A clinical definition of lattice degeneration of the retina and its variations. Lattice degeneration has certain invariable histologic features but presents clinically in a variety of similar and dissimilar forms. Photographic documentation and statistical data on the evolution of round atrophic holes and of white lines are represented which tend to support the view that all of these clinical forms actuallysent one basic disease process.


Hereditary detachment of the retina in emmetropes and hyperopes. In a nonselected material of 103 retinal detachments in emmetropes and hyperopes, only 2 familial cases were found (2%).


Tears of the peripheral retina; pathogenesis, incidence and classification in autopsy eyes. A pathogenic analysis of full-thickness tears of the peripheral retina and their incidence in autopsy eyes is presented. Tears were classified according to their location (ora or postora, quadrant and zone), type of traction (zonuloretinal or vitreoretinal), morphological features (flap or operculum), presence or absence of posterior vitreous detachment, and their association with other ocular lesions. Tears were present in 2% of eyes. They were postoral in 92%, uniformly distributed in the quadrants, in the equatorial zone in 95%, related to vitreoretinal traction in 94%, of the flap type in 64%, accompanied by posterior vitreous detachment in 79% and were significantly more prevalent in eyes with lattice degeneration (17%). A simple classification of postoral tears is recommended which incorporates these pathogenic principles and includes three types according to their topographical relationship to the vitreous base: intrabasal--caused by avulsion of zonular traction tufts; juxtabasal--related to traction of the posteriorly detached vitreous on irregularities in posterior border of vitreous base; extrabasal--resulting from avulsion of cystic retinal tufts.


[Are the symptoms "white with pressure" and "white without pressure" related to peripheral retinal sclerosis?]. Collagenic formations occur increasingly with age in the retinal periphery of adults. They grow from the vitreous cortex and from the vessels. In extensive growth they form intraretinal networks. Different inflammatory, degenerative and malformative diseases of the retina lead secondarily, and this already in young persons, to an extensive development of such structures. The name 'peripheral retinal sclerosis' is proposed for such alterations in the peripheral retina. Since the peripheral retinal sclerosis occurs at the same areas where the symptom 'white with pressure' is found, one believes that these formations are its organic substrate. The opacification is thought to be a consequence of the stretching of these collagenic formations during the indentation. Deposition of lipids in these formations can show the symptom 'white without pressure'.


Fine structural changes of peripheral cystoid degenerations during life. Peripheral cystoid degeneration is the result of malnutrition of the retinal tissue, already observed in postnatal development. The morphological substrate for a disturbance in the function of the blood-retinal barrier at the ora is the presence of a perivascular space around the capillaries.


[The changing clinical pattern of rheumatic fever (author's transl)]. During the last years a remarkable change in the pattern of rheumatic fever has been observed. Severe carditis and polyarthritis have almost disappeared. Accordingly the mortality rate decreased considerably milder forms of rheumatic fever may become a diagnostical problem so that adequate therapy may be delayed. These cases may present as chronic heart disease with an unspecific history. The modified Jones criteria alone have limited value. Laboratory tests are increasingly important. Not only improvement of hygiene or therapy with Penicillin are causes for the declining incidence of rheumatic fever, but also the change in the behaviour of Streptococci. This assumption will be supported if the equally dranged course of scarlet fever and the uniform ASO-titers in children as a measure for contacts with Streptococci are taken into account.


[Hypophosphataemia as early sign of septicaemia in childhood (author's transl)]. The early diagnosis of septicaemia in children is difficult because the clinical and laboratory findings can be inconclusive. Results of blood cultures are usually available after two days only. Especially in the neonate, delayed or uncritical use of wide spectrum antibiotics can have negative consequences. We tested whether inorganic serum phosphate determinations could be helpful for diagnosing septicaemia in children. As in adults hypophosphataemia is a frequently occurring symptom in children with septicaemia. Hypophosphataemic values below 4.3 mg/100 ml in the neonate and below 3.2 mg/100 ml in an older child support the diagnosis of septicaemia. The possiblity of quick evaluation has some diagnostic importance.


[Familial vesico-ureteral reflux and familial urinary tract infection (author's transl)]. In 6 families several members had vesico-ureteral reflux and/or recurrent urinary tract infections. From the analysis of the case reports the following tentative conclusions could be drawn: Familial reflux may be caused. 1. by primary insufficiency of the vesico-ureteral junction. 2. possibly by secondary changes consequent to a familial tendency to recurrent urinary tract infections.


Reoperation and recurrence in Crohn's colitis and ileocolitis Crude and cumulative rates. To determine the risks of reoperation and clinical recurrence in Crohn's disease involving the colon, we analyzed by both crude and actuarial (life-table) methods follow-up data from 160 patients hospitalized with Crohn's colitis or ileocolitis from 1964 through 1973. A total of 100 patients (63 per cent) underwent major operation; of these, 58 required reoperation. By the 15th year after initial operation, there was a cumulative reoperation rate of 89 and an overall clinical recurrence rate of 94 per cent. Crude data implied that the reoperation rate diminished with each succeeding operative procedure, from 58 per cent after the first operation to 47 per cent after the fourth. By contrast, actuarial analysis revealed that at the three-year follow-up point, the cumulative chance of reoperation increased from 37 per cent after the first surgical procedure to 60 per cent after the fourth. The inexorable tendency of Crohn's ileocolitis to require repeated operations is demonstrable by actuarial methods.


Planning for a pediatric disaster -- experience gained from caring for 1600 Vietnamese orphans. The sudden arrival of 1600 Vietnamese orphans in San Francisco required the rapid development of a co-ordinated disaster plan, including the overnight establishment of a 1000-bed pediatric field hospital. The plan required rapid identification and involvement of lay and governmental resources, acute medical triage and provision of ongoing medical care and basic nurturing services and eventual discharge to adoptive families. Because one third of the orphans were under six months of age, conventional nursery resources were insufficient, and a "warehouse" model was implemented. This process required development of a specialized transportation and communication system, the services of 800 physicians, 1400 nurses, and 3200 volunteers and 162 back-up acute hospital beds. Disaster planning in most sizable American cities has focused on the problems of adults. Because of the unusual problem presented by infants and small children, we recommend that cities carefully evaluate their disaster planning with special reference to the needs of children.


Hepatitis B virus infection in dentists. To evaluate viral hepatitis as a hazard in general dentistry, we surveyed participants in an annual health-screening program at the 1972 American Dental Association session. Of 1245 practitioners, 0.9 per cent were positive for hepatitis B surface antigen, and 12.7 per cent were antibody positive. Of those who had had clinical hepatitis while studying or practicing dentistry, 43 per cent were seropositive. The frequency  of evidence for prior infection with hepatitis B virus increased uniformly with increasing years of professional experience. The proportion of seropositive dentists did not vary with geographic region of the United States, or size of community. Only 10.5 per cent recognized illicit self-injection among patients, and their infection rate was not increased. These data indicate an increased frequency of infection with hepatitis B virus among general dentists, and are compatible with relatively uniform endemicity of subtype/ad strans of that agent in the general population for several decades.


Thyroid hormones and thyrotropin in amniotic fluid. Thyroid hormone and thyrotropin concentrations in amniotic fluid were studied by radioimmunoassays during pregnancy. The mean thyroxine concentration was 398 ng per 100 ml at 15 to 19 and 440 ng per 100 ml at 36 to 42 weeks. Although 3,3',5-tri-iodothyronine was undetectable (less than 25 ng per 100 ml), 3,3',5'-tri-iodothyronine levels were very high (range, 132 to 605 ng per 100 ml) at 15 to 30 weeks, but decreased substantially (range, 54 to 130 ng per 100 ml) thereafter. Thyrotropin was undetectable. The mean thyroxine and 3,3',5-tri-iodothyronine levels in amniotic fluid were much lower and the mean 3,3'5'-tri-iodothyronine much higher than the corresponding values in maternal serum at both 15 to 19 and 36 to 42 weeks of pregnancy. Measuring thyroid hormones in amniotic fluid, especially 3,3',5'-tri-iodothyronine, may aid in the diagnosis of fetal thyroid dysfunction and in identification of pregnancies of less than 30 weeks' gestation.


Chronic autoimmune neutropenia due to anti-NA2 antibody. In exploring the immunologic causes of chronic neutropenia, we identified a persistent neutrophil-specific antibody with NA2 specificity in the blood of a nontransfused two-year-old girl with severe neutropenia. No such antibody was detected in the maternal blood. The antibody was first studied and identified when the patient was 11 months old, but she had had clinical manifestations since the age of one month. After a trial of steroid therapy, a marked but temporary reduction in the antibody titer occurred, accompanied by the rise of the neutrophils to normal level. Neutropenia reoccurred, however, when the antibody titer began to rise, despite continuation of steroid therapy. This transient response allowed the patient's neutrophils to become available and identified as NA2-positive. Although the cause of this disorder remains obscure, the data presented indicate that the anti-NA2 autoantibody is responsible for the neutropenia observed.


Phenylketonuria due to a deficiency of dihydropteridine reductase. The onset of neurologic symptoms in a child who had markedly elevated blood phenylalanine levels during the first two weeks of life and who was promptly treated with a low phenylalanine diet, with excellent control of serum phenylalanine levels, suggested that this child had an unusual form of phenylketonuria. In assays of the components of the phenylalanine hydroxylating system (open liver biopsy at 14 months), the activity of phenylalanine hydroxylase was 20 per cent of the average normal adult value. By contrast, no dihydropteridine reductase activity was detected in the patient's liver, brain or cultured skin fibroblasts. Since dihydropteridine reductase is also essential for the biosynthesis of dopamine, norepinephrine, and serotonin, disturbed neurotransmitter function may be responsible for the patient's neurologic deterioration. On the basis of these results, assay of reductase in cultured skin fibroblasts may be advisable in the initial diagnosis of phenylketonuria.


Elevated serum levels of estrogen and prolactin in daughters of patients with breast cancer. Demographic risk factors in sisters and daughters of 150 patients with breast cancer were compared to those of controls. Plasma hormone levels in 36 teen-age daughters of patients and 31 controls were also studied to ascertain whether an "abnormal" hormone pattern underlies these risk factors. The patients' sisters had, on the average, menarche four months earlier and first full-term pregnancy 12 months later than the controls. The patients' daughters did not show these differences -- apparently owing to low fertility in the patients with early menarche. The patients' daughters had higher 22d-day estradiol-plus-estrone levels than controls (24.4 vs. 19.1 ng per 100 ml, P less than 0.05). Sixth-day prolactin was also elevated (19.0 vs. 14.2 ng per 100 ml, P less than 0.05). About half the patients' daughters could clearly be distinguished from the controls' daughters by means of the sixth-day information on both estrogens and prolactin. Hypersecretion of these hormones may be important factors in breast cancer.


The radiographic resolution of Streptococcus pneumoniae pneumonia. To determine the characteristics of the radiographic resolution of bacteremic Streptococcus pneumoniae pneumonia we examined serial chest roentgenograms in 72 patients. Consolidation disappeared in all patients by eight to 10 weeks; volume loss (9 per cent), plural disease (9 per cent), and stranding (19 per cent) often persisted beyond eight weeks. Resolution occurred earlier in patients less than 50 years old (P less than 0.05) and in the absence of alcoholism and underlying airways disease regardless of age (P less than 0.05). Delayed clearing occurred when these complicating factors were present in patients over 50. Lung cancer was not responsible for delayed resolution of pneumonia. We conclude that an appropriate interval for serial radiographic examinations after therapy for pneumococcal pneumonia is six weeks.


Three-dimensional model of purple membrane obtained by electron microscopy. A 7-A resolution map of the purple membrane has been obtained by electron microscopy of tilted, unstained specimens. The protein in the membrane contains seven, closely packed, alpha-helical segments which extend roughly perpendicular to the plane of the membrane for most of its width. Lipid bilayer regions fill the spaces between the protein molecules.


Critical species, including man, within the biosphere. The protection of critical ecosystems appears to be a sounder management strategy than the protection of critical species. Environmental quality-control systems designed to protect ecosystems are described. These quality-control systems will make it possible to optimize the ability of ecosystems to assimilate and transform wastes and protect them from degradation.


[Living-polymerization and enzymatic synthesis of polysaccharides]. The kinetics of anionic polymerization are shown to be largely analogous to those of enzymic polycondensation )amylose synthesis). The two systems are compared as regards their capacity to synthesize linear and branched polymers of well-defined size and shape.


Benzodiazepines: specific competitors for the binding of L-tryptophan to human serum albumin. By means of the gel filtration technique, the effect of nine benzodiazepine derivatives on the binding of L-tryptophan to human serum albumin was investigated. Using equimolar tryptophan and benzodiazepine concentrations, all benzodiazepines with binding constants higher than 10(4) (M(-1), displace L-tryptophan from its binding site to a high degree. The mechanism of the displacement was characterized as a competition for a common binding site. Some of the benzodiazepines displace L-tryptophan to a greater extent than salicylic acid. The benzostereospecific binding to human serum albumin. This study shows that there is only one binding site on the human serum albumin molecule, which binds tryptophan and the benzodiazepines in a highly stereospecific manner. Therefore it is concluded that the benzodiazepines and L-tryptophan must have similarities in their molecular structure, so that both can bind to the common binding site in such specific manner. These considerations are discussed in regard to the known influence of benzodiazepine derivatives on the L-tryptophan metabolism in brain. A direct involvement of the reported displacement in the pharmacological actions of the drugs seems not to be relevant because of their small therapeutical plasma levels.


Inhibition of RNA synthesis, a possible mode of the embryotoxic action of hydroxyurea. 14C-u-glucose and 32P-phosphate were given intravenously to pregnant rats, treated and untreated with hydroxyurea (HU). The incorporation of radioactivity into a variety of cell components of the embryo was measured. With this double-labelling technique it is possible to survey the effects of embryotoxic drugs on various pathways in mammalian embryos in vivo. Onset, extent and duration of the metabolic changes were measured after application of "non-teratogenic" and teratogenic doses of hydroxyurea (HU). 3 hrs after application of hydroxyurea only DNA synthesis is affected, whereas after 5 hrs RNA synthesis is also inhibited.


Renal effects of adenosine and their inhibition by theophylline in dogs. The action of adenosine on renal blood flow and kidney function in dogs was studied with bolus injections and infusion of adenosine into the renal artery. Simultaneous infusions of theophylline, 1-5 x 10(-6) mol/min into the renal artery which did not affect renal function by itself inhibited the adenosine induced vasoconstriction. From the bolus injection studies a dose response curve (DRC) was constructed. Theophylline shifted the DRC to the right in a parallel manner. pA2-pA10 was 0.98 indicating that theophylline inhibition of the adenosine effects may be interpreted as a competitive antagonism. Infusions of adenosine (0.3-1.1 mumol/min) caused a reduction of urine volume, sodium excretion and glomerular filtration rate (GFR). The decrease of GFR after adenosine infusion by 31.4% could be diminished by theophylline. It is suggested that adenosine action is based mainly on a constriction of the vasa afferentia in the outer zone of the cortex.


The effects of lanthanum on electrical and mechanical events in mammalian cardiac muscle. 1. The effects of various concentrations of lanthanum (La3+) on the force of contraction and on action potentials was investigated in isolated papillary muscles of the guinea-pig. 2. The force of contraction was initially reduced by La3+. During long exposure to high concentrations (i.e. 50, 100 and 500 muM) the contraction amplitude was increased again and a rise in resting tension was observed. These late changes in force of contraction also occurred after short exposure to 500 muM La3+ (2 min) when La3+ had been removed from the medium. 3. The action potentials were shortened at 20% of repolarization (plateau level) during La3+ exposure, whereas at 90% of repolarization a transient prolongation was observed. The resting potentials were reduced only at high concentrations and long duration of exposure. 4. 500 muM La3+ reduced the force of contraction to the control value obtained before addition of ouabain (5x10(-7)M). The ouabain-induced shortening in action potential duration at the plateau level was not reversed by the same concentration of La3+. 5. It is concluded that the action of La3+ on cardiac muscle cannot be explained by a simple displacement of superficially bound calcium. The characteristic effects observed at high concentrations reduce the value of La3+ as a pharmacological tool used in the study of calcium turnover.


Inotropic action, myocardial uptake and subcellular distribution of ouabain, digoxin and digitoxin in isolated rat hearts. In experiments on isolated, electrically driven (240/min) rat hearts, perfused via the aorta at a constant flow (3.8 ml/min), the pharmacologically effective concentration range, the myocardial uptake and the subcellular distribution of three cardiac glycosides (digitoxin, digoxin, ouabain) were determined. The following results were obtained: 1. The effective range varied depending on the cardiac glycoside tested: With digoxin and ouabain very similar results were found- the positive inotropic concentration ranges being within 8x10(-6)M and 6x10(-5)M, the maximum positive inotropic effects attainable being about 100% and the concentration for half maximum effects (ED-50) being 2.4x10(-5)M and 2.3x10(-5)M, respectively. With digitoxin the inotropic concentration range was found to be within 3.6x10(-6)M and 2.4x10(-5)M with a maximum inotropic effect attainable of about 50% only and an ED-50 of 9.5x10(-6)M. The analysis of the time course of the inotropic action revealed extremely short half times for all cardiac glycosides studied (between 48 and 54 sec). 2. The myocardial uptake correlated with the physicochemical behaviour of the three cardiac glycosides studied and was found-depending on the perfusion time (5 to 60 min)-to be in the range of 23 and 36 (ouabain), 66 and 98 (digoxin) and 169 and 264 (digitoxin) nmoles/g wet weight. The respective computed half times for these uptake processes were 2.5 min (digoxin, ouabain) and 3.4 min )digitoxin). 3. Regarding the subcellular distribution an accumulation exceeding an "unspecific" binding (non-perfused hearts) was found mainly in the nuclear-membrane fraction. On the basis of these results (very short half times of either the pharmacological action and the cardiac uptake) the site of action of cardiac glycosides in the rat heart is supposed to be located at the surface membrane of the heart muscle cells. Furthermore, the above results are discussed with respect to those obtained in digitalis-sensitive species.


Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart. 1. Isolated rabbit hearts were perfused with a modified Tyrode solution containing noradrenaline in concentrations increasing stepwise from 5.9 nM to 5.9 muM at 5 min intervals. This dose regime was applied twice before and once 20 min after starting perfusion with one of 9 tricyclic drugs. Ventricular rate and right atrial and ventricular tensions were recorded using the transverse method. 2. Infusions of noradrenaline evoked ventricular arrhythmias in hearts perfused with amitriptyline 4.8 muM, chlorpromazine 5.0 muM, desipramine 5.0 muM, dibenzepine 34.7 muM, doxepin 4.7 muM, imipramine 4.7 muM, noxiptiline 9.1 muM and opipramole 9.2 muM. The incidence of arrhythmias increased with the concentration of noradrenaline applied and the dose of tricyclic drug administered. Whenever arrhythmias had started they continued as long as noradrenaline was infused. Noradrenaline failed to produce arrhythmias in hearts not exposed to drugs and after iprindole 4.7 muM or cocaine 2.9-18 muM. 3. Propranolol 0.1 muM inhibited the incidence of arrhythmias after doxepin 4.7 muM plus noradrenaline 5.9-190 nM. 4. Neuronal uptake of exogenous noradrenaline in the rabbit heart was inhibited by the tricyclic drugs in the following order of declining p potency: doxepin, noxiptiline, amitriptyline, desipramine, chlorpromazine, imipramine, dibenzepine, opipramole and iprindole. 5. Among tricyclic drugs the potency to inhibit amine uptake is related to the incidence of arrhythmias evoked by a submaximal concentration of noradrenaline. It appears, however, that these two parameters are not causally linked. 6. The isolated rabbit heart perfused with noradrenaline might be used as a model for testing the arrhythmogenic actions of tricyclic drugs and the treatment of such arrhythmias.


Drug-induced phospholipidosis. II. Alterations in the phospholipid pattern of organs from mice, rats and guinea-pigs after chronic treatment with chlorphentermine. In three species chronic treatment with the anorectic drug chlorphentermine causes a profound alteration of the phospholipid/lipid metabolism in the organism, resulting in an increase of the fractions of phospholipids and lipids, e.g. in lungs, livers and adrenals. The results are interpreted as drug-induced generalized phospholipidosis, which is caused by amphiphilic drugs, like chlorphentermine and others. Its extent depends on several factors, like content, pattern and turnover rate of phospholipids in different organs, and on the species.


Characterization of pharmacological receptors. The isolation of macromolecules that bind drugs and neurohumoral mediators at receptor sites will require analytical methods adequate to detect these substances in homogenates and crude mixtures. Although the binding of isotopically labeled agonists has been useful in a few instances, equilibrium binding studies of radioactive, lipophilic antagonists promises to be more useful with beta-adrenergic receptors. Alkylation by radioactive reagents that seek out specific receptors or specific functional groups on protein have been used in attempts to label other receptors. Conformationally directed labeling of receptor and receptor-related proteins by the latter group of alkylating agents has been used with receptors for cardiac glycosides and may be applicable to other systems.


On the mechanism of the accumulation of 3H-bretylium in peripheral sympathetic nerves. The uptake of bretylium-(N-3H-methyl) iodide in the rat heart atrium in vitro was examined. The uptake was linear for at least 1 hr and was strongly inhibited by (+)-amphetamine, (-)-noradrenaline, desipramine, cocaine, DSP 4 [N-(2-bromobenzyl)-N-(2-chloroethyl)ethylamine hydrochloride], guanethidine and ouabain. The amphetamine sensitive part of the uptake was almost completely abolished by pre-treatment of the rats with 6-hydroxydopamine and was dependent on the presence of sodium ions. Reserpine had no effect. (+)-Amphetamine but not desipramine caused an increase of the efflux of bretylium from the tissue. The apparent Km value of the active bretylium uptake was 3 x 10(-6) M, which was 10 times higher than that of the uptake of (-)-noradrenaline in the rat heart atrium (Km = 3 x 10(-7) M). The inhibition constants (Ki) for bretylium in inhibiting the noradrenaline uptake and for (-)-noradrenaline in inhibiting the bretylium uptake were 7 x 10(-6) M and 4 x 10(-7) M, respectively. The results obtained support the hypothesis that bretylium is taken up by the same mechanism as that carrying noradrenaline into the nerve terminals but is not bound in the noradrenaline storage vesicles.


Functional antagonism between calcium-antagonists and noradrenaline on isolated guinea-pig atria. In the isolated electrically driven guinea-pig atrium the influence of D 600 and nifedipine on the action of noradrenaline was investigated. 1. The calcium-antagonists caused a dose-dependent negative inotropic effect. 10(-7) M of D 600 or nifedipine inhibited the contractile amplitude by 75 and 55%, respectively. 2. In spite of the pronounced negative inotropic effect evoked by the two calcium-antagonists, the maximal response to noradrenaline was not changed. The sensitivity of the myocardium to noradrenaline was only slightly diminished i.e. by a factor of 4.6 and 3 as calculated from the pD2-values. 3. The functional antagonism between noradrenaline and calcium-antagonists, therefore, offers the possibility to overcome cardiac side-effects of calcium-antagonists.


Acute pulmonary edema and plasma kininogen consumption in the adrenaline-treated rat: inhibition by acetylsalicylic acid and resistance to salicylate and indomethacin. Pulmonary edema and plasma kininogen consumption caused by intravenously administered adrenaline, were inhibited in rats pretreated with acetylsalicylic acid, but not in rats pretreated with indomethacin or sodium salicylate. The possibility of a connection between this edema and mast cell-linked activation of kallikrein by adrenaline is discussed, as well as the possible role of acetylsalicylic acid acting as an acetylating inhibitor of these processes.


Ontogenesis of neostriatal cholinergic neurones in the rat and development of their sensitivity to neuroleptic drugs. Simultaneous determinations of the striatal contents in acetylcholine (ACh), choline acetyl-transferase (ChAc) and acetyl-cholinesterase (AChE) were made in neonate rats from day 4 to day 16 after birth. While, during this period, ChAc and AChE increased 14 and 5-fold, respectively, the change of ACh levels was smaller and more gradual. ACh levels were unaltered following the injection of thioproperazine (5 mg/kg) until day 8, then within 6 days the cholinergic neurones developed a full sensitivity to this drug. The sensitivity to haloperidol (4 mg/kg), pimozide (4 mg/kg) and to the dopamine receptor stimulating drug apomorphine (10 mg/kg) appeared along with that to thioproperazine. These data confirm and extend previous reports that rat striatal cholinergic neurones are immature at birth; they suggest, in addition, that the development of dopamine receptors occurs prior to the appearance of functional cholinergic synapses or concomitant with this event.


Intestinal transport of 3H-digitoxin in vitro incompatible with simple diffusion. On everted jejunal segments of mice the transfer and tissue uptake of 3H-digitoxin, over a concentration range from 2 times 10(-10)--1 times 10(-4)M, was investigated from the mucosal ("m") to the serosal ("s") side as well as in the opposite direction. 1. The time course of the absorption of 3H-digitoxin and some other compounds investigated (glucose, urea, p-aminohippurate) gave evidence of functional integrity throughout the 75 min-periods of the experiments. 2. When 3H-digitoxin was applied to the mucosal side the permeability coefficient showed a dose-dependent increase but returned to lower values at higher concentrations. When 3H-digitoxin was administered to the serosal side the permeability coefficient showed a dose-dependent decrease at high concentrations. The ratio of both coefficients "m" leads to "s"/"s" leads to "m" increased dose-dependently from 0.4--2.6. 3. The uptake of 3H-digitoxin--applied on the serosal side--into the tissue was independent of dose. However, having administered 3H-digitoxin on the mucosal side the tissue accumulation was 2--5 fold higher and the tissue/medium (T/M) ratio increased within the concentration range from 3.0-9.0 4. Under DNP (1 mM) the asymmetry and dose dependence of the permeability and tissue uptake up 3H-digitoxin observed in controls were almost abolished. Therefore it is likely that the transfer of 3H-digitoxin in the intact intestine involves a mechanism more complex than simple diffusion. The existence of more than a two compartment system and/or the contribution of an active transport mechanism is suggested.


Affinity-labelling of the muscarinic receptor of the guinea-pig illeum. 1. The activities of some cholinergic compounds were investigated on the terminal ileum of the guinea-pig and their muscarinic potencies were found to be in the following order: acetylcholine (ACh) greater than diazoacetylcholine (DACh) greater than iodoacetylcholine (IACh) greater than azidoacetylcholine (AACh). 2. Protection experiments with atropine showed a decreased affinity of the four cholinergic compounds for the muscarinic receptor, demonstrating a direct interaction of the drugs and the receptor. 3. The maximal contractions (intrinsic activity) caused by DACh were greater than those casued by ACh, IACh and AACh. 4. Incubation of the ileum with ACh was followed by a reversible loss of its ability to contract (desensitization). The time course of recovery was similiar to that after incubation with AACh. 5. IACh caused a partial (50%), irreversible paralysis of the muscle. 6. The furaziridines seem to react partially irreversibly (30%), whereas paranitrophenyldiazonium fluoborate (p-NDP) caused a complete, irreversible blockade of the muscarinic receptor.


On the localisation of d-tubocurarine in rat liver lysosomes in vivo by electron microscopy and subcellular fractionation. After i.v. injection in the rat, d-tubocurarine is taken up and concentrated by the liver. A method is developed for the visualisation of d-tubocurarine inside the liver cell by electron microscopy. Glutaraldehyde fixed liver blocks were immersed in an ammonium molybdate solution; d-tubocurarine was precipitated at sites of high concentration by molybdate, to form an insoluble d-tubocurarine-molybdate complex. This precipitate was found predominantly at the surface of lysosome-like particles, but also inside these organelles. In subcellular fractionation experiments, d-tubocurarine was found with a high relative specific "activity" in the lysosomal fraction, lending support to a lysosomal localisation of d-tubocurarine.


Preparation and pharmacological activity of the condensation product of adrenaline with acetaldehyde. In vitro incubation of adrenaline with acetaldehyde resulted in the formation of an amorphous product (MA 3) which gave origin to two spots on chromatography plates. Preparative TLC allowed us to separate the corresponding substances, MA 4 and MA 5. Gas chromatography-mass spectrometry, ultraviolet and infrared spectra of MA 4 agree with the structure corresponding to 1,2-dimethyl-4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline. MA 5 is very unstable and was not further characterized. Pharmacological experiments were carried out with MA 3 and MA 4 (and in some cases, MA 5) on isolated saphenous vein strips and isolated guinea-pig atria; responses of the nictitating membrane, blood pressure and hind-limb perfusion pressure were obtained in the anaesthetized dog. There were only quantitative differences between the effects of MA 3, MA 4 and MA 5 (where tested). Therefore, these effects are described as effects of TIQs (tetrahydroisoquinolines). TIQs contracted isolated saphenous vein strips, behaving as total agonists; the dose-response curves were displaced to the right by phentolamine and to the left by cocaine (potentiation factor: 2.7 +/- 0.1). In the dog, contractions of the nictitating membrane, rises of blood pressure and of the perfusion pressure (after i.a. injection) were observed. On isolated guinea-pig atria, weak beta adrenergic receptor activation was found. With higher concentrations, beta receptor blockade was observed, for both cardiac and vascular smooth muscle receptors. The effects of TIQs were short-lasting, showing that a rapid inactivation occured both in vitro and in vivo; neuronal uptake appears to play an important role in inactivation, since cocaine was able to block about 70% of the inactivation capacity of isolated vein strips. The effects of nerve stimulation on the vein strips or on the nictitating membrane were reduced by TIQs; however, this did not affect responses to noradrenaline and enhanced those to tyramine or DMPP. Simultaneously with reduction of the effects of electrical stimulation, blockade of inactivation of endogenous and exogenous noradrenaline was induced by TIQs. Marked depletion of noradrenaline levels in the heart, hypothalamus and aorta of the guinea pig was caused by MA 3 (1-3 mg/kg). It is concluded that the condensation products of adrenaline with acetaldehyde are not devoid of pharmacological activity, are taken up by adrenergic nerve terminals and may act as false transmitters. The similarity of effects of TIQs and acetaldehyde suggests that formation of TIQs may occur in vivo, after acetaldehyde (or ethanol) administration, both in the adrenal gland and in sympathetic nerve terminals. These TIQ alkaloids could play an important role in alcoholic intoxication and in the ethanol withdrawal syndrome.


Muscarinic suppression of the nicotinic action of acetylcholine on the isolated, blood-perfused atrium of the dog. 1. The isolated canine right atrium perfused through the sinus node artery at a constant pressure of 100 mm Hg with blood led from a support dog was suspended in a bath filed with blood and kept at constant temperature. This preparation maintained its constant tension development and rate over 5 hrs in all 5 control experiments. 2. A relatively small amount of acetylcholine (ACh) induced a negative inotropic effect at 0.01 mug and a negative chronotropic effect at 0.1 mug. 3. A relatively large dose of ACh induced a biphasic inotropic response, i.e., initially a negative inotropic response and secondarily a long-lasting positive tropic response. These positive chronotropic and inotropic responses were abolished by propranolol, hexamethonium or tetrodotoxin. 6. In the papillary muscle and atrial muscle preparations isolated from one canine heart, ACh caused negative and positive inotropic effect in both paced papillary and atrial muscle preparations. In contrast to the results obtained with atria, the positive inotropic response of the papillary muscle preparation was completely blocked by treatment with propranolol or tetrodotoxin. 7. From these results, it is suggested that in the canine atrium muscarinic mechanisms predominate over nicotinic ones. This may well be due to the known inhibition  of nicotinic responses by stimulation of muscarinic receptors.


Effects of intraventricularly injected 6-hydroxydopamine on carotid sinus baroreceptor reflex in rabbits. Effects of 6-hydroxydopamine (6-OH-DA) injected into the lateral brain ventricle on the carotid sinus baroreceptor reflex were studied in rabbits anesthetized with alpha-chloralose and urethane. As short term effects, injection of 500 mug/kg of 6-OH-DA caused a fall in blood pressure and heart rate, enhanced the depressor and bradycardia responses to electrical stimulation of the carotid sinus nerve (CSN), and inhibited the pressor response to carotid occlusion. These effects reached the maximum with 2 hrs and disappeared by the 4th hr. Intraventricular injection of noradrenaline (NA) could mimic most of these effects. At 4.5 hrs after injection of 6-OH-DA, NA content of the brain was definitely reduced: 21% of control in the hypothalamus and 14% in the pons-medulla. Rabbits treated with 6-OH-DA under penthobarbital anesthesia 24 hrs before showed a slight fall in resting blood pressure and almost normal baroreceptor function. Intraventricular application of phentolamine abolished the responses to CSN stimulation in 6-OH-DA pretreated as well as normal animals. These results suggest that the acute effects of 6-OH-DA are based on the increased release of NA from the affected nerve terminals and that noradrenergic neurons are involved in the central pathway of baroreceptor reflex. Moreover, the relfex may be functionally maintained by a small portion of brain NA content, even when noradrenergic neurons are greatly affected by 6-OH-DA.


Pharmacology of scorpion toxin II in the skeletal muscle. 1. Scorpion toxin II is potent in inducing contracture and spontaneous contractions of the chick biventer cervicis muscle. In addition, this toxin induces membrane depolarization and blockade of neuromuscular transmission in this muscle preparation. The purpose of the present study is to explore the possible mechanism of actions of toxin II. 2. The muscle contracture induced by toxin II is moderately accelerated by Ca2+-free Krebs solution, delayed by high Ca2+ (10 mM), high Mg2+ (10 mM) and low Na+ (60mM) Krebs solution. Moreover, this action is inhibited slightly by d-tubocurarine and completely by either procaine or tetrodotoxin, but unaffected by beta-bungarotoxin. All these findings suggest that toxin II induces contracture mainly by increasing the Na+ permeability of the muscle membrane. 3. Spontaneous contractions induced by toxin II are abolished by Ca2+-free Krebs solution, inhibited partially by either d-tubocurarine or beta-bungarotoxin and completely by tetrodotoxin or procaine. These results suggest that toxin II induces spontaneous contractions partially by releasing acetylcholine from nerve endings and partially by increasing the Na+ permeability of the muscle membrane.


The effects of increased glucose supply and thiopental anesthesia on energy metabolism of the isolated perfused rat brain. The effects of glucose concentrations in the perfusion medium ranging from 5 to 15 mM and thiopental, on cerebral energy metabolism were studied using the isolated perfused rat brain. After a perfusion time of 30 min brain levels of the following substrates and metabolites were determined: P-creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6P, fructose-6-P, pyruvate, lactate, alpha-ketoglutarate, glutamate, ammonia. In control experiments increasing the glucose concentration in the perfusion medium produced an increase of intracellular brain glucose concentration only, revealing a linear relationship between glucose content in brain and blood. Neither high-energy phosphates nor glycolytic intermediates were markedly affected by the changes in blood glucose. With an anesthetic dose of thiopental (0.15 mM) in the perfusion medium identical metabolic alterations occured in all experiments: P-creatine and glucose were significantly increased whereas ADP, AMP, lactate and pyruvate were diminished. Also with thiopental brain glucose was linearly related with the glucose concentration in the perfusion medium. The calculated regression line was apparently parallel with that from control experiments; that means thipental always caused an elevation of brain glucose by the same amount of 0.9 mumoles/g--irrespective of the initial cerebral glucose content. The results yield further evidence that glucose transport is not the rate-limiting step in glycolysis. The action of thiopetal on glycolytic pathway is discussed.


Influence of papaverine, D600, and nifedipine on the effects of noradrenaline and calcium on the isolated aorta and mesenteric artery of the rabbit. The effects of papaverine and of the organic calcium-antagonistic agents D 600 and nifedipine on the contraction induced by noradrenaline and calcium were studied on the isolated aorta and mesenteric artery. The affinities of both agonists, given as pD2-values, were significantly higher on the aorta than on the mesenteric artery. Under our experimental conditions D 600, nifedipine and papaverine were found to act as antagonists against calcium and noradrenaline in a non-competitive fashion. In either vessel, the calcium-antagonistic activity of D 600 and nifedipine was about 1000-fold greater than that of papaverine, whereas their antagonistic activity against noradrenaline was bout 1000-times weaker, i.e. D 600 as well as nifedipine were about equipotent with papaverine. The comparison between the calcium- and the noradrenaline-antagonistic activity offers the possiblity to evaluate the specifcity of calcium antagonistic agents.


[Intercentral relations in rat spinal cord with local depression of the inhibitory processes]. The changes in certain reflex responses of the rat spinal cord after local depression of inhibitory processes by tetanus toxin (the so-called phenomenon of "determinative dispatch station") were studied. It is shown that the tonic and rhythmic activity generated by this locus in the lumbar part of the spinal cord evokes generalized activity of all spinal motoneurons with similar time characteristics. The depression of its neurons by glycine removes this phenomenon. The excitation of "determinative dispatch station" neurons in cervical segments causes a pathologically enhanced scratch reflex in the ipsilateral hind limb. The enhancing of the scratch reflex is not connected with the depression of inhibitory processes of lumbar motoneurons. The formation of the "determinative dispatch station" in cervical segments produces both excitatory and inhibitory influences on monosynaptic reflexes of the lumbar flexor motoneurons. The role of local inhibitory processes depression in the functioning of the nervous system is discussed.


[Interaction between the horizontal cells of the turtle retina]. The interaction between horizontal cells in the turtle retina was tested by means of two microelectrodes, polarizing and recording ones impaling two cells at different distances between each other. The direct electrical coupling is shown to exist between L-cells of the same type (type I - with big receptive fields and type II - with small receptive fields). The value of this coupling changes with the conditions of illumination as well as with the level of the membrane potential. This can be accounted for by the known properties of subsynaptic and nonsynaptic membranes of the horizontal cells. There is no direct electrical coupling between L-cells of different types. However strong hyperpolarization of L-cells of type I by extrinsic current or by a light annulus evokes a depolarization in L-cells of type II. This indirect interaction between L-cells also dependent on the conditions of illumination may be explained by a mechanism of feedback between the horizontal cells and photoreceptors. Polarization of L-cells of both types has no effect on the cells of C-type.


[Electrical characteristics of the sensory neurons of the medical leech]. The electrical characteristics of three types of sensory neurons (N, T and P) were determined in the leech Hirudo medicinalis. Statistically significant differences were found between the values of tau, Cs and Rs in the neurons of N- and T-types. The same parameters show the least variation coefficients. The value of time constant (tau) is 17.000-46 ms, the resistivity of the soma membrane TRs) is 19.50 kphi-cm2 in T-neurons and 35 kphi-cm2 in N-neurons. The surface of the neurons estimated by their capacitance (Cs) can be 4-10 times larger than the surface of a sphere of the same size. The possible influence of electrical characteristics of the neurons on the peculiarities of their electrical reactions is discussed.


[Microionophoretic study of the cholinoceptor neurons of the visual cortex of cats]. The optic cortex unit responses to the microionophoretic acetylcholine application were studied in acute experiments on unanesthetized cats restrained with diplacine. Of total amount of registered units 59% were sensitive to acetylcholine and revealed excitative (predominantly) or inhibitory responses.


Transplacental and direct action of benzo(a)pyrene studied in organ cultures of embryonic lung tissue. Transplacental effect of benzo(a)pyrene was studied in organ cultures of embryonic lung tissue explanted from mouse donors injected by the carcinogen. Hyperplastic alteration of epithelium, followed by adenomatous changes were seen in embryonic lung tissue cultures from donor mice injected by benzo(a)pyrene. No alteration was seen in control cultures in which the mice were injected by a non-carcinogenic hydrocarbon (pyrene). Besides the blastomogenic action, a growth-promoting effect of the benzo(a)pyrene was observed in the particular organ cultures of the embryonic lung tissue.


Methodological approaches to the study of carbohydrate surface receptore on macrophages and tumor cells. Ultracytochemical visualization of specific carbohydrate receptors by means of lectins can provide valuable topological information about the functional status of cell surfaces in normal and transformed cells. In addition to the concanavalin A (Con A) rection and precoupling of lectin--peroxidase (PO) a new method is suggested using precoupling of the marker enzyme (PO) with an appropriated glycoprotein (glycopeptide) containing a lectin-specific carbohydrate. Furthermore, quantitative estimations of Con A reaction by means of automatic umage analysis are performed on peritoneal macrophages which point out a cluster formation, but give no hints for a loss of glycocalyx during the preparation process contrary to tumor cells.


Different sensitivity to cytostatic drugs of primary tumor and metastasis of the Lewis carcinoma. Differences in cytostatic sensitivity between subcutaneously transplanted Lewis lung carcinomas and metastases from them were studied in vitro. Sensitivity to vinblastine sulphate and melphalan was determined as the reduction of the incorporation of H3-thymidine into drug-treated cells compared with control cells. The main result of the present study is that tumor cells obtained from pulmonary metastases are more sensitive to cytostatic drugs in vitro than are the cells obtained from the corresponding subtaneous tumors. When cells from pulmonary metastases are transplanted subcutaneously, the sensitivity of the resulting tumor closely resembles that of other subcutaneous tumors. However, when the tumor cells have been passed through many cycles where the pulmonary metastases from subcutaneous tumors were re-transplanted subcutaneously and then allowed to metastasize again, a selection of tumor cells has apparently occurred: they have become more sensitive even when grown subcutaneously. Different explanations of this phenomenon are discussed.


Experimental study of the combined effect of leukeran, degranol and predisolone. The effect of the combined treatment with leukeran, degranol and prednisolone on the lymphoid tissue and marrow hamopoiesis in rats is studied. The simultaneous administration of these drugs is shown to cause a more effective inhibition of the lymphoid tissue and a less suppression of the marrow, as compared with their separate administration.


In vitro incorporation of tritiated thymidine by the Sternberg-Reed cells in Hodgkin disease. The study of the possibilities of new DNA synthesis by the Sternberg-Reed cells of Hodgkin disease was done with tritated thymidine and autoradiography. The results showed that after incubation pulses of 30 and 60 minutes cells with lobulated nucleus, binucleated and trinucleated cells, identifiable to the diagnostic Sternberg-Reed cells, had possibilities of new DNA synthesis. This points to a more dynamic interpretation of this cell that was considered without chances of cnromosome replication.


Comparative study of the amino acid composition of some tumor and normal melanosomes. The amino acid composition of melanosomes from human and Harding-Passey mouse melanomas and from pigmented tissues of cattle eyes isolated according to BOLT was studied. The 18 current amino acids and moreover dopa were found in all the hydrolysates studied. By means of apolar/polar amino acid ratio suggested by HATCH the possible properties of melanosomal protein(s) were infered. The higher level of cysteine and lysine in mouse melanosomes as compared with tyrosinase supports the theory of special matrix protein in melanosomes. Lysine seems to have a role in regulation of the quantity of synthesized melanin.


Phosphatases XII. Isoenzymes of alkaline phosphatase and radionuclear investigation (85Sr) of patients with neoplastic affection of the skeleton. In a group of 30 patients with neoplastic processes, 13 were found to have a significantly increased serum alkaline phosphatase activity. This finding correlated with the results of investigation with 85Sr in 7 patients, but owing to a concomitant hepatal symptomatology, it proved of differential diagnostic value in only one of them. On the other hand, the activity of bone isoenzyme of alkaline phosphatase was significantly altered in 15 patients. In 14 of them the increase in bone isoenzyme activity corresponded to an X-ray and a radionuclear finding of a tumor process in the bones. This activity was within the normal range of values in only one patient with a positive result of the 85Sr investigation. An agreement between the results of determination of bone isoenzyme activity of alkaline phosphatase and those of radionuclear investigations was found in 27 patients. In addition, a correlation was established between the increased activity of bone isoenzyme and that of intestinal isoenzyme of alkaline phosphatase. Enzyme investigation can be suitably utilized, alongside radionuclear examination, for early detection of a bone process.


Phagocytic activity of leukocytes in tumors (clinical studies). 1. A method of evaluating in vitro phagocytic activity of leukocytes, using inert latex particles has been described. 2. 363 investigations have been carried out according to the method in clinically healthy donors, in patients with and without malignant disorders. The subjects have been divide into groups according to nature of the disease (operable and inoperable tumors, non-malignant, acute anc chronic disorders). 3. A statistical evaluation of the results revealed that the phagocytic capacity of leukocytes is significantly activated in the presence of a pathological process in the organism and this to a considerably higher degree in tumorous disorders than in non-malignant affections. The degree of activation of the phagocytic capacity of leukocytes can be measured by this method and the latter can be used in every haematological laboratory.


Combination chemotherapy of Hodgkin disease in children. MOPP chemotherapy program was employed in 20 children with advanced Hodgkin disease (stages III and IV). Complete remissions were achieved in 13 patients (65%)within an average duration rate of 17.1 months varying from 2 to 40 months. If thses only one patient developed recurrency and died 10 months after the onset of treatment. The remaining 12 children are alive and well; an average survival rate since the onset of MOPP chemotherapy being 20 months. The patients with partial remission died from further progression of the disease within the period from 2 to 15 months. The study showed that histological type and mode of previous treatment had an influence on the results of chemotherapy used. The complications of MOPP chemotherapy were insignificant and easily controlled.


Inhibition of hamster cell transformation and of benz(a)pyrene hydroxylation by antioxidants. Addition of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (bht) to benz(a)pyrene (BP) exposed cell cultures results in slight reduction of transformation. The benz(a)pyrene hydroxylation is reduced when antioxidants are added to the incubation mixture.


Antitumor effect of 2-thio-4-hydrazinouracil on transplantable tumors. The cytostatic activity of 2-thio-4-hydrazinouracil (THU) on some transplantable tumors has been studied. A strong effect of this compound (between 60% and 100% suppression) has been found in the case of Myeloma P-8 (MOPC-21) and Sarcoma 180 (Crocker). A less pronounced effect has been observed on Yoshida sarcoma, while the development of Jensen sarcoma is not influenced.


DNA measurements on cell nuclei of normal, proliferating and neoplastic thyroid tissues in rats. Nuclear DNA content was measured in 3 normal, 9 hyperplastic and 16 neoplastic rat thyroid glands. Thyroid hyperplasia and tumor growth were induced after treatment of the animals with X-rays and methylthiouracil. In the control animals only diploid thyroid epithelial cells were observed. At the stages of diffuse and nodular thyroid hyperplasia, the total DNA content per nucleus indicated for a diploid chromosome number and only a few cells were hyperdiploid. In the thyroid adenomas and carcinomas a scattering of the diploid region and an increase in the number of hyperdiploid cells was found. Among the various types of thyroid tumors neither difference in the number of hyperdiploid cells, nor typical pattern of distribution of these cells in the histogram was found. The increased number of hyperdiploid cells in the hyperplastic and neoplastic thyroids suggest an increase in the proportion of the cells entering the cell cycle and does not indicate for appearance of a neoplastic stemline.


Preliminary analysis of failures in the radiotherapy of head and neck cancer with a dynamic dose-fractionation in combination with breathing oxygen at ambient pressure. Treatment failures were analysed in 43 head and neck cancer patients treated with a dynamic dose-fractionation in combination with breathing oxygen at ambient pressure. Infiltrative T3-4 lesions with necrosis showed poorer results than exophytic and necrosis-free infiltrative lesions. Possible differences in the oxygenation of the different types of lesion were considered to explain the results.


Clinical analysis of 43 surgically-treated patients with thyroid carcinoma. The authors have analysed 43 patients with thyroid carcinoma who had been treated at the surgery department of the Oncological Institute between 1960 and 1970. The patients are distributed in four groups according to the histologic tumor structure. Considering the specific properties of each particular group, the occurrence of metastases, treatment, survival and prognosis are being discussed. An outline is given on the characteristics of the various forms of thyroid carcinoma from the histological but mainly clinical aspects. The development of regional and distant metastases, surgical treatment, postoperative irradiation or application of radioiodine and hormonal tumor dependence are presented in the paper. The best results were obtained in the papillary and the follicular form, the prognosis in the latter being dependent on the degree of vascular invasion. The solid carcinoma of thyroid shows considerable differences in survival of patients depending on regional metastases and histologic grade. The anaplastic carcinoma has the worst prognosis where survival is expressed in months, exceptions are rare.


Rotational obstructions of the vertebral artery at the atlantoaxial joint. Two patients with vertebrobasilar ischemia are described in whom angiography demonstrated obstruction of one vertebral artery at the C1-2 level on rotation of the head. The possible anatomical explanation and physiological significance of this finding are discussed.


Trigeminal artery connection to the posterior inferior cerebellar arteries. An example of the internal carotid artery supplying the posterior inferior cerebellar artery directly is reported. The direct PICA supply comes from a trigeminal trunk. There was no basilar artery opacification. An embryological explanation is given.


Cerebral venous angioma.

Cerebral venous angioma. A case of venous angioma involving the frontal lobe is presented with surgical and histological confirmation. Only two other angiographically diagnosed cases have been reported previously in the literature. This case tends to support the entity of cerebral venous angioma as a distinct, though rare, type of cerebral vascular malformation.


Autoregulation in external carotid artery branches in the baboon. The effects of changes in systemic blood pressure upon external carotid branches of the baboon have been measured by cerebral angiography. They have been shown to have an autoregulatory type of response down to a blood pressure of about 60 mmHg, below which they constrict.


A clinical and radiological study of chronic lower spinal arachnoiditis. A critical evaluation revealed no distinct clinical complex of symptoms related to the radiological picture of chronic adhesive arachnoiditis in the lower lumbar sac in 72 patients. In all cases the arachnoiditis was diagnosed by myelography with water soluble contrast media and, in 16 cases, verified by operation and microscopy. The assumed cause of arachnoiditis was, in more than half of the cases, the combination of myelography and operation in close relation, and, in ten cases, a previous operation.


Superselective internal carotid arteriography and embolization. Superselective arteriography and superselective embolisation is the future of a part of neuroradiology. After the first realisation in the territory of the external carotid artery, it was logical to extend it to the territory of the internal carotid artery. The technic of the balloon-catheter of Serbinenko is described and problems of embolisation in the internal carotid artery are discussed.


Results of brain scanning with different radioisotopes (99m Tc-PP, 99m Tc-DTPA, 67Ga citrate). Part 1: Study of meningiomas. A comparison of the results obtained by 99m Tc-DTPA, 99m Tc-PP and 67Ga-citrate scanning in ten meningioma patients is reported. The association of conventional brain scanning, bone scanning and "tumor-positive" scanning makes it possible to identify the primary tumor, its real extent, the perifocal damage and the contiguous bone damage.


Orbital phlebography in the diagnosis of painful ophthalmoplegia. Three cases of painful ophthalmoplegia have been described in which symptoms suggesting a tumor of the orbit justified neuroradiological assessment. Phlebography in each case revealed stenosis of the superior ophthalmic vein in its third portion, and non-opicification of the cavernous sinus. Hirtz incidences revealed contralateral cavernous sinus opacification and venous drainage through the coronary sinus. These neuradiological findings helped to differentiate this syndrome from other affections which have similar signs and symptoms.


[Coagulation disorders due to burns. Disseminated intravascular coagulation (DIC) and its possible prevention]. Coagulation data were studied in 77 patients with severe burns divided into two groups (A, 45 cases, and B, 32 cases). Increased PDF, platelet deficiency, enhanced fibrinogen turnover, and paracoagulation tests showing disseminated intravascular coagulation were frequent in both groups. Platelet deficiency was significantly more frequent in group A (64.9% of cases) than in group B (37.5%). Patients in the latter group received small subcutaneous doses of heparin from the moment of admission.


[Clinical use of a test for determination of coagulation factors II, X and VII]. A new clotting test, the Hepato-Quick, indicated in the study of liver insufficiency was used in 102 patients comprising 22 cases of acute hepatitis, 15 of chronic hepatitis, 21 of cirrhosis of the liver, 11 with liver conditions of various nature, 23 cases with a number of diseases without liver impairment and 10 normal subjects. Quick's test was carried out at the same time in all subjects. Results show that the Hepato-Quick test is more sensitive than Quick's test for identifying liver impairment. The greater sensitivity is statistically significant. The test presents excellent standardization and can be carried out on automatic equipment.


[Further aspects of combination antibiotic therapy. Critical review and personal case studies]. A brief account of the aims sought by multiple antibiotic management is followed by an assessment of the antagonism and synergism displayed by associations of two bactericidal antibiotics, two bacteriostatic antibiotics, and one bactericidal and one bacteriostatic antibiotic. Instances of synergism between bactericides (particularly penicillins and aminosides) are mentioned. Stress is laid on recent studies on the mechanism of action of antibacterial drugs showing unmistakeable synergism between trimethoprim and sulphamethoxazol and between chloramphenicol and tetracycline. The antagonism between bactericides and bacteriostatics noted by Jawetz et Al. has not been confirmed clinically in a number of reported series. The main indications for combined antiobiotic therapy are reviewed: endocarditis, purulent meningitis, staphylococcia, brucellosis, salmonellosis, shigellosis, other Gram-negative infections and fever in the course of blood diseases. References is made to personal experience in the management of 35 cases of bacterial endocarditis, 15 cases of purulent meningitis and various forms of serious Gram-negative infection. Leaving aside exceptional cases, the clinical effects of antibiotic associations are uncertain and influenced by too many variables. The technique is still of importance, however, despite the introduction of many new antibiotics. It must not be thought of as a handy method for indiscriminate use, however; its indications (which are summarised) are quite clear.


[Peripheral disorders of intraventricular conduction in ischemic cardiopathy]. The complex question of peri-infarction blocks is examined. Whereas this term was once used for conduction disturbances now interpreted as fascicular blocks, a distinction is drawn here between these and parietal, post-Hisian blocks and infarctual blocks. Their vectorcardiographic picture are described, along with the possible expression of segmentary blocks at the peripheral branches of the posterior fascicle of the left branch. These electrogenetic interpretations are discussed in the light of data obtained by phonomechanographic methods in cases of parietal block.


[Iatrogenic pathology in the cardiovascular field]. The possible iatrogenic effects of some drugs commonly employed in heart cases (digitalis, quinidine, procainamide, antihypertensives, etc.) and the possible risks of electrical stimulation techniques are described. Attention is also given to the dangers associated with erroneous laboratory data, or the mistaken interpretation of correct data by the physician. Some illustrative cases are presented.


[Atrio-ventricular and intra-ventricular conduction disorders in a case of acute cerebrovascular disease]. Transient atrioventricular (1st-degree and 2nd-degree (type II) block, coronary node rhythm, dissociation) and intraventricular (left anterior hemiblock) disturbance were noted in a 67-yr-old man with acute cerebral thrombosis. It is suggested that one of more of the following factors were responsible from time to time for these unusual ECG signs: disturbance of neurovegetative regulation with predominant vagal hypertonus, circulation deficiencies in the conduction tissue due to decreased cardiac output, and histological lesion of specific tissue.


[Ultrastructural observations on amastigote forms of Leishmania donovani in a case of laryngeal leishmaniasis]. An ultrastructural study on the amastigote stage of Leishmania donovani, in a rare case of laringeal involvement, was carried out. Many details of the fine morphology of this protozoon were observed under the electron microscope, i.e.: the outer membrane of host origin, periplast, subpellicular microtubules, kinetoplast, flagellum, flagellar pocket, multivesicular bodies. A presence of a new organelle (4 microtubules structure close to and running parallel to the flagellar pocket), previously not described in Leishmania donovani's species, was demonstrated in this indigenous strain (from Central Italy). The Authors found a limited number of subpellicular microtubules in this strain, i.e.: 72 microtubules. Differences in size and number of microtubules between strains must be investigated in more rigorous morphometric studies. It's possible that the number of the subpellicular microtubules represents a new taxonomic character.


[Theory concerning a possible mechanism of displacement of intracavitary electrode catheters]. Reference is made to three cases in proposing an explanation for the shifting of endocavitary catheters, namely traction of the lead attached to the lower side of the stimulator owing to movement of the apparatus, resulting in displacement of the tip. It is pointed out that the intravasal length of the displaced catheter is markedly decreased in 3 out of 4 cases. Attention is therefore drawn to the importance of the relation between catheter and stimulator in causing a high percentage of the case of displacement observed.


[Neural regulation of bronchial smooth muscle]. A brief account of the anatomical features of the smooth musculature of the entire bronchial tree is followed by an examination of the various components of the broncho-constrictor reflex. Stress is laid on the importance of the sympathetic and parasympathetic pathways in determining the reflex and the release of chemical mediators in the bronchi is discussed. Clinical situations leading to an enhanced reflex are described and their pathogenesis is explained. It is submitted, however, that existing knowledge of bronchospastic syndromes is still insufficiently clear. This explains the lack of success frequently encountered in their treatment.


[Effects of verapamil on the electrical and mechanical activity of smooth muscle]. Verapamil inhibited both the electrical and the mechanical activity of isolated guinea-pig taenia coli. The action of the drug was similar in some respects to that of quinidine as far as the electrical activity was concerned. Closer similarities were observed between it and diphenylhydantoin. The conclusion is drawn that the drug has points of attack at the electromechanical junction and the membrane.


[Diagnosis and early treatment of juvenile delinquency]. Longitudinal research has shown that social failure to adjust can be prevented by early removal of ambiental factors encouraging pathological development of the Ego, and the detection and treatment of psychological tendencies towards the acquisition of deviant stimuli.


[Failure in adaptation: a premise in juvenile delinquency]. The cause of failure to adjust are examined and measures that should be taken by families, school and society in general to prevent such failure from passing into juvenile delinquency are discussed.


[Environmental factors in juvenile delinquency]. Experimental data are cited for the proposition that the complicated aspects of juvenile delinquency can only be understood and explained by adopting a simultaneous psychological and sociological approach. It is also shown that the manifestations of delinquency, though not its actual presence, may be influenced by sex and a depressed city or rural background. Environmental factors serving as stimulating features and hereditary (i.e. predisposing) factors undoubtedly contribute to the formation of the Ego. The former, however, are elaborated by their receipient and are not sufficient to explain a certain type of behaviour. The influence of cultural models should not be underestimated. These, where predominant, tend to render normative what may be considered as deviant.


[Psychology of war (civilization as Thanatos or civilization as Eros)]. Freud saw war as the prevailing of death over love, this being a metapsychological concept whose roots lie in the dynamics of urges within the individual and civilisation in general. In his opinion, this dialectic tension could not be overcome. Reich noted that the analytic theory was in conflict with practice. Freud's premisses concerning the philosophy of civilisation and their implications have been taken up by Marcuse, who solves the conflict between the love-death urges by treating work as reduced to love or a game, in which death is merely the negative to be overcome.


[Problems and perspectives of psycholinguistics]. A brief historical and critical analysis of psycholinguistics is followed by the assertion that the claim of relevance, which has divided psychologists and linguists for so many years, and the conflicts between the different approaches to research evident in the anthropopsycholinguistic sciences reveal the lack of a single, interdisciplinary approach on the part of psycholinguistic research. Attention is also directed to certain fundamental aspects of psycholinguistics, such as: the psychological problems of translation, linguistic apprenticeship, and the psychological analysis of style.


[Psycholinguistics and logopathies. Processes of communication and language disorders]. The evolution of an idiolect and the acquisition of speech patterns are discussed. The need to examine speech disturbances with a view to the adoption of more suitable rehabilitation techniques is emphasised.


[Psycholinguistics and logopathies. New prospects of speech therapy]. Certain aspects of language in growing children are examined. In the field of linguodental dyslalia, reference is made to improvement in speech therapy techniques and the hope is expressed that these may be extended to the management of other forms.


[Dehiberations over the semantics of mass communication media]. The radio, cinema and T.V. have developed their own idiolects and aesthetic standards. These in turn have influenced social relationships and education. Their effect is the reduction of society to a common mass, in which no attentuon is paid to individual motive forces.


[Reform of the Italian radio and TV and the active presence of TV watchers. Psychological aspects]. The psychological aspects of television reception are reviewed. It is suggested that the choice of programmes should take account of the value of viewing as a mental and individually affective stimulus, and with a proposal for contents directed to social groups.


[Use of amino acids in major burns].

[Use of amino acids in major burns]. The results of protein deficiency in major burn cases are examined. They include diminished organ resistance, deleyed wound haeling, proneness to infection, and increased sensitivity to liver-toxic substances, leading to the protracted course of the patient's conditions. Since his caloric intake also needs to be increased, the importance of protein replacement is apparent. A standardised 15-day treatment with daily administrations of 1000 cc of a 7.5% natural amino acid solution was experimented during the period following shock, to prevent loss of amino acids through the vessel walls, since permeability is high in this periodo. Marked improvement in blood proteins was noted, with normalisation in some instances. No chagens in blood chemistry attributable to the treatment were noted.


[A case of incomplete paralysis of the sciatic nerve during anticoagulant therapy]. A case of incomplete paralysis of the sciatic nerve during anticoagulant management.


[Possibilities and limitations of the direct radioimmunological method with double guinea-pig antibody in the detection of serum Australia antigen]. The results obtained with the direct radioimmunological method and electrosyneresis in the search for Australia antigen were compared in 3100 donor sera. In a limited number of sera, the positivity of radioimmunological examination was tested by neutralization tests with human antibody and with the serum of normal guinea-pigs. Electrosyneresis proved positive in 4% of cases, while radioimmunological examination produced a clearly positive result in 6.7% of cases and a faintly positive or doubtful result in 1.8%. The presence of doubtful results is due to the fact that the distribution of values obtained shows some overlapping between normal population and population of subjects carrying the antigen. The neutralization tests have shown a high incidence (45%) of aspecific positivity between the sera proving positive at radioimmunological examination and negative at electrosyneresis. This inconvenience should be resolved by the recent introduction of a radioimmunological method which provides for use of labelled antibody of human origin.


Vacuum extraction.

Vacuum extraction. In the past twenty years, the vacuum extractor has gained wide use in Europe with an associated decrease in perinatal mortality. There, its use is considered by many to be much safet than a forceps delivery. Certain complications are associated with its use, but in general these are minor and transitory. On analysis, most of the serious complications reported in the literature are considered to be due to other associated factors, or to misuse of the vacuum extractor. Experience with the vacuum extractor in the United States has been minimal, and most authors feel that there are few indications for its use. Perhaps it is time that obstetricians in the United States take a more careful look at the European experience, and give the vacuum extractor a fair trial.


Host resistance to intraamniotic infection. In this review the mechanisms whereby amniotic fluid serves to protect the fetus from microbial disease have considered. It appears from the data reviewed that the principal mode of antibacterial action of amniotic fluid is bacteriostasis. Thus, the host is able to cope with a small number of organisms introduced into the amniotic cavity; however when the amniotic fluid is grossly contaminated the host resistance capacity of the amniotic fluid may be overwhelmed. This may be understood best by the quantitative description of disease theroized by Theobald Smith (94). Smith suggested that disease was a function of the number of organisms with which a host is initially infected multiplied by the virulence of the organism. The effects of the number and virulence of the organism in producing disease is lessened by the host's resistance capacity. This concept of disease is summarized by the equation: Disease equals (number) (virulence)/resistance. Although these parameters do not possess numeric values, it is possible to see at least conceptually their interplay with respect to intrauterine infection. For example, the number of organisms reaching the amniotic fluid may be increased by various modes, namely maternal viremia or bacteremia; premature rupture of the fetal membranes, antenatal vaginal examination and possibly intrauterine fetal monitoring. While these circumstances may result in increased rate of infection, some reports conversely indicate that minimal bacterial contamination in the amniotic fluid is not an extraordinary occurrence and may not result in any maternal or fetal complication (73,74). The intrinsic host resistance capacity of the amniotic fluid likewise represents an important part of the Smith equation for disease. We have found that amniotic fluids may vary in antibacterial efficacy from almost no inhibitory activity to profound bactericidal activity (90). Obviously, the likelihood of the production of disease by an equivalent inoculum of a particular organism would be quite different depending upon the intrinsic inhibitory capacity of the amniotic fluid. The measurement of the inhibitory capacity of amniotic fluid holds some promise for enabling a physician to determine which patients may be at special risk of intrauterine infection.


Complications following prostaglandin F2alpha-induced midtrimester abortion. Prostaglandin F2alpha (PGF2alpha) was injected intraamniotically in 122 patients between 14 and 20 weeks' gestation in the dosage schedule recommended by the drug manufacturer to induce abortion. Significantly more multiparous (47.5%) than primagravida patients (21.5%) aborted within 16 hours, but the mean duration between PGF2alpha injection and abortion was not significantly different. Complications occurred in 52 (42.6%) patients and included: fall in hematocrit of more than 5 percentage points, failure to abort within 48 hours after injection, infection requiring antibiotic therapy, cervical laceration or fistula, and uterine rupture. The atypical dilatation and effacement of the cervix occurring with PGF2alpha-induced contractions may possibly lead to cervical incompetence with later pregnancies. Although the efficacy of PGF2alpha as an abortifacient is confirmed, the large complication rate with the procedure cannot be ignored.


Can the oxytocin challenge test serve as the primary method for managing high-risk pregnancies? The purpose of this investigation was to determine whether the oxytocin challenge test (OCT) could serve as the primary method for managing pregnancies characterized by possible placental insufficiency. One hundred and five patients underwent 225 oxytocin challenge tests; no perinatal deaths occurred. Eight tests were positive, 21 suspicious, and 196 negative. Because of data obtained in a preliminary study, all 8 fetuses with positive tests were delivered by cesarean section. Four of the 8 had repetitive suspicious tests prior to a positive test, suggesting that utero-placental function may deteriorate gradually. Urinary excretion of estriol did not decrease significantly in any patient, suggesting that the OCT is a more sensitive indicator of placental function than excretion of estriol. Except for patients with preeclampsia who were induced for maternal indications, all pregnancies with a negative OCT were allowed to terminate spontaneously. Five of the 97 fetuses with negative tests developed late-onset deceleration patterns during labor. This indicates that a negative OCT will not necessarily predict fetal tolerance to labor, contrary to assertions made by some other investigators. It is concluded that the OCT can serve as the primary method for assessing the fetal status in pregnancies characterized by placental insufficiency.


Maternal febrile morbidity associated with fetal monitoring and cesarean section. The maternal febrile morbidity for 793 patients undergoing cesarean section was analyzed. The influence of length of labor, duration of ruptured membranes, and fetal heart rate monitoring was studied in both clinic and private patients. Morbidity among private patients was found to be consistently higher in monitored patients with comparable lengths of labor and durations of membrane rupture. The number of vaginal examinations, duration of monitoring, or number of fetal scalp electrode applications did not effect morbidity outcome.


Parturition-induced changes in maternal plasma cortisol levels. Total maternal plasma cortisol levels were measured by a radioassay method in 9 patients who were in spontaneous labor and 10 patients who were electively induced at term with oxytocin. Determinations were made at onset of labor and repeated at full cervical dilatation. Total maternal plasma cortisol levels were also measured in 7 patients undergoing elective cesarean section without labor, determinations being made just prior to the procedure and at the time of uterine incision. Computerized analysis showed the mean initial cortisol level (+/- SE) in the spontaneous labor group (15.4 +/- 1.6 mug/100 ml) to be significantly less than the mean initial level of the group electively delivered by oxytocin induction (37.2 +/- 6 mug/100 ml), with P less than 0.01. The former value was also found to be significantly less than that of the group electively delivered by cesarean section (32.1 +/- 9.3 mug/100 ml), with P less than 0.05. A significant rise was noted at full cervical dilatation in the spontaneous labor group (P less than 0.05), whereas no change occurred in the two elective groups. No significant correlation was found between the maternal cortisol levels on the one hand and the cord cortisol levels. These findings indicate that a) maternal participation is unlikely in bringing about a surge of fetal plasma cortisol which is thought to precede spontaneous labor, b) elective termination of term pregnancy by oxytocin induction or cesarean section may be initially more stress-provoking to the mother than spontaneous labor, and c) maternal stress as measured by plasma cortisol level is not reflected in the fetus.


Oxytocin in maternal and fetal blood.

Oxytocin in maternal and fetal blood. Radioimmunoassayable plasma oxytocin (OT) has been measured in maternal and fetal blood. Simultaneous samples were obtained in maternal forearm venous blood and in umbilical venous and arterial blood in 29 patients at term delivery. In addition, maternal forearm venous blood samples were also obtained 10 minutes prior to delivery. Mean OT level in maternal plasma at delivery was 82 +/- 12 muU/ml, and at 10 minutes prior to delivery the mean OT level was 90 +/- 11 muU/ml. The umbilical arterial plasma OT showed 95 +/- 12 muU/ml and the umbilical vein plasma OT was 60 +/- 10 muU/ml. Oxytocin levels higher in maternal blood than in fetal blood were found with the following incidence: In 51% of samples there was more OT in maternal venous blood than in umbilical arterial blood, and in 84% of samples there was more OT in maternal blood than umbilical vein blood. During the postpartum period, the mean maternal plasma OT was 66 +/- 8 muU/ml for the first day, and 50 +/- 9 muU/ml and 54 +/- 9 muU/ml for the second and third days, respectively. This study indicates that both the fetus and the mother are active producers of oxytocin.


Effects of freezing and thawing on certain properties of early gestation amniotic fluid. The effects of repeated freezing and thawing. on certain properties of early gestation amniotic fluid were studied. Six anmiotic fluids from 15- to 17-week gestations were investigated. Total protein determinations revealed that there was no significant loss of total protein with rapid freezing and thawing up to 10 times in the space of a few days. Immunoelectrophoresis revealed that the antigenic properties of the amniotic fluid, as ascertained by counting the number of precipitin bands, were unaltered by the repeated freezing and thawing


Prophylactic use of hydroxyprogesterone caproate in abdominal surgery during pregnancy. A retrospective evaluation. Abdominal surgery (unrelated to delivery) during pregnancy is not common. Review of a recent 17-year experience at our institution revealed 112 surgical procedures among 25,189 deliveries--an incidence of 0.44% (1 case for every 225 deliveries). Progestational agents have been used prophylactically in such procedures, but few studies have adequately assessed the effectiveness of these drugs to prevent onset of premature labor. The present study involved 35 gravid patients who had been treated with various doses of hydroxyprogesterone caproate before and after operations unrelated to delivery. These 35 patients were matched with 35 gravid control patients who had undergone similar operations but who had not received progestational compounds. Analysis revealed no significant difference in the abortion rate between these two groups.


Cholecystectomy in pregnancy.

Cholecystectomy in pregnancy. During the 17 years 1955 through 1971, 20 gravid patients underwent cholecystectomy. This represented 1 case for every 1259 deliveries (0.079% of 25,189 deliveries). The primary indication for surgery was repeated attacks of gallbladder colic. Generally, surgery was performed between the 10th and the 20th week of gestation. There was one spontaneous abortion; this occurred at 10 weeks of gestation, 42 days after surgery.


Temporal relationships critical to progesterone-induced acceleration of ovum transport. Previous investigators have demonstrated that 2.5 mg fo progesterone, administered intramuscularly to rabbits on the day of ovulation and the 2 preceding days (Days -2, -1, and 0) significantly and consistently accelerates ovum transport. In contrast, when given on the day of ovulation and the 2 following days (Days 0, +1, and +2), progesterone does not accelerate ovum transport. The experiments reported were designed to define more precisely the temporal relationships critical to progesterone-induced acceleration of tubal ovum transport. Our observations suggest 3 important conclusions: 1) Progesterone, when given at least 1 day, and not more than 2 days, prior to ovulation does induce accelerated ovum transport. 2) The progesterone responsive mechanism is dose dependent. 3) The acceleration is partially antagonized if progesterone treatment is begun 3 days prior to ovulation.


Further study of d-norgestrel for fertility control. In a continuing oral contraceptive study of d-norgestrel, the 1,0-mg dose--the dose previously found to give the best cycle control--was administered cyclically on a "21-7 day" schedule to 284 women during 2650 cycles. None of the women conceived, and cycle control, though often altered, was generally acceptable. Side effects were minimal, and laboratory determinations performed prior to and during the administration of this agent revealed no clinically significant changes.


Serum gonadotropin levels in Japanese women. Plasma gonadotropin levels throughout the regular menstrual cycle in 10 Japanese women were measured daily using radioimmunoassay. At the peak of ovulation, mean FSH levels were 17.6 +/- 7.9 mlU/ml and mean LH levels were 75.2 +/- 26.0 mlU/ml. At midcycle, the mean gonadotropin levels were significantly lower in Japanese women than in Nigerian women who, as reported by Nylander (1973), had a high frequency of twinning. It is, therefore, suggested that the low frequency of dizygotic twinning in Japanese women might be related to their low output of gonadotropin.


Isosexual development of women with late-treated congential adrenal hyperplasia. Twelve women with congenital adrenal hyperplasia are reported. Initial diagnoses were made at ages ranging from 12 to 32, with epiphyseal fusion complete in all patients. During 6 to 10 years of corticosteroid therapy there occurred substantial reduction of hypertrichosis, disappearance of temporal recession, and decrease in eroticism. In 11 patients menstrual bleeding occurred within 4 months. Urinary excretion of total gonadotropins remained unchanged; total estrogens decreased slightly. By the end of followup, 7 patients with a mean age of 17 years had regular menses, 6 were ovulating, and 1 had a pregnancy. The other 5 patients, who continued to have irregular, anovulatory menstrual cycles, had a mean age of 28 years. The findings suggest that when excessive androgenization continues for a considerable period of time after puberty (as judged by bone age) noncyclic functioning of the gonadotropic mechanism is rendered irreversible.


Vaginal atresia and cryptomenorrhea.

Vaginal atresia and cryptomenorrhea. Six cases of congenital vaginal atresia are described. Three of these patients had cryptomenorrhea while the other 3 had severe coital difficulties. Despite the fact that normal coitus was impossible in these 3 women, 2 of them achieved successful pregnancies and had to be delivered by emergency cesarean section followed by resection of the occluding membranes. The third patient (with dyspareunia) resorted to paraurethral coitus for more than 2 years before seeking advice. The management of vaginal atresia proved difficult because of the recurrence of stenosis at the site of the excised membrane. This was particularly marked in the young adolescent females not exposed to regular coitus. An operative method that could minimize this complication is discussed.


Cellular detection of vaginal adenosis.

Cellular detection of vaginal adenosis. Cellular samples obtained by vaginal scrapings from 204 women exposed to diethylstilbestrol (DES) in utero were evaluated and compared with samples collected from a like number of controls. Several different sampling methods were evaluated. Vaginal scrapings contained columnar cells existing alone or in combination with squamous metaplastic cells and less frequently were characterized only by metaplastic cells. None of the control samples contained columnar cells and only 1 of 200 control samples contained metaplastic cells. The cellular findings in the offspring of women exposed to DES in utero varied in relation to age. Cellular abnormalities were demonstrated in 90.4% of women having scrapings of visible lesions and in 88.1% of women studied by 4-quadrant vaginal scrapings in the absence of clinical disease. Of 58 women with histopathologically proven adenosis, 57 (98.3%) had similar cellular abnormalities. Abnormalities were demonstrated in squamous epithelial cells of the vagina in 8 (3.9%) of the women exposed to DES in utero, and in 5 of these women there were similar changes in the uterine cervix. Only 2 (0.9%) of the women had cellular changes suggesting dysplasia of the vagina.


Crohn's disease of the vulva.

Crohn's disease of the vulva. Over the past 10 years, it has been well established that Crohn's disease may involve any segment of the gastrointestinal tract from the mouth to the anus and may also cause destructive extraintestinal lesions. Extensive cutaneous ulceration has recently been recognized as  one of the rare extraintestinal complications. A case of chronic vulvar ulceration due to Crohn's disease is reported. The clinical manifestations and management of such a lesion are discussed.


Carcinoma in situ of the vagina. A study and review. A retrospective study has been carried out on 25 patients treated at the University of Michigan Medical Center for carcinoma in situ of the vagina. Intraepithelial carcinoma of the vagina occurred as a primary entity, following treatment for preinvasive and invasive carcinoma of the cervix, and following hysterectomy for benign disease of the uterus. These patients were treated with either radium implantation or some form of surgery. Five patients had recurrences. These 5 were all subsequently retreated and are alive and without evidence of further recurrent neoplasm. This series of carcinoma in situ of the vagina is compared to other reported series. Emphasis is directed toward the need for continued use of Papanicolaou smear cytology tests in posthysterectomy patients, regardless of the reason for hysterectomy.


Diagnosis of an intact hydatidiform mole with coexistent fetus by amniography. A case hydatidiform mole with coexistent living fetus is presented and the steps by which the diagnosis was reached are given prominence. The diagnosis in utero of an intact hydatidiform mole with associated fetus is extremely difficult, and the author thinks that the most useful diagnostic means for this rare situation is amniography.


Brain changes and survival of animals with tumors implanted in the brain. The effects of tumor cells implanted into the brain of animals on survival rates and gross and microscopic brain changes have been ascertained.  Walker carcinosarcoma 256 cell suspensions were injected at several brain sites in rats and leukemia L1210 and P388 and Ehrlich ascites tumor cells, intracerebrally into BDF1 mice.  Such neoplasms provided for rapid and rather predictable growth increments.  The survival rates were dependent on the number of cells introduced, those receiving the higher counts succumbing first.  The brains of the animals revealed fairly discrete space-occupying lesions and neurological symptoms became apparent only hours before death due to intracranial pressure.


Studies of tumor cell lines derived from patients with malignant melanoma. Fourteen long-term human malignant melanoma cell lines established from biopsy specimens, malignant effusions and the peripheral blood are reported. Methods of culture, heterologous transplantation studies and characterization of these cell lines are presented. Several of these cell lines have retained the ability to produce pigment over a period of years, permitting bioassays at a subcellular level. Studies of cell lines grown with and without tyrosine and some of the theoretical uses of human melanoma cell lines are presented.


The decision to operate in rheumatoid arthritis. The physician caring for the patient with rheumatoid arthritis should not look upon surgery as a last resort to be turned to when all else has failed and the situation is desperate. Surgical intervention may be important at any stage in the disease. Wrist fusion to obliterate pain and to restore a strong grip is advantageous whenever pain and instability compromise the function of that extremity. The knee with good painless flexion and extension cannot help but insure the patient's ability to get up and down from a chair. There are many goals that may be achieved through surgical intervention, and each of these should be considered and reviewed every time the physician sees the patient. Consider the benefits of prevention of disease progression, the stopping of bone resorption, the relief of pain, the restoration of motion, strength, and stability, and the preservation or restoration of the patient's confidence and determination to remain an independent member of society.


Reconstructive surgery in the rheumatoid hand. Reconstructive hand surgery is an established, proved, and effective method to correct deformities and increase function in rheumatoid patients. As more experience has been gathered, the indications for both arthrodesis and arthroplasty have been better established, and a better approach to reconstructive hand surgery has developed. In this discussion we have evaluated in detail the surgical treatment indicated for wrist, metacarpophalangeal joint, and thumb deformities. The treatment of swan-neck deformities and boutonniere deformities is discussed in other sections in this volume.


Alpha-ketoadipic aciduria: a description of a new metabolic error in lysine-tryptophan degradation. Our studies of a mentally retarded male with extremely elevated levels of alpha-aminoadipic acid and alpha-ketoadipic acid in his urine have led to the description of a new metabolic defect, alpha-ketoadipic aciduria. Analysis of the urine and serum from the patient's family revealed that the patient (KW) had a mentally and physically normal sister (CW) with the same metabolites elevated, but the rest of the family appeared normal.


Fetomaternal potassium relations in the fetal rat on the twentieth day of gestation. Time-corrected measurements of transplacental and transamniotic potentials were made in the fetal rat on the 20th day of gestation. These averaged 14.3 mV and 18.4 mV, respectively. The measured maternal potassium concentration in plasma of 4.8 mEq/liter and these potential measurements were used in the Nernst equation to predict the fetal concentrations in plasma. The concentration in amniotic fluid was predicted, using the potentials and either the fetal or maternal plasma concentration. The predicted concentrations in fetal plasma and amniotic fluid were 2.8 and 2.5 mEq/liter, respectively. The sampling time-corrected potassium concentration in fetal plasma was 2.9 mEq/liter and the mean in amniotic fluid was 4.6 mEq/liter. The observed concentration in amniotic fluid is significantly higher than the predicted level.


Leukocyte urea cycle enzymes in hyperammonemia. All enzymes of the urea cycle are demonstrable in circulating leukocytes. They show the same relative activities as those in liver except for argininosuccinate synthetase + lyase (combined) which seems to be disproportionately active. To see whether leukocytes reflect liver activity, blood from patients with three hepatic urea cycle disorders was tested. In each case, the leukocytes showed the same enzyme deficiency as was apparent from a liver biopsy (Table 4). Leukocyte assays appear to be reliable indicators of the enzyme lesions in inherited urea cycle enzyme defects and therefore may obviate the need for liver biopsy.


Interaction of endogenous growth hormone, cortisol, and catecholamines with blood glucose in children with brittle diabetes mellitus. Hormonal balance was studied in eight insulin-treated diabetic children who had excessive glycosuria. Glucose, growth hormone, and cortisol in plasma were determined every 0.5 hr for 48 hr. Total catecholamines and glucose were measured and tests for ketones done in 2-hourly collections of urine. Intermittent hypoglycemia as low as 20 mg/100 ml and swings of the blood sugar curve by 200-300 mg/100 ml within 2-4 hr were documented in most patients. Peaks of growth hormone concentration in plasma (8-78 ng/ml) followed almost every sharp fall in blood glucose; these peaks were usually followed by abrupt rises of glucose and prolonged hyperglycemia. Cortisol concentration was usually within the high normal range; there was no consistent relationship to the concentration of glucose. Urinary excretion of catecholamines in most patients was between 1 and 6 mug/hr; three patients excreted up to 8-23 mug/hr during short periods and up to 190 mug in 24 hr. The causes for the high excretion of catecholamines are unknown and may not have included hypoglycemia.