Tubal pregnancy: a review of 404 cases.

Tubal pregnancy: a review of 404 cases. In the two years - 1st January, 1973 to 31st December, 1974 - 533 patients had operation for tubal pregnancy at the Gynaecology Unit of the Korle-Bu Teaching Hospital. About five cases per week were seen during this period. The incidence was 44 for every thousand deliveries at the Hospital. The case notes of 404 of the 533 patients have been reviewed. The age range was 15 to 44 years; 78% were in the 21 to 35 years age group. 81.4% had had pregnancies which went beyond 28 weeks. Only 13.7% had never had an intrauterine pregnancy.  Tubal pregnancy is therefore not a disease of the primarily infertile as is commonly thought. There was no significant difference between the incidence on the right side and the incidence on the left side. The ampulla was the commonest site of implantation in the tube (45%). Tubal rupture (89.6%) was commoner than tubal abortion (10.4%). The principal signs and symptoms were abdominal pain, amenorrhoea, abdominal tenderness, abdominal distension, and signs of free fluid in the abdomen, syncope, anomalous vaginal bleeding, pallor and vomiting. The absence of amenorrhoea does not rule out the possibility of an ectopic. On pelvic examination the major signs were tenderness in a fornix and cervical excitation pain. Abdominal paracentesis and culdocentesis if positive are useful in diagnosis; negative results prove nothing. Laparascopy is of great value and should be employed in the difficult case. Beware of the patient in the reproductive age with anomalous vaginal bleeding, vague abdominal pains, syncopic attacks and anaemia. The mortality rate in the series was 0.7%.


Evaluation of vaginal tubal ligation.

Evaluation of vaginal tubal ligation. A series is described of 150 cases of sterilization through posterior colpotomy. The operation was mainly elective or postabortal. The average hospital stay was short--1 or 2 days and complications were few-mainly pelvic peritonitis. There was only 1 death in the series covering 5 years--from peritonitis. The method is recommended for widespread use throughout the country both in rural and urban centres.


A successful caesarean section after death from acute bacterial meningitis. A case of post mortem Caesarean Section is presented with a successful outcome. The urgency of the operation to achieve the delivery of a live and healthy baby is stressed. The mother died of Acute bacterial meningitis.


Occurrence of volvulus with intestinal obstruction after ventriculo-peritoneal CSF diversion: a case report. This paper presents a four-year-old Nigerian male child who developed volvulus of the small intestine three years after the successful establishment of ventriculo-peritoneal shunt for his hydrocephalus. There is only one other report in the literature of this complication. In view of the increasing use of ventriculo-peritoneal CSF diversion for hydrocephalus, it is necessary to be aware of the rare and unusual cause of an acute abdomen.


The role of autotransplanted spleen in the erythropoietic recovery of the mouse. Erythropoietic recovery was studied in mice subjected to subcutaneous splenic autotransplantation and compared with that observed in normal and splenectomized animals. Radioiron uptake into spleen and erythrocytes and splenic weight were measured at different times after lethal irradiation and injection of 5 x 10(5) bone marrow cells. Dose-response curves were also performed with increasing amounts of cells injected. Hematocrit recovery as a function of time after a single large dose of phenylhydrazine was also studied. Results indicate that autotransplants act qualitatively as normal spleens, but their erythropoietic capacity is diminished and the animals show an intermediate response between normal and splenectomized mice. Histological observation showed no obvious differences in morphology and spatial distribution between colonies developing in normal and transplanted spleens. It is concluded that transplants lead to normal lodgment, proliferation and erythroid differentiation of circulating stem cells. However, changes in transplant size, anatomical position and other factors such as fibrosis and blood flow may decrease their trapping area and their capacity of expansion even under conditions of high erythropoietic stimulation.


Oscillatory flow in a y-shaped bifurcation. Fluid particle trajectories in oscillatory flow in Y-branched tubes of equal radii were quantitatively analyzed for an oscillatory number square root 2pi/Tv.ro of the order of unity and qualitatively for an oscillatory number of the order of 25. Radial distribution of trajectories and secondary motions are described. This work is an attempt to know some of the features of oscillatory flow present in blood and air motion with similar boundary conditions.


Characteristics of the hypothalamic and hypophyseal cytoplasmic estradiol binding substances. Effects of neontaal castration and testosterone administration. Some physicochemical characteristics and binding capacities of the cytoplasmic estradiol-receptor complexes of the rat hypophysis and hypothalamus, were determined in intact males and females, neonatal castrated males and neonatal and adult testosterone injected females. By gel filtration and density gradient centrifugation the hormone receptor complexes obtained in vitro, shared the same properties in both tissues. The hydrodynamic radius was estimated to be 60 A, The sedimentation coefficient 8.5 S, the frictional coefficient f/fo was 1.42 corresponding to axial ratio (prolate) of 7.85. The molecular weight was 263 000. The data suggest a highly asymmetric molecule similar to the uterine soluble estradiol-receptor complex. No differences were observed in the hypothalamic binding capacities of diestrous females and adult males. The results expressed as fmol of hormone bound/mg cytoplasmic protein were 2.40 +/- 0.32 and 2.54 +/- 0.26, respectively. For estrous females it was 3.72 +/- 0.44. Neonatal castration or testosterone administration increased significantly the binding activity in adulthood. Adult females treated with testosterone showed the lowest level of the hypothalamic estradiol receptors (1.41 +/- 0.56). No differences were observed in the in vitro titration of the pituitary cytoplasmic estrogen binding sites.


Studies on the mechanisms of learning. IV. Ontogeny of calcium channels in the rat's cortex. The sensitivity of some electrocortical potentials of rats to topically applied tetrodotoxin (TTX), manganese, lanthanum, calcium, mescaline and strychnine was followed from the age of 6 to 20 days and compared with that of adult animals. Sensitivity to TTX was relatively greater in the younger rats. In contrast, the blocking effect of Mn2+ or La3+ was small initially but increased with age. Similarly, the ability of mescaline or strychnine to give rise to giant spikes (dendritic action potentials) increased with maturation of the brain cortex. Finally, an increase in external calcium concentration depressed cortical potentials in the younger animals and had the usual increase of the mescaline or strychnine spikes in the older rats. It is concluded that the formation of calcium channels in dendritic membranes is part of the maturation process of cortical neurons and possibly related to the learning mechanisms. The depressant action of high external calcium during the first days of life was ascribed to an unspecific reduction in membrane permeability.


[Effect of an essential fatty acids free diet on the lipidic composition of rat testicles (author's transl)]. The effect of a fat free diet on the fatty acid composition and histological changes of the testis of old rats was studied to investigate the possible function of docosa-4,7,10,13,16-pentaenoic acid in rat testicles. The lipidic composition, the fatty acid composition, the conversion of docosa-7,10,13,16-tetraenoic acid to arachidonic acid and the activity of the 6-desaturase were determined during the different periods in which the rats received a fat free diet. Comparatively, the changes in the fatty acid composition of the liver were also studied. Only the liver showed a change in the triglyceride content during the first month of treatment, and it regained its normal values afterwards. Both liver and testis changed the fatty acid composition. An increase of the acids of the oleic series and a decrease of the components of the linoleic series were shown. These changes were similar to the ones provoked by an essential fatty acid deficient diet on young animals. The amount of docosa-4,7,10,13,16-pentaenoic acid was very little changed. No significant change was shown either in the retroconversion of docosa-7,10,13,16-tetraenoic acid to arachidonic acid. However, the 6-desaturase activity of the testis was enhanced by the fat deficient diet. The possibility that arachidonic acid in the adult rat is mainly supplied by linoleic acid and not by the retroconversion of docosa-4,7,10,13,16-pentaenoic acid is discussed.


[Inestability of fatty acid desaturation enzymes in liver slices (author's transl)]. A study was made on the microsomal oxidative desaturating activity of fatty acids in rat liver slices incubated in different media. [1-14C] linoleic acid desaturation activity decreased during the incubation in Krebs-Ringer-Bicarbonate. The addition of glucose or pyruvate in the incubation medium did not alter the decrease of the linoleic desaturation activity compared to the controls. Linoleic desaturation to gamma-linolenic acid descreased even when the slices were incubated in different media and at different temperatures. However, the inclusion of aminoacids in the media prevented the decrease of linoleic acid desaturation. Microsomal stearic acid desaturation to oleic acid in liver slices was less modified by incubation than linoleic acid desaturation. Glucose inclusion in the medium enhanced 9-desaturation. The stability of the desaturases in the liver slices is discussed. The results evidence once more that 9-desaturation and 6-desaturation are accomplished by different enzymes controlled by separate mechanisms.


Effects of sodium pentobarbital upon cardiovascular responses to mesencephalic reticular stimulation in rats. In nineteen rats the cardiovascular responses to the electrical stimulation of the lateral mesencephalic reticular formation (MRF) were recorded before, during and after different doses of sodium pentobarbital injected intravenously. Before pentobarbital, stimulation of the MRF induced cardiovascular changes in 100% of cases. The following four patterns were observed: a) hypertension plus bradycardia (N = 11; 57.9%); b) hypertension without chronotropic effects (N = 4; 21%); c) hypertension plus tachycardia (N = 3; 15.8%), and d) hypotension without chronotropic effects (N = 1;5.3%). Administration of small doses of sodium pentobarbital induced drastic variations in the incidence of the aforementioned patterns of response as follows: a) N = 3; 15.8%; b) N = 2; 10.4%; c) N = 11; 58%; d) N = 0. Other two complementary patterns appeared: e) no changes in blood pressure plus bradycardia N = 1; 5.2%, and f) lack of response: N = 2; 10.4%. When the cumulative doses were over than 19 mg/kg no systematization was possible due to the extreme variability of the responses. This change in the characteristics of the cardiovascular effects of the stimulation of the MRF is supposed to be due to a demasking effect of barbiturates which depressing reticular neurons allows a cardioacceleratory component of the response to become apparent.


Effect of ouabain on the renal response to furosemide. The aim of this work was to investigate whether the natriuretic effect of furosemide can be wholly explained by the inhibition of a ouabain-sensitive Cl transport in the thick ascending limb of Henle. For this purpose 6 dogs undergoing moderate saline diuresis received 100 mug ouabain/kg into the left renal artery followed by 2 mg furosemide/kg IV. Urine was collected from both kidneys and blood samples taken at regular intervals. Ouabain produced a unilateral increase in Na excretion and little change in CCR and water and K excretion. IV furosemide increased Na, K and water excretion in both kidneys. Since Na excretion in the left kidney was already exhanced by ouabain the increment was lesser than in the right kidney. As a result water and electrolyte excretion became similar in both kidneys. Although ouabain did not prevent the renal response to furosemide, the effects of both drugs were not additive. This suggests that in addition to the thick ascending limb, furosemide acts in some other tubular segment which is insensitive to ouabain. Since furosemide is known to also inhibit passive Cl movements, a second site of action could be in the thin ascending limb of Henle, which lacks any active transport mechanism but is highly permeable to Cl.


Erythropoietic restoring capacity of hematopoietic stem cells from liver of adult mice recovering from cyclophosphamide. A comparison of the erythropoietic restoring capacity of colony-forming units (CFU) found in the liver of adult mice recovering from a single high dose of cyclophosphamide (CY) with that of CFU derived from fetal liver and from adult bone marrow and spleen was made. In this respect CFU in the liver of adult mice differ notably from CFU in fetal liver but have a striking similarity with adult splenic CFU.


Extraction of biologically active erythropoietin from kidneys of carbon monoxide intoxicated mice. Carbon monoxide injected subcutaneously in mice produces a profound intoxication during a six hour-period. From 2 to 4 hr after the start of carbon monoxide (CO)-hypoxemia large amounts of erythropoietin (ESF) are released in the plasma. Renal extracts obtained at the same time showed higher specific activity than that found in the plasma extracts. No activity was recovered from liver and spleen extracts. Removal of the kidney abolishes totally the production of ESF.


Electrical activity of the olfactory bulb. Changes induced by lesions of contralateral olfactory areas. Control values for a) trains of sinusoidal waves, b) slow potentials and c) basal activity, were determined in rabbits whose olfactory bulbs (O.B.'s) had been implanted with chronic electrodes. One olfactory epithelium was destroyed in one group of animals and the activity of the contralateral O.B. was analyzed for 7 days. Then, the olfactory peduncle homolateral to the olfactory epithelium previously destroyed was sectioned and the bulbar activity recorded for 15 days. In another group of animals, the olfactory peduncle was sectioned and the activity of the contralateral O.B. analyzed similarly to the previous group. It was observed that no changes occurred in the contralateral O.B. after the destruction of the receptors. The sectioning of the olfactory peduncle produced a temporary increase in the amplitude and duration of the trains of sinusoidal waves from the contralateral O.B. and, only in few cases, in the amplitude of the slow potentials. These results were related to the various nervous structures that had been damaged during the operations.


Certificate of need: the Massachusetts experience. Certificate of Need legislation is one of several regulatory programs designed to control the allocation of health care delivery resources. This paper examines the Massachusetts experience with Certificate of Need, focusing on two major administrative law controversies--the extent of the regulatory agency's power to participate actively in the planning process, and the scope of review of agency decisions permitted under a non-judicial appeals mechanism. The study concludes that any Certificate of Need program may be strengthened by accurately defining the roles of the participants and by providing for safeguards within the system itself.


Health Care Institution Amendments to the National Labor Relations Act: an analysis. Ira M. Shepard, J.D. herein analyzes the legislative history and the substantive provisions of the 1974 Health Care Institution Amendments to the National Labor Relations Act. The Amendments bring private, non-profit health care institutions and their employees under the coverage of the NLRA, the goal of Congress being to reach a successful compromise of the public's right to receive uninterrupted health care; the health care institution's obligation to provide these services to the fullest extent possible; and the right of health care employees to have the same voice in the determination of their wages, hours, and working conditions accorded other workers under the NLRA.


Sudden infant death syndrome (SIDS): a burgeoning medicolegal problem. This Article presents a summary analysis of the administrative and statutory bases for the documented, prevalent mismanagement of Suddern Infant Death Syndrome (SIDS) cases by a majority of local death investigation agencies in the United States. Herein, Alan P. Cleveland, J.D. advances the theory that the unsatisfactory handling of cases of SIDS by the medicolegal community is the inevitable outgrowth of state laws that expressly require investigative agencies to approach a sudden, unexplained death from the direction of determining first whether or not a criminal act has occurred. In so doing, most statutorily mandated autopsy procedures are socially counterproductive since, in ignoring an acute medical need for supportive family counselling, they often constitute an insuperable obstacle to the effective management of SIDS as a public health problem. The author recommends that a requisite first step in implementing an SIDS management program at the state level is to insulate surviving family members form criminal investigative procedures by appropriate amendment of state laws governing local death investigation systems.


The "new" genetics: emerging medicolegal issues in the prenatal issues in the prenatal diagnosis of hereditary disorders. Major advances in prenatal genetic diagnosis have occurred in the past few years which pose difficult challenges to the law. This paper raises questions relative to family history taking, genetic counseling, carrier detection, amniocentesis, and prenatal genetic studies, and also raises questions with respect to the rights and responsibilities of the patient, the fetus, the physician, and society in light of such modern advances. Law reform often occurs only after prior harm to an individual, family or group. Perception and delineation of the most important issues in this area should serve to stimulate the development of medicolegal guidelines and corrective legislation prior to the occurrence of a genetic tragedy.


The interfaces of law and medicine.

The interfaces of law and medicine. The relationship between the legal and medical professions is improving, but many problems remain. There has been been and continues to be substantial growth in medicolegal organizations of various kinds. Better medicolegal investigative methods are being developed, and medicolegal teaching programs are on the increase. The two professions have worked together successfully on such problems as human heart transplantation and drug abuse. On the other hand, several problem areas continue to cause difficulty and friction, including medical experimentation on humans, the legal definition of death, abortion, euthanasia, and medical malpractice. The author calls on the existing medicolegal organizations to apply their expertise and influence to define and resolve these problems.


Law and medicine: myths and realities in the medical school classroom. One way to increase cooperation between the professions of law and medicine is to teach law in medical schools in a way that emphasizes methods of approaching problems, and seeks to dispel the major myths that doctors have about the law. In this Article, Professor George Annas presents an outline of a core course in legal medicine "tailor-made" for inclusion in the medical (and, with appropriate modifications, dental) school curriculum.


Hospital committee proceedings and reports: their legal status. This Article examines the legal status of hospital committee proceedings and reports, focusing on how they may be used in a medicolegal context. Specific topics dealt with include the hospital medical staff in legal perspective, the concept of institutional responsibility, liability considerations arising from committee work, and the discovery and admissiblity of committee records in litigation cases. The author concludes that the danger of committee members facing liability for their activities is slight and that the fear that these reports and proceedings may be subject to discovery or be admissible into evidence in subsequent litigation is remote because candid and conscientious evaluations of clinical practices within every institution are essential and, therefore, public policy must encourage such evaluations by maintaining the confidentiality of committee activities.


Role and functions of the International Pharmacopoeia. The role of a modern pharmacopoeia is to furnish quality specifications for drug substances and general requirements for dosage forms. The existence of such specifications and requirements is necessary for the proper functioning or regulatory control of drugs. Parmacopoeial requirements form a base for establishing quality requirements for individual pharmaceutical preparations in their final form. One hundred and forty independent countries are at present employing some 30 national and 3 regional pharmacopoeias. The aim of the international Pharmacopoeia issued by the World Health Organization as a recommendation, is to achieve a possibly wide global uniformity of quality specifications. The actual second edition of the International Pharmacopoeia was published in 1967 followed by a supplement in 1971. The Expert Committee on Specifications for Pharmaceutical Preparations, which is the body established by the World Health Organization to advise on quality specifications for drugs, during its 25th meeting, held in November 1974, recommended that the new edition of the International Pharmacopoeia should primarily include: -specifications for raw material comprising active and inactive ingredients used in pharmaceutical products; -general methods and tests necessary to support such specifications. Work on the new edition of the International Pharmacopoeia will comprise the revision of existing specifications and requirements, establishing specifications for new pharmaceutical substances, as well as establishing chemical reference substances, necessary to support such specifications. The actual procedure foresees appropriate consultations among the members of the WHO Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations. Extensive consultations with pharmacopoeia commissions are taking place to achieve a possibly high degree of unanimity on a global scale towards the quality requirements for pharmaceutical substances.


[Role and functions of the European Pharmacopoeia]. Following an agreement between the Common Market on one side and the Partial Agreement of the Council of Europe on the other, it was decided in Rome in April 1963 to compile gradually a Pharmacopeia to be called "European", which would be mandatory in Germany, Belgium, France, Italy, Luxembourg, the Netherlands and the United Kingdom. Switzerland joined the group in 1964. A Commission entrusted with full powers was created: each country is represented on it by a three-member delegation. It started its work in 1964, with prof. Marini-Bettolo as president. The work of the Commission was planned by approximately 150 experts, subdivided into about 15 groups of specialists in the various fields. The first volume was published in 1969, the second in 1971, followed by a supplement in 1973; the third volume was supposed to appear in April 1975 with another supplement planned for the end of 1975. The collection of these volumes will represent the first edition of the European Pharmacopeia and will consist of about 1,500 pages; half of these will cover general rules and the rest will include about 320 monographs. With the addition of Denmark and Ireland, which joined the Common Market at a later date, the European Pharmacopeia will be in force in an area with a population of 260 million. Any country belonging to the Council of Europe is entitled to join the Convention and several countries have already expressed the desire to do so.


Role and functions of the Nordic Pharmacopoeia. It was proposed as early as in 1860 that a common pharmacopoeia should be worked out in the Nordic countries but it took more than a hundred years before such a pharmacopoeia was published and put into force. Ever since that early date the Nordic countries have, however, been striving for common regulations in the drug field with more or less intensity. The accomplishment of the common pharmacopoeia is therefore to be regarded only as a milestone on the long way to complete conformity of the different national drug regulations. The Nordic Pharmacopoeia has definitely broken through the borderlines of the earlier national pharmacopoeias, which were designed for the activities of the pharmacies, and has obtained recognition as a work on drug standards possible to apply in the manufacture and control of drugs no matter where they are produced or controlled. The Nordic Pharmacopoeia thus has wider functions and a greater responsibility than the earlier pharmacopoeias. This depends partly on the pharmacopoeia itself, partly on the development in the field of drug control. On the other hand the Nordic Pharmacopoeia has left some of the tasks of the earlier pharmacopoeias to different national formularies, manuals and other sources of information. This applies especially to galenical preparations. As expected the Nordic Pharmacopoeia has facilitated drug trade in the Nordic countries to a certain extent and it is no doubt of greatest value in the different control activities of the national health authorities. It is also a guide-book and a reference work for manufacturers and control laboratories of different kinds. But this is what it should be, what it is intended to serve as. In addition to that the Nordic Pharmacopoeia has played an essential role in many other respects; not least as initiator of different progressive work and drawer of guide-lines for future development in the drug field.


Role and function of the "Compendium Medicamentorum". The increase of the co-operation among countries of Council for Mutual Economic Aid (CMEA = COMECON) in the area of drug production has forced these countries to elaborate a collection of unified quality specifications and test procedures for pharmaceutical preparations: the Compendium Medicamentorum (CM). The CM is in hands of the Expert Panel on Drug Standardization, the president of which is prof. J. Richter, head of the Institute for Drugs and Drug Control of the GDR, Berlin. It is issued in Akademie-Verlag Berlin in russian and german. The aim of the CM is to enable the multilateral contact among CMEA countries, above all on the basis of the specialization of drug production.


[The problem of selection of monographs]. The problem of selecting the monographs to be inserted in a pharmacopoeia does not actually exist on a national, but only on an international scale, as was realized during the compilation of the European Pharmacopoeia. The problems encountered at that time are discussed here. The first section of this paper describes the various principles, ideas and interpretations that are at the root of the divergent opinions expressed by the delegations at Strasbourg in facing this problem each time it comes up for discussion. These divergent opinions are centered mainly on the following: -developments and progress in the pharmaceutical profession; -differences existing among various national legislations; -basic concepts concerning pharmacopoeias; -more or less broad interpretations of the obligations set down in the Convention and in the General Rules of the European Pharmacopoeia; that is, in essence, the principle of the possibility of opposing the monographs and the application of this principle. On the basis of these considerations, the author advances, and tries to justify, the criteria that, according to him, should be adopted in order to arrive at common rules. The criteria are the following: -therapeutic interest, provided it is medically confirmed; -importance of usage, under the four specific aspects to be considered. On the subject of a new substance: -necessity that the product be produced by several manufacturers; there are three cases, where the rules to be observed have not been obeyed by all concerned. -obligation that the product be marketed in bulk, except in cases specifically established. While making this report, the author intends to emphasize the fact that a great effort is needed in order to narrow the gap separating certain points of view.


Pharmacopoeia as a pharmaceutical code for public health authorities. In every country drug control depends on the existence of technical norms which are generally represented by the Pharmacopoeia. In effects, since the beginning of XIII century, when the profession of pharmacist was for the first time established by law, pharmacopoeias have had not only the purpose of supplying the composition and the preparation of drugs, but also to establish and enforce the quality of the drugs. In the present times the pharmacopoeias adopted throughout the world by the different countries are intended mainly as a codex of specifications for the control of drug quality. These pharmacopoeias are national, regional and international. Nevertheless several difficulties can be found in the use of the pharmacopoeias for control of drugs, owing to the fact that not all the drugs, allowed and in therapeutical use are included in pharmacopoeias, and also because, in some cases, the final control is not sufficient to establish drug quality especially in the case of biological preparations. The existence of a Formulary or "Codex", beyond pharmacopoeia, may be of help for the control authorities but generally is not sufficient. Some suggestions are made in order to envisage a modern pharmacopoeia, considered as a dynamic collection of specifications of drug quality, always up to date, and thus in condition to fulfil its task for the need of the drug control by the health authorities in the aim of a better protection of public health.


Pharmacopoeia as quality codex for the manufacturers. Three are the basic features of a medicine legally introduced on the market: efficacy, safety and quality. With regarding to drugs listed in a national or international pharmacopoeia, the ratio between efficacy and safety, within the range of dosage established by the codex, must be considered as official by the industry. As far as quality is concerned, the pharmacopoeia plays a fundamental role in establishing methods of analysis and technical control intended as official reference in case of controversy. The quality of drugs, pharmaceutical adjuvants or preparations listed in a modern pharmacopoeia must be considered by the industry as the minimum level of the acceptable standard for medical use, to ensure efficacy under proper storage conditions. In fact, the specifications are largely based upon suggestions made by manufacturers. Pharmaceutical specialties, being registered by Health Authorities following suitable documentation, do not have to be subjected to the standards established by the pharmacopoeia for new drugs or formulation adjuvants. The constant effort of the manufacturers to minimize risks leads to optimum quality levels, considering that samples used for control by the Health Authorities are usually picked from commercial packages containing a small number of units. To ensure statistical compliance of every sample with official pharmacopoeial standards, manufacturers are forced to exercise the highest care in every process of production and packaging. There cannot possibly be a guarantee that every single unit at the consumer's disposal will actually comply with the quality level established by a modern pharmacopoeia. Optimum quality level in every package of medical products can be achieved by following the "Good Manufacturing Practice" sponsored by the WHO; this goal requires skilled people and sophisticated equipment. The practice of quality control as an essential part of the manufacturing process in a wide range of pharmaceuticals, provides an excellent experience that may be useful to the pharmacopoeial commissions. Therefore a closer co-operation between health officials and industry's experts must be considered the best way to improve the specifications, to speed-up the revision of monographs and to collect reports on stability tests. The part of a modern pharmacopoeia, devoted to tests and standards appears today as the most important for the pharmaceutical industry because, when a controversy arises about drugs, the official methods established by the pharmacopoeia play a fundamental role in the enforcement of law. The task of compiling each new edition of a modern pharmacopoeia is becoming increasingly difficult; to speed revision any time a problem arises, the revision committees may seek advice from the numerous experts of the pharmaceutical industry thus achieving a most profitable collaboration.


Relations between sales authorisation and pharmacopoeia. At a time when the production and distribution of drugs and drug products is no longer confined within the national boundaries of particular countries, many thoughtful people are concerning themselves with the idea of standardisation of quality control procedures and specifications. For medicines currently marketed in different countries, a multitude of standards and specifications for both the raw materials and finished products exists. Plans for the regionalisation of drug standards have been put into operation but realistic estimates of progress agree that it will be measured and dignified. In one area there is the possibility for earlier action in reaching agreement on adequate specifications. The process of registration of a new drug substance for the first time presents an opportunity to make known to drug regulation authorities, academic and industrial pharmaceutical specialists, and other interested parties, the qualities and characteristics of the newly proposed agent and its dosage forms. A wide range of information will be needed on the chemical, physical, biological and physicochemical properties of the dosage forms as well as the raw materials of the active and inactive ingredients. Many of these requirements have already been described (3). There may be apprehension that the disclosure of some of this information could imperil the confidentiality of certain manufacturing processes or trade secrets, and adequate steps would be demanded to prevent this happening. The promulgation of a standard, at or shortly after the time of registration, should have been preceded by experimental tests, in the laboratories of the Authority, to verify the robustness of the analytical methodology. In some cases more extensive confirmation by collaborative study may be warranted. The elaboration of these concepts will be presented and examples brought forward of problems that have occurred in the past, and means to prevent them in the future.


Information chapters in pharmacopoeias.

Information chapters in pharmacopoeias. Pharmacopoeias have been established by governmental authorities to serve three primary purposes: 1) to compile a select list of currently utilized drugs, including the most efficient forms for their application; 2) to distinguish these articles by convenient and definite names; and 3) to publish objective standards and analytical methods suitable for testing the integrity of commercially available preparations. In addition, some pharmacopoeias also offer informational text intended to instruct pharmacists on the compounding, use, storage and labeling of drugs; to advise physicians about dosage regimens and preferred modes of administration; to counsel producers about good manufacturing practices, and to edify drug analysts by explaining the theories underlying methods employed in compendial tests and assays. Examples of informational chapters in USP XIX are those on Pharmaceutical Dosage Forms, Stability Considerations in Dispensing Practice, and Sterilization. Because of the official status of national pharmacopoeias and their use as regulatory instruments in drug control, pharmacopoeial text intended merely for the information of the reader should be identified as such, and should be separated and distinguished from the mandatory, legally enforceable requirements.


[General methods and specifications].

[General methods and specifications]. The reasons are explained why general methods are described in pharmacopeias. With the help of examples taken from European Pharmacopeias, the United States Pharmacopeia, and the International Pharmacopeia, the author reports the general chemical and physical methods that were used in compiling these pharmacopeias. The description of these general methods, and particularly of the instruments, goes often beyond the actual bounds of a pharmacopeia and may fulfill a didactic function. The methods used in the various pharmacopeias, especially the chemical ones, are here compared and subjected to the author's critical analysis. The author explains also that technical progress in the analytical field should not be hampered by the rigidity of the pharmacopeia's rules; this can be easily avoided by resorting to alternate methods.


The role of the pharmacopoeia in the control of pharmaceutical preparations. Pharmacopoeia commissions have a responsibility to protect the public in the sphere of medicines against error, ignorance or fraud. This responsibility is discharged by defining the standards with which the substance shall comply when offered for medicinal use and the methods by which compliance will be adjudged. The pharmacopoeia is one instrument among several which have been developed by society for ensuring safety in the use of medicines. Others are: -control by legislation over the training and practice of pharmacists; -limitation of the supply of certain medicines to doctors' prescriptions; -the limitation of sale to pharmacists (in most European countries) of all but a small proportion of medicines; -inspection for licensing of premises in which medicines are manufactured; -evaluation by expert committees of the formulations proposed by manufacturers and registration of such formulations for sale; -analysis of samples of medicines on the market. Many pharmacopoeias, including those having the widest territoral application, include monographs on pharmaceutical preparations. Others restrict their interest to the substances used as medicines. The arguments in support of these policies have been examined. It is claimed that the pharmacopoeia has a valid regulatory function to perform which is not incompatible with but complementary to that of the registration system.


Use of reference substances in pharmacopoeia specifications. The use of reference substances in pharmacopoeial specifications has increased enormously during the last decade. In many cases the specification printed in a pharmacopoeia is worthless unless it is supported by a reference substance whose authenticity and integrity has been established beyond doubt and which is maintained and distributed in a satisfactory manner. The types of test procedure for which reference substances might be considered necessary will be reviewed and the criteria which such substances should be required to meet will be considered. Problems associated with the establishment, maintenance and distribution of reference substances for pharmacopoeial purposes will also be reviewed and the need for greater international collaboration in this field will be stressed.


Biological standards and pharmacopoeias. The use of standards in the control of biological substances is of particular importance because the potency of such substances cannot be adequately determined by physical or chemical means. For these substances, therefore, it is necessary to compare the activity or potency of a given quantity with that of a similar quantity of a standard or reference preparation to which a unitage has been assigned. In order to eliminate as far as possible the inherent variables in biological tests, especially in tests involving animals, the comparison between the standard and the unknown must be made in a single test. Furthermore it is essential that the biological activity of the standard has the same properties as those products for which the standard is used as a control. The master standards are the International Standards held by the World Health Organization and it is necessary to establish European or National Standards calibrated in International Units in order to conserve the stocks of the master standards. Criteria for the quality of preparations suitable as standards will be considered and some examples of their use will be presented.


Effects of pentobarbitone and decerebration on the clonidine-induced circulatory changes. Clonidine 5 and 15 mug/kg i.v. was given to conscious rats, to rats under pentobarbitone anaesthesia and to decerebrated rats. Clonidine 100 mug/kg was given to conscious and to decerebrated rats. Blood pressure and heart rate were recorded via indwelling catheters. The low dose of clonidine gave virtually no response in the conscious rats but produced hypotension and bradycardia in decerebrated and in anaesthetized rats. After clonidine 15 mug/kg the blood pressure of decerebrated rats decreased further, while conscious and anaesthetized rats showed a hypertensive response. The basal blood pressure and heart rate were significantly higher in the decerebrated rats than in the conscious rats. After the highest dose of clonidine, however, the blood pressure of the decerebrated rats decreased below the basal level of the conscious rats and the blood pressure of the conscious rats increased above the basal level of the decerebrated rats. The results suggest that the hypotensive response is caused by a mechanism located in the medulla oblongata. At higher concentrations clonidine may elicit a hypertensive effect by activating suprabulbar centers. The importance of this suprabulbar effect is attenuated by pentobarbitone anaesthesia.


Effects of E prostaglandins, diphenoxylate and morphine on intestinal motility in vivo. The mechanism of the gastrointestinal motility effects of diphenoxylate and morphine in preventing E prostaglandin (PG) diarrhea was investigated. Duodenal motility studies were conducted in the anesthetized dog. Two contractile force transducers were oriented to record contractions from both the circular and longitudinal muscles. In some experiments the basic electrical rhythm (BER) was also recorded. Blood pressure was monitored from the femoral artery and drug injections were made in the femoral vein. Diphenoxylate shared with morphine the capacity to stimulate circular muscle contractions which correlated with the appearance of spike potentials on the BER. Prostaglandin E1 methyl ester (PGE1ME) showed marked relaxation of the circular muscle and abolishment of spike potentials. PGE1ME also blocked the stimulatory effects of diphenoxylate and morphine on the circular muscle. PGE1ME and PGE2 were found to be equally potent in producing diarrhea in mice. Diphenoxylate and morphine were found to be equally potent in inhibiting PG's diarrhea. These studies suggest that the constipating actions of diphenoxylate and morphine are a consequence of the increased circular muscle activity of the intestine.


Acetylcholinesterase-containing neurons in the neostriatum and substantia nigra revealed after punctate intracerebral injection of di-isopropylfluorophosphate. Infusion of 1 mul arachis oil containing 1.5 mug bis-(1 -methylethyl)phosphorofluoridate (di-isopropylfluorophosphate: DFP) into the caudate--putamen nucleus and substantia nigra of rats produced a considerable reduction of histochemical staining for acetylcholinesterase (AChE) in these two brain regions 30--120 min after injection. Thereafter, regeneration of AChE occurred within the zone of DFP effect. These new stores of AChE were associated with discrete neuronal perikarya and their processes. Intracerebral DFP administration had little or no histochemically detectable effect on NADH-diaphorase. Thionin staining was similarly unaffected. The results with punctate intracerebral application of DFP were replicated by intramuscular injection of 1.5 mg/kg DFP. Although the significance of dopaminergic--cholinergic interactions in the neostriatum could not be elucidated on the basis of these histochemical data, the thesis was advanced that dopamine neurons in the pars compacta of the substantia nigra also contained AChE, possibly to inactivate acetylcholine released from cholinergic fibers afferent to this neural structure.


Studies on the mechanism of the protective and antidotal actions of diazepam in organophosphate poisoning. The effect of diazepam on soman-induced bradycardia and respiratory depression in rabbits has been investigated. Diazepam prevents the bradycardia produced by soman in conscious rabbits. Although atropine will reverse the respiratory depression produced by soman in anesthetized rabbits, diazepam enhances the depression and renders rabbits less susceptible to this action of atropine.


Excitatory and depressant effects of dieldrin and aldrin-transdiol in the spinal cord of the toad (Xenopus laevis). An investigation was made into the action of the insecticide dieldrin and one of its metabolites, aldrin-transdio, on the isolated spinal cord of the toad, Xenopus laevis. Conventional electrophysiological techniques were used for stimulating and recording of dorsal and ventral spinal roots. An augmentation of polysynaptic reflex activity along with a marked reduction of orthodromic postsynaptic inhibition could be demonstrated in preparations isolated from dieldrin-poisoned animals. However, application of dieldrin to the isolated spinal cord failed to produce any significant effect. Application of aldrin-transdiol, on the other hand, caused a potentiation of spinal reflex activity and an increase in spontaneous activity of ventral and dorsal roots. Aldrin-transdiol also produced a marked reduction of spinal inhibitory mechanisms. The excitatory effects of aldrin-transdiol were followed by a strong depressant action on spinal excitability.


Role of the ventral surface of the brain stem in the hypotensive action of clonidine. The areas S of the ventral surface of the brain stem and the immediately surrounding zone were superficially destroyed by the means of electro-coagulation, in 14 cats. This destruction produced a drop in blood pressure, which was transient in 9 and definitive in 4 animals; in one cat only the arterial pressure did not change after the destruction. In 6 animals which have been sham-operated, clonidine (15 mug/kg, i.v.) always induced a marked fall in blood pressure whereas in 10 animals which had maintained or recovered a normal blood pressure after the destruction of the area S, clonidine (15 mug/kg) injected intravenously no longer produced any decrease of the arterial pressure. These results suggest that the integrity of the areas S is necessary for the development of the hypotensive action of clonidine. This hypotensive drug may act, at least at the level of the ventral surface of the brain stem, through inhibition of a vasopressive structure.


d-Amphetamine as a releaser or reuptake inhibitor of biogenic amines in synaptosomes. The effect of d-amphetamine on the release of tritiated norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) was analyzed in synaptosomes from different brain area. 3H-NE release was unaffected in the hypothalamus, a region which is rich in noradrenergic terminals, and in cerebellum and pons-medulla, but was substantially increased in corpus striatum and moderately in cerebral cortex. 3H-DA release was strongly enhanced in corpus striatum, a region rich in dopaminergic terminals, substantially increased in cerebral cortex, and slightly increased in the hypothalamus. Since the regional pattern of d-amphetamine-stimulated release was similar with the two catecholamines, but the stimulation was greater with 3H-DA than with 3H-NE, and was more evident in areas richer in dopaminergic terminals, it is suggested that the drug can release 3H-DA or artificially stored 3H-NE from dopaminergic terminals, but not 3H-NE, from noradrenergic terminals. d-Amphetamine also seems capable of releasing 3H-5-HT from serotoninergic terminals. In contrast with the two catecholamines, 3H-5-HT release was more enhanced in cerebral cortex than in corpus striatum.


Modifications of canine vascular smooth muscle responses to dihydroergotamine by endogenous prostaglandin synthesis. Changes in tension were monitored isometrically on spiral strips from canine saphenous veins and arteries. Dihydroergotamine (DHE) (1.7 X 10(-8) M) contracted vein strips about 30% more strongly than arterial strips when the effects were compared to a standard noradrenaline (NA) response. Phentolamine (3.6 X 10(-6) M) reduced the DHE-induced contraction in veins by about 30% and in arteries by about 10%. Indomethacin (2.8 X 10(-7) M) reduced DHE-induced contractions in veins by about 60% but enhanced the DHE effects in the arteries. When arachidonic acid (AA) was added to stimulated vascular strips it caused further contractions in veins but relaxation in arteries. Both effects were inhibited after indomethacin. In veins AA was significantly more effective in the presence of DHE as compared to controls, to NA- or to KCl-stimulated strips. In arteries AA showed the strongest relaxant activity in the presence of NA. Low doses of prostaglandin E2, however, relaxed both venous and arterial strips. The results suggest that contraction of canine vascular smooth muscle is associated with synthesis of a prostaglandin-like substance of substances having constrictor activity in veins but relaxant activity in arteries and that in venous smooth muscle cells the formation of this material is enhanced by dihydroergotamine.


Differential blockade of guinea-pig atrial rate and force responses to (--)-noradrenaline by practolol - an uptake phenomenon. The relative blockade of rate and force responses of guinea-pig isolated atria to catecholamines by practolol was compared. pA2 determinations revealed that with (--)-noradrenaline as the agonist, practolol was more effective in antagonizing rate (pA2, 6.99) than force (pA2, 6.44). This difference was absent in either atria from reserpinized animals incubated with phenoxybenzamine and tropolone or atria incubated with cocaine. Similarly, when (--)-isoprenaline was the agonist, force and rate pA2 values were identical, suggesting that rate and force beta1-adrenoceptors do not differ. The preferential blockade of (--)-noradrenaline-induced rate responses in untreated atria was attributed to the operation of a saturable neuronal uptake mechanism which differs between left and right atria. To avoid high (--)-noradrenaline concentrations encountered during pA2 determinations, the % reduction of responses to single doses of (--)-noradrenaline by practolol were measured in untreated atria. Far from confirming the lack of receptor differentiation indicated by the pA2 determinations, this study revealed force to be more practolol sensitive. The relative merits of the two methods are discussed in an attempt to resolve the question whether rate and force beta1-adrenoceptors differ.


Acute morphine effects on regional brain amines, growth hormone and corticosterone. Morphine sulfate was injected in doses of 5, 10 and 20 mg/kg i.p. to male rats at 3:00 pm. At 4:00 pm, the rats were decapitated and norepinephrine, dopamine and serotonin levels were measured in seven brain regions (cortex, striatum septum, amygdala, hypothalamus, midbrain and pons). Growth hormone and corticosterone levels were assayed from plasma. Saline-injected animals served as controls. The only significant change in brain amine level was an increase in striatal dopamine which occurred after 5 mg/kg morphine. 20 mg/kg caused an increase in plasma corticosterone; lower doses were ineffective. The dose for maximum growth hormone release was 10 mg/kg, although all three doses were effective. It was not possible to relate changes in brain amine levels with these hormonal responses to acute morphine administration.


Effects of ethanol on the secretion and mucosal blood flow of a denervated gastric pouch in the dog. Mucosal secretion and blood flow of a Heidenhain pouch were measured in dogs after orally administered ethanol at doses from 0.25 to 2 g/kg of body weight. Under these conditions, the volume, free and total acidity of the gastric juice as well as mucosal blood flow increased linearly with the dose up to 1 g/kg. In all cases volume secreted and acidity chanm the other parameters and could not be correlated with blood flow. The influence of gastrin and the modification of membrane permeability are discussed with regard to these data.


The influence of metiamide on ouabain cardiotoxicity. The effect of metiamide on the cardiotoxicity produced by ouabain was studied in pentobarbital-anesthetized cats. The onset of ouabain-induced ventricular tachycardia and fibrillation was significantly delayed in cats treated with metiamide as compared with cats that did not receive metiamide. Although the mechanism by which metiamide inhibits ouabain toxicity is speculative, the data suggest that histamine H2-receptor blocking agents may be useful as anti-arrhythmic drugs in digitalis cardiotoxicity.


Selective impairment of atrioventricular conduction by 2-(2-pyridyl)-ethylamine and 2-(2-thiazolyl)-ethylamine, two histamine H1-receptor agonists. To further characterize the receptor mediating histamine-induced impairment of atrioventricular conduction, the effects of two selective histamine H1-receptor agonists, 2-(2-pyridyl)-ethylamine (PEA) and 2-(2-thiazolyl)-ethylamine (ThEA), were investigated using the isolated guinea pig heart. These effects were compared with those of histamine and other selective agonists. PEA and ThEA produced a weak stimulation of cardiac rate and contractility; however, they produced a marked prolongation of atrioventricular conduction. The orders of relative potencies observed substantiate the hypothesis that H2-receptors mediate the positive inotropic and chronotropic effects and H1-receptors mediate the negative dromotropic effect of histamine.


Chronic morphine effects on regional brain amines, growth hormone and corticosterone. This study was designed to examine the relationship between regional levels of brain amines (norepinephrine, NE; dopamine, DA; serotonin, 5-HT) and plasma hormone levels (corticosterone, CS; growth hormone, GH) in rats following chronic morphine administration (40 mg/kg twice daily). Rats were sacrificed at 4:00 pm (and the final injection was made at 9:00 am). Amine and hormone levels were determined after 1, 2 and 6 weeks of daily injections of morphine. Increased plasma CS was found after 1 and 2 weeks of injections and decreased GH levels were present after 2 and 6 weeks. In another 2 week study when morphine was administered 1 hr before sacrifice, plasma levels of CS were decreased and GH increased. Serotonin levels were decreased in all brain regions after 2 and 6 weeks of morphine administration and DA was decreased in the amygdala after 6 weeks. In 2 weeks treated rats injected 1 hr before sacrifice 5-HT levels had returned to control levels and DA was decreased. Inverse correlations were found to relate with 5-HT and CS levels, CS with GH levels and GH with brain DA. A direct correlation was present in GH and 5-HT levels.


A new method for evaluating antitussives in cats using an electrode-cannula. An emplaced laryngo-tracheal electrode-cannula was employed to induce and to measure cough in cats anesthetized with either sodium pentobarbital or Dial--urethane. Carbetapentane citrate, codeine sulfate and dextromethorphan hydrobromide were tested for antitussive action by this method. Relative antitussive potency obtained in order of decreasing effectiveness was dextromethorphan hydrobromide, codeine sulfate and carbetapentane citrate.


Evidence for a cortical locus for the stimulus effect of nicotine. This study investigated the stimulus properties of nicotine in the rat with the objective of determining the time course of the nicotine-produced interoceptive cue and its relationship to specific brain levels of the drug. The behavioral task employed was shock-escape in a T-maze apparatus. After the injection of nicotine entrance into the nicotine-correct arm of the T-maze resulted in termination of a 0.6 mA shock. When saline was administered, entrance into the opposite arm was rewarded by termination of shock. A high level of discrimination between nicotine and saline was obtained and the degree of discrimination was observed to decrease as the length of time period between nicotine administration and the test of discrimination was increased. This decline in discrimination was closely correlated with the decline in brain levels of nicotine in the cortex suggesting that the stimulus effect of nicotine is directly related to the concentration of nicotine in the cortex.


[Determination of serum digoxin concentrations using radioimmunoassay. Evaluation and application of the analytical method]. The different laboratory technich for the determination of digoxin serum concentrations are analysed. Special emphasis is placed on the radioimmunoassay technic. The advantages and disadvantages of this technic are studied and the standard curves obtained in our determinations (n=39) are analysed. It can be seen that they can be reproduced in all cases with a high degree of similarity. The possible causes of error in this microtechnic are also analysed and a modification in the decanting fase, with which the number of repetitions in our laboratory has decreased, is suggested. Finally the criteria for the actual evaluation of the seric digoxin levels used in our laboratory are described and new possibilities in pharmacological investigation by this technic are mentioned.


[Postoperative evaluation of Carpentier's mitral rings]. 38 patients with Carpentier's ring inserted in the mitral position at surgery, are studied. The grade of the pre and postoperatory mitral murmur is correlated and compared with the radiographic size of the heart and left auricle as well as the pre and postoperatory angiocardiographic study. Only 3 (7'8%) of the 38 patients presented significant elevation of the pulmonary artery sistolic pressure together with important angiographic regurgitation. These three patients had to be operated on again, 60'52% did not present murmurs on these were grade I murmurs, while 76'32% did not present mitral reguritation. Only 8 of 14 patients with grade II sistole murmur in the postoperative period had grade II regurgitation. This no correlation was observed between the intensity of the murmur and the grade of angiocardiographic mitral regurgitation. We conclude that Carpentier's ring restores the mitral valve function to normal in the majority of cases and the angiocardiographic results are favorable.


[Corneal ulcer as a complication of general anesthesia]. The frequency of exposure queratitis over 177 patients in extracardiac surgery is determinate. Differents prophilactic methods are discussed. The best results are obtained with palpebral occlussion, and preious instillation of methulose solution.


[Diagnostic usefulness of the LUNDH test in the functional examination of the exocrine pancreas]. We have revised the diagnostic utility of the "LUNDH TEST" in chronic exocrine pancreatic disease. The results obtained by the different authors consulted suggest, that it is likely to be more useful in clinical practice because of its practical advantages.


[Chordoid sarcoma of the femur. Electronic and optical microscopy study of a case]. Areas of chordoma and chondrosarcoma have been reported extensively in the same tumoral mass located in espheno-palatine region. The same association in long bones of the extremities have been reported recently, with the name of "chordoide sarcoma", "parachordoma" or "chondroid chordoma". We present a case of "chordoid sarcoma". The cells of this tumor have morphologic features of chordoma and chondrosarcoma in both the optical and ultrastructural study. However some morphological, radiological and clinical aspects, suggest that this tumor possesses characteristics that define it as a separate entity.


[Clinical evaluation of amiodarone hydrochloride as an anti-arrhythmia agent]. 15 patients with ventricular and supraventricular arrhythmias treated with Amiodarone hydrochloride via oral were studied. The results obtained show that in 86'6% of the cases the arrhythmia disappeared immediately, in 6'6% the arrhythmia disappeared late and in only one case the arrhythmia persisted. Statistical significance was found in the reduction of cardiac frequency as well as in the corrected QT interval for the frequency. The latter is an indirect consequence of the mode of action of the drug. The only side effect observed was the appearance of corneal opacification. It was demonstrated that this side effect is negligible when low doses which are equally effective are administered. The conclusion that Amiodarone is an excellent oral antiarrhythmic drug is reached. A daily dose of 400 mg during the first 20 days of each month with a rest of 10 days is recommended. In this way, the corneal opacification is minimal or nil. The possibility that the association of the drug with Quinidine could be effective in maintaining sinus rhythm post D.C. is suggested.


[Initial results in the treatment of pituitary dwarfism using growth hormone]. Ten cases out of 25 patients with stunted growth were proved to have total or parcial deficiency of human growth hormone. Inmunoradioassay levels were detected by stimulation with insulinic hypogycemia. Throughout a period of observation of 3 up to 12 months, they were treated with H.G.H. in proper doses and a favourable response were recorded in all of them, with statural increments ranging from 138% up to 500%. The responses were evaluated by mathematical analysis of the slopes of growth. Therapeutic results obtained from the cases of other different etiologies are also presented.


[Analgesic and neuroendocrinal response in heart surgery: II. Adreno-medullary response]. In fifty-five patients who had undergone open-heart surgery, plasma levels of catecholamines and urinary excretion of adrenalin and noradrenalin were studied. We have divided the patients in three groups, according to the analgesic administered during the operation: group A, patients anesthesized with Pentazocina; group B, with Morfine; group C with Fentanest. By determining these catecholamate levels, we have been able to show an increase in sympathetic activity in all three groups. However, during the peroperative period. Fentanest gave the smallest increase and Pentazocina the largest. The more prolonged analgesia of Morfine manifested itself during the post-operative period in a smaller elimination of adrenalin. We then studied the influence of Fentathinil on the sympatho adreno-medullar system. This recently-acquired analgesic, used in extracorporeal perfusion, grave a catecholamine elimination inferior to that found with Fentanest.


[Analgesics and neuroendocrine response in heart surgery: III. Metabolic aspects]. A study done in 121  patients undergoing extracorporeal perfusion heart surgery for the correction of valvular cardiopathies. In a first stage, we evaluated, in 77 patients, the influence of different analgesics on renal function, acid-base balance, glucemia and lactic acid. Afterwards we completed our observation with analysis of insulin in 44 patients. We observed no important difference in glomerular filtration rate, urinary output per minute, acid-base equilibrium, or oxigenation, according to administration of the different analgesics. After the glucose overload which the extracorporeal perfusion imposes, we observed a better insulinic response and consequently a faster recuperation of normal levels of glucemia in patients who received Fentathienyl. The lowest response was obtained in patients anesthesized with Pentazocina. In view of these results we can affirm that analysis if the inter-relation between glucose and insulin is a good exponet for evaluation of the grade of analgesic protection, offered by a drug, against nociceptive stimuli triggered by surgery.


[Emergencies in internal medicine. General management in coma situations]. One of the most important aspects of the Emergency Medicine is the coma status as much as intra and extrahospitalary ambient. The interest of om study is based according the hardness of anamnesis, and the severity of symptoms induced by a altered conscience and by the need of a emergency therapy. This work summarized the general semiology of the patient in order to diagnostic, severity and etiology of the coma. The general behaviour therapeutic and some criterions about an irreversibility is also studied.


[Renal enzymology: experimental patterns and clinical symptoms]. This is a study of the changes, both in serum and urine, of a wide enzymatic pattern whose origin is well known to be the renal parenchyma (LDH, LAP, AP and lysozyme), in the course of two experimental prototype lesions induced in rats. Simultaneously a similar enzymatic study was carried out in a group of patients with nephropathies. The experimental lesions were a toxic tubular dysfunction using a mercury salt and an immune glomerulonephritis of two types: by foreign proteins (human albumin) and by rabbit nephrotoxic serum. In all these cases, there has been a convincing evidence, both direct (histological and inmunofluorescent) and indirect (marked proteinuria), of the induced lesions which were similar to the experimental models reported in the literature. The isolated enzymatic changes we observed in serum made us conceed less value to this pattern in comparison to the urinary one which proved to be more important in our study. It was possible to define the following urinary enzymatic patterns for each of the experimental groups: a) The acute toxic tubular dysfunction has a marked rise in the activity of LDH and LAP, and less so in the activity of AP and lysozyme. The retarded tubular lesion has a moderate rise in LAP. b) The glomerular lesion has a moderate and exclusive rise in the activity of LDH and LAP. Likewise the clear similarity between each experimental group and its clinical equivalent was demonstrated as refers to the urinary enzymatic pattern.


Immunotherapy of brain tumors.

Immunotherapy of brain tumors. The fight against neoplasia still represents a formidable challenge. At the present time the mechanism of cell-mediated immunity seems to offer the most promise. At the same time, one is cautioned by the implication that minimal cell-mediated responses threaten acceleration of tumor growth. Therefore, one is impressed with the need for investigation of these approaches in a model system prior to their application to humans. The data currently available suggest that when active tumor growth is present within the host, a state of immune deficiency exists: cell-mediated immune responses may be quantitatively deficient or this response may be negated by the presence of blocking factor in the serum. Efficient and effective immune responses imply adequate cell-mediated immunity and the absence of blocking factor activity within the serum.


Diagnosis and staging of ovarian carcinoma. The early diagnosis of ovarian carcinoma will await the development of adequate and accurate screening tests. In the interval prior to development of these tests, ovarian cancers will frequently be discovered in an advanced stage. Improved methods of treatment must be based on an adequate trial of existing treatment methods founded on an understanding of factors influencing survival. FIGO stage grouping identifies many of these factors and should be used to identify patients with similar characteristics. Other prognostic factors such as tumor grade, volume of residual disease and the presence of ascites must be recorded and considered in evaluating therapeutic trials. The adoption of a routine method for patient evaluation and exploration may enhance the amount of information available for each patient and assure that adequate information is available with which to place the pateint in FIGO stage and substage.


Results of chemotherapy as an adjunct to surgery in patients with localized ovarian cancer. One hundred and forty-nine patients with early cancer of the ovary who were suitable for postoperative radiotherapy were treated in a random study in which whole abdominal irradiation with additional treatment to the pelvis was compared to chemotherapy with Melphalan. The number of patients without evidence of disease at 2 yr seems to show that the results of treatment are similar. When the Berkson-Gage method of projection is used, however, the survival rate in stage I is apparently improved with irradiation; there is only a minor difference in the results of the two methods in stage II, and survival rates are improved for patients with stage III disease who were treated with chemotherapy. The complications of treatment in this study were quite different. Melphalan was well tolerated, and only one patient had serious bone marrow depression as a result of this treatment. All had prompt recovery of blood counts to normal after completing the prescribed chemotherapy. Seven patients treated by radiotherapy developed a small bowel injury which required surgery. Six of these were treated with irradiation to the pelvis followed by strip irradiation to the entire abdomen. This treatment plan probably gives excessive doses of irradiation to the pelvis and has been discontinued. This type of complication is much less frequent with the other sequence of treatment--strip irradiation to the whole abdomen and subsequent treatment to the pelvis. The cost to the patient of the two treatment programs varied considerably. Patients who received irradiation had the added expense of living in Houston for the duration of treatment. Patients treated with chemotherapy were often seen a 2- or 3-mo intervals and had their chemotherapy supervised by their personal physician.


Correlation between nerve terminal size and muscle fibers diameter in urodela extrinsic eye muscle. Extrinsic eye muscles of newts and salamanders were investigated by means of electron microscope. It was possible to distinguish two types of muscle fiber tonic-slow and twitch-fast acting ones. It was shown that mioneural junctions in both types of fibers differ in their ultrastructural organization because of lack of post-synaptic infoldings on the surface of slow tonic fibers. After "cholinesterase" "staining" it was possible to measure the surface of junctional area and correlate it with the diameter of particular muscle fiber. The results show a positive correlation.


Ultrastructure of the joint receptors of the tortoise (Testudo graeca. Emys orbicularis). The ultrastructure of the spray-like ramified encapsulated corpuscles with the primitive inner core from the joint capsules of the large limb joints of the tortoise (Testudo graeca and Emys orbicularis) was examined. Each of the branches of the receptor consists of three components. Through the middle of the receptor branche runs the nerve terminal, containing in the receptor matrix numerous mitochondria, tiny light vesicles and neurofilaments and neurotubules running in the axial way. The nerve terminal gives off on some places among the inner core cells tiny finger-like processes. The axon is surrounded by the inner core cells and their irregular plasmatic processes. Among the inner core cells and their irregular plasmatic processes there is a labyrinth of spaces, connected centrally with the periaxonal space and with the boundary space on the periphery. The inner core cells are covered on the surface, turning to the boundary space by the basal membrane. The inner core has a very primitive structure, it still lacks the typical lamellar structure. The capsule of the receptor is formed by flat cells, which surround the inner core in 1--3 layers. Between the capsule of the receptor and the inner core is the boundary space, containihg sporadical collagenous fibrils. The structure of the spray-like ramified encapsulated corpuscles with the primitive inner core from the joint capsules of the tortoise is analogous to the simple lamellar receptors from the skin of some reptiles (Von Düring 1973, 1974). The primitive structure of the inner core of the joint receptors in the tortoise reminds of the structure of the inner core of the developing simple (paciniform) corpuscles (Poláĉek and Halata 1970) and Pacinian corpuscles (Malinovský 1974). The observed nerve endings represent a primitive, early stage in phylogeny development of the lamellar mechanoreceptors.


The activity of some dehydrogenases and NADH and NADPH tetrazole reductases in the seminiferous epithelium of reserpinized white rats. Investigations on the effect of reserpine on the histochemical reactions to some dehydrogenases (succinic, lactic, glucose-6-phosphate dehydrogenase) as well as to NADH and NADPH tetrazole reductases in the seminiferous epithelium of white rats have been performed. A weakening of the dehydrogenase activities has been mainly observed in the young cells of seminal epithelium i, e. in spermatogone and spermatocytes. The changes in histoenzymatical reactions caused by reserpine may be the evidence of the inhibition of oxidation-reduction processes in the studied reproductive cells.


[Epidermal ball cells of the Ascaphus truei Stejneger (Amphibia, Salientia, Ascaphidae) larva: a biometric contribution]. 1. With regard to orientation the in the larva of Ascaphus truei characteristic excretory special cell (mucosa cell) was analysed in plain preparations of epidermis from head-trune in four test regions - praeoral, postoral, craniodorsal and post spiracle -, the speciman (stage 32 according to Gosner 1960) being investigated was excellently fixed, 50 cells at times biometrically are used therefore. The element with adequate safety must be called ball cell because of its shape. 2. Elements only praeoral present a more little volume dividing from other average (and more unimportant occurence of an outlet). In respect of frequency distribution of different big ball cells in whole material significant differences are missed. A definite size of volume independent of region is prefered. 3. In 69% of all ball cells being considered there is an outlet, the existence is not fixed to a definite volume of cell. Shape of opening in 88% is round to a little ellipsoidal, its size is reaching to 10% more than half of maximal flat plain of cells; with regard to regions differences are absent. 4. In 3 regions thereupon being investigated (postoral, craniodorsal and post spiracle) a real correlation exists between height of single ball cells and thickness of epidermis.


[Macrophagic and neuroglial reactions during axonic degeneration following transection of corpus callosum: a radioautographic and ultrastructural study]. The macrophagic and neuroglial reactions occurring in the corpus callosum following transection were studied by radioautography and electron microscopy in adult rats. The animals were killed at intervals ranging from two days to three months after operation. In the lesion itself and the immediately surrounding tissues an important proliferation of hematogenous macrophages was observed. Further away from the point of severance no significant numerical increase in the neuroglia could be noted. However the accumulation of glial filaments, lipid droplets and fragments of myelin sheath in the astrocytes seems to indicate that this type of cell plays a phagocytic role. As for the oligodendrocytes, there is no evidence of their participation in phagocytosis, whereas the microglia plays an important part. In the removal of the tissue debris the role and the origin of the macrophages and the microglia are discussed, as is the share of each type of cell in the phagocytic response depending on the extent of the lesion and the degree of axonal degeneration.


[Autoradiographic studies of the effect of desmethylimipramine (DMI, Pertofran) on the incorporation of 3H-leucine into the rat brain]. The influence of Desmethylimipramin (PertofranR) on the regional uptake of 3H-leucine in different areas of rat brains has been investigated with autoradiographic methods. Male rats were injected 10 m/kg Desmethylimipramin (DMI, PertofranR) i.m. and 1 hr later 8,33 mCi 3H-leucine i.p.. 1 and 7 hrs after application 3H-leucine the animals were sacrificed. Concentrations of silvergrains of 3H-leucine activity were countered under surface illumination in varions brain areas by means of strippingfilmautoradiograms. DMI markedly depressed the concentrations of 3H-leucine-activity in all layers of the parietal cortex after 8 hrs and the depression was greater with the increase of nerv- and gliacellvolumendensity of the layers. Within 2 hrs such an influence of DMI on 3H-leucine uptake could not be found. There was a smaller decrease of 3H-leucine incorporation after DMI applications in some layers of ammon's horn, dentate gyrus and cerebellum. Some further effects of DMI and IP (Imipramine) on components concerned with protein metabolism are discussed.


Structure of muscle fibres and motor end plates in extraocular muscles of the grass snake, Natrix natrix L. Six extraocular muscles of the grass snake, Natrix natrix L. together with their motor end plates were examined in the light and electron microscope, and the measurements of the diameter of muscle fibres and the area of their motor end plates were performed. Morphologically, two types of muscle fibres: tonic and red phase ones were distinguished. The former fibres, 2,3 to 14,5 mum in diameter possess single or multiple (up to five on a single fibre) "en grappe" motor end plates, without postsynaptic junctional folds. The latter fibres, 10...40 mum in diameter have single, "en plaque" motor end plates, with numerous postsynaptic junctional infoldings. The morphological features of muscle fibres and motor end plates as well as the correlation between the diameter of muscle fibres and the area of motor end plates are discussed.


[Quantitative histological studies of the variability of Golgi-impregnated cortical neurons in rats and cats]. Quantitative GOLGI-studies are executed about the layer V pyramidal neurons of the albino rat and the cat sensorimotor cortex. To this the length LP of the perikarya, the lenth LAD of the apical main dendrites, the spine-densities (spine-dendrite-quotients) DQ and the length NZ of the spineless ("nude") initial zone of the apical dendrites are measured in several male animals descending of the same litters. The neuronal signs are compared within the specimens of the same age. There are no statistical significant differences (level: 0,05) between these neuronal signs in all specimens of the same age and species. Relating to the examined marks of the cortical pyramids it is allowed to decline the hypothesis of variability between animals (rats or cats respectively) of the same age and sex. By this it is legal and sufficient to examine only one specimen (animal) for each stage of age in histological researches of ontogenetic series. This specimen is representative to this stage of evolution.


Scanning electron microscope observations of the rat subcommissural organ. Under the scanning electron microscope, the rat subcommissural organ (SCO) appears as an oval zone, rich in kinocilia and well delimited from the non-specific ependymal epithelium. This zone surrounds the cranial and posterior part of the mesencephalic canal's entrance. The ependymal cells of the SCO show coniform processes with microvilli and kinocilia. In contact with the apical pole of the peripheric SCO-ependymocytes lie scarce supraependymal axons. The Reissner's fiber is composed by the twining of the fibrillary structures emerging from the area of the SCO.


[Expermental contribution on the genesis of arteriosclerosis caused by hypertension]. Autoradiographic tests carried out on rats with renal hypertension using 3H-proline resulted in an acclerated collagen synthesis by media cells of aorta and coronary arteries. Electronmicroscopically an increased content of collagen fibers and an enrichment of ruthenium-red-positive substances in the extracellular space were found. The 35S-sulfate-incorporation in aorta and coronary arteries of animals with hypertension is also increased. These changes in the extracellular space of the vascular wall have an atherosclerosis promoting effect, probably caused by a distrubance of the permeability.


[Intratubular bodies in testicles of children]. Intratubular bodies are not rarely to be found in testicles of children. They are 5 times more freqlently noticed scrotal ones. These storages frequently cause a swelling of the tubuli seminiferi, which are thatswhy called as Ringtubuli. With the help of the fluorescence - and polarisation microscopy and the laser microspectrochemical analysis examinations of the delicate tissue tock place. Intratubular bodies predominant consist of protein and they have an amorphous fine structure.


The hypothalamo-hypophysial system in the ground squirrels, Citellus erythrogenys  Brandt and Citellus undulatus Pallas. I. Microanatomy and cytomorphology of the gomori-positive neurosecretory system with special reference to its state during hibernation. Microanatomy of the peptidergic hypothalamo-hypophysial neurosecretory system in the ground squirrels, C. erythrogenys and C. undulatus, is similar to that of other rodents, but differs in details. Bundles of neurosecretory fibres with single neurosecretory cells along their course connect the hypothalamic neurosecretory centers into the one system. The dorso-caudal portions of the NPV reach the level of the columna fornix. The NPO is a special indepedent formation and appears to have some specific functions in the HHNS. The infundibular recess penetrates deeply ihto the hypophysial stem, but does not reach the posterior pituitary. The glandular epithelium of the tuberal portions of the adenohypophysis surrounds the median eminence and a considerable part of the lateral surface of the tuber cinereum. Different functional types of neurosecretory cells reflect certain phases of their secretory cycle. Correlations between their size, structure and the content of NSM are found. A low activity of the HHNS is observed in both C. erythrogenys and C. undulatus during December-January. A higher activity of the HHNS in torpid C. undulatus than in C. erythrogenys is established. This correlates with a difference in deepness of torpor in C. erythrogenys and C. undulatus. An important role of the HHNS in hibernation, i.e. in realization of adaption of species in ontogenesis is suggested.


Nominal standard dose and tumor standard dose. Tables for radiation therapy planning and analysis. The method of treatment planning for a predetermined NSD value is described in detail using various example-problems. The Fret tables allow the finding of the total number of fractions needed (NT) for the NSD. This is done through the NSD/d ratio, d standing for the fractional dose in rad. The Fret tables are for 1 to 7 fractions-per-week treatment schedules. The corresponding value of T (elapsed days) are shown for different week days of the therapy initiation with their respective Fret and NSD/d values. The handling of the rest and multi-rest periods is described. A method of finding the NSD value for a treatment which has reached the maximum connective tissue tolerance is described, covering even the most complex treatment plans. Fret-tumor tables for NSD-tumor and their use are described by appropriate example-problems. Ret equivalent therapy planning through direct NSD methods (Fret tables) and through an approximation method (tables provided) is described and the usage demonstrated by example-problems. The usage of parallel opposing and multiple portals is evaluated in ret-dose values (peripheral radiobiologic effect) and certain conclusions drawn to guide the therapist. These show in which situations all portals per session should be used and when alternate portals are more beneficial. The effect of portal weighting is included in this analysis. The application of ELLIS' NSD method for radium therapy is described. If, in the future, any changes in the power factors of the present NSD formula become necessary, the basic handling of the NSD problems described in this manuscript will remain unchanged. The values obtained from these tables can then be adjusted by the appropriate factors.


The effect of glucose-1 phosphate calcium on the epiphyseal cartilage of the rat. Electron microscopic investigations were carried out on the proximal tibial epiphyseal cartilage of albino rats treated with 2 mg G-1-P-Ca daily for one and three weeks. The treatment--enhanced the secretory activity of the upper cells of the zone of maturing cartilage with a consequential enlargement of the Golgi region, depletion of secretory products, and an increase in the number of microtubuli. --In addition, the treatment increased the number of matrix vesicles in the extracellular space showing incipient calcification. This findings confirm the earlier light micriscopic observation of the calcification stimulating effect of G-1-P-Ca.


Effect of neonatal thymectomy on rabbit tonsils. An intensive lymphocyte migration takes place through the venules lined with high endothelium and situated in the extrafollicular areas of the tonsils. After thymectomy the migration of lymphocytes is less marked and in the areas surrounding the vessels lymphocyte depletion, connective tissue proliferation and a disintegration of the intimate contact between reticular cells and reticular fibres can be observed. A similar lymphocyte depletion appears also in the epithelium. Similarly as the deep cortical substance of the lymph nodes the extrafollicular regions of the tonsils belong to the peripheral lymphoid organs.


Structure of the osteocyte capsule in rats with hypervitaminosis-D and rickets. A histochemical and topo-optical study was made of the changes of the osteocyte capsule (OC) of the cortical and spongious bone layers of the tibia and vertebra of rats with hypervitaminosis-D and rickets. In hypervitaminosis-D the number of stained OCs was found to decrease. After treatment with high doses of vitamin D, a broadening of the OCs was noted in the area of demineralizing bone. Under the polarization microscope a decrease occurred in the proportion of birefringent OCs, more marked in birefringence than in staining. Since bone demineralization due to vitamin D was not followed by a rise in the number of osteoclasts, it is concluded that osteocytic activity has an important role in demineralization as shown by the broadened OC. In rachitic rats considerably fewer OC took the stain and showed birefringence than in the controls. Thus, alteration of the OC structure disturbs the nutrition of bone tissue and thereby aggravates the pathological process.


Selective 5-HT uptake by epithelial cells of the rat lung. Some of the epithelial cells of the rat lung take up serotonin from the circulation whereas the precursor of serotonin, 5--HTP, or histamine and histidine are not taken up. The observations raise the possibility that serotonin accumulation could be a manifestation of the general potentials of the entoderm.


Balbiani's vitelline body in the oocytes of vitellogenic and nonvitellogenic females of the domestic fowl: a correlative cytological and histochemical study. A cytological and histochemical study has been made of Balbiani's vitelline body in the oocytes of nonvitellogenic and vitellogenic females of the domestic fowl (Gallus domesticus), which consists of yolk nucleus, mitochondria, Golgi bodies and lipid bodies of diverse nature. The yolk nucleus consisting of RNA, protein and lipoprotein shows the greatest development and morphological complexity in the growing oocytes of vitellogenic females. Its possible significance has been discussed in relation, to the variable metabolism and hormonal status of the female during sexual maturation.


Scanning electron microscopic investigation of thermal damage of the teeth. Sound teeth were heated to 200 degrees C and 1300 degrees C and the gradually developing morphological changes have been studied. The cementum structure was destroyed at about 500 degrees C, the enamel structure between 700 and 900 degrees C, whereas dentine preserved its canalicular structure even after the inorganic salts had melted at 900 degrees to 1000 degrees C. At 1300 degrees C the mineral substances of the tooth were melting into atypical, globular formations. Scanning electron microscopic examination of dental residues damaged by high temperature seems valuable from forensic, criminological as well as anthropological aspects, since the origin of the finding can be determined, from a small fragment, the material can be identified with a tooth and conclusions can be drawn concerning the temperature inducing the damage.


Spontaneous reversibility of advanced toxic liver cirrhosis. The spontaneous restoration of liver cirrhosis induced by 6 and 9 month CC14 treatment has been studied. The OH-proline content of the liver stroma, the DNA content of the parenchyma, and the Co/DNA ratio were determined. Observations lasted for 4 months after completion of treatment. Cirrhosis developed after 6 month, CC14 administration was reversible in 3--4 months after the discontinuation of treatment; the normal stroma parenchyma ration had gradually normalized. Nine month treatment exhausted the capacity of the stroma for spontaneous recovery and the parenchyma regenerated to a lesser extent. Fibrosis remained practically irreversible 4 months after CC14 administration.


Splenic lymphocytic response to acute haemolysis. Adult albino rats, weighting 150--250 g, were administered a sublethal dose of copper sulphate, phenylhydrazine and anti-rat erythrocyta 1 serum by the intracardiac route to produce equivalent haemolysis of 3 mg se-bilirubin in 24 hr. The animals were sacrificed at intervals of 1, 2, 3, 5 and 7 days and the spleen was studied with particular reference to the lymphatic sheath. Copper sulphate treatment was followed by an initial increase in the number of lymphocytes within the perivascular sheath, indicating a rapid mobilization of thymic lymphocytes. Later these lymphocytes displayed blastic transformation and increased mitotic activity. After phenylhydrazine treatment activity was slight. Antiserum caused a complete loss of lymphocytes which were then replaced and germinal centers were formed. Erythrophagocytosis did not play a part in the conversion seen after phenylhydrazine treatment. The response to antiserum was slow. As copper increases the glycolytic activity of the cell on raising the copper level the quiescent small lymphocytes are converted into metabolically active blast cells.


Histopathological changes of some organs in the course of experimental Salmonella agona infection of rabbits. Organ changes evoked by infection with Salmonella agona were evaluated in 30 rabbits. Pathological changes were found not only in the intestines but also in the liver, lungs, spleen, kidney and suprarenal glands. The changes were different from those induced by other serotypes of Salmonella.


Mesenchymal reaction and serum glycoprotein concentration in chronic hepatitis and liver cirrhosis. In liver biopsy specimens of 45 patients with chronic persistent hepatitis, chronic aggressive hepatitis and liver cirrhosis the number of lymphoid cells and fibroblasts as well as in the sera of the same patients the concentration of IgG, IgA, IgM, alpha-2-macroglobulin and coeruloplasmin have been studied. The number of lymphoid cells and fibroblasts, was significantly elevated in chronic aggressive hepatitis and liver cirrhosis; a close correlation could be demonstrated between the number of the lymphoid cells and the IgG concentration; the serum alpha-2-macroglobulin level changed parallel to the number of liver fibroblasts in chronic aggressive hepatitis and liver cirrhosis.


Work organization of heavy load handling in India. The physical work rate, the energy and the cardiac costs of twenty-seven young male workers from the eastern part of India in five groups handling loads of about 30, 60, 75, 90, and 125 kg, respectively, were ascertained with the objective to rationalize the rate of work based on the physiological responses of the workers. The mean rate of usual work of the groups (I to V) was 4,715, 8,020, 7,350, 6,100, and 7,600 kg-m/min, respectively, which was considered to be extremely heavy. From the mean values of all the groups for the average work pulse rate of 143.1 beats/min, the recovery-pulse-sum of 119 beats for the first five minutes of recovery, the first and third minute recovery pulses of 127 and 114, respectively, the oxygen-pulse of 0.25 ml/pulse/kg, and the energy cost of 9.1 kcal/min, it was suggested that excepting the first group, the workers were working at a level much higher than the 50% level of their maximal working capacity. The simple and multiple linear correlation coefficients between the rate of work and the various physiological parameters were significant and different linear regression equations were suggested. In conclusion, for extremely heavy types of work in India, 1,200 kcal as the net optimal energy output in an 8-hr working day is suggested.


Driving and subsidiary behavior of taxi drivers working alternate-day shifts. A field study on taxi drivers working alternate-day shifts of prescribed duration of 16 hr of work revealed that most of them actually worked longer for 16 hr 50 min on the average, starting from 7:00 and ending later than 2:00. The mean hourly income greatly increased in hours later than 22:00 due to the increased fare per hire and higher speed, so that these hours were regarded by the drivers as the most important period of the day. This resulted in retarded mean bedtime of 5:31 after the shift end and in reduced sleep. The total rate of subsidiary activities of the drivers decreased during the middle of the day, but increased towards the shift end. Those activities having a relatively low rate at the beginning, such as subsidiary lower limb movements, shoulder-neck movements, and yawning, remarkably increased in the late evening and midnight hours. These activities increased even during frequent driving operations and tended to relate with each other, often recurring in bursts especially while feeling drowsy. The incentive wage system of the drivers thus accounts not only for the extraordinarily long working hours but also for intensified night work.


Monotony effects of the work of motormen dlring high-speed train operation. The results of investigations done in 1965, 1966, and 1972 on the workload of motormen of high-speed trains operating on railroads with maximum speeds of 210 km/hr were compared in an attempt to discuss the physiological implications of the driving task. The driving time of a 515 km section was 4 hr in 1965 and was lowered to 3 hr 10 min since 1966 for the fastest super-express trains. The mean heart rate was maintained around 80 beats/min during the entire driving period in 1965, but declined gradually in 1966 or 1972. Although in 1966 the operations at constant high speed appeared to favor cerebral activities, drivers in the 1972 investigation not only showed lowered perceptual and choice reaction performances but also experienced significant increase in errors in detecting signal tones given as a subsidiary task. Polygraphic recordings in 1972 indicated that drivers sometimes fell into drowsing of short duration intermittently, accompanied by temporary drop in heart rate, absence of controller action, and increase of detection errors. These effects were dominant in periods after 90 min of driving. The need to reduce the monotomy effects during underloaded train driving is suggested.


Labor performance measurement in visual inspection and packing operations. A methodological procedure for identifying and measuring the variables involved and their impact on labor performance in manual inspection and sorting operations is presented. The applicability of the procedure is shown as it applies in an analysis of canning asparagus spears. Worker output rates for any given spear size index tended to decrease along successive work stations, with exceptions where there were changes in proportion to specific sizes available. The canning performance was influenced by interactions among the size, positional line-load, and worker position variables as the product moved along the supply conveyer. Because linear regression equations computed to estimate the number of can per canner per minute were not effective in indicating the effect of spear size distribution nor that of interactions among other relevant variables, a more comprehensive model was developed to estimate cans per worker per minute as a function of line-load, worker position, and three binary variables representing interactions between these variables and spear-size indices. The results of this and similar studies may be used as a basis for suggesting better planning of raw product delivery schedules, introduction of innovative processes, and crew reorganization.