived the first 24 h died in the following 4 weeks, whereas 20 out of 384 in the older age group did: a significant difference at a 5% level. The incidence and mortality rates are presented for both AMI and FCA, subdivided in the age groups 35-44, 45-54, 55-64, and 65-69, per 1000 person years. The incidence was 1, 5, 10, 14 in males, and 0, 1, 2, 6 in females, respectively. Mortality was 0, 1, 3, 5 in males, and 0, 0, 1, 3 in females. The set-up of the survey, the diagnostic criteria and the comparability with recent studies are discussed.


Plasma concentrations of propranolol in patients with essential hypertension. Sixteen patients with essentialy hypertension were treated with propranolol 160 to 640 mg daily for three months. Significant decreases both in recumbent and standing blood pressure were observed after three days treatment and subsequently. Reduction of blood pressure was more pronounced when the dose of propranolol was increased. However, neither the mean dose nor the plasma concentration of propranolol could be correlated with the mean decrease in blood pressure. There was great interindividual variation in the plasma concentrations of propranolol produced by the same daily dose. The initial stimulation of plasma renin activity and the therapeutic response to propranolol could not be correlated.


Elimination of canrenone in congestive heart failure and chronic liver disease. The elimination half-life (T1/2) of canrenone, the principal unconjugated metabolite of spironolactone, was 59 h (range 32-105 h) in 5 patients with chronic liver disease and 37 h (range 19-48 h ) in 7 patients withcongestive heart failure. In comparison the T1/2 in normal subjects was 13.5-24 h in previous reports and 20.5 h in the present study, However there was no evidence of greater cumulation of canrenone in the plasma of those patients with a prolonged T1/2.


Methodology and results of a survey of adverse reactons to a drug in private practice. A survey of tolerance of a drug, determined in private practice under "naturalistic" conditions by 591 physicians, and involving 22277 patients is presented. The procedure used in private practice to gather systematic information about reactions to the drug involved a system of data sheets with detachable cards for optical reading and computer analysis. The survey was conducted under the responsiblity at regional level of a team of scientific coordinators-hospital pharmacologists and poison control centres. Possible side effects were noticed in 13,82% of patients, a figure similar to known nocebo reactions. Tolerance was significantly related to sex, age, weight, geographical area, duration of treatment, association with other durgs and therapeutic result. When related to individual physicians, the overall number of side effects and the frequency of three of them in particular did not follow a binomial distribution; the rate of adverse reactions was significantly related to the number of years of practice of the physicians.


Clozapine-induced agranulocytosis: a situation report up to August 1976. The frequency of agranulocytosis in association with clozapine therapy has been estimated and compared with data reported for phenothiazine-induced agranulocytosis. Apart from the "epidemic" in Finland, where the frequency was 21 times that in other countries, there is no evidence that clozapine-related agranulocytosis is more common than the phenothiazine-related disorder. Furthermore, results are given to show that strict adherence to precautionary measure (e.g. weekly blood counts) reduces the mortality-rate of this condition.


First pass hydroxylation of nortriptyline: concentrations of parent drug and major metabolites in plasma. Nortriptyline was given orally and intramuscularly to six depressed patients. Plasma concentrations of parent drug and the unconjugated and conjugated principal metabolite, 10-hydroxynortriptyline, were determined by mass fragmentography. There was a significant decrease in the area under the nortriptyling plasma concentration- time curve after the oral route of administration, whilst the elimination rate was unchanged. With the oral dose, plasma concentrations of the metabolites were higher and peaked earlier than after intramuscular administration, whilst the opposite was true for the parent compound. This proves that the difference in bioavailability between the two routes of administration was due to first pass metabolism. As determined from the ratio between  corresponding areas, the relative bioavailability of the oral dose was 66 +-21 S.D. per cent. This fraction is higher than that reported previously when intravenous nortriptyline was used as the reference dosage form.


Some effects of ORG GC 94, a potential anti-migraine drug, on human platelets. Some effects of Org GC 94 (1,3,4,14b-tetrahydro-2,7-dimethyl-2H-dibenzo[b,f]pyrazino[1,2-d][1,4]oxazepine maleate) on human platelets have been investigated. Without pretreatment with ADP, 5-HT-induced aggregation of humam platets was completely inhibited by 2.5 x 10(-8) M of Org GC 94. Aggregation triggered by noradrenaline (2.5 x 10(-5) M) and uptake of 5-HT by human platelets were inhibited only at the high concentrations of 10(-5) and 10(-4) M of Org GC 94 respectively. Up to millimolar concentrations, Org GC 94 did not liberate lactate dehydrogenase from human platelets. Org GC 94 did not block the oxidative deamination of benzylamine by human platelet rich plasma up to 2.5 x 10(-4) M.


Further evidence for central histamine H2-receptor involvement in the hypotensive effect of clonidine in the rat. In urethane-anaesthetised rats, the administration of the specific histamine H2-receptor antagonist metiamide intracerebroventricularly (i.c.v.) raised the blood pressure and increased the heart rate. Metiamide (i.c.v.) antagonised the hypotensive effect of clonidine (i.c.v.) in an apparently competitive manner. 4-Methylhistamine i.c.v. did not significantly change the blood pressure. The results are consistent with the concept that the hypotensive effect of clonidine is at least partly due to a stimulation of cerebral H2-receptors. The existence of cerebral H2-receptors mediating hypotensive effects is supported by the hypertensive effect of metiamide but not by the lack of hypotensive effects of 4-methylhistamine.


Reduction in blood pressure, sympathetic nerve discharge and centrally evoked pressor responses by methysergide in anesthetized cats. Methysergide (1 and 3 mg/kg i.v.) caused dose-dependent reductions in blood pressure and heart rate of anesthetized cats. In addition, sympathetic nerve discharges of the postganglionic renal nerve were also markedly reduced by the same doses of drug. Pressor responses to electrical stimulation of the diencephalon were inhibited by 3 mg/kg but not 1 mg/kg of methysergide. These results suggest that methysergide acts to decrease blood pressure by a centrally mediated reduction in sympathetic nervous outflow and, at higher doses, can additionally prevent pressor changes caused by electrical activation of suprabulbar central structures. These results are in agreement with previous reports that methysergide has little or no peripheral effects on the cardiovascular system.


Inhibitory effect of propranolol on tetanic contraction in rabbit. The effects of propranolol on electrical and mechanical activity during tetanic stimulation of the diaphragm and leg muscles, and on the heart rate, were studied in the anaesthetized rabbit. Propranolol (from 0.5 mg/kg) reduced the EMG evoked in diaphragm by phrenic nerve stimulation (50/sec) and the EMG and force of contraction during periods of increased respiratory drive obtained by partial tracheal obstruction. The heart rate was lowered by 10-25%. In the indirectly or directly stimulated leg muscles, the drug induced high frequency inhibition of EMG and tetanic contractions (100/sec) without affecting twitch contractions. The inhibitory effect of propranolol on skeletal muscle was probably not caused by beta-adrenergic block, but by stabilization of the sarcolemma. The results suggest that the high frequency inhibitory effect might contribute to the fatigue and reduced work capacity frequently observed when high doses of propranolol are given to man and animals.


Effect of harmaline on pacemaker activity of guinea pig sinus node. Transmembrane potentials of pacemaker fibers of the sinus node were recorded to analyze the effect of harmaline (HME) on cardiac automaticity. A short exposure to HME 2.1 X 10(-5) or 8.3 X 10(-5) M produced a long lasting non-cholinergic depression of the automaticity: the slope of diastolic depolarization of the pacemaker fibers was depressed, but the maximum diastolic potential remained unmodified. The automaticity of the sinus node was not abolished by prolonged exposure to HME 8.3 X 10(-4) M, but a reversible sino-atrial block developed.


Incorporation of 14C-leucine into acid-insoluble material and tRNAleu from light stimulated rat brain. Rats kept in the dark (i.e., less than 0.1 lux) from birth until 15 days were exposed to light. In vivo incorporation of 14C-leucine into acid insoluble material and in vitro aminoacylation of tRNAleu were studied in visual, somaesthetic and motor brain cortices. A significant increase of both 14C-leucine incorporation into acid insoluble material and tRNAleu aminoacylation with respect to the controls were found only in the visual cortex of light stimulated animals.


The production of cerebrospinal fluid in experimental communicating hydrocephalus. Utilizing an atraumatic model to produce chronic hydrocephalus, CSF production was measured during and after development of communicatin hydrocephalus. CSF volume production was significantly lower in animals with increased pressure. Animals with chronic hydrocephalus and normal pressures had abnormal CSF production. Diminished CSF production appears to offer a potential compensatory mechanism when CSF absorption is altered.


[Chemoluminescence during ATP hydrolysis by rat brain ATPase under the influence of agents of a narcotic nature]. The activity of the cerebral ATP-ase and chemoluminescence in hydrolysis of the ATP with the cerebral ATP-ase in rats with ether, thiopental and electrically-induced anesthesia was investigated. In the ether anesthesis the ATP-ase activity and the chemoluminescence level decrease. In the thiopental anesthesia they increase, whereas with electrically-induced one they first go up and then fall off. Once the action of the study agents is discontinued the mentioned parameters return back to their control levels.


[Distribution of different groups of indirect sympathomimetics between aqueous and "fatty" phases]. Ionization constants were measured and distribution between the "fatty" and aqueous phases of the drugs (amphetamine, ephedrin, tyramine, methylphenidate, pipradrol), belonging to two groups of indirect sympathomimetics differing in the mechanism of their action, was studied. The lipophilic nature of the study compounds is shown to correlate with some pharmacological properties determining the difference in action produced by these drugs.


[Features of ethmozine metabolism].

[Features of ethmozine metabolism]. A study of the aethozine metabolism in the urine of rats detected 14 metabolites, a number of which was identified, namely: 2-aminophenothiazine, 2-acetylamide-phenothiazine, ethyl ether of phenothiazine-carbamine-2-acid, their sulphoxides and also aethmozine sulphoxide. Of the aethmozine biotransformation processes is characteristic formation in the organism of the animals of significant quantities of transformation products with complete degradation of the side chain.


[Effect of sydnophen and caffeine on reflex shifts in arterial pressure arising during skeletal muscle contraction]. The influence of sydnophen (5-20 mg/kg) and of caffein (10-40 mg/kg) on the pressor reaction of the arterial pressure, provoked by contraction of skeletal muscles following stimulation of the anterior spinal cord roots (L6, L7, S1) was investigated in 17 tests set up on decerebrated non-narcotized cats. The intraveonus injection of sydnophen was attended by a fall of the arterial pressure and inhibition of the pressor reflex. Caffein reduced the intensity of the pressor reflex to a lesser extent and did not modify the initial level of the arterial pressure.


[Effect of heparin on enzyme processes in the myocardium and liver of animals of different ages]. Experiments conducted with albino mice and male-rats of different age have brought evidence that heparin is capable of raising the resistance of the organism to hypoxic hypoxia, stimulating the activity of NAD-dependent and inhibiting that of flavine-dependent dehydrogenases in the liver and myocardium of rats. It also inhibits peroxidation of lipids and the activity of lyzosomal enzymes in the liver, particularly in old animals. The expediency of a course-wise application of heparin, especially in old age, is suggested.


[Effect of phepracet and its derivatives on the development of neurogenic dystrophy of the stomach wall and the concentration of noradrenaline in it]. The "weighted" phenamine derivatives--phepracet (beta-phenyl isopropylamide of paraaminophenylacetic acid) and preparations IZM-611 ((phenylisopropylamide of paradipropylaminophenylacetic acid) and IZM-487 (phenylisopropylamide of paradietylaminophenylacetic acid) positively prevented the development of hemorrhagic erosions in the gastric wall and forced down the nerepinephrine level in it caused by a 3-hour electric stimulation of immobilized rats. The greatest prophylactic effect produced the preparation IZM-611. A direct relation between intensity of the antiulcerous action of the drugs and their ability to block the reticular formations of the midbrain was noted.


[Effect of prostaglandin F2alpha on the systemic and regional hemodynamics of dogs]. The effect of PGF2alpha on the systemic and regional hemodynamics was studied in experiments on narcotized dogs. After an intravenous injection of F2alpha (in a single dose of 10 mg/kg) aortal hypertension, tachycardia, an increased pressure in the pulmonary artery and a slightly greater cardiac output were recored. The total peripheral and pulmonary resistance was up. The left and right ventricles showed a higher activity. However, in spite of an increased myocardial contractility a short-lived deterioration in the pumping function of the heart was noted. Under the influence of PGF2alpha the coronary blood flow was becoming more intensive. PGF2alpha caused a significant reduction of the circulation rate in the femoral and superior mesenteric arteries while in the carotid and renal ones a biphasic change of the blood flow was in evidence.


[Experimental study of the new medicinal form of the antiviral preparation fluorenal]. Repository forms of a 0.1% fluorenal solution prepared with buffered polyglucin and a 1% polyacryamide were found to be curatively effective in experimental herpetic keratitis in rabbits. When stored in small tube-droppers for not less than 12 months (observation time) the repository fluorenal eye drops retain their therapeutic activity. In its new presentation the drug is highly effective, stable and convenient in use. This medicinal preparation of fluorenal permits reduce its concentration and the number of instillations.


[Comparative reactivity of the neo-, paleo- and archicortex of the brain under conditions of ether and hexanal anesthesia]. In acute experiments on dogs subject to investigation under ether- and hexobarbital sodium-induced anesthesia was comparative reactivity of the neo-(sensomotor region), paleo-(hippocampus) and archicortex (olfactory lobe) of the brain. It was found that following administration of low and medium doses of general anesthetics more marked EEG changes, with but an insignificant inhibition of respirations and a slight fall in arterial pressure, were observed to occur in the hippocampus and in the olfactory lobe, as against the biocurrents in the sensomotor region. Such a regularity continued for as long as the oxygen tension in the neocortex was maintained at a level higher than in the paleo-and archicortex. Upon introduction of toxic ether and hexobarbital doses the oxygen tension in the neocortex dropped earlier and the inhibition of its bioelectric activity would set in concurrently or sooner than in the olfactory lobe and in the hippocampus.


[Relationship between concentration and the character of the effect of adrenaline on the excitatibility of giant neurons]. The nature of the epinephrine action on the excitability of giant neurons depends on its concentration. With a concentration of 1-10(-5) M changes in electrophysiological parameters of the somatic neurons membrane produced by its bore proof to the rising and with that of 1-10(-4) M -- to its falling excitability. Propranolol was indifferent in regard to both epinephrine effects, while dihydroergotoxin abolished the inhibitory effect of epinephrine.


[Cyclic hydrazides. III. Synthesis and anti-inflammatory activity of 2-amino-3,4-dihydroisoquinolin-1(2H)-one]. The synthesis and the antiinflammatory activity of of 2-amino-3,4-dihydroisoquinolin-1(2H)-one and of a series of its derivatives on the amino function are described. Some of theses new componds show high activity in inhibiting the carrageenin oedema and granuloma formation in rats.


[Synthesis of pi-aminotricyclene].

[Synthesis of pi-aminotricyclene]. In continuation of reasarch on polycyclic terpenoid amines and their derivatives, the synthesis of a new tricyclic amine: 7-methylamine-1,7-dimethyltricyclic[2,2,1,0(2,6)]heptane is described.


[Theophylline and theobromine derivatives of nitrogen heterocyclic compounds]. 7-Theophylline derivatives with 4,6-dihydroxy-5-pyrimidinyl-, 3-oxopiperazinylmethyl- and 4-methyl-3,5-dioxopiperazinylmethyl substituents are described: they can be viewed as structural analogues of a nucleic base pair in the Hoogsteen arrangement; theobromine could be converted into the 1-(3,5-dioxo-4-pyrazolidinyl) derivative, similarly analogous to a base pair in the Watson-Crick arrangement.


[Isochroman-4-spiro-4'-piperidine: synthesis and analgesic properties]. The synthesis of some isochroman-4-spiro-4'-piperidines by intramolecular O-methylation of 4-aryl-4-hydroxymethylpiperidines with formaldehyde and their analgesic activity ("hot plate"test in mice) are reported. The introduction of the new ring led to compounds with weak analgesic activity.


Macromolecular drugs.

Macromolecular drugs. Some principles at the basis of the present or potential interest of pharmacologically active synthetic polymers are discussed, together with some chemical aspects of a proper design of these polymers. The synthesis and properties of heparin complexing polymers, prostaglandin releasing polymers, and nicotinic acid releasing polymers are described.


[Antibodies to mediators of inflammation as its inhibitors and analyzers]. Experiments with rabbits showed the formation of antibodies in response to introduction of histamine-, serotonin-, kalllikrein-, bradykinin-proteinic conjugates. The influence of antibodies on the exudative reaction following introduction of histamine, serotonin, kallikrein, bradykinin, dextran and agar to rats was studied. The ability of antibodies to block both the introduced from outside specific mediators of inflammation and their natural analogues is demonstrated. This bears proof to the possibility of utilizing the specific antibodies in the study of the mediating structure common to various types of inflammation and for the regulation of the inflammatory process.


[Effect of diacarb and furosemide in combination with cytostatics on the mitotic activity of tumor and intestines of rats with sarcoma 45]. A cytological analysis of proliferating neoplasic and intestinal epithelium tissues of rats under the effect of cyclophosphane, 6-mercaptopurine, furosemide, diacarbum and of their combination with course-wise introduction was effected. The treatment of rats with the combination of these agents is shown to have led to a stronger inhibition of the mitotic activity in sarcoma 45 and to deeper morphological changes therein, as compared with separate administration of the antiblastomatous drugs. The mitotic activity of the intestinal crypts epithelium inhibited by cytostatics was completely restored up to the control level when the latter were used in combination with diuretics.


[Glycine-14C and methionine-35S incorporation into liver and gastric mucosa proteins during sperm oil treatment of experimental stomach ulcer]. The effect of a course-wise introduction of the sperm oil on the intensity of the proteinic synthesis in experimental gastric ulcer was investigated. Tests were conducted on albino male-rats in which an experimental gastric ulcer failing to heal for a long time had been induced through introduction of a 5% acetic acid solution into the subserous membrane of the stomach. The intensity of the proteinic synthesis in the liver and gastric mucosa was assessed by the rate of the glycine-14C and methionine-35S incorporation in the total, mitochondrial and nucleonic proteins on the 7th, 14th, 21st and 28th days of the experimental ulcer course. The sperm oil secured a more effective production and thereby created propicious conditions for an intensified proteinic synthesis. It also contributed to an earlier normalization of the proteinic synthesis rates and to  a quicker cicatrization of the ulcerous defect.


[Effect of several derivatives of ortho-hydroxybenzoic acid on the glutamate and ketoglutarate oxidation activity of rat liver mitochondria]. Tests conducted with isolated hepatic mitochondria showed that introduction of acetylsalicylic acid (ASA) to rats in a dose of 300 mg/kg for 5 and 20 days inhibited the oxidation systems of glutamate and alpha-ketoglutarate. This effect depends on the stationary concentration of the compound in the organism. Thus, administration of a high ASA dose (300 mg/kg) for 5 and 20 days, as well as its single administration in doses of 400 or 600 mg/kg had the effect of persistently suppressing the activity of these systems without causing any changes in the degree of the energy-generating conjugation.


Correlation between elemental composition and motility of human spermatozoa. X-ray microanalysis of human sperm cells in donor semen having a range of motilities from 0% to 85% showed that elemental composition is not strongly correlated with spermatozoal motility. Only copper in the midpiece was positively correlated with motility when high- and low-fertility groups were compared. Aging of cells in semen caused large changes in subcellular elemental concentrations as motility decreased, notably with uptake of zinc, but these changes were not reflected in the range of motilities in the clinical samples. Electrolyte balance as measured by sodium to potassium ratios also appeared not to be correlated with motility. Subcellular elemental distribution is not a major factor in determining sperm motility in normal human semen.


Influence of pregnancy and the postpartum period on estrogen uptake of the rat fallopian tubes and uterus. After incubation with 6,7-3H-estradiol, the uptake of radioactivity was measured in rat fallopian tubes and uterus during diestrus, estrus, early and late stages of gestation, and the postpartum period (PP). Uptake patterns during early and late pregnancy reflect the critical endogenous estogenic influence on in vitro hormonal (estrogenic) sensitivity of fallopian tubes and uterus. Very low levels of uptake are observed during the middle and late stages of pregnancy, i.e., day 12 to day 20 postcoitum, followed by a sharp increase during the puerperium (days 1 to 6 PP). However, a close similarity exists between tubal and uterine estrogen uptake patterns during the estrous cycle and critical stages of implantation, followed by pregnancy and the postpartum period.


Pathogenetic factors in utricaria in children. A clinico-experimental study. Results of a study in 62 patients with urticaria and 30 controls, all under 12 years of age, are reported. The study involved history taking and assays of immunoglobulins A, G, M, D, E, of complement fractions C3c and C4 and estimation of C1 estease inactivator activity in the plasma. Acute urticaria is more frequent than chronic urticaria in children, expecially in subjects with atopic diathesis; papular urticaria (or strophulus infantum) is particularly frequent in children under 6 years of age and in the male. Assays of plasma immunoglobulins demonstrated selective deficiency of IgA in two and significant reduction of this immunoglobulin in a further three cases. The mean levels of IgE proved normal in chronic urticaria, raised in acute urticaria, and very high in papular urticaria. Complement assays demonstrated, in one case, a reduction of C3c below 60 mg/100 ml, persisting after the disappearance of urticaria.


Studies of human semen in topical corticosteroid-treated and in methotrexate-treated psoriatics. Ejaculates were studied from ten men with severa psoriasis treated with topical corticosteroids and from ten similar patients who had received methotrexate therapy from 1 to 9 years. It was not possible to demonstrate any unfavorable effect on the semen quality during the methotrexate therapy. The semen analysis was more frequently found normal (p = 0.04) in the methotrexate treated group, and no specific abnormality was found in spermatozoa of methotrexate-treated patients. Methotrexate therapy to male psoriatics seems safe and in agreement with this no congenital abnormalities have been reported. A remarkable number of the ejaculates had reduced sperm qualities, and it is proposed that this might be due to psoriatic lesions in the genital tract.


[Cellular immune phenomenon in scleroderma]. The leucocyte-migration-inhibition test was performed to examine 10 patients with progressive systemic sclerosis and 6 patients with linear scleroderma for evidence of cell-mediated immunity to RNA, DNA, human muscle antigen and collagen human type I. An inhibition of cell migration was detected in 6 patients with progressive systemic sclerosis (PSS) and in 3 patients with linear scleroderma in presence of RNA. No cellular reactivity in presence of DNA was observed. Seven cases with PSS, and all 6 cases with linear scleroderma showed a migration inhibition when human muscle antigen was tested. Cell-mediated immunity to collagen human type I was discovered 7 times in PSS and 2 times in linear scleroderma.


The two-step model of ligand-receptor interaction. The theoretical properties of a "two-step" receptor, consisting of two independent molecular entities, a regulatory (R) and an effector (E) unit, which are supposed to diffuse freely in the plane of the fluid and mosaic membrane, are presented. The ligand (L)-hormone, drug, neurotransmitter-binds to the regulatory unit (first step), so that it then becomes able to interact with the effector unit (second step) which is then activated.


Stimulation by androgens of the production of androgen binding protein by cultured Sertoli cells. The formation of androgen-binding protein (ABP) by cultured Sertoli cells, prepared from testes of immature rats, is increased when androgens or follicle-stimulating hormone (FSH) are present in the medium. Testosterone and 5alpha-dihydrotestosterone are equally effective in stimulating the synthesis and secretion of ABP, but non-androgenic steroids examined (progesterone, 17beta-estradiol and corticosterone) are without influence. Maximal increases are observed when androgens are added at the time of cell plating. Cells maintained in culture medium devoid of hormones become progressively less sensitive to subsequent addition of testosterone or FSH. Data are discussed in relation to the sites of androgen requirements for spermatogenesis.


Estimated life expectancy of diabetics.

Estimated life expectancy of diabetics. Life expectancy among diabetics in Iowa was estimated by using mortality data for the state. The Iowa general population had a higher life expectancy than the diabetic population at every age, except at ages 80 and over for men and ages 75 and over for women. The estimated life expectancy of 59.7 years at birth for diabetic males and of 69.8 years for diabetic females was lower than that for the Iowa general population by 9.1 years among males and 6.7 years among females. This difference narrowed with increasing age. The Iowa figures were similar to the estimates of life expectancy for the diabetic popullation of Pennsylvania.


Diabetes and neutrophil chemotaxis.

Diabetes and neutrophil chemotaxis. The chemotaxis of PMN cells from adult and juvenile diabetics and proper control subjects was found to be comparable. Similarly, chemotactic activity generated from diabetic sera was not different from the activity generated from the normal sera.


Correlation of serum triglyceride levels and hemoglobin AIc concentrations in diabetes mellitus. Studies in 10 nonketotic diabetic subjects (five juvenile- and five adult-onset) before and after control of carbohydrate metabolism showed a high degree of correlation between hemoglobin AIc (HbAIc) concentrations and serum triglyceride levels. Serum triglyceride levels were found to correlate more closely with Hb AIc (r = 0.91, p less than 0.001) than did serum cholesterol (r = 0.47, p greater than 0.05), thus indicating a more direct relationship to carbohydrate metabolism.


The high prevalence of diabetes mellitus on a Central Pacific Island. A diabetes prevalence study on an isolated urbanized Central Pacific Island has established a prevalence rate of 34.4% in individuals aged 15 years and over. Of these, 10.4% had previously known diabetes; in the others the diagnosis was made on the basis of a plasma glucose level of at least 160 mg/100 ml 2h after a 75 gm oral glucose load. A further 11.3% of the subjects had borderline diabetes as judged by a 2-h plasma glucose of between 140 and 159 mg/100 ml. Of the diabetics, 72% had a positive family history of diabetes. The high prevalence rate appears to be related to a number of factors including a diabetic genotype, urbanization, and obesity.


Prolactin: a diabetogenic hormone.

Prolactin: a diabetogenic hormone. During an oral glucose tolerance test (OGTT) glucose and insulin levels were measured in 26 patients with prolactin-producing pituitary tumours without growth hormone excess. Basal glucose and insulin levels did not differ from the values of an age-matched control group. After glucose load the hyperprolactinaemic patients showed a decrease in glucose tolerance and a hyperinsulinaemia. Bromocriptine (CB 154), which suppressed PRL, improved glucose tolerance and decreased insulin towards normal in second OGTT. Human PRL or CB 154 had no significant influence on  insulin release due to glucose in the perfused rat pancreas. These findings suggest a diabetogenic effect of PRL. CB 154 might be a useful drug in improving glucose utilization in hormone-active pituitary tumours.


[The high frequency components of the heart sounds in normal subjects (author's transl)]. A technical set up for recording high frequency components of the cardiac vibrations is described. This was based on the use of several amplifiers, taking the third derivative of the displacement tracing, and using a high pass filter with a sharp slope. The tape-recorded high frequency tracing, at 500 Hz, 1000 Hz, or higher, was replayed at slower speed for accurate recording of the high speed signals. A study of the first and second hearts sound at 500 Hz and 1000 Hz was made in 14 young, normal volunteers. The high frequency vibrations of these sounds are analyzed and discussed.


[Open heart mitral commissurotomy: experience with 286 cases (author's transl)]. A total of 286 patients with mitral stenosis or predominant mitral stenosis underwent open heart mitral commissurotomy at the San Camillo Hospital between May 1969 and May 1975; mitral annuloplasty was performed on 71 patients, subvalvular apparatus correction on 43. The operative mortality rate was 0,7% (no deaths among the last 220 patients). Early results, evaluated from intraoperative data, clinical course, acoustic and polygraphic postoperative findings, were good in 228 patients (80%), fairly good in 41 (14%), bad in 17 (6%).


[Increased atrial refractoriness: an explanation for the rarity of atrial arrhythmias in chronic cor pulmonale (author's transl)]. Right atrial monophasic action potential was recorded using a suction electrode catheter in 20 patients with chronic cor pulmonale. The duration of right atrial monophasic action potential was recorded using suction electrode catheter in 20 patients with chronic corpulmonale. The duration of right atrial monophasic action potential was 397 +/- 17 msec, longer than the normal value of 325 +/- 37 msec found in 30 normal subjects. The conclusion of our work is that the long right atrial monophasic action potential duration may explain the sinus rhythm stability and the rarity of atrial arrhythmias in chronic cor pulmonale.


[Tricuspid atresia: hemodynamic and surgical considerations (author's transl)]. Recently some patients with tricuspid atresia underwent physiological correction, as indicated by Fontan, as an alternative to classical procedures. The aims of the hemodynamic and contrastographic study are illustrated and exemplified, in view of the type of surgery. 49 patients underwent palliative operations: 47 shunts and 2 banding. The most frequent procedure was the Waterston shunt. The total mortality was 10.2%, but no deaths occurred after the third month of life. Finally, the future and the limits of "total" correction are discussed.


[Idiopathic cardiomyopathies in children: a description of two rare cases (author's transl)]. Two cases of idiopathic cardiomyopathy in children are described. Although classifiable respectively as of the non-obstructive or dilating type (in case 1) and of the restrictive type (in case 2), some peculiar clinical and angiocardiographic aspects could be found which differentiated them from the typical forms. In case 1 multiple semilunar dilatations were present at the posterobasal level of the left ventricle. In case 2 the restriction of the ventricular chamber with markedly reduced compliance affected only the left ventricle, with marked dilatation of the left atrium and right side cavities. As occurs in the field of idiopathic cardiomyopathies, intermediate forms of anatomical variations can be found with clinical and angiographic atypical features.


[The significance of ventricular arrhythmias during muscular work: correlations with coronary heart disease (author's transl)]. The incidence of ventricular arrhythmias during muscular work in 400 patients hospitalized for clear or suspected coronary artery disease who underwent coronaroangiography and exercise test was studied. The correlations between the arrhythmias and some hemodynamic parameters and the coronaroangiogrphy patterns and left ventricle cineangiography were investigated. None of the factors that were supposed to be significant in the mechanism of the ventricular arrhythmias, such as high left ventricular end dyastolic pressure, modified myocardial contractility, previous myocardial infarct, or higher lesions of coronary arteries, gave significant correlations. In the present study, the ventricular arrhythmias during muscular work do not seem to be of diagnostic significance.


[Echocardiographic aspects of supravalvular aortic stenosis (author's transl)]. Seven patients with hemodynamic and angiocardiographic diagnosis of supravalvular aortic stenosis were studied by single plane echocardiography. 3 patients had the hypoplastic and 3 the "hourglass" type of the disease. 3 patients underwent surgical repair of the malformation, with postoperative echocardiographic control. There was no relationship between the lumen dimension variations as measured by echocardiography and the transtenotic pressure gradient. With respect to angiocardiography, echocardiography underestimates the severity of the disease. The method was always diagnostic, but the anatomic type of stenosis could not be determined. The severity of the disease can be only indirectly assessed by evaluating left ventricular hypertrophy induced by pressure overload.


[Serum digoxin levels in the pediatric age (author's transl)]. Serum digoxin levels during maintenance therapy in children of four different age groups were determined by a radioimmunoassay technique. For each patient, three determinations, at the peak level, at the plateau and at the final phase, were done. The newborn group showed in all three phases serum digoxin levels significantly higher than those found in the other groups, in spite of an only slightly higher dosage of digoxin used in comparison to the other groups.


Induction of mitochondrial aldehyde dehydrogenases in livers of senescent rats. Senescent rats were administered ethanol by gastric intubation at hourly intervals. After 1 h, there was a rapid increase in the specific activities of two isoenzymes of liver mitochondrial aldehyde dehydrogenase which was sustained for the next 2 h. No further changes were observed during the course of the following 2 h.


Protein intake and serum albumin levels in the elderly. Protein intakes, energy intakes and serum albumin levels were measured in a long-stay geriatric unit. There was a significant positive correlation between albumin levels and protein intake in women, but not in men. A positive correlation was found between albumin levels and protein to calorie ratios in both men and women. This suggests that the protein intakes of long-stay geriatric patients may be suboptimal.


Effects of intravenous infusion of glycerol on regional cerebral blood flow in cerebral infarction. Regional cerebral blood flow and its autoregulation after intravenous glycerol infusion have been studied in eight patients in the acute phase of cerebral infarction. Glycerol seems to improve the cerebral blood flow in the damaged region but does not seem to restore autoregulation.


Architectural design: the spatial location and interactions of old people. Residents' interactions in the sitting spaces of purpose-built Homes for old people were studied by participant and structural observation. Eight Homes were sampled from a larger number to represent factors of size (large and small), design (institutional and family) and mental designation of residents (confused or rational). Verbal exchanges between residents were analysed in terms of initiators' and respondents' mental designations. The residents' locations within the sitting spaces and in the sleeping and dining areas of the Homes were recorded. Examination of these data suggests that residents of different mental designations are segregated from each other. Some architectural design elements of physical settings that might foster integration are outlined.


Human intestinal ion transport in vitro. The transport of sodium and chloride across human jejunal and ileal mucosa was studied using an in vitro technique. Specimens of mucosa removed at operation were stripped of muscle coats, mounted in specially designed Perspex flux chambers and bathed in warmed oxygenated and stirred buffer solutions. Evidence was obtained for the active transport of sodium in both jejunum and ileum and of chloride in the ileum. Sodium absorption was enhanced by glucose in both regions of the gut but net chloride transport was unaffected. Glucose had a greater effect on sodium transport in the ileum than the jejunum. The electrical potential difference and resistance was greater and undirectional ion fluxes smaller in jejunal than ileal mucosa. Many of these results with human intestine are similar to results reported with in vitro animal intestine. Apparent discrepancies between the behavior in vivo of human intestine and in vitro of animal intestine are thus likely to be due predominantly to technical rather species differences.


Ultrasound and jaundice.

Ultrasound and jaundice. We have examined 26 consecutive jaundiced patients referred to the ultrasound clinic. A differentiation between extrahepatic and other causes of jaundice was possible in 23 of the 24 patients satisfactorily examined. The use of ultrasonic techniques in the jaundiced patient offers a high degree of accuracy to the clinician, and little or no discomfort to the patient.


Morphological and pharmacological studies of the parietal cells of the stomach in the dog during periods of maximal acid output and after the gastric secretory inhibitor UK-9040. UK-9040, a derivative of the antihistamine triprolidine, is a potent gastric secretory inhibitor. Given orally to dogs it reduced gastric acid, pepsin and volume output in response to food, insulin, histamine, N-methyl histamine, and pentagastrin. Doses of 6-36 mg/kg administered orally four to five hours before the secretagogues produced a dose-dependant and up to 100% inhibition in the outputs of innervated gastric fistula and denervated Heidenhain pouch. Inhibition was still present 24 hours after administration of UK-9040 but was absent at 48 hours. Blood pressure and pulse rate were not affected. Studies with the electron microscope revealed that the normal ultrastructural responses to gastric secretory stimulation were arrested. UK-9040 showed no cumulative effect, tolerance did not occur, and after withdrawal of the drug the physiological and morphological gastric responses of the parietal cells rapidly returned to normal.


Effect of cimetidine on the human lower oesophageal sphincter. Lower oesophageal sphincter pressures in healthy volunteers were measured by a rapid pull-through technique during intravenous infusion of the histamine H2-receptor antagonist, cimetidine. No consistent effects on sphincter pressure were observed which are liable to be of clinical importance. Serum gastrin concentrations during cimetidine infusion were measured by radioimmunoassay and showed no significant variation. In a further series of experiments, the response of the lower oesophageal sphincter to intravenous bolus injection of pentagastrin was measured before and during cimetidine infusion. Cimetidine infusion had no significant effect on the sphincter response to pentagastrin.


Plasma secretin and pancreatic bicarbonate response to exogenous secretin in man. The dose response of duodenal bicarbonate production during synthetic porcine secretin infusions was studied in six healthy volunteers and related to plasma secretin immunoreactivity. Secretin was infused in each individual at four different doses from 0-1 to 2-7 CU/kg/h, each infusion lasting for 60 minutes. Mean maximal bicarbonate secretion was 33 +/- 4 mEq/h. The secretin plasma level for half maximal bicarbonate response was estimated to be 22 pmol/l. As this level is reported to be achieved by intraduodenal acidification in man, it is concluded that secretin may well play a part in the control of duodenal pH.


Glucosamine synthetase activity of the colonic mucosa in ulcerative colitis and Crohn's disease. Glucosamine synthetase is the first enzyme in glycoprotein biosynthesis, catalysing the formation of glucosamine-6-phosphate, from which N-acetylglucosamine is formed. The levels of this enzyme in normal human colonic mucosa (in colectomy specimens and rectal biopsies) were found to be 13-8 +/- 4-0 micron mol glucosamine synthesised/h/g wet wt. In the colonic mucosa in ulcerative colitis and Crohn's colitis the enzyme level was diminished when there was loss of epithelial cells in the mucosa, although not when there was just loss of goblet cells. In patients recovering from an acute attack of ulcerative colitis, the enzyme levels rose to a peak above the normal range, an effect which did not occur in patients who did not recover promptly. This recovery peak may be related to the synthesis of gastrointestinal mucus, or immunoglobulin, or the secretory component of IgA, all of which contain large amounts of N-acetylglucosamine.


Effect of sodium chenodeoxycholate on oxalate absorption from the excluded human colon--a mechanism for 'enteric' hyperoxaluria. A perfusion technique has been used to study the effect of sodium chenodeoxycholate (5 mmol 1-1) on absorption of oxalate (2 mmol 1-1) from the surgically excluded colon in two patients with chronic liver disease. Colonic absorption of oxalate increased at least fivefold when sodium chenodeoxycholate was incorporated in the perfusion solutions. This observation may explain enteric hyperoxaluria after ileal resection and in some other gastrointestinal disorders.


Helminths of wild ruminants introduced into Czechoslovakia. The paper contains results of helminthological studies on ruminants introduced into Czechoslovakia from other regions and continents. It is pointed out that introduction of wild ruminants is not only of theoretical importance in the adaptation of parasites to a new environment, but also of practical consequence in the mutual exchange of parasites between the imported and autochthonous game animals.


Possibilities of persistence in new biotopes of ticks imported by birds. Survival and development of 6 tick species (Hyalomma anatolicum, Rhipicephalus sanguineus, Haemaphysalis punctata, Dermacentor marginatus, D. reticulatus and Ixodes ricinus) were studied in 3 groups differing in the range of distribution with respect to the place of importation, as a model for the knowledge of their possible inclusion in the new local biocenosis during transportation by natural hosts.


Development and survival of the tick Hyalomma dromedarii Koch under laboratory conditions. Developmental cycle of the tick Hyalomma dromedarii as influenced by changes of temperature and humidity was studied under laboratory conditions. Feeding and metamorphosis of developmental stages were observed under standard laboratory conditions, the metamorphosis was traced at exposure to temperature of 28 degrees C, 80% RH to alternating diurnal climate 40 degrees C, 25% RH and 20 degrees C, 80% RH and alternating humidity of 40/100% and 60/100% RH at a constant temperature 30 degrees C.


Synanthropy and faunistics of some Phoridae (Diptera) from Cuba. Material of 498 specimens of 23 species of Phoridae collected by a trapping method in Cuba in 1966 is quantitatively and qualitatively analysed. A review of faunistic data, chorology, seasonal incidence and food preference is given and possible importance of the main species, mostly of the genus Megaselia, as potential vectors and causative agents of myiasis, is discussed.


A new nematode parasite, Esocinema bohemicum gen. et sp. nov.(Skrjabillanidae) of the European pike. A new nematode genus and species, Esocinema bohemicum gen. et sp. nov., is described from the serosa of the air bladder of the pike (Esox lucius L.) from Czechoslovakia (North Bohemia). It is characterized largely by the tubiform buccal capsule, division of the oesophagus into the muscular and glandular sections, pointed tip of the female tail, and character of caudal papillae in the male. Agrachanus Tikhomirova, 1971 is considered a synonym of the genus Skrjabillanus Shigin et Shigina, 1958.


Dental identification: certainty V probability. The article attempts to explain that the dental expert cannot base his identification of an unknown body on the relative frequency of occurrence of any singular dental feature, its particular discrimination potential. Instead, he must make a quantitative and qualitative evaluation of the combination of features involved. The author submits his thoughts on the latter and the guidelines which he, so far, has established for himself.


[Behavior of arterial oxygen-partial pressure under stress in persons with healthy lungs and patients with bronchitis]. In 20 healthy volunteers and 13 patients with chronic bronchitis arterial oxygen tension during and after bicycle ergometer exercise was measured continuously. With additional hemodynamic and ventilatory parameters and further analysis of bloodgases a typical pattern of oxygen tension in the group with chronic bronchitis was found. The results are put in prospect evaluating patients with pulmonary diseases under exercise.


[Therapy and prognosis of chronic hepatitis]. The classification of chronic hepatitis in a chronic persistent and a chronic aggressive form, the latter with mild or strongly inflammatory activity, has proven valid and had been widely accepted. The long-term therapy of the chronic persistent form (to be confirmed histologically several times) consists merely in a basis-therapy (diet, abstinency from alcohol, physical rest, vitamins). With same caution chronic aggressive hepatitis with little activity is being treated. Rival therapeutic measures for forms with a strongly inflammatory activity are only corticosteroids alone or in combination with azathioprine as well as D-penicillamine in small quantities.


Fluorescent Y-chromosomes in hairs and blood stains. Y-chromosome detection by way of fluorescence microscopy in biological materials has made sex determination possible in various areas of investigation. The present report describes the results of sex determination on hairs and blood stains. Significant differences were found between the Y-body count for female and male materials. In blind trials it was demonstrated that a reliable sex determination of hairs was possible for at least 27 weeks and of blood stains on cotton cloth and glass for 6 weeks. There were no false positive findings, but there was one male with a "female" blood smear count, who revealed an abnormally small fluorescent region on his Y-chromosome. The existence of such variants calls for caution when evaluating a low count.


Impairment of cerebral bloodflow by chest compression. A 5-year-old boy had his chest compressed by the moving belt of an escalator for about 10 to 15 minutes. The patient suffered seizures and was unconscious for eight months. The clinical and histological findings are reported, and compared with the findings of experiments on fatal chest compression in rabbits.


[Myocardial scintigraphy using 201 thallium]. Myocardial scintigraphy with 201Thallium is a non-invasive method for detection of myocardial infarction and coronary heart disease. Redistribution-analysis as a sequential-scintigraphy of an exercise-scan permits to distinguish between myocardial scars and coronary vessel disease.


[Early diagnosis of malignant thyroid neoplasms]. Description of the value of cytology in the ambulant diagnosis of the thyroid gland bases on more than 4000 aspiration-punctions of thyroid gland (Wohlenberg and Pfannenstiel 1974). The indications and contraindications of the aspiration-punction are specified; the scintigraphic cold area is elaborated as a domin of the aspiration-punction. The applied technique and classification of the cytological diagnoses are 99 per cent identical with the histological diagnoses. Because of the large number of pathological modifications of the thyroid gland that have been identified as definitely benign a great many operations can be avoided. The knowledge of the history and the clinical results resp. of the course of the disease prevents delay of urgently indicated operations in cases of uncertain cytological diagnoses.


[Clinical and pharmacologic aspects of various betamethasone crystalline suspensions]. The commercially available betamethasone suspensions for injection used in this study have clearly shown quantitative differences in the combination of their easily hydrosoluble betamethasone esters and those difficult to dissolve in water, as well as in the shapes and sizes of their crystals. With regard to their influence on the endogenous cortisol production the two preparations have shown a highly deviating pharmaco-dynamic duration of action-corresponding to their different galenic composition (betamethasone phosphate/acetate approx. 7-8 days; betamethasone phosphate/dipropionate approx. 16-18 days). During the phase of suppression the reduced endogenous cortisol is largely compensated by the pharmaco-dynamic activity of the exogenous steroid.


[The rectal carcinoma. Characteristics of the tumor and its position within the framework of colonic neoplasms]. For the period of 15 years (May 1960 till the end of April 1975) all cases of colon carcinoma (1752) were checked. Of these 851 carcinoma were located in the rectum. Results concerning anamnesis, diagnosis and therapy between these groups are compared and discussed. The necessity of early recognition and the possibilities of practical use are underlined and described.


["Custom-tailored" pancreatic surgery].

["Custom-tailored" pancreatic surgery]. For the surgical treatment of chronic pancreatitis the surgeon has to make a choice between pancreatic resection, drainage procedure, biliary-tract surgery and operations on the vegetative nervous system. In the predominant number of these cases, resection should be considered as the treatment of choice in the management of subjective complaints of patients and the removal of the lesion. All the large number of ineffective previous operations as well as the frequency of postoperative complaints and recurrences speak in favour of this procedure.


[Bronchial carcinoma and paraneoplastic neuromyopathy]. Paraneoplastic neurologic syndromes in patients suffering from bronchial carcinoma were found by Croft and Wilkinson (Croft et al. 1965, Croft and Wilkinson 1965) in 16%. We examined the question whether in patients suffering from bronchial carcinoma neurologic syndromes are as frequent as in a comparative group of patients with different bronchial diseases. Out of 99 patients 61 had histological proof of bronchial carcinoma, 38 were suffering from chronic inflammatory bronchial diseases. The groups were statistically comparable to each other. Cases with carcinoma in situ (TINOMO) showed no significant difference from patients without bronchial carcinoma. In patients who showed intrathoracic metastases of lymphatic ganglions we found neurologic syndromes in 31% (p less than 0.01). Differing from the extension of tumor metastases there was no correlation between duration and frequency of neurologic syndromes. This corresponds to the experience of our hospital in the last 10 years; 5.7% of all patients with extracerebral tumors showed neurologic syndromes, most frequently polyneuropathies. In 10-15% of a normal population one can find these symptoms (Skre 1972), this means they are polygenetic. We did not find frequently an oat cell carcinoma in our material. Cases in which the neuromyopathy preceeded the manifestation of the bronchial carcinoma were not seen. Altogether it can be stated that paraneoplastic neuromyopathies in patients suffering from bronchial carcinoma are more seldom than it was to be assumed from the anglo-saxon literature.


[Potassium deficiency].

[Potassium deficiency]. A survey of the causes, clinical manifestations and differential diagnosis of patassium deficiency is given. Intention is to point out that the potassium cation plays a significant part in a number of metabolic reactions and has an important influence on neuro-muscular physiology and kidney function. The supply of potassium can be of vital importance.


[Clinical aspects and diagnosis of intrauterine growth retardation]. Low birthweight infants add to a great extent to perinatal mortality. Among this group children with intrauterine growth retardation differ from premature children with respect to their pre-, intra- and postnatal risk. Early prenatal diagnosis and monitoring is of great importance for the outcome and later development of these children.


[Legasthenia. Diagnosis, therapy--experiences in a child and adolescent psychiatric ambulatory]. Legasthenic children have undergone a psychological training program adjusted to each individual case. In order to possibly increase therapeutic effect, patients were subjected to an additional medication with Piracetam. This pilot-study reports on the results of combined treatment using psychiatric parameters. Improvement of school-performance and social behavior has been observed.


[Radiosensitivity of lymphocyte stimulation]. Experiments on radiosensitivity of lymphocyte stimulation in vitro and in vivo are described. Mainly the effects on DNA-synthesis and mitotic activity were measured. The effects of delay and inhibition are not specific for stimulated lymphocyte populations, they are common radiobiological characteristics of stimulated proliferation in contrast to spontaneous proliferation. Cells under stimulated proliferation are more radioresistant than the same cells without stimulation or other cells under spontaneous proliferation. In these basic and additional experiments lymphocyte stimulation proved to be a good radiobiological model system.


Enzyme induction in Streptomyces hydrogenas, VII. Short-term accumulation of guanosine polyphosphates. Cells of Streptomyces hydrogenans (ATCC 19631) synthesize guanosine 3'(2')-diphosphate 5'-triphosphate (pppGpp) and guanosine 3'(2')-diphosphate 5'-diphosphate (ppGpp). 10 to 20 min after addition of steroids to the culture medium, the amount of pppGpp and ppGpp increases 2- to 3-fold. At the same time, the cellular amount of both ATP and GTP has been found to increase. While "shift down" experiments arrest growth of the cells temporarily, steroids do not impair cell division of Streptomyces hydrogenans. It is suggested that ppGpp and pppGpp mediate the regulatory shut off of nucleic acid synthesis or control their increased turnover triggered by the steroids.


Snake venom toxins. The amino acid sequences of two toxins (CM-2a and CM-3) from Naja haje annulifera (Egyptian cobra) venom. Two toxins, CM-2a and CM-3, were purified from the venom of Naja haje annulifera by gel filtration on Sephadex G-50 and by ion-exchange chromatography on CM-cellulose. Whereas toxin CM-2a contains 61 amino acid residues, toxin CM-3 comprises 60 residues. Both toxins are cross-linked by four intra-chain disulphide bridges. The complete amino acid sequences of the toxins have been elucidated. The properties of the toxins were compared with those of a cytotoxin, a short neurotoxin, a long neurotoxin and an angusticeps type. The sequences of toxin CM-2a and CM-3 and some of the invariant residues do not show a high degree of similarity with those of the other toxins. The toxicities of toxins CM-2a and CM-3 are much lower than those encountered for the cytotoxin or the neurotoxins and their immunochemical properties are distinct from both the cytotoxin and the neurotoxins. They probably represent a new class of toxins.


Selective isolation of Vibrio cholerae neuraminidase using an immobilized 4-(nitrophenyl)oxamic acid. N-(4-Nitrophenyl)oxamic acid[1] (1) was coupled with Sepharose 4B containing 1,6-diaminohexane as spacer group. This material was used as a specific adsorbent in the purification of Vibrio cholerae neuraminidase. The enzyme was completely retarded and separated from the bulk of the protein when washed with 50mM sodium acetate buffer, pH 5.0. A stepwise increase of sodium chloride concentration from 1.0 to 2.0M was found to be necessary for a sharp elution of neuraminidase activity. The purification was tenfold, and a recovery of more than 90% was obtained. Neuraminidase is only weakly retarded on a column of 1,6-diaminohexane coupled with Sepharose 4B and is not adsorbed by Sepharose 4B.


[The sequence of alpha-chains from pig and llama hemoglobins (aspects on the respiration in highlands) (author's transl)]. The primary structure of the alpha-chains from pig (Suidae) and llama (Lama lama, Camelidae) hemoglobins is given. They differ in the exchange of 22 and 25 amino acid residues, respectively, compared to human alpha-chains. Some aspects and the physiological significance of these results are discussed.


Adamantinoma of long bone. An analysis of nine new cases with emphasis on metastasizing lesions and fibrous dysplasia-like changes. Nine new cases of adamantinoma of long bone are presented. The age range, location, and symptomatology are similar to those in precious reports. Histologically most of the tumors have a "basaloid" or "spindled" pattern. A squamoid pattern with keratinization or an "angioblastic" pattern is seen less frequently. In all cases with adequate material there has been an associated frbrous dysplasia-like lesion is interpreted as being a part of the spectrum of mesenchymal differentiation of which the tumor is capable. Two cases in which metastasis occurred are compared to previously reported metastasizing cases. Few criteria are available that identify the potentially  metastasizing tumor.


The renal pathology of Chediak-Higashi disease: usefulness of the urinary sediment as a confirmatory diagnostic test. The presence of large cytoplasmic inclusions, thought to be abnormal lysosomes, seems to be the cytological hallmark of Chediak-Higashi disease in both humans and animals. This cell anomaly, originally reported in the leukocytes, is also present in various tissue cells, including kidneys. In the patient described, the abnormal inclusions were identified in renal cells of the urinary sediment. Thus, urine could provide a convenient source of diagnostic material in patients with Chediak-Higashi disease. In addition, the ultrastructure of these inclusions is described for the first time in human renal tissue.


The pattern of goblet cell hyperplasia in human airways. Three types of mucosal alterations were found in the large and small airways in eight surgically resected human lungs. These changes were linear depressions and the formation of furrows and diverticula. Goblet cell hyperplasia, mucus retention, and macrophages were frequently associated with these surface deformities, and inflammatory cells were found both in the mucosa and in the underlying bronchial wall. Linear depressions, furrows, and diverticula may be sequential and may persist in the lungs of a patient with or without causing symptoms.


The impact of an elective curriculum in pathology. Under the revised medical curriculum at Duke University, elective courses were offered in the third and fourth years beginning in 1968-1969. Departmental electives in autopsy, surgical, and systemic pathology were offered as major courses, and the subspecialty courses in cardiovascular, renal, pulmonary, pediatric, and neuropathology were taught by specialists in those areas. Special topics in subcellular and molecular pathology, neoplasia, environmental diseases, and experimental pathology were subscribed by medical and graduate students alike. To determine the impact of elective courses in pathology, these electives were compared to those offered by other basic science disciplines. Tabulation of total courses offered, student enrollment, and total academic credit hours were constructed for each basic science area. The data show that over the six year study period the students elected more courses in pathology than in any other basic science. The most heavily subscribed electives in pathology were those that were clinically oriented, such as cardiovascular or renal pathology. One impact of this elective system may be to enhance recruitment. During the period studied, 29 Duke graduates interned in pathology compared to six under a comparable time period in the traditional curriculum.


Nodular transformation of the liver: report of a case. Cases of portal hypertension, other than those caused by cirrhosis, are uncommon. We report a rare disorder of the liver parenchyma causing portal hypertension, which can be difficult to diagnosis ante mortem, even with a full liver work-up including biopsy.


Four new cases of Dicentric Y chromosomes. Dicentric Y chromosomes are rare in man. Four new cases of dicentric Y chromosomes are described. The cases of the literature so far reported are reviewed. Among the cases, a wide range of variation in phenotype, external genitalia, histology, and chromosomal findings was observed. The relationship of the clinical picture and structural abnormalities of the Y chromosomes is discussed.


Benzpyrene-induced sister chromatid exchanges in lymphocytes of patients with lung cancer. The effect of benzpyrene on sister chromatid exchange was determined in PHA-stimulated lymphocytes of 18 patients with lung cancer and 11 controls without cancer or bronchopulmonary diseases. Patients and controls did not differ either with respect to the spontaneous rate of sister chromatid exchanges or in their response to the carcinogen. We conclude that individual susceptibility to lung cancer cannot be detected by an individual response to benzypyrene, at least in lymphocytes and at the chromosomal level.


The Coffin syndrome.

The Coffin syndrome. Two brothers with Coffin syndrome are presented and the fifteen other cases availabe in the literature are reviewed. The molecular defect causing this clinically recognizable syndrome is unknown, and the mode of inheritance may be a sex-linked recessive, but a sex-limited autosomal dominant or autosomal dominant with variable degree of expression cannot be fully excluded at the present time.


Serum hexosaminidase activity in I-cell disease carriers. Serum heat stable hexosaminidase activities are used to identify 47-I-cell disease heterozygotes in a large kindred. Serum beta-hexosaminidase isozyme patterns in normal individuals, Tay-Sachs disease carriers, I-cell disease carriers and in cord blood samples are compared.


Residual family resemblance for PTC taste sensitivity. Complex segregation analysis reveals no evidence for incomplete dominance, polygenic variation, or an effect of family environment on PTC sensitivity. Estimates of gene frequency and displacement from a phenotypic trichotomy agree closely with conventional values for the the dichotomy of tasters vs. nontasters.


Partial deletion of the long arm of chromosome no. 13. A case of partial deletion of chromosome No. 13 identified by G banding as 46, XX, del(13)(q21--ater) is reported in an infant with severe microcephaly, microphthalmos, talipes calcaneovalus, and a single crease on each of the little fingers. A review of other cases of chromosome No. 13 deletion that were identified by banding is presented and the correlation between clinical features and deletion of specific bands is discusses.


Mosaic 45,x/47,xy,+18.

Mosaic 45,x/47,xy,+18. A poorly developed female infant with buphthalmia, Turner phenotype, and mental retardation is described. Blood culture revealed a 45,X/47,XY,+18 chromosomal mosaicism; fibroblast culture showed only 45,X cells. The baby was dead at 11 months. Post mortem examination exhibited an ovarian agenesis and a calcified aortic stenosis.


Toxicity of prostaglandins A1 and A2 for cells in culture. Prostaglandins A1 and A2, in concentrations near 3 x 10(-5) M, produced striking toxicity to muscle, skin and liver cells in culture. Prostaglandins E and F2alpha were much less active in this regard. Toxicity could be measured by reduction in viable cell number, protein and DNA synthesis in the cultures. The sensitivity of cultured cells was related to their age and population density. Dense cultures were sensitive early, in the first 2 days, and resistant after they manifested confluent growth. Sparse cultures remained sensitive later while they continued DNA synthesis and active cell division. It is hypothesized that the prostaglandin A effect is related to active cell division and DNA synthesis.


Culture and morphoogenetic response of a lethal, chlorophyll-deficient mutant of tobacco to hormones, amino acids and sucrose. This report describes the culture of Su/Su, Su/su and su/su tissue in vitro. High levels of auxin and low levels of cytokinin increase growth of the cells. The cells do not need exogenous amino acids for rapid growth and the chlorophyll deficiency cannot be overcome by amino acids. Reduced levels of auxin and sucrose enhance differentiation, whereas cysteine in the autoclaved medium inhibits differentiation. The Su chlorophyll mutant of tobacco provides a marker for in vitro studies on photosynthesis and photorespiration, chloroplast genetics and cell fusion techniques.


Conditioning of a glass surface for the outgrowth of insect epidermis (Leucophaea maderae, Blattaria). A method has been developed by which the surface of cover slips can be condition for rapid outgrowth of the epidermis of cockroach legs. The method permits in vitro observation of wound-healing processes. The conditioning is brought about by materials given off by the hemocytes, possibly materials from the granules of plasmatocytes which are extruded during the flattening of the cells; Coating of the glass surface with other proteins (including cockroach hemolymph serum) and carbohydrates was completely ineffective.


Description of a new hamster ventral prostate cell line containing androgen receptors. Using chemical transformation of primary monolayers of hamster ventral prostate tissue, we have established the HVP-G3 and HVP-B1 cloned cell lines which have been growing in our laboratories for over 18 months. Both cell lines contain high-affinity, saturable androgen receptors which migrate into the nucleus when exposed to physiological doses of androgen. However, neither cell line demonstrates a growth response to androgens. Each cell line will produce a tumor in 6 to 8 weeks when injected subcutaneously into male or female Syrian hamsters. In vitro cell doubling times range from 12 hr in the presence of luteinizing hormone (LH-NIH-S-18) to 18 hr in the presence of 5% serum. Both cell lines have a diploid stemline.


Development and characterization of cell lines of normal mouse bladder epithelial cells and 2-acetylaminofluorene-induced urothelial carcinoma cells grown in monolayer tissue culture. Normal urinary bladder epithelial cells and cells derived from 2-acetylaminofluorene-induced urothelial carcinomas from male Balb/c mice were grown in monolayer culture and were characterized. Cell lines of normal bladder epithelium were mononucleated, sheet-forming cells, with a modal chromosome number of 40. Bladder epithelial carcinoma cells induced by 2-acetylaminofluorene were polynucleate, relatively fast growing, grew in soft agar, demonstrated a higher cloning efficiency than normal cells and formed tumors when inoculated into syngeneic hosts. Differences in morphology were recorded by photomicrography using phase optics and scanning electron microscopy.


Determination of L-ascorbic acid levels in culture medium: concentrations in commercial media and maintenance of levels under conditions of organ culture. The method of Deutsch and Weeks was modified to provide a reliable and reasonably quick method for assaying the L-ascorbic acid content of culture medium. The modified method was used to determine the decay of L-ascorbic acid under various conditions of culture and the concentration of the vitamin in commercially prepared media. The half-life of L-ascorbic acid in a modified New circulator gassed with 95% O2 + 5% CO2 was 1.5 hr.; and when gassed with 20% O2 + 5% CO2 + 75% N2, about 2 hr. In Petri dishes gassed with 20% O2 + 5% CO2 + 75% N2, the half-life of L-ascorbic acid was 0.9 hr. About 4% of the L-ascorbic acid was lost per day when medium was stored at 0 degrees C and about 9% per day when stored at 5 degrees C. When medium with an initial content of 300 microng per ml was stored at room temperature, the half-life was found to be 15.5 hr. The L-ascorbic acid in five commercially available media, which contain the vitamin in their formulations, was assayed immediately after their delivery to the laboratory. The values of L-ascorbic acid measured in these media were in all cases far lower than prescribed. A continuous-flow organ culture system has been designed which allows the provision of a relatively constant level of L-ascorbic acid to explant by taking advantage of the slow oxidation of L-ascorbic acid at 0 degrees C.


A clinical evaluation of the tolerance to pivampicillin tablets. The clinical tolrance of 350 mg pivampicillin tablets was evaluated in 470 hospitalized patients in Denmark, Norway and Iceland. The tablets were given to 229 fasting patients and to 241 non-fasting patients at mealtime. Side-effects were reported in 44 patients (9.4%). Upper gastro intestinal disturbances occurred in 3.6% of the patients and lower gastrointestinal disturbances in  4.5% (including diarrhoea in 1.9%). There were no differences in the frequency of gastrointestinal side-effects in fasting and non-fasting patients receiving pivampicillin tablets. The frequency of exanthema was 2.6%.


[Urinary tract infection following prostatic surgery (author's transl)]. A comparative study was conducted on the severity and course of postoperative urinary infections in prostatic adenoma patients with preoperative bacteriuria and patients without infection. In both groups urinary infections showed a similar tendency to resolve, whereas a significant increase of polyresistant bacterial strains was noted in patients with preoperative bacteriuria. A comparison of 100 patients who had undergone transurethral resection and 100 patients who had undergone prostatectomy showed that severity and course of the postoperative urinary tract infection did not differ.


[Seroepidemiological investigations on the prevalence of chlamydial antibodies in the human (author's transl)]. 1,075 serum samples taken at random from blood donors and 524 samples from patients were investigated with a group-specific antigen for chlamydial antibodies. Antibodies were detected in 9.9% of the blood donors and in 25.7% of the patients, with titers from 1:5 to 1:160 in the former group and up to 1:640 in the latter group. In general, patients had significantly higher titers than blood donors. More attention should therefore be paid to the possible role of Chlamydia in infections of unknown origin.


Neural regulation of respiration.

Neural regulation of respiration. During the last decade, we have seen our knowledge of the neural regulation of respiration progress from the concept of "respiratory centers" to that of densely packed groups of respiratory neurons located within specific medullary nuclei. By careful neurophysiological and histological studies employing intra- and extracellular recording, the sequence of processing of afferent information through these nuclei and the axonal projections from respiratory neurons have been determined. However, the site and the mechanism of respiratory rhythm generation remain unknown.


Evaluation of RAST inhibition as a method for standardization of ragweed pollen extracts. The RAST inhibition technique was evaluated as a method for standardization of ragweed pollen extracts. Seven different ragweed extracts were examined. There was no relationship between the RAST inhibition results and the commonly used parameters of extract potency including weight/volume, PNU and total protein measurements. Intradermal skin test end point titration was variable in different patients and could not correlated with RAST inhibition results. However, RAST inhibition potency did correlate with the antigen E content of the extract and this finding suggests that RAST inhibition might provide a method for better standardization of allergen extracts.


Arthritogenicity of wax D from various mycobacteria related to oil vehicle composition and to the combination with  poly I:C, cord factor and acetylated wax D. Most of wax D (peptidoglycolipid) used here appeared to be ineffective for production of arthritis when given in a water-in-oil emulsion, while the same wax D in squalane was very effective for production of arthritis. Arlacel A as an emulsifier appeared to suppress the arthritogenicity of wax D in squalane, probably through some interaction with the arthritogenic portion of wax D. Poly 1:C seemed to remarkedly enhance the arthritogenicity of wax D, even in water-in-oil emulsion. Acetylated wax D and cord factor (trehalsoe-dimycolate) were much less effective than poly 1:C. Delayed skin hypersensitivity to PPD, peptidoglycan and poly 1:C was also remarkedly affected by oil composition. However, there was no correlation between these delayed hypersensitivities and development of arthritis.


Diagnosis of reaginic allergy with house dust, animal dander and pollen allergens in adult patients. IV. An evaluation of the clinical value of skin test, radioallergosorbent test, case history and combinations of these methods. With the assumption that a provocation test gives the correct diagnosis, the possibility of predicting an allergy by means of the case history, a skin test, radioallergosorbent test (RAST) and combinations of these methods was evaluated for house dust, cow-, cat-, dog-, and horse-dander, timothy-, marguerite-, dandelion- and birch-pollen allergens. All procedures were found to give a reliable diagnosis provided that a group with doubtfoul group, requiring further diagnostic investigations, was smallest when all three methods were used in combination. It is suggested that, in addition to the case history, the first procedure in routine diagnosis with inhalant allergens should be a skin test. RAST should be used primarily for selected cases and as a complement to the case history and skin test, making provocation tests superfluous for the majority of patients.


Industrialization and occupational health in underdeveloped countries. This paper examines world political economic relationships, especially the growing disparities between "developed" and underdeveloped countries and the role of multinational corporations in exploiting the people and resources of underdeveloped lands. Workers in these lands are identified as high risk for both new and old forms of occupational health hazards. To protect themselves, workers must establish governments on their own behalf rather than client governments serving external capitalist interests.


Multiple clear-cell acanthoma (Degos): histochemical and ultrastructural study of two cases. Two patients with clear-cell acanthoma with multiple lesions are reported; histologic and histochemical findings are similar to previous descriptions. The ultrastructural study confirms the overload of glycogen in keratinocytes, associated with an increase of mitochondria and nuclear deformations. The abundance of Langerhans' cells is emphasized. Extrusion of glycogen by keratinocytes and its phagocytosis by Langerhans' cells is suggested.


A simplified technique for casting anatomical models. For anyone desiring to cast anatomical models, a simplified technique for external casting has been developed using dental impression materials readily available in dental supply houses. These impressions yield life-like permanent models retaining topographical features of normal as well as pathological skin and nails.


Synthesis of N-acetyl-muramyl-L-alanyl-D-isoglutamine, an adjuvant of the immune response, and of some n-acetyl-muramyl-peptide analogs. A relatively easy synthetic method is reported for the production of the immunoadjuvant glycopeptide, N-acetyl-muramy-L-alanyl-D-isoglutamine (MDP). Most of the details in this method were also applied to the preparation of some analogs, that were synthesized in order to study structure-activity relationships.


A study of proteinase inhibition by simulation of inhibitor reactive site regions: interaction of the C-terminal undecapeptide of ovein prolactin with some proteinases. The C-terminal undecapeptide of ovine prolactin, H-Leu-Asn-Cys-Arg-Ile-Ile-Try-Asn-Asn-Asn-Cys-OH possesses several structural features common to protein proteinase inhibitors, yet has no inhibitor properties. The undecapeptide is completely hydrolysed by trypsin (Arg-Ile bond) and by chymotrypsin (Tyr-Asn bond), with a proteolytic coefficient of approximately 3,000 M-1 sec-1 and 240 M-1 sec-1 respectively. On the basis of these results, a consideration of entropy, and studies by other workers, we agree with the view of Nishino et al. that the best models for small synthetic peptides with inhibitor properties would be those naturally-occurring inhibitors whose reactive site is located within a small disulphide loop.


Limitations of mammography.

Limitations of mammography. The aim of mammography is to aid in the discovery of cancers of the breast at an early stage and to supply information about breast changes. It is not 100% reliable, and in most circumstances the decision to biopsy should not be based solely on the radiographic report. A relevant example is presented to reaffirm the need for a definitive surgical diagnosis when clinically indicated.


Incidence of cholelithiasis in India.

Incidence of cholelithiasis in India. Incidence of cholelithiasis in the teaching hospital population of India has been reported. The study suggests that North Indians are more prone to cholelithiasis than South Indians. Apparently this variation is related to dietary and geographical factors.


Purified carbon as a tissue replacement. Tissue reactivity to carbon cloth, graphite cloth and vitreous carbon in the solid was studied in dogs. The materials were found to be quite inert and caused no inflammatory reaction or sensitivity changes in the dogs' tissues. No unusual changes were noted on the hemopoietic or enzyme systems. The materials are probably the best biocompatible substances known and seem to meet the major criteria for tissue replacements.


Retinal neoplasia and dysplasia. II. Retinoblastoma occurring with persistence and hyperplasia of the primary vitreous. The occurrence of retinoblastoma in an eye with persistent hyperplastic primary vitreous (PHPV) is reported. These are both rare lesions. The absence of previous reports of their association has led to the clinical impression that the occurrence of PHPV in a microphthalmic eye precludes the presence of retinoblastoma. The coexistence of these lesions in the present case may represent a coincidence. Their occurrence in the same eye is felt to be noteworthy, nontheless, because of its clinical implications and the possibility of a common underlying etiology.


Vitreoretinal juncture; epiretinal membranes and vitreous. This report reviews current knowledge of the ultrastructural features of the vitreoretinal juncture in its normal state, in eyes with posterior vitreous detachment (PVD), and in eyes with epiretinal membranes (ERM's) and then presents new concepts concerning the interrelationship of ERM's and the vitreous. Results show no vitreous residues on retinal surface following uncomplicated rhegmatogenous (senescent) PVD. In eyes that develop ERM's before vitreous detachment, however, a layer of vitreous may be entrapped beneath the ERM and on adjacent membrane-free retina when PVD ocurs. ERM's may be a cause as well as an effect of PVD.


Permeability and patency of retinal blood vessels in experimental diabetes. Increased permeability of retinal blood vessels in human diabetic retinopathy is well known clinically. Its morphologic equivalent is unknown. In dogs with 5 years of poorly controlled alloxan diabetes and nonproliferative diabetic retinopathy comparable to that of man, permeability and patency of retinal blood vessels were tested with the protein tracer horseradish peroxidase and evaluated by electron microscopy. A breakdown of the blood-retinal barrier was found associated with extensive tracer leakage around retinal blood vessels. Tracer had seemingly permeated endothial junctions, and was not transported through the endothelial cytoplasm. Blood vessels which had lost their endothelial cells and were partially occluded by glial cells retained some patency to tracer. These findings suggest the following. (1) Endothelial tight junctions are not a static cell specialization but one that can open due to chronic metabolic or osmotic factors prevailing in diabetes. Opened tight junctions may account for plasma leakage seen clinically in human diabetic retinopathy. (2) In the absence of endothelial cells perfusion does not necessarily end abruptly. The tracer method and electron microscopy may show details of vascular obstruction that are not readily demonstrated clinically.


Hemodynamic changes distal to selective arterial injections. It has been assumed previously that the act of selectively injecting fluid through a catheter into an artery does not significantly alter hemodynamics in that vessel, provided open communication is maintained between the distal portion of the artery and the aortic lumen. In this study, blood flow was measured with an electromagnetic flow probe in distal branches of the left coronary or superior mesenteric arteries of 9 dogs while heparinized arterial blood was injected selectively into the parent vessels at varying rates up to 7 ml/sec. This resulted, in all experiments, in an abrupt and substantial rise in blood flow which was maintained for the duration of the injection. This phenomeon is due primarily to an increase in intraarterial pressure distal to the catheter tip, caused by the injection.


Myocardial response to contrast media: effects on electrolyte metabolism and subcellular structures. The success of coronary angiography depends upon appropriate use and administration of contrast media. We used guinea-pig hearts to study tolerance to various contrast media, with particular attention to electrolyte changes. Changes in myocardial subcellular structures appear to correspond to changes in electrolyte flow produced by contrast media.


Experimental carotid aneurysms: I. Simple surgical production and radiographic evaluation. Using simple surgical techniques, experimental carotid aneurysms are created which simulate some types of human berry aneurysms, both in hemodynamic and radiographic behavior. End to side anastomoses of an external jugular vein graft to the common carotid artery can be carried out by radiologic personnel with no formal surgical training. Factors which cause the aneurysms to fail and fill with clot are infection, incorporation of venous valves into the aneurysm sac, poor suturing technique, and perhaps a sac too large in comparison with its neck. The models are studied and followed by percutaneous catheter angiography, and show the swirling flow seen in clinical practice. These models may be used to study and refine percutaneous catheter occlusive techniques.


Nonsurgical closure of patent ductus: an experimental study. A technique is described for potential use in the nonsurgical closure of patent ductus arteriosus. Occlusion is accomplished with an Ivalon umbrella, inserted via a catheter placed percutaneously into the femoral artery. The technique was tested in thirteen dogs with surgically created shunts closely simulating patent ductus arteriosus. In two cases, the Ivalon plug was undersize; and incomplete occlusion occurred, but without embolization of the plug. In one case, the umbrella emoblized due to improper positioning. Several dogs with successfully occluded ductus were observed from two weeks to six months postoperative. In all cases, the ductus remained closed. The technique has potential application in patients with a small and long patent ductus.


A comparison of three radionuclide techniques for measuring blood flow to rat extremities. A detailed comparison of three radionuclide techniques to estimate blood flow was done in the rat hind limb under reduced, normal and increased blood flow. The techniques compared were the washout of intra-arterial and intra-muscular Xenon-133 and the accumulation of radioactive microspheres in the reference organ technique. There was no significant difference between the three techniques at each of the three flow states. This confirmed that the simpler I.M. Xenon technique is a useful and accurate technique in estimating low blood flow rates in small animals. It was found that the skin puncture had to be sealed after the intra-muscular injection of Xenon to obtain valid results.


Vertebral and peripheral bone mineral content by photon absorptiometry. Dual photon absorptiometry with 153Gd was used to determine the bone mineral content of the lumbar spine of 46 subjects. The bone mineral content of the radius and ulna were measured on these same subjects using single photon absorptiometry. The bone mineral content at the peripheral sites was not a very accurate indicator of absolute bone mineral content in the spine. However, the rate of bone loss with age was greater in the peripheral bones than in the spine. Measurement sites on the appendicular skeleton may provide a more sensitive indication of age changes in bone mineral content throughout the skeleton than would sites on the axial skeleton.


Film-screen sharpness in complex motion tomography. An unsharp radiologic image is created in tomography by the combined motion of the x-ray tube and the film-screen cassette. This image is generally recorded at angles other than normal to the film-screen plane. A metbd for determining the influence of this recording angle on film-screen sharpness is described. The method involves imaging an edge target at various angles between the x-ray beam and the film-screen plane. The MTF is then calculated from the edge images. The effect of film-screen sharpness and quantum noise on subjective image quality in temporal bone tomography is discussed.


Effect of 1alpha-hydroxycholecalciferol in senile osteoporosis and in bone loss following prednisone treatment. Synthetic 1alpha-hydroxycholecalciferol, a potent vitamin D analogue, was given daily together with calcium to seven patients with senile osteoporosis and to three patients with prednisone-induced bone loss. Quantitative bone histology indicated increased formation and mineralization after three months of treatment. The bone resorption was reduced, a finding supported by a decrease in the urinary hydroxyproline excretion. Photon absorptiometry of the forearm showed a significant rise in the bone mineral content, in accordance with the histological findings. Serum calcium rose in all patients and severe hypercalcemia developed in one case. Urinary excretion of calcium and magnesium increased significantly. The findings indicate that treatment with 1alpha-hydroxycholecalciferol may be useful in osteoporosis due to aging or following corticosteroid administration. The patients must be carefully followed up because of the risk of hypercalcemia.


Acid esterase activity in the pathogenesis of atherosclerosis: effect of partial aortic ligation in rabbits. Partial ligation of the aortas of rabbits below the ostia of the renal arteries resulted in a proliferative intimal reaction. Myocytes in the media of the ligated area showed little or no acid esterase activity. This reduction in acid esterase activity is believed to play an important role in atherogenesis.


Surgical correction of congenital dislocation of the hip in children aged two to six years. We report on a consecutive series of 68 children, between the ages of two and six years, with 97 neglected dislocated hips. The standard treatment consisted of traction, open reduction and innominate osteotomy. The results were satisfactory in most cases and the number of complications decreased significantly with improved surgical techniques. Additional operations, such as femoral varisation derotation osteotomy or Colonna arthroplasty, were performed only in exceptional cases for the treatment of complications. The treatment of neglected congenital dislocation of the hip after the patient has begun walking is a difficult orthopedic problem and and uniformly good results cannot be expected. Open reduction and innominate osteotomy appear to be the best form of treatment in the age group studied.