A glimpse of the early history of the cephalosporins.

The cephalosporins, like the penicillins, came from research that was partly academic but that led to results which found application in medicine. A number of events followed the isolation of a Cephalosporium in Sardinia in 1945. Research at Oxford resulted in the discovery of cephalosporin C in 1953, in the elucidation of its structure in 1959, and in the determination of many of its characteristic properties. Further work in the United States opened the way to large-scale production of a series of semisynthetic cephalosporins. A change in the attitude of the Government toward the application of academic research in the United Kingdom and the establishment of a National Research Development Corporation were responsible for certain differences between the commercial development of the cephalosporins and that of penicillin.


Evolution of ribosomal RNA.

1. The G + C content of ribosomal RNA of animals seems correlated with the length of periods required for maturation of those organisms. 2. In Protostomes of the animal kingdom, the size of the 28S rRNA molecule does not seem to correlate with the evolutionary stage of the organism. 3. Aphids and water-fleas as well as some protozoa have the 18S rRNA with mol. wt of 0.9 x 10(6) against an overwhelming pressure of evolution to conserve the rRNA molecule of 0.7 x 10(6) daltons. 4. All the Deuterostomes examined were distinguished from Protostomes by having the 28S rRNA's void of the hidden break at the central point. 5. Aphids and nematodes are exceptional Protostomes in that they have the 28S rRNA's without the hidden break. This was discussed in the light of the evolutionary stage of these organisms. 6. Molecular properties of chloroplast rRNA seem to evidence for endosymbiotic origin of this organelle. Mitochondrial rRNA differs considerably from prokaryotic rRNA with respect to molecular size and base composition.


Schistosoma mansoni: inhibition of cercarial "penetration" proteases by components of mammalian blood.

1. Normal human sera and plasma were fractionated in order to identify inhibitors of the "penetration" proteases of Schistosoma mansoni cercariae. 2. The main inhibitor, accounting for 90% of the total activity of serum, appears to be alpha 1-antitrypsin (alpha 1-AT) as identified by separation on DEAE-cellulose and Sephadex, by immunoelectrophoresis and by anticercarial protease activity of purified alpha 1-AT preparations. 3. The inhibition profiles of purified preparations of the 6 known serum antiproteases suggest that the parasite protease is similar to vertebrate chymotrypsin. 4. On a molar basis, the order of inhibitory activity against the cercarial protease is: alpha 1-AT = alpha 2-macroglobulin; C'-1-inactivator; alpha 1-antichymotrypsin. No inhibition was obtained with inter-alpha-inhibitor or antithrombin III.


On the carbohydrate metabolism of pectoral muscle in the ontogeny of chicken.

1. Immediately after hatching, the pectoral muscle has a low glycogen content, and exhibits very low glycogen and high glucose and oxygen consumptions. 2. Drastic metabolic changes occur during the second day and again during the second week of life ("critical periods of the ontogenesis"); the above metabolic pattern is reversed. 3. The insulin sensitivity of the muscle is very low during these critical periods, and high between them. 4. The overall trend of metabolic ontogenesis in the pectoral muscle of the domestic fowl (non-flying bird) seems to have no functional but genetical determination.


Lipid composition of Trypanosoma cruzi.

1. Lipid composition of Trypanosoma cruzi epimastigote form in culture consist of 35% of phospholipids and 65% of neutral lipids. 2. Among the phospholipids, phosphatidylcholine is the more abundant (44%), followed by phosphatidylethanolamine (28%), phosphatidylinositol (12%), sphingomyelin (4%), and smaller amounts of cardiolipin, phosphatidic acid, lysolecithin, phosphatidylserine (traces), and an unidentified phospholipid (3%). 3. Pulse labeling with 32P showed highest specific incorporation in phosphatidylethanolamine, followed by phosphatidylinositol and phosphatidylcholine, suggesting a more active role for phosphatidylethanolamine in these organisms.


Comparative aspects of bile pigment formation and excretion.

Breakdown of haem which is of key importance in most organisms, involves oxidative CO-evolving cleavage of the macrocyclic ring with formation of biliverdin-IX. In two major pathways established so far formation of biliverdin-IX alpha is followed by (a) biliary secretion or (b) reduction to bilirubin-IX alpha, formation of more hydrophilic derivatives (usually glycosidic conjugates) and biliary secretion. The scattered comparative information available indicates marked species variation with regard to the methin-bridge carbon atom removed from haem and the metabolic site of cleavage, the nature of bilirubin conjugates and the developmental sequence of maturation of enzyme activities and transport proteins involved in the chain of events leading from breakdown of haem to the excretion of the final end products.


The effect of bile acids on liver alcohol dehydrogenase in different mammalian species.

1. The effect of bile acids on the activity of liver alcohol dehydrogenase (L-ADH, EC 1.1.1.1) from different mammalian organisms is species dependent. 2. The kinetic behaviour of purified L-ADH from rat and rabbit liver in presence of deoxycholic acid and with ethanol as substrate shows two rather different patterns: for rabbit enzyme deoxycholic acid acts as a full competitive inhibitor, while for rat enzyme an activation effect is observed, with an increase of both Km and Vmax. Similar patterns are obtained with the steroid substrate 3 beta-hydroxy-5 beta-androstane-17one. 3. These results show that in some species, including man, L-ADH activity can be regulated by bile acids, that could control both ethanol oxidation and their own biosynthesis since L-ADH is involved in both metabolic pathways in liver cell.


Alcohol-oxidizing enzymes from various organisms.

1. Enzymes that catalyse the oxidation of aliphatic alcohols to aldehydes are reviewed. 2. Special attention is given to phenazine methosulphate-linked alcohol dehydrogenases from bacteria and to flavin-containing alcohol oxidases from yeasts, moulds and higher plants. 3. Some properties of the microsomal ethanol-oxidative system of rat liver are discussed.


A comparative study of the tissue and species distribution of NADPH-dependent aldehyde reductase.

1. NADPH-dependent aldehyde reductase (AR) is widely distributed among animal species. It also occurs in flowering plants and fungi (yeast). 2. AR is located mainly in the kidney or renal tissue of all species examined, with the exception of fish where it occurs mainly in the liver. 3. The enzyme from each species is monomeric and has a molecular weight between 30,000 and 40,000 daltons. 4. The enzymes exhibit similar substrate specificities and pH profiles and are inhibited by barbiturates. 5. In the reduction of D-glyceraldehyde the monomeric AR of each species catalyzes the stereospecific transfer of the A hydrogen from NADPH.


Comparative study of alpha-glucosidase activities in liver, plasma and urine of carp, rat and dog.

1. pH profiles and activity levels of alpha-glucosidase from liver homogenate, plasma and urine of carp, rat and dog are investigated using a sensitive fluorometric method. 2. A strong "neutral" activity is found in the livers of all species, the significance of which is considered in the context of hydrolytic pathway for glycogen breakdown.


Amino acid differences between major and minor hemoglobins from lemmings (Lemmus and Dicrostonyx).

1. Dual hemoglobins were isolated from both Lemmus and Discrostonyx, two genera of microtine rodents of the tribe Lemmini. 2. The dual hemoglobins result from dual alpha-chains and the charge difference Asp----Ala at position alpha 5. 3. The beta-chains of Dicrostonyx and Lemmus hemoglobins differ in charge by Ala----Asp at beta 125. 4. Cladograms are presented for the hemoglobin chains of microtine rodents.


Phylogenetic distribution of glutathione peroxidase.

1. The enzyme glutathione peroxidase (E.C.1.11.1.9), known to be a selenoprotein from mammalian sources, was detected in the following vertebrates: fish, frog, salamander, and turtle. 2. Among invertebrates, the enzyme was detected in crayfish and snail but not in insects or earthworm. 3. No plant tissues or microorganisms showed any evidence of the enzyme activity. 4. The presence of the enzyme activity in so many animal groups implies the widespread occurrence of genetic information for the specific assimilation of the selenium atom.


Purine biosynthesis in Helix aspersa: metabolic fate of labelled precursors.

1. The hepatopancreas of terrestial snails actively synthesizes purines from labelled formic acid. 2. The guanine nucleotides are initially labelled to the highest specific activity followed by adenine and hypoxanthine. 3. The labelling patterns suggest that uric acid synthesis is the primary catabolic process for nitrogen excretion while guanine excretion is due to an inability to reutilize the base.


Inhibition of the NADP-linked glutamate dehydrogenase from Trypanosoma cruzi by sulfhydryl reagents.

1. The NADP-linked glutamate dehydrogenase purified from epimastigotes of Trypanosoma cruzi was strongly, but not completely, inhibited by sulfhydryl reagents, in the presence of Tris-HCl or phosphate buffers. 2. The enzyme modified by preincubation with o-iodosobenzoate had a kinetic behaviour different from that shown by the enzyme modified with other inhibitors, such as N-ethylmaleimide or p-chloromercuribenzoate. 3. The inhibition by o-iodosobenzoate was additive with the inhibition by the other reagents tested. 4. It is suggested that two or more different sulfhydryl groups, placed probably near the active site, are involved in these effects.


Evolution of homologous physiological mechanisms based on protein sequence data.

1. Genetic duplications can give rise to homologous physiological mechanisms that include structurally related protein components. There are many such examples of related proteins within the human body. 2. Evolutionary histories showing the origins and subsequent divergences of these distantly related proteins can be derived from the protein sequences and correlated with the functional characteristics of these proteins. 3. The hormones related to glucagon provide an example of homology of physiological mechanisms and emergence of new functions subsequent to gene duplications. 4. The proteins related to troponin C illustrate the participation of distantly related proteins in the same mechanism (muscle contraction), the relationship of proteins characteristic of a specialized tissue to proteins found in all eukaryote cells, and the correlation of genetic duplications with the evolutionary appearance of different types of muscle.


Diffuse fasciitis with eosinophilia (Shulman's disease).

A case of diffuse fasciitis with eosinophilia (DFE, or Shulman's disease) is presented. A review of the literature of the condition is presented, and the salient features are summarized. Diagnostic criteria and the management of patients with this unusual condition are discussed.


Antenatal detection of fetal pleural effusions and neonatal management.

The ultrasonic findings in a living fetus with bilateral pleural effusions are described, and the possible lines of management are discussed.


Results of treatment of head and neck carcinoma with high dose methotrexate.

Forty four patients with squamous cell carcinoma of the head and neck from a variety of primary sites were treated with high dose methotrexate with folinic acid rescue from 1975 to 1977. The overall response rate was 66%. Response duration was short with a mean of 16 weeks. The usefulness of this technique in the treatment of head and neck cancer is discussed.


Complications of tumour overkill when associated with high dose methotrexate therapy.

Three patients, in whom tumour overkill by cytotoxic treatment, including high dose methotrexate with folinic acid rescue, resulted in the 'phosphate shower syndrome' (hyper-uricaemia, hyperkalaemia and hyperphosphataemia with hypocalcaemia and tetany, with metabolic acidosis and acute renal impairment) are described. Severe methotrexate toxicity occurred in two of these patients. High dose methotrexate would appear contra-indicated in situations where massive tumour lysis is possible.


Widening perspectives of lead toxicity. A review of health effects of lead exposure in adults.

Lead has a wide range of applications, and its production and use result in contamination of the environment, including food and drinking water. Geochemical studies indicate that the majority of lead in ecosystems originated from industrial operations, and that human lead intake has increased 100-fold above the "natural" level. Prehistoric human skeletons contain about two orders of magnitude less lead than present-day samples. Biochemical interference with heme biosynthesis can be detected as a result of current lead exposures, inhibition of aminolevulinate dehydratase and accumulation of zinc protoporphyrin in erythrocytes being the earliest effects. Anemia is uncommon except for cases of lead poisoning, but even slightly increased lead absorption results in a decrease in hemoglobin concentrations. Modern neurobehavioral test methods have disclosed increased prevalence of psychological dysfunction associated with augmented lead absorption. Biochemical and behavioral changes occur below the recommended limit for blood lead concentration of 60 micrograms/100 ml. Several diagnostic tests for lead toxicity are available. The protoporphyrin concentration in the blood seems to be the best risk indicator. The highest occupational lead exposures occur in lead smelters and storage battery plants, but several other industrial operations may result in high lead levels. As much as 1% of the working population may have a significantly increased lead absorption with possible adverse effects.


A review of parameter values used to assess the transport of plutonium, uranium, and thorium in terrestrial food chains.

A general methodology of predicting the food chain transport of atmospherically deposited radionuclides is reviewed with an emphasis on variation in parameter values important for realistic behavioral characterization of environmental releases of plutonium, uranium, and thorium. Parameters important to generic simulations of food chain transport, given a known constant deposition onto vegetation, include: fractional interception of particulates by vegetation, vegetation density, effective half-life of contamination on vegetation, soil-to-plant transfer factors, consumption rates by cattle and man, and transfer of nuclides from forage to meat and from forage to milk. Variation in these parameters, which has been encountered in field studies, is summarized. A partial reduction in the variation of predicted concentrations of actinides in foods can be accomplished by more accurately determining critical parameter values like fractional interception of deposition by vegetation, vegetation biomass, and the effective half-life of contamination on vegetation. Field research describing the site dependency and time dependency of probability density functions for model parameter values is needed to make probabilistic predictions concerning Pu, U, and Th transport in food chains and to reduce the uncertainty associated with model predictions and generic assessments of environmental impact.


Histopathological and enzymological studies on the effects of chronic lead nitrate intoxication in the digestive system of a freshwater teleost, Channa punctatus.

The effect of lead nitrate on the digestive system of a teleost fish, Channa punctatus has been studied after 125 days of exposure to a sublethal concentration (6.8 mg/liter). The results show that considerable degenerative changes are produced in the histological structure of liver, intestine, and pyloric caeca. In the liver, the damage is in the form of liver cord disarray, necrosis, inflammation of portal areas, hardening of connective tissue, shrinkage of nuclei, and septa formation around blood vessels. No fatty infiltration or glycogen depletion has been observed. Lipofuscin granules accumulated in the cytoplasm of hepatocytes. In the intestine and pyloric caeca flattening of villi at a number of places, inflammation, and necrosis are the most conspicuous changes. The activities of alkaline phosphatase and aminotripeptidase are inhibited in the liver. In stomach, alkaline phosphatase is inhibited but an elevation in amylase activity was noted. Acid phosphatase showed an increase in the intestine and pyloric caeca while aminotripeptidase and glycylglycine dipeptidase were inhibited.


Convention on psychotropic substances, 1971. The role and responsibilities of the World Health Organization.

1. The world community has realized as early as the beginning of this century that collective action between nations is to be more effective in controlling drugs of abuse. A number of international drug control treaties including the Single Convention on Narcotic Drugs, 1961, controls drugs primarily obtained from plant material (opium, coca leaves and cannabis) and synthetic analogues of morphine. The Convention on Psychotropic Substances, 1971, is aimed at controlling psychotropic substances and was formulated in Vienna in 1971. 2. The Convention on Psychotropic Substances, 1971, lays a great responsibility on the World Health Organization to recommend to the United Nations Commission on Narcotic Drugs notifications initiated by the World Health Organization, or by a party to the Convention, regarding international control.


The future of communication in psychopharmacotherapy.

1. Communication among scientists of similar professional interest is an often neglected but critical factor in medical research and practice. 2. Dissemination of information is vital for keeping abreast of one's field, for planning studies and treatment regimens, and for avoiding unnecessary research. 3. Today's communication channels by printed material, audio-visual equipment, satellite, and other traditional or innovative means aid the transferral of information; nevertheless, they are undergoing constant change to fill existing gaps. 4. The paper discusses present deficiencies in communication and proposes solutions to some of the problems.


The future role of communications in psychopharmacological research and practice.

1. Communication of psychopharmacologic data is seen as a system whose structure should be determined by efficient information dissemination. Suggestions are made to improve the efficiency. 2. The author suggests ways to improve information accessibility for auxiliary medical personnel, medical personnel and for basic researchers. 3. The International Reference Centre for Information on Psychotropic Drugs is discussed with reference to a weakness in its function and corrective suggestions.


Spina bifida children in ordinary schools.

When followed-up at 6 years, 62 of a cohort of 155 spina bifida children had been placed in ordinary schools. The children's handicaps were relatively mild overall, and placements were generally successful. However, discussions with school staff and parents indicated that not all placements had been trouble-free. In common with previous research, a need for better communication between schools, medical authorities and other support services was revealed, as was the desirability of welfare-assistant provision where handicaps were appreciable. Suggestions are made about the support education and community medical services will need to consider if they wish to implement a more radical integration policy. The appointment of an advisory teacher to effect liaison and to mobilize support for ordinary schools accepting a handicapped child would seem desirable, particularly to ensure that the resources and expertise concentrated in special schools would be made more-widely available.


Pharmacokinetics and pharmacodynamics of amitriptyline in depression.

1. The therapeutic effect and pharmacokinetics of amitriptyline were assessed in thirty-five patients suffering from primary depressive illness during inpatient treatment. 2. Contrary to our previous study, no significant correlation was obtained between the plasma concentrations of amitriptyline, nortriptyline or total tricyclics with Hamilton rating score at 6 weeks or percentage improvement after 6 weeks treatment. 3. There was also no correlation with the plasma concentrations of tricyclics with the corrected subjective side-effects score. 4. A linear correlation (rs = 0.80; p less than 0.001) was observed between the plasma concentration of nortriptyline and decreased tyramine sensitivity, an index of noradrenaline reuptake blocking effect. 5. The corrected side-effect score during the trial correlated (r = 0.64; p less than 0.001) with Hamilton rating score at week 6, i.e. the patients who complained of more side-effects had less clinical benefit during amitriptyline therapy.


Problems with ethical aspects of psychotropic drug use.

1. Research is an important area within the purview of medical ethics. The Nuremberg Code and the Helsinki Declaration provide well established guidelines in this field. 2. Specific ethical issues still requiring clarification in psychopharmacological research are the informed consent, the benefit/risk ratio and the choice of placebo or standard. 3. Peer review committees, if well chosen for their objectivity, general competence and special expertise, are likely to be the best arbiters regarding such questions. 4. Legislation and other political interventions--unfortunately not always objective, competent or expert in the exercise of their powers--have recently developed into rampant paraethical problems that are plaguing medical treatment and research in many parts of the world and need to be dealt with urgently through internationally coordinated efforts. The WHO would appear to be the most appropriate agency for such action.


Some ethical considerations in the development of psychopharmacological research and practice in the future.

1. The author sees this issue as philosophical with paradoxical moral overtones. Ethical questions may have an inhibiting effect on drug research. 2. The individual morals and professional ethics of physicians and researchers are seen as central to the conduct of psycho-pharmacotherapeutic research. 3. The effect on ethics of religion, culture and social setting is discussed. 4. Human subjects in drug research are discussed. 5. Control of the drug industry (research, quality control, distribution) is discussed and supra national control advocated.


Persistence of the Fc cytophilic antibody receptor in macrophage hybrid cells.

Hybrid cell clones were obtained from mouse macrophase/Ehrlich ascites cell fusions which showed the 'Fc' cytophilic antibody receptor site, phagocytosis and motility typical of macrophages. With continued growth of the clones for 11 weeks, the receptor became undetectable but could be unmasked by dilute trypsin treatment; subsequent remasking of the receptor could be prevented with cycloheximide treatment of the hybrid cells. These hybrids produced cystic anaplastic tumours in neonatal irradiated mice. Chinese hamster/mouse interspecific macrophage hybrid cells did not show macrophage markers. This was probably due to rapid loss of macrophage chromosomes from the hybrid cells.


Ethics of psychopharmacological research.

1. Psychiatry is in dire need of research in all areas--from psychopharmacology to psychotherapy. 2. It is unethical not to undertake research as long as hundreds of thousands of patients suffer from incapacitating mental disorders. 3. It is unethical not to apply proper research principles to obtain maximal information from the observations of patients treated by different drugs or techniques. 4. The Tokyo (Helsinki II) declaration takes cognizance of the special problems in psychiatric (and certain other areas of) research, and should help to heighten the standard of all clinical research. 5. Psychopharmacology is based on the principles of the biological sciences. In the behavioral aspects of clinical psychopharmacological research non-objective observations cannot solely be based on these principles, but we should always be able to aim at: a. Description of spontaneous history. b. Description of diagnostic and therapeutic techniques and processes. c. Description of goals. d. Description of results (with as detailed information on treatment failures as on treatment successes). e. Prospective studies instead of retrospective ones. 6. Psychopharmacology is probably the area within psychiatry where the ethical issues have been most protected against the uncritical introduction of unproven therapeutic principles.


Ethical problems in psychopharmacological research.

1. Scientific research poses considerable ethical problems which in human psychopharmacological studies are frequently faced by singling out consent as the only reliable source of human respect, although it is never free, spontaneous, or informed. 2. On the other hand, various ethical problems present in the "life" of a new substance in the case of industry and preclinical, clinical and mass experiments, are left behind. 3. Thus there arise justified protests which go so far as disowning science and technology. To criticize science and technology is of no use: incorrect use of them must be prevented. 4. Such a guarantee can only come from an international control committee, capable of coping with a multinational power such as industry, supported by peripheral elective committees, which grant the citizens a direct participation in the administration of health.


Clinical trials in psychopharmacology: scientific and ethical issues.

1. The ethical and scientific use of medicines for the treatment of illness rests upon proof that the medicines to be used are effective and safe for the condition to be treated. The use of the clinical trial is the method by which such evidence is produced. 2. Recent activities by some to decry clinical trials as unethical and restrict their conduct results in the totally unacceptable situation of withholding potentially valuable treatments from patients or subjecting patients to the unnecessary risks of treatments not proven safe and efficacious. These actions can lead to a new dark age of "chemotherapeutic blood letting and purgatives" under the guise of higher ethical purposes.


Ethical aspects of psychopharmacology.

1. A series of topics are presented for the purpose of eliciting discussion and clarification of issues. These include parameters on the ethical implications of: a. Psychopharmacological research in human subjects with special emphasis on the use of placebo for drug trials and problems related to the choice of research methods. b. Prescription of psychotropic drugs, the role of physicians, and the problem of the delegation of functions to para-medical personnel. c. The administration of psychotropic drugs: Issues related to informed consent of the patient, side effects, and groups at special risk. d. Availability and cost of drugs, generic and trade name preparations, as well as selective use of drugs for different populations. 2. Special reference is made to points contained in the "Declaration of Hawaii" (1978).


World Health Organization activity in psychopharmacotherapy.

1. The Division of Mental Health of the World Health Organization is developing a series of closely-linked activities concerned with research, information exchange and training in biological psychiatry, including psychopharmacology. One of the main mechanisms utilized in WHO programmes is joint work in a network of Collaborating Centres. These Collaborating Centres of WHO, which carry out projects on clinical psychopharmacology and biological psychiatry, are distributed over the different geographical regions of the world. 2. The successful development of these collaborative activities has permitted the rational integration of efforts of Collaborating Centres and the creation of optimal conditions for international collaboration towards rational treatment approaches of mental disorders.


Effects of GABA-mimetic agents on the cat spinal cord.

Muscimol, ibotenic acid, isoguvacine, 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol (THIP) and gamma-aminobutyric acid (GABA) injected intravenously exerted the following dose-dependent effects on the lumbosacral spinal cord of spinal cats: 1. The excitability of primary afferents and the amplitude of dorsal root reflexes were enhanced; segmental monosynaptic ventral root reflexes and dorsal root potentials as well as the spontaneous gamma-fibre activity and, to a smaller extent, the excitability of motoneurons and polysynaptic reflexes, were depressed. 2. Muscimol was the most potent compound (0.3-1 mg/kg produced significant effects), followed by ibotenic acid (3-10 mg/kg), isoguvacine and THIP (10-30 mg/kg) and GABA (100 mg/kg). 3. Most effects were reversibly antagonized by bicuculline, but not by strychnine, indicating that they were due to a specific interaction with GABA-receptors. 4. These results suggest that the systemic injection of GABA-mimetic agents affects spinal cord activities by actions related to GABA-receptors located on primary afferent endings, intrinsic spinal neurons, and motoneurons.


Effects of cocaine on sensory evoked potentials recorded from hypothalamus and limbic structures.

1. The present investigation was intended to examine the effects of the acute administration of several doses of cocaine on sensory evoked responses of freely moving rats. 2. Each structure and each component of the average sensory evoked potentials were affected by cocaine differently. 3. The changes induced by cocaine differ from those observed following other drug treatments. Therefore, it may be assumed that the changes observed are related directly to cocaine. 4. The present observation demonstrated a greater degree of sensitivity to low doses of cocaine than other types of electrophysiological recordings. In general cocaine in the lower doses (0.25 or 0.5 mg/kg) induced an increase in the sensory amplitude response while in the highest dose (10.0 mg/kg) attenuation of the sensory responses was obtained. 5. We assume that the euphoric effect induced by cocaine is due to the potentiation of sensory input within the limbic-hypothalamic system. In higher doses, the fatality caused by the drug may be due to the depression of the sensory input.


Metabolic interaction between amitriptyline and perphenazine in psychiatric patients.

1. Steady-state plasma level samples of sixty-five schizophrenic patients from two psychiatric hospitals assigned to three treatment groups (amitriptyline 150 mg/day, perphenazine 20 mg/day and a combination of amitriptyline and perphenazine at 150 mg and 20 mg/day) were assayed for amitriptyline (AT), endogenous nortriptyline (NT) and perphenazine (PPZ) using gas-liquid chromatography. 2. Results reveal that AT and NT levels are independent of sex and hospital environment. 3. PPZ significantly increased the steady-state NT plasma levels, probably through inhibition of the hydroxylation biotransformation pathway, but had no effect on AT levels, thus indicating that PPZ has no influence on the desmethylation pathway, or alternatively, the hydroxylation of AT.


Transport of neutral amino acids across the human red blood cell membrane.

1. Genetic markers are important in the search for genetically transmitted entities related to clinical nosology with implications for etiology, prophylaxis and treatment. 2. Rafaelsen (1976) has proposed a membrane transport model of affective disorders focusing on phase-independent transport deficiencies. 3. The transport of some neutral amino acids (L-leucine, L-phenylalanine and L-tryptophan) has been studied in the human erythrocyte at 25 degrees C. 4. A group- and a tryptophan-specific amino acid transport system have been described. 5. The relation to the model of Rafaelsen is discussed. 6. It is concluded that clinical studies should be undertaken to test whether these biological characteristics consistent with a specific theory are biological-etiological markers.


Monoamine oxidase inhibitors and whole blood, platelet and plasma monoamine oxidase.

1. Whole lysed blood monoamine oxidase activity using benzylamine as substrate, represents an addition of platelet and plasma activity. 2. Enzyme activity measured in whole lysed blood in the presence of 10(-4)M pargyline gave a value equivalent to plasma monoamine oxidase, and by subtraction gives a value for platelet enzyme activity. 3. This method of measuring platelet and plasma monoamine oxidase activities from a single whole blood sample, has the advantage of not requiring physical separation of the blood fraction.


The effects of two "anti-aggressive" compounds, an indenopyridine and a benzothiazepin, on shock-induced defensive fighting in rats.

1. An indenopyridine (YG19-256) and a benzothiazepin (thiazesim) were investigated in rats for possible effects on shock-induced defensive fighting, shock reactivity and locomotor activity. 2. YG19-256 significantly reduced aggression at the higher dose levels employed. Thiazesim produced no significant decrease in aggression at the dose levels used. 3. Neither compound produced any consistent effect on shock reactivity or locomotor activity.


Construction of a new psychiatric rating instrument, the Comprehensive Psychopathological Rating Scale (CPRS).

1. The CPRS (the Comprehensive Psychopathological Rating Scale) is a recently constructed rating instrument consisting of 65 scaled items, covering a wide range of psychiatric symptoms. Explicit definitions in a non-technical language are provided for items as well as scale steps. 2. The CPRS is mainly intended for evaluation of treatment effects, but due to the explicit descriptions, it has also been found useful for teaching purposes. It can be used in full, or as an item pool for which subscales for different psychiatric syndromes can be designed. Subscales exist, inter al., for depression, schizophrenia, obsessive-compulsive disorder, neurasthenic syndromes and mental distress in connection with severe physical illness. 3. The CPRS is available in parallel Swedish and English versions. It has been translated into all Scandinavian languages, and into German, Italian and Spanish. French and Russian versions are in preparation. 4. The rating is based on an interview which will require less than an hour in most cases if the scale is used in full. Due to the non-technical language used, raters without formal training in psychiatry (i.e. nurses, psychologists, general practitioners) can use the scale without reduction in reliability.


Reliability and validity studies of the comprehensive Psychopathological Rating Scale (CPRS).

1. The most important properties of a rating instrument aimed at detecting possible changes in psychopathology are as follows: a) communicability to not yet experienced raters; b) satisfactory levels of reliability and validity; and c) sensitivity to changes. Since its construction some years ago these properties of the Comprehensive Psychopathological Rating Scale (CPRS) have been investigated in several sessions, both experimental, and in the course of clinical drug trials. 2. Raters with a different training background (physicians, psychologists, social workers, nurses), and a different level of experience in ratings have participated in the sessions. 3. In all instances the CPRS has proved to be highly reliable and highly sensitive. It appeared to be easily communicable, also in its international versions, and its content seems to fit very well with different cultural contexts. Information about its validity has been inferred from the studies mentioned above, and, also from correlations with other well known rating instruments.


Comparison between Comprehensive Psychopathological Rating Scale (CPRS) and association for methodology and documentation in psychiatry (AMP) system.

1. 5 AMP experienced raters examined 28 depressed and 22 psychotic patients. Symptoms were documented using the CPRS (preliminary German translation) and the AMP system. The two rating scales were compared from the raters point of views and using descriptive statistical methods. 2. The high number of CPRS symptoms showing significant correlations to AMP symptoms demonstrate a strong similarity between the two rating scales. 3. The AMP system gives a more differentiated and comprehensive picture of the psychopathology than the CPRS. 4. The CPRS seems to us to be easily communicable, mainly due to the exact description of the scale steps and the differentiation of reported and observed items. 5. For the measurement of changes during treatment half steps should be used to increase the sensitivity of the CPRS.


Depressive symptoms in acute schizophrenia.

1. The incidence of psychopathological symptoms rated by the CPRS was compared in 54 English depressed patients and 52 Swedish depressed patients. 2. A new rating scale for depression was created from the 10 items shown to be most sensitive to treatment change. The Montgomery and Asberg Depression Rating Scale (MADRS) was found to be more sensitive to treatment change than the Hamilton Rating Scale (HRS). 3. The incidence of psychopathological symptoms was assessed using the full Comprehensive Psychopathological Rating Scale (CPRS) in 50 patients with unequivocal acute schizophrenia. 36 patients were rated again after treatment and a 12 item rating scale for schizophrenia was derived from the items best able to discriminate between responders and non responders. 4. The schizophrenia scale was found to be a more sensitive discriminator between responders and non responders than the Brief Psychiatric Rating Scale (BPRS) in the 25 patients rated on both scales simultaneously. 5. There was a relatively high incidence of depressive symptoms rated on the MADRS in acute schizophrenia suggesting that depressive symptoms are a commoner presenting feature of acute unequivocal schizophrenia than is normally acknowledged.


Depression and monoamine oxidase.

1. The first part of the paper is devoted to a critical review on the possible relationships between depression and monoamine oxidase. 2. This study describes the results of an investigation of MAO-activity in depression, using new approaches and methodology. This methodology was developed because the literature data indicated that a) previous results are difficult to compare because of varying methods and diverse target populations used; b) previous methodological deficiencies do not allow to draw definite conclusions about the relationship between MAO-activity and depression. 3. The present investigation selected 35 psychiatric patients according to clearly defined diagnostic criteria (20 endogenous depressive, 10 neurotic depressive, and 5 manic patients) matched to 25 healthy control-subjects. 4. The Michaelis-constant (Km), the maximum reaction speed (Vmax), and the 50% enzyme inhibition by tranylcypromine (IC50) of platelet-MAO were determined during and after recovery from the depressive or manic episode using 3 substrates (tyramine, tryptamine, and phenylethylamine). 5. The present investigation, in contrast to conventional methodology, utilized three different substrates at different concentrations. Significant correlations were demonstrated for the Vmax-values of each of the three substrates, whereas the Km and the IC50 (tranylcypromine)-values varied for each substrate. 6. The results show that there were no differences between the characteristics of the platelet-MAO in depressive or manic patients and those of normal subjects. Furthermore, treatment with tricyclic antidepressants had no effect on MAO-activity. A previous investigation indicated that the MAO-properties in human brain tissue were similar to that in human platelets.


A reexamination of apomorphine induced stereotypy in the rat in light of self administration experiments.

1. Apomorphine is known to both elicit stereotypy and to support behavioral self administration. The present report examined a possible contribution of stereotypy to self administration. 2. Non-contingent intraperitoneal injection of apomorphine in adult male Sprague-Dawley rats immediately prior to their placement in an experimental chamber significantly elevated barpressing above operant rates. 3. This indicates a novel dopamine induced behavior which may play a role in determining self administration behavior. 4. The data suggest three interpretations of previous self administration experiments.


Potentiation of apomorphine-induced climbing behaviour in mice by d-LSD.

1. The climbing behaviour in mice was used for studying possible interaction(s) of d-LSD with dopamine receptors. 2. Doses of d-LSD ranging from 0.25 to 2.5 mg/kg injected intra-peritoneally constantly inhibited the climbing behaviour. 3. In contrast, when similar doses of d-LSD were injected 10 min before apomorphine (5 mg/kg), a constant potentiation of the apomorphine-induced climbing was observed. 4. Subsequent experiments performed with a neuroleptic (haloperidol) or a serotonin precursor (5-OH-tryptophan) compared to those of d-LSD with and without apomorphine would indicate that d-LSD alone displays typical serotoninergic syndrome (including inhibition of the climbing), whereas in the presence of apomorphine, an interaction at presynaptic receptors may possibly modulate dopaminergic activity.


Symptomatic volunteers in multicenter drug trials.

1. Symptomatic volunteers were recruited at two collaborating institutions for anti-anxiety and antidepressant drug trials. Advertisements were placed for volunteers with significant symptoms of anxiety, depression, or both, and who were not currently in treatment. 2. It was possible to recruit adequate numbers of volunteers who met the numerous criteria for severity of distress; and who were not ruled out by various exclusion criteria, such as medical contraindications, etc. 3. Acceptable homogeneity across the samples at the collaborating institutions was found for demographic characteristics, level of distress, duration of symptoms, etc. 4. Attrition rates for these volunteers were lower than for the typical anxiolytic and antidepressant trials using outpatients. 5. Symptomatic volunteers appear to present a feasible alternative to the increasingly diminishing pool of outpatients.


The central noradrenergic system and affective response to MAO inhibitors.

1. In humans, norepinephrine (NE) has been postulated to be involved in the regulation of mood and behavior and to be altered in patients with manic-depressive illness. 2. Recent methodological advances have made possible a more direct assessment of central noradrenergic activity by the accurate measurement of the small amounts of NE and of the enzyme responsible for the conversion of dopamine to NE, dopamine-beta-hydroxylase (DBH), found in cerebrospinal fluid (CSF). 3. Cerebrospinal fluid samples were obtained from depressed patients both before and after treatment with two monoamine oxidase-inhibiting antidepressant drugs, clorgyline and pargyline. 4. Patients were rated twice daily by nursing staff on a modified 15-point scale for severity of global depression and anxiety. Patients were also rated using the Hamilton depression rating scale. 5. High negative correlations were observed between the drug-related changes in CSF NE and the changes in depression ratings on both the global ratings (r = -.95, p less than .001) and the Hamilton rating scale (r = -.81, p less than .01). Changes in NE were also highly correlated with changes in global anxiety ratings (r = -.85, p less than .01) calculated on the basis of changes from baseline for each measurement. Drug-related changes in CSF DBH similarly showed negative correlations with clinical response (r = -.79, r = -.38, r = -.68 respectively). In contrast, no significant correlations were found when drug-related changes in CSF MHPG were compared to changes in clinical state.


The effects of papaverine in tardive dyskinesia.

1. The therapeutic efficacy of papaverine for tardive dyskinesia was tested in 23 psychogeriatric and 18 chronic schizophrenic patients. Papaverine was given in slow-release capsules at 150 mg BID for one week followed by 300 mg BID for five weeks. A single blind design was used with blind raters and a 6-week no drug control condition. 2. Oro-facial dyskinesia was significantly reduced by papaverine in the psychogeriatric group during the first six weeks. Only a few patients showed at least 50% improvement of dyskinesia scores. Overall the drug effects were modest. 3. Other findings of interest were a) EEG showed increased per cent time of alpha and reduced beta 1. b) Parkinsonian side effects tended to confirm dopamine antagonism by papaverine. c) No tolerance was seen after six weeks. d) Elderly female patients and those with oro-facial dyskinesia appeared to respond best to papaverine.


Dopamine-beta-hydroxylase activity in serum of patients with hepatic damage.

1. The activity of dopamine-beta-hydroxylase (DBH) was assayed in the serum of 102 patients, mostly with varying degrees of hepatic dysfunction. 2. DBH activity was not elevated in those with liver disorder and did not correlate with serum bilirubin, transaminase, lactic dehydrogenase, alkaline phosphatase or creatine phosphokinase. 3. It is concluded that the liver is not necessarily involved in the inactivation of DBH.


Inhibition of 3H-thymidine incorporation into the DNA of developing rat brain by amphetamine treatment.

1. The incorporation of labelled thymidine into the brain of 10 day-old rats, used as the index of mitotic activity, was decreased two hours after administration of 20-40 mg/kg doses of amphetamine phosphate. 2. The entry of precursor from the blood to the brain tissue was not disturbed. 3. The observed elevation of plasma corticosterone levels did not appear to mediate the effect. 4. Changes in the normal balance of tissue norepinephrine and dopamine levels are considered as possible inhibitory factors in glial cell proliferation.


Clinical experience with fluotracen HCL: report of a case.

This article describes a depressed patient who experienced an excellent initial response to fluotracen, a new thymoneuroleptic. The patient then developed a syndrome of amphetamine-like hyperstimulation which necessitated discontinuance of the medication. Rapid, marked deterioration ensued. Hyperstimulation and agitation have not been described previously for fluotracen. Another group found that this drug is rapidly effective, even in treatment refractory patients, but that premature termination of therapy can provoke a rapid relapse; our experience confirms the earlier findings. We discuss fluotracen in relation to other neuroleptics and thymoleptics, and we suggest that comparative studies with thiothixene might be informative.


Glucocorticoid receptors and inhibition of bone cell growth in primary culture.

We have previously identified glucocorticoid binding proteins in cytosol of cells dispersed from fetal rat calvaria by collagenase digestion. The present study, employing primary culture of these cells, provides further evidence that these binding proteins represent glucocorticoid receptors. [3H]Dexamethasone bound to cytoplasmic extracts of cultured cells with an apparent Kdiss of 6.8 nM and exhibited approximately 8500 binding sites/cell. Nuclear translocation of [3H]dexamethasone was demonstrated with approximately 50% of bound steroid extractable from the nuclear pellet after incubation at 37 C; little nuclear transfer occurred at 0 C. The specificity of these binding site was characterized by competition studies with other steroids in whole cells, the order of affinities being: triamcinolone acetonide greater than dexamethasone greater than progesterone greater than cortisol greater than corticosterone = cortexolone. Non-glucocorticoids except progesterone competed only poorly. Sedimentation analysis of [3H]dexamethasone-protein complexes on sucrose gradients revealed a cytoplasmic peak of 6.5 S in salt-free gradients and 3.8 S in 0.3 M KCl gradients. Dexamethasone addition to the culture medium resulted in a dose-dependent inhibition of cell growth with approximately 40% reduction in cell number at 13 nM. That this inhibition was receptor mediated was substantiated by the partial blockade of the dexamethasone effect in the presence 1.3 microM progesterone. Functionally, dexamethasone inhibits the growth of these cells. These data provide evidence for receptor mediated inhibitory effects of glucocorticoids directly at the level of the bone cell.


Effect of hydroxy-vitamin D3 derivatives on 45Ca release from rat fetal bones in vitro.

Several hydroxy vitamin D3 (OH-D3) derivatives were tested for biological activity by measuring 45Ca release from prelabeled rat fetal bones, in vitro. In a 72 h continuous culture, 1 alpha,25-(OH)2-D3 produced a significant effect at 10 pg/ml. A similar effect was produced by 50 ng/ml of either 25-OH-D3 or 5,6-trans-25-OH-D3, and by 500 pg of 3 deoxy-1 alpha,25-(OH)2-D3. 24R,25-(OH)2-D3 was more active than 24S,25-(OH)2-D3, and the R isomer had activity that more closely resembled the biosynthetic compound. 3-deoxy-1 alpha-OH-D3 was inactive at a concentration of up to 1 microgram/ml. Using a 24 h preincubation period with no added vitamin D3 derivative, a steep dose-response curve could be obtained with 1 alpha,25-(OH)2-D3 over a range of 2-10 pg/ml during a subsequent 96 h incubation period, and 1 alpha,25-(OH)2-D3 was found to have about 5000 times the activity of 25-OH-D3.


The physiological release of specific individual neurophysins into the circulation of pigs.

Specific homologous radioimmunoassays for the two major porcine neurophysins have been developed and utilized to measure plasma neurophysins during events known to release vasopressin (dehydration and hemorrhage) and oxytocin (parturition and suckling). During hemorrhage plasma neurophysin I increased 2-25 times and decreased toward basal levels after reinfusion of the blood while plasma neurophysin II was low and showed only minor fluctuations. Neurophysin II was released during parturition and suckling in a pattern similar to that reported for oxytocin release during these events. A rise in plasma neurophysin II occurred towards the end of parturition and spurt release occurred in suckling. The function of neurophysins in the plasma is unknown but porcine neurophysin I has been shown to be released independently into the circulation in response to hemorrhage. Independent release of neurophysin II during parturition and suckling was not demonstrated. In the pig, release of neurophysin I may be associated with vasopressin release and neurophysin II associated with oxytocin release.


Thyroid hormone receptors: release of receptor to the medium during in vitro incubation of isolated rat liver nuclei.

Isolated rat liver nuclei show a substantial amount of T3 receptor release to the medium during in vitro incubation. This has been shown to be a general feature of nuclei compared after several methods of isolation and incubation. About 50% of nuclear receptors are released to the medium when incubated in sucrose-MgCl2-Tris, pH 7.85, for 2 h at 20 C.DNA, histones, and non-histone proteins (NHP) are also released. CaCl2 inhibits about 90% of the release of DNA and histones, but has less effect on inhibiting leakage of NHP and nuclear T3-binding protein (NTBP). The highest leakage for each fraction was found when incubating nuclei in the presence of EDTA. The receptor released to the medium has an affinity virtually identical to the receptor remaining in the nuclei. At least 1 mM dithiothreitol is needed to avoid degradation of the receptor. The NTBP has a sedimentation constant of 4.5 S when studied in low ionic strength gradients. Increasing KCl concentration decreases progressively its sedimentation constant, and in gradients containing 0.4 M KCl the receptor sediments as a single peak of 3.4 S. Since release of receptor to incubation medium decreases free T3 concentration, it must be taken into account in calculating receptor affinity. Total nuclear capacity in vitro is obviously underestimated, unless receptor released to medium is measured. Receptor exchange between cytosol and nucleus may be of physiologic significance.


The relative contribution of thyroxine and triiodothyronine to the hormone secretion from the perfused canine thyroid during various degrees of stimulation.

The effect of constant infusions of bovine TSH in different concentrations on the pattern of T4 and T3 secretion was examined in perfused canine thyroids isolated in situ. Each of the thyroid lobes was isolated and perfused in each animal. It was thus possible to examine the effect of two different concentrations of TSH in the same animal. The latency period was found to be shorter and the increase in hormone release was steeper when a high concentration of TSH (100 microU/ml) was infused than after a low concentration of TSH (2 microU/ml). The increase in T4 and T3 release started simultaneously; however, at all TSH concentrations employed a phase of relatively high secretion of T3 was induced. Despite continued infusion of TSH, the T4 T3 ratio in the effluent always returned to near prestimulation values at the end of the experiment. Accordingly, there was no support for a sustained enhancement of the preferential secretion of T3 from the thyroid during prolonged stimulation of the thyroid.


Isolation of gamma-amino butyric acid from pig hypothalami and demonstration of its prolactin release-inhibiting (PIF) activity in vivo and in vitro.

A non-retarded fraction with prolactin-release inhibiting factor (PIF) activity obtained by chromatography of a concentrate of porcine hypothalami on carboxymethyl-cellulose was chromatographically distinct from catecholamines. This fraction was purified further by six steps involving chromatography on Sephadex G-25, countercurrent distribution, free-flow electrophoresis, and chromatography on triethylaminoethyl cellulose. The PIF-active substance was isolated and identified as gamma-amino-butyric acid (GABA) by: 1) amino acid analyses using sodium as well as lithium-based buffers for resolution of biological fluids, 2) thin-layer chromatography of underivatized material as well as phenylthiocarbamyl derivatives, and 3) mass spectroscopy. Natural and synthetic GABA inhibited prolactin, but not LH release in vitro from isolated rat pituitary halves at doses as low as 0.1 microgram/ml. The inhibition was proportional to the dose; natural and synthetic GABA possessed identical PIF activity. Synthetic GABA also decreased prolactin release in monolayer cultures of rat pituitary cells and inhibited TRH-stimulated prolactin release. The inhibition of prolactin release in vitro by GABA could not be blocked by perphenazine, which inhibits PIF activity of catecholamines. GABA also suppressed prolactin release in vivo, although large doses were needed. Either rapid iv injection or infusion of GABA in doses of 1 to 100 mg in rats significantly decreased serum prolactin levels, which were previously elevated by pretreatment with monoiodotyrosine perphenazine, chlorpromazine, haloperidol, or sulpiride. beta-hydroxy GABA significantly depressed prolactin release, but beta-(p-chlorophenyl)-GABA (Lioresal, CIBA) and 4 other analogs of GABA were not effective in vivo and/or in vitro. The results indicate that GABA can inhibit prolactin release by a direct action on the pituitary gland, but whether this effect is physiologically meaningful still remains to be determined.


Further evidence that serotonin is a neurotransmitter involved in the control of prolactin secretion.

Administration of a new specific serotonin uptake inhibitor, fluoxetine, depressed the firing rate of raphe neurons. A highly significant increase in serum prolactin levels was observed after ip injection of 30 mg/kg of 5-hydroxytryptophan (5-HTP) in male or female rats pretreated with 10 mg/kg (ip) of fluoxetine. Neither 5-HTP nor fluoxetine given separately had any effect on serum prolactin levels. In animals pretreated with methysergide the combination of fluoxetine and 5-HTP did not increase significantly serum levels of prolactin. In addition, the serotonin agonist quipazine elevated significantly serum prolactin levels in male and female rats. The results of this study strengthen the idea that 5-HTP is acting via serotonin-containing neurons that influence anterior pituitary prolactin release, and that serotonin receptor activation leads to prolactin release.


Nuclear accumulation of androgens in perfused rat accessory sex organs and testes.

The uptake of androgens into the nuclei of caput epididymis, ventral prostate, seminal vesicle and testis was studied by recirculating physiological and pharmacological concentrations of [3H]testosterone in an artificial medium through the lower half (hemicorpus) of castrated or hypophysectomized rats. The accumulation of dihydrotestosterone in accessory sex organ nuclei was saturable, inhibited by perfusion of excess testosterone or cyproterone acetate, and associated with binding to 3S salt-extractable molecules. In castrated preparations the mean saturation levels (pmol/mg DNA) were different in the three organs: seminal vesicle, 2.8; ventral prostate, 1.8; caput epididymis, 0.9. The saturation level was significantly lower in ventral prostate of hypophysectomized rats (1.2) treated with testosterone to regenerate the accessory sex organs. Testosterone was the major nuclear androgen in the testes of mature hypophysectomized preparations perfused with testosterone. Although there was a large amount of nonspecific accumulation, testosterone binding to 3S molecules was shown by sucrose gradient centrifugation. Binding of dihydrotestosterone to 3S molecules in testicular nuclei was also demonstrated. The ratio of dihydrotestosterone to testosterone was different in immature and mature testicular nuclei and was altered by treatments known to affect testicular 5 alpha-reductase activity. The results suggest that in rat accessory sex organs and immature testis the major active androgen is dihydrotestosterone, whereas in mature testis it is testosterone. The shift in the predominant nuclear androgen in the testis from dihydrotestosterone to testosterone is most simply explained by the maturational change in 5 alpha-reductase activity.


Evidence for a role of prolactin in prostate and seminal vesicle growth in immature male rats.

To determine if prolactin secreted endogenously by anterior pituitary grafts could augment male accessory organ weights, single anterior pituitary grafts were placed under the kidney capsule of male rats, whereas control animals received a graft of muscle. Three weeks after transplantation, the animals were sacrificed by decapitation and a significant increase in plasma prolactin was observed, which was accompanied by a highly significant increase in the weights of seminal vesicles, ventral and dorsal prostates, and adrenals. To determine the importance of testicular steroids in the response, animals were castrated. The increases in prolactin, seminal vesicle and ventral and dorsal prostate weights still occurred whether or not a small dose of testosterone replacement therapy was employed. In the presence of the pituitary graft, adrenal weight usually increased in these animals as well. To rule out a requirement for adrenal steroids in the response, adrenalectomized-castrate animals were also studied, and the increases in prolactin and prostate weights still occurred although there was no significant increase in the size of the seminal vesicles. To rule out the participation of other pituitary hormones, pituitary grafts were also placed in hypophysectomized animals, and in these animals, there was also a significant increase in prolactin, accessory sex organ and testicular weights, but the adrenals did not increase in size. The grafts failed to alter gonadotropin titers in any experiment. It is concluded that single anterior pituitary grafts are capable of secreting sufficient prolactin to increase the size of the sex accessories and sometimes the testes and adrenals of the rat. Furthermore, the effects on the male sex accessory organs were demonstrable in the absence of testicular or both testicular and adrenal steroids. The data suggest that prolactin may play a physiological role in the growth of the testes, adrenals and sex accessories.


The role of central noradrenergic neurons in the control of thyrotropin secretion in the rat.

To investigate the role played by hypothalamic noradrenaline (NE) in the regulation of TRH-TSH release during tonic and cold activated conditions, drugs and surgical procedures able to interfere with central NE tonus were utilized. The time course of the effect of alpha-methyl-para-tyrosine (alpha-MpT) on basal TSH secretion was followed. The tyrosine hydroxylase (TH) inhibitor was unable to modify TSH plasma levels, whereas NE hypothalamic content decreased beginning with the third hour. The acute release of TSH evoked by cold exposure (CE) was prevented by pretreatment with alpha-MpT 1 h before; when alpha-MpT was followed 40 min later by clonidine, a central noradrenergic stimulating agent, TSH response to cold, previously blocked by the TH inhibitor was restored. Intraventricular injection of 10 micrograms of clonidine hydrochloride in unstimulated rats caused a significant rise of basal TSH levels 3, but not 10 min after the administration. Complex deafferentation of the medial basal hypothalamus (MBH), which destroys all the NE fibers afferent to this area, caused no change of thyrotropin secretion in basal conditions. Deafferented animals did not show any acute increase of TSH in response to CE. The results of this study provide evidence that NE may be the catecholamine (CA) mediating the rise in TSH following CE and that the direct stimulation of central NE receptors can evoke a massive TSH release from the anterior pituitary gland also in basal conditions.


Seasonal changes of plasma estradiol and progesterone in the Japanese monkey (Macaca fuscata fuscata).

The plasma levels of estradiol and progesterone in 5 mature female Japanese monkeys (Macaca fuscata fuscata) throughout a breeding and nonbreeding season were measured by radioimmunoassay. As the breeding season approached, plasma estradiol levels started to increase and a few elevations were detected. However, neither a plasma progesterone rise nor menstrual bleeding was seen. Menstrual bleeding began in December and recurred regularly 4 or 5 times at 4 week intervals until April. During this period, cyclic estradiol elevations (150-250 pg/ml) and luteal progesterone rises (2.0-5.3 ng/ml) were observed. After the last menstruation in March or April, two animals showed an estradiol elevation, but progesterone levels remained in the basal range and amenorrhea persisted. These data indicated that female Japanese monkeys ovulate 4 or 5 times a year, i.e., their breeding season is definitely defined. The changes of both steroids in transitional periods between nonbreeding and breeding, and breeding and nonbreeding seasons, suggested that some follicle development occurred in these periods. The elucidation of the mechanisms involved in the seasonal variation of reproductive functions in the Japanese monkey may provide useful information concerning some aspects of amenorrhea in human females.


Role of TSH in the changes in thyroidal metabolism of [35S]methimazole in phenobarbital and thyroxine-treated rats.

The effect of phenobarbital (PB) and/or thyroxine on the thyroidal accumulation and oxidation of [35S]methimazole (MMI) and serum TSH levels was studied in rats. PB treatment increased the accumulation of MMI and the serum TSH levels, but concurrent administration of T4 reversed these effects. It was concluded that increased TSH secretion in PB-treated animals was likely to be the major mechanism involved in the increased MMI accumulation. PB also increased the intrathyroidal oxidation of MMI to sulphate. However, in contrast to the PB effect on accumulation, concurrent T4 administration only partially reversed the effect on oxidation. The results suggested that the increased oxidation of MMI in PB-treated animals was due to a direct effect of PB or possibly a combination of this direct effect and the indirect TSH effect. Possible mechanisms postulated for a direct effect were thyroidal microsomal enzyme induction and/or changes in thyroidal protein binding of MMI.


Effect of testosterone propionate on levels of carnitine and testicular androgen binding protein (ABP) in rat epididymis.

Twenty-one day old rats were treated for 10 days with various doses of testosterone propionate (TP) (10 micrograms to 10 mg/day) and the levels of L-carnitine and testicular androgen binding protein (ABP) were measured in the 105,000 x g supernatant fractions of epididymis. Treatment with TP in increasing doses had a biphasic effect on the level of ABP in the epididymis; thus, with doses of TP of 10-100 micrograms/day, the ABP level was reduced in a dose-dependent way, whereas with higher doses of TP (0.2 to 1 mg/day) the extent of reduction of ABP levels was less as the dose of TP increased. Treatment with high doses (5 mg or 10 mg/day) did not change the ABP level compared with non-treated control rats. The concentration of carnitine increased linearly (log dose-response) with increasing doses of TP (10-200 micrograms/day) and there was no further increase after treatment with higher doses of TP. In adult rats TP (175 micrograms and 17.5 mg/day) reduced the level of ABP but not the level of carnitine in the epididymis. These studies suggest, therefore, that ABP is of minor importance for the supply of androgens to the carnitine-concentrating cells in the corpus and cauda epididymis.


Corpus luteum and fetoplacental functions in monkeys hypophysectomized during late pregnancy.

The hormonal regulation of corpus luteum (CL) function during late pregnancy was studied in hypophysectomized monkeys. Between days 149-154 of gestation, 9 days after hypophysectomy, progesterone in the uteroovarian vein (UOV), uterine vein (UV) and peripheral circulation (P) averaged 179.7 ng/ml, 38.9 ng/ml and 5.5 ng/ml, respectively. Amniotic fluid prolactin ranged from 2150-6700 ng/ml and monkey chorionic somatomammotropin (mCS) in mothers carrying live fetuses ranged from 11.4-30.8 micrograms/ml in the UV and P. Prolactin and monkey chorionic gonadotropin in the UV and P were low or nondetectable as was mCS in 2 mothers carrying dead fetuses. CL function was further studied 7 and 39 days after removal of the fetus alone or both the fetus and placenta. Placental delivery was extremely variable, ranging from 2-greater than 63 days post-fetectomy. Although progesterone was not detectable in the P7 days after cesarean section in those animals in which both fetus and placenta were absent, surprisingly, progesterone was measurable in the UOV (range 1.6-48.2 ng/ml). At 39 days, progesterone was either nondetectable or very low. We have interpreted these data to mean: 1) neither the maternal pituitary gland nor a live fetus is necessary for placental or corpus luteum production of progesterone during late pregnancy, 2) the presence of high levels of circulating prolactin and mCS are apparently not necessary for continued secretion of progesterone from the CL during late pregnancy, 3) the fetoplacental unit may be the source of the luteotropic stimulus of late pregnancy since progesterone in the UOV decreases markedly in the absence of the fetoplacental unit or disruption of the unit brought about by fetectomy, and 4) regression of the CL following cesarean section in hypophysectomized monkeys is exceedingly slow when compared to the precipitous regression characteristic of the CL of the nonfertile menstrual cycle.


Chorionic gonadotropin, chorionic somatomammotropin, and prolactin in the uterine vein and peripheral plasma of pregnant rhesus monkeys.

Seven adult female rhesus monkeys were laparotomized at days 22, 42, and 157 of pregnancy and blood was collected from the uterine vein and peripheral circulation. Plasma samples were analyzed for monkey chorionic gonadotropin (mCG), monkey chorionic somatomammotropin (mCS), and prolactin by radioimmunoassay. Levels of mCG at day 22 of pregnancy were approximately 250 ng/ml; however, during the later stages of gestation mCG was either nondetectable or less than 0.7 ng/ml. There was no statistical difference in prolactin concentrations between days 22 and 42 of pregnancy, mean levels being between 176-424 ng/ml, but by day 157 prolactin levels of greater than 2,000 ng/ml were recorded. No statistical difference existed between peripheral and uterine vein concentrations of either mCG or prolactin at any of the stages of gestation examined. At day 22, mCS was not detectable; however, at day 42 of gestation mCS titers averaged 1.5 micrograms/ml and 2.3 micrograms/ml in the peripheral and uterine vein plasma, respectively. A statistically significant mCS increase occurred by day 157, levels in the periphery and uterine vein averaging 11.0 micrograms/ml and 16.3 micrograms/ml, respectively. Uterine vein titers of mCS were significantly higher than peripheral titers at both days 42 and 157. Thus, the highest levels of mCG were present during early pregnancy, whereas the highest levels of mCS and prolactin were present during late pregnancy.


Immunoreactive LH-like substances in serum of hypophysectomized and prepubertal monkeys: inactive in an in vitro LH bioassay.

Serum LH levels in rhesus monkeys are commonly measured by a radioimmunoassay (RIA) utilizing ovine LH as the radioligand and a novel antiserum to ovine LH. Although meeting most criteria of validity, this RIA cross-reacts with serum from demonstrably hypophysectomized monkeys as well as serum from pre-pubertal monkeys. We have utilized the recently developed rat interstitial cell-testosterone assay (RICT) for measurement of serum LH in rhesus monkeys during various endocrine states and have compared the results with those obtained by RIA. The RICT in vitro bioassay was as sensitive, precise, and accurate as the RIA. Partially purified pituitary monkey LH preparations, varying by as much as 100-fold in purity, had similar potency estimates by both assays. The expected biphasic pattern of serum LH levels during the menstrual cycle as well as the usual increase in serum LH levels after ovariectomy was observed with both assays. In each case, however, basal serum LH levels were overestimated by the RIA and peak serum LH levels were underestimated by the RIA as compared to results obtained by the RICT bioassay. The most striking differences between the two assays were observed with serum from hypophysectomized and prepubertal monkeys. Whereas LH-like activity in such samples was high when measured by the RIA, it was undetectable by the RICT bioassay. The ratios of serum LH (RIA/RICT) varied from greater than 7.2 to greater than 17.4 in such sera. These results demonstrate the serious limitations of the ovine LH RIA for measurement of serum LH in rhesus monkeys. It appears that the RICT bioassay may be a suitable alternative method, especially in circumstances other than the menstrual cycle and after ovariectomy.


New technique of injection of estradiol into preoptic-anterior hypothalamic area of newborn rats: technique limiting diffusion and duration, with preliminary results on postpuberal block of ovulation.

Previous studies have shown that sc administration of androgen or estrogen into newborn female rats will disturb postpuberal ovulatory function, as evidenced by a higher incidence of vaginal estrus, few ovarian corpora lutea, and the abolition of estrogen-induced luteinizing hormone surges after ovariectomy and chronic estrogen maintenance. Studies of the uptake of labeled estrogen and intracerebral lesion studies have indicated the preoptic area and anterior hypothalamic nuclei (POA-AH) as possible sites of steroid uptake and control of certain sexual functions in the rat. Attempts to localize the site of steroid effects to the POA-AH of newborn rats by chronic implants have been hampered by lack of definition of extent of localization in space and time. The present study introduces a microinjection technique for the delivery of subpicogram quantities of estradiol to these areas of the central nervous system in newborn rats, and statistically defines the extent of steroid localization in three dimensions as well as the duration of exposure. Delivery of estradiol by this method in the POA-AH region yielded an increased incidence of postpuberal vaginal estrus; a decrease in the number of corpora lutea; and in many but not all, led to abolition of estrogen-progesterone induced LH surges after castration and estrogen replacement. Injection 0.5 mm more caudad did not result in blockade of the estrous cycle.


Termination of pseudopregnancy following hypothalamic implantation of prolactin.

Pseudopregnancy (PP) in the rat is characterized by maintenance of the corpora lutea and twice daily surges of prolactin at 1500-2100 h and 0100-0900 h. Four days after PP was induced by cervical stimulation with a glass rod, rats were cannulated via the right carotid artery and one day later received an implant of ovine prolactin (200-250 mg) or albumin (controls) into the median eminence of the hypothalamus. Forty-five of 54 rats implanted with prolactin showed a termination of PP within 4 days. Ova were recovered from 19 of these rats whereas all of the controls remained pseudopregnant and did not ovulate. Ovarian and uterine weights were increased in rats implanted with prolactin. Plasma prolactin levels in the rats implanted with prolactin were lower each day (45-89%) at 0100, 0300 and 1800 h compared to controls. Plasma LH levels rose gradually after prolactin implantation, and in those rats in which ovulation occurred, a preovulatory LH rise was detected at 1800 h on the previous day. It is concluded that daily surges of prolactin play an essential role in maintaining PP in the rat, and that implantation of prolactin into the median eminence results in inhibition of prolactin. The stimulation of LH secretion, which led to ovulation, may be the result of a direct neural action of prolactin on the LH release mechanism or may simply result from the termination of PP.


Developmental patterns of plasma and pituitary growth hormone (GH) in the female rat.

Circulating GH levels measured by RIA in developing female rats were elevated between day 5 and 12. Titers declined by day 15, reaching a nadir at day 20 and by day 25 they began to increase again. During the pubertal period (days 32-38), plasma GH was elevated in the anestrous phase, reaching peak values in the afternoon of the early proestrous phase. Levels were also elevated the day of the first preovulatory discharge of gonadotropins, showing peak values in the afternoon of that day. Thereafter, plasma GH declined, reaching a nadir in the morning of diestrus 1 (day 2 after vaginal opening) and remained slightly more elevated during the afternoon of that day and throughout diestrus 2. Plasma GH levels at this time were similar to those of adult diestrus females. Pituitary GH concentration was low between days 5 and 15 and increased markedly thereafter, reaching adult concentrations by day 25. Body weight increased linearly between day 5 and 25. At this time, the slope of the curve of body weight gain increased significantly. Although the majority of animals revealed open vaginae only after they had reached a body weight of 100 g, a critical weight for vaginal opening could not be established. The pronounced changes in circulating GH levels which preceded by several days the surge in gonadotropin release that normally accompanies the onset of puberty in the rat suggest that GH may play a physiological role in the control of the pubertal process in this species.


H1 and H2 histamine receptor participation in the brain control of prolactin secretion in lactating rats.

The aim of the present research was to evaluate the histaminergic regulation of prolactin secretion in the lactating rat and the possible involvement of H1 and H2 histamine receptors in this control. Prolactin was measured by radioimmunoassay in blood samples withdrawn through an intrajugular silastic catheter from undisturbed lactating mothers 10 to 15 days after delivery. In some of those rats a stainless steel cannula was placed in the third ventricle. The tested drugs, H1 and H2 receptor agonists and antagonists, were injected either by the intrasilastic route or intraventricularly immediately before the onset of suckling and after a basal sample was taken. New samples were withdrawn 10, 20, 30 and 60 min thereafter. Suckling caused a 12- to 18-fold increase in serum prolactin by 10 min in control saline-injected mothers. In non-suckled mothers (NSM) injected with saline, prolactin levels were low at all times. Systemic or intraventricular diphenhydramine and mepyramine, H1 receptor antagonists, suppressed the increment in prolactin observed in suckled mothers (SM). Intraventricular metiamide, an H2 receptor antagonist, did not modify prolactin secretion in SM but drastically increased serum prolactin in NSM. A small but significant increase in prolactin titers was observed in NSM injected intraventricularly with histamine. 4-Methylhistamine, an H2 agonist, was ineffective when used intraventricularly in NSM, but clearly suppressed prolactin enhancement in SM. It is postulated that in lactating mothers, brain histamine has a dual control on prolactin secretion. H2 receptors mediate events related to inhibition of prolactin release, since the agonist 4-methylhistamine blocked the prolactin rise in SM, while the antagonist metiamide promoted release of the hormone in NSM. H1 receptors seem to be related to a facilitatory mechanism since classical antihistamines suppress the serum prolactin increase that follows the onset of suckling, while histamine itself is able to release prolactin in NSM.


Computerized tomography in the assessment of diseases of the thorax.

Many of the diseases of the chest wall, heart, mediastinum, pleura and lungs can be successfully imaged by computerized tomography. Radiation therapy ports can be calculated and transcutaneous biopsies monitored. This paper deals with the many uses that we have had for computerized tomography in assessing diseases within the chest and thorax.


Computerized tomography in pulmonary sarcoidosis.

Six patients with documented pulmonary sarcoidosis were selectively studied with the ACTA scanner. The CT scans were correlated with the standard chest radiographs of these patients. CT scans readily confirmed adenopathy, calcification, and pleural disease. Likewise, diffuse and isolated parenchymal disease was detected and in some cases unexpected lung involvement was noted.


Computed tomography of the skull and facial structures: preliminary evaluation of direct coronal sections.

Skull and facial structures may be evaluated on computed tomography (CT), as well as the brain. A valuable new dimension to the study has been added with the feasibility of obtaining direct coronal sections using a wide gantry aperture. The patho-anatomical details of bone and soft tissues including the orbit and paranasal sinuses are well demonstrated. Direct viewing on a display console of an enlarged quadrant of the scan is of prime importance in diagnosing fine changes involving the thin facial bones.


CT studies of tumors of the skull base, facial skeleton and nasopharynx.

Fifty cases of tumors of the base of the skull, facial skeleton and nasopharynx were studied by CT. The tumoral densities were measured and compared to the pterygoid muscle density which was used as reference. Results showed no relationship between tumoral density and histology, and intravenous contrast medium injection was not useful. CT, however, does offer many advantages in the diagnosis of nasopharynx tumors, (5 cases) and in the determination of the extension of facial skeleton tumors.


Leukemic infiltration of the optic nerves: demonstration by computerized tomography.

Enlargement of the optic nerves by leukemic infiltration has been demonstrated by computerized tomography (CT) in two cases. A follow-up CT scan shows reduction in size of the optic nerve after central nervous system radiation in one case. The pathophysiology of central nervous system leukemia is discussed.


Cerebral ischemia with CT.

One hundred fifty-eight patients with cerebral ischemia, and divided into four clinical groups were studied with CT. The results were correlated with those of angiography, scintigraphy and regional cerebral blood flow measurement. CT evolution was closely correlated with clinical and anatomical evolution. Changes in cerebral parenchyma density, in relation to the ischemic lesion, are the result of two phenomena: first, edema showing a fairly stable peak of intensity in the 2nd week and disappearing totally before the 20th day; and second, necrosis, variable in extent from patient to patient at the onset with subsequent evolution towards cavitation and thus a density similar to that of cerebro-spinal fluid.


Diagnosis of sellar and parasellar lesions by computed tomography and other diagnostic modalities.

A review of 5,000 computed tomographic (CT) brain scans revealed 76 patients with proved pathology involving the sellar and parasellar areas. The overall diagnostic accuracy of CT scanning was 93.4%, whereas the accuracy of isotope scanning, angiography, and pneumoencephalography was 55.4, 81 and 100% respectively. The criteria used in making the diagnosis with CT scanning are listed. The results indicate that CT scanning is the initial diagnostic procedure of choice, but that other modalities, particularly angiography, are still required for more accurate evaluation in the majority of cases.


Computed tomography of tumors of the pineal region.

Eight pathologically proven cases of pineal region tumors examined by computed tomography (CT) were found upon reviewing 11,000 consecutive CT studies at the Massachusetts General Hospital. The CT scan findings of the eight cases are described and related to a pathological classification of pineal tumors.


Radiotherapy treatment planning using the ACTA-scanner.

Computerized tomography is useful in radiotherapy treatment planning in the following ways: (1) Its image provides the most accurate possible contour of the patient and demonstrates the internal structures in their proper relation to each other. (2) The tumor and its extension are accurately demonstrated. (3) Corrections for tissue heterogeneities can be accomplished in one of two ways, either by arbitrary assignment of densities to tissues or by direct scanning with a therapy source. This latter procedure is under investigation. (4) The computer can be programmed to demonstrate summations of dose delivered from multiple fields.


A computerized tomographic evaluation of malignancies of the bladder and prostate.

Twenty cases of malignancies of the bladder and prostate were evaluated by computed tomography. This study was performed in a community hospital adjacent to a large retirement community in Southern California. Although the series was small, the results indicate that, for example, staging of carcinoma of the bladder malignancy beyond Jewitt-Marshall A can be accomplished with some ease using this modality. The extensive malignancies are easily demonstrated and their extents, in relationship to surrounding pelvic structures, are seen with considerable clarity. The use in radiation treatment planning is obvious.


Computed tomography of the paranasal sinuses and their adjacent structures.

Forty-five computed tomographic examinations were performed on 34 patients with diseases of the paranasal sinuses and their adjacent structures. Coronal sections were obtained in addition to transverse axial tomographic sections. Evaluation was made whether CT could provide more informations compared with plain roentgenography and whether there were additional informations on coronal sections. CT showed soft tissue abnormality and its extension to better advantage. Especially, involvement of the orbits, pterygoid fossa, nasopharynx, skull base and brain were shown well. Coronal sections were useful in evaluation of superior and inferior extension of the tumors such as involvement of the superior and inferior orbital walls and skull base as well as intracranial extension. Since CT has the ability to better define the total extent of the lesion, this technique should be added to the conventional roentgenologic techniques preferably with the use of coronal sections.


Computed tomography of the head in children: experience with 1024 scans performed in an outpatient facility.

Our experience in 1,024 computed tomography examinations of the head in 954 infants and children performed in a private office is reported. Immobilization in infants was achieved using relatively large dosages of chloral hydrate (as high as 75 mg/kg) supplemented, when necessary, by I.M. Benadryl. The usual dose of chloral hydrate recommended for children is 25 mg/kg as a sedative and 50 mg/kg as a hypnotic. Satisfactory immobilization was accomplished in 350 of the 360 children under 6 years of age. Thus, routine general anesthesia was avoided. The wide spectrum of conditions demonstrated has been tabulated and selectively illustrated.


Demonstration of a little known cause of infantile epilepsy, occipital porencephaly, by computerized tomography (CT).

Among 500 epileptic patients studied by Computerized Tomography, 11 patients presented an occipital porencephaly (or a dilation of the occipital horn with a "porencephalic" aspect) sometimes associated with a ventricular dilation. These 11 patients represented 2.2% of our patients and 5% of those less than 20 yr of age which is frequent in relation to lesions of the same type having a different topography. Clinical and EEG studies of these 11 patients revealed hemiplegia or hemiparesis in 8 cases, hemianopsia in 7 cases, a severe partial epilepsy in 6 cases which was temporal in 5 patients, a secondary generalized epilepsy in 3 cases, and an epilepsy unable to be classified in 2 cases. The "porencephalies" responsible for these clinical signs are most likely of encephalomalacic origin, secondary to circulatory troubles in the peri- or postnatal period. Remillard et al. maintain that perinatal occlusion of the posterior cerebral artery is responsible. However, in our personal series, the results obtained from CT, PEG and angiography do not permit us to be as affirmative as to the vascular etiology responsible.


New applications of old radiographic techniques applied to computed tomography.

Established techniques of routine radiography can be applied to a computed tomography (CT) examination of the body. The planned use of various positive and negative contrast agents placed intravascularly and intraluminally can yield important information not otherwise obtainable. When purposefully combined with selected positions, these agents allow the radiologist to tailor a CT examination to a specific clinical problem. Several combinations of these modalities which have been found useful in CT of the body, are described.


Evaluation of intracerebral hematoma by computed tomography.

The CT scan appearances of acute intracerebral hematoma are usually diagnostic, and can be differentiated from hemorrhagic tumor and infarction. Some prognostic evaluations can be made, depending on the site and size of the hemorrhage. Sequential studies indicate resolution of the density of the hematoma over a period of approximately six weeks. This however does not appear to correlate with pathological resolution, but does reflect the hemoglobin concentration in the hematoma. Angiography is indicated when an underlying AVM or aneurysm is suspected, whereas contrast infusion studies are not of great value in detecting these lesions.


Unexpected brain hemorrhages and the value of computerized tomography.

Intracerebral hemorrhage has been thought in the past to be manifested by sudden onset of hemiplegia, severe headache and deep coma proceeding to death in most cases. There are patients who present with less ominous symptoms who have heretofore been though to have cerebral infarction or transient ischemic attacks who in reality have intracerebral hemorrhages. Computerized tomography has allowed us to identify these patients and to separate them from the large group of patients with ischemic infarcts either due to thromboses or emboli. Six patients were reported with unexpected brain hemorrhages and their good prognosis is emphasized.


Abortion in the United States, 1977-1978.

There were 1.32 million legal abortions in the United States in 1977 and a projected 1.37 million in 1978, an increase of four percent between 1977 and 1978 compared with one of 12 percent between 1976 and 1977. In 1978, 29 percent of pregnant women chose to terminate their pregnancies by abortion. Almost three percent of U.S. women of reproductive age obtained an abortion in 1978. From 1967 through 1978, approximately six million women obtained almost eight million legal abortions; about one in eight U.S. women of reproductive age has had a legal abortion. The number of hospitals reporting that they provided abortion services dropped slightly from 1,695 in 1976 to 1,661 in 1977, but the number of nonhospital abortion clinics increased from 448 to 522, and the number of physicians who reported performing abortions in their offices grew from 424 to 533. Between 1976 and 1977, the average number of abortions per hospital facility decreased from 246 to 237, while the average number per nonhospital provider increased from 875 to 879. The percentage of abortions performed in hospitals declined from 35 in 1976 to 30 in 1977, while the percentage reported by free-standing clinics increased from 61 to 66; the percentage performed in physicians' offices remained at four. Ninety-five percent of abortions in 1977 occurred in metropolitan areas, where 75 percent of the women in need of abortion services live. In 1977, there were identified abortion providers in only 23 percent of U.S. counties. Nine percent (more than 118,000) of the women who obtained abortions in 1977 had to travel to another state for services, and many traveled to other, often distant, counties in their home states. One in three abortions in 1977 were obtained by teenagers, and three in four were obtained by unmarried women. Twenty-eight percent of the women estimated to be in need of abortion services in 1977, and 26 percent in 1978, were unable to obtain them. In FY 1977, before Hyde amendment restrictions on government financing of abortions for poor women, 133,000 of the estimated 427,000 Medicaid-eligible women in need of publicly funded abortion services were unable to obtain them.(ABSTRACT TRUNCATED AT 400 WORDS)


Organized family planning services in the United States, 1976-1977.

In 1977, an estimated 4.2 million women received contraceptive services from organized family planning programs in the United States. The number of patients has grown each year since the late 1960s, but since 1973, growth has slowed concurrently with a diminished increase in the level of federal funding for family planning services. The proportion of clinic patients who are teenagers increased from 20 percent in 1969 to 31 percent in 1977. An estimated 1.3 million adolescents received services in 1977, compared with just 214,000 in 1969. Contraceptive services were provided during 1977 by 2,574 agencies at some 5,300 clinic sites. Health departments served 42 percent of all family planning patients; Planned Parenthood affiliates served 27 percent; hospitals served 13 percent; and community action groups, free clinics, neighborhood health centers and women's health programs together served 18 percent. Federal expenditures for medical family planning services provided by organized clinics and private physicians rose from an estimated $13.5 million in 1968 to $239.1 million in 1977. Estimated federal expenditures for clinic services were $192.5 million--three-quarters of the total $252.6 million in public and private expenditures for such programs. Federal project grant funds under Title X of the Public Health Services Act accounted for 42 percent of all medical family planning expenditures in clinics, and for 55 percent of all federal funds expended for this purpose. These findings are based on data from the most recent study of the organized family planning service network conducted by The Alan Guttmacher Institute (AGI) for 1977.(ABSTRACT TRUNCATED AT 250 WORDS)


Disulfiram hepatitis.

A case of an adult with disulfiram-induced hepatitis is presented. An etiological role for the drug was proved when the patient underwent a provocative challenge and developed evidence of hepatocellular damage, reversible on withdrawal of the drug. Disulfiram-induced liver injury is difficult to detect in a population with a high incidence of alcohol-related hepatic disease. Liver chemistries should be screened before beginning disulfiram therapy and periodically during treatment.


Liver pathology in hycanthone hepatitis.

Histological examination of liver tissue from 3 patients who died 6, 4, and 9 days, respectively, after an intramuscular injection of 3 +/- 0.5 mg of hycanthone per kg of body weight for schistosomiasis, showed features of a toxic hepatitis with massive hepatic necrosis, many acidophil bodies and minimal inflammatory response in 2 patients, and confluent necrosis with early fibrosis in 1. Liver cells showed prominent fatty change. The former 2 patients had evidence of schistosomal granulomatous hepatitis. A follow-up liver biopsy in a 4th patient who had had hycanthone hepatitis with liver failure 1 year before showed good recovery with features of chronic persistent hepatitis.


Sex education and knowledge of pregnancy risk among U.S. teenage women.

Seven in 10 never-married U.S. women aged 15-19 have had a sex education course, almost all of them in school. Young black women are slightly more likely than whites to have had such a course. About half of all never-married teenagers have had courses which included some teaching about modern contraceptive methods; six in 10 have had some formal instruction about VD, and seven in 10 have had courses that included detailed instruction about the monthly menstrual cycle. Six in 10 of those who have had a course with information on the menstrual cycle claim to know the period of greatest pregnancy risk; but only one-third of those who have had such a course can in fact correctly identify the time when the risk of pregnancy is highest. Young white women are nearly two times more likely than blacks to identify the period of risk correctly. Knowledge of the period of risk is a particularly important issue in relation to teenage pregnancy, because many sexually active teenagers say that they do not use contraception because they believe they are protected from the risk of pregnancy by the time of month when they have intercourse. Among those who claim to know the period of greatest risk, a sex education course is the most common source of information for both blacks and whites, with home a distant second. Medical personnel and facilities convey information about pregnancy risk the most effectively, but they are the first source for only a tiny fraction of teenagers.(ABSTRACT TRUNCATED AT 250 WORDS)


Jejunal bleeding from a solitary large submucosal artery. Report of two cases.

Two young patients with massive intestinal bleeding resulting from a solitary submucosal arterial abnormality of the jejunum are reported. In one case, the bleeding lesion was localized only by emergency abdominal angiography, while a previous exploratory laparotomy proved negative. The vascular lesion encountered in both patients consisted of a wide caliber artery lying in the jejunal submucosa; there was no evidence of true aneurysm on serial sections. The clinicopathological picture closely resembles that of lesions previously described in the stomach under the name of "gastric submucosal aneurysms" in the English literature, or of "gastric Dieulafoy's erosion" in the French literature. It is suggested that the vascular lesions herein reported should be called "solitary large submucosal artery" or "Dieulafoy-like erosion" of the jejunum.


Budd-Chiari syndrome associated with protein-losing enteropathy.

Budd-Chiari syndrome associated with protein-losing enteropathy is reported. A 26-year-old male suffered from ascites, edema in the lower extremities, and engorgement of ascending veins on the abdominal wall. The diagnosis of Budd-Chiari syndrome was made by inferior vena cavography. The 131I-polyvinylpyrrolidone test showed the association of protein-losing enteropathy. The surgical operation was performed successfully, resulting in a marked improvement of signs and symptoms. To date, no similar case has yet been reported. There are, however, a number of reported cases of hypoproteinemia in Budd-Chiari syndrome, which might have been associated with a protein-losing enteropathy.


A cell-mediated immune model of inflammatory bowel disease in the rabbit.

A model of ulcerative colitis related to cellular immunity has previously been produced by sensitization of the colon of guinea pigs with dinitrochlorobenzene (DNCB). We have confirmed and extended these studies in rabbits. Rabbits were skin-sensitized to DNCB and challenged 10 days later with an intrarectal instillation of DNCB. The histology of the colon was examined at various time intervals. Three days after challenge the mucosa was ulcerated; there were crypt abscesses and epithelial basophilia with increased mitotic figures. The increased inflammatory infiltrate in the lamina propria contained polyps as well as mononuclear cells. Submucous edema was common in this phase. This was compatible with active ulcerative colitis. These lesions changed to those consistent with the healing phase of ulcerative colitis at 2 weeks, and at 5 weeks there was still mild crypt disorganization and loss along with a paucity of goblet cells and submucous fibrosis. Rabbits that received repeated instillations of DNCB converted from a negative delayed hypersensitivity skin response to rabbit-colon extract to a positive response. Thus, a nonspecific cellular immune reaction in the colon produces histological changes compatible with ulcerative colitis and leads to the production of lymphocytes which are sensitized to colonic antigen.