[Goiter in pre-school children from the Rzeszów district]. The examination included 1594 children at the age of 3 to 6 from the city Rzeszów (834) and from villages in the Rzeszów district chosen at random (760). There were 865 boys (54.3%) and 729 girls (45.7%) in the group. The size of thyroid gland was measured according to the modified classification of WHO from 1974. All the examined children were in the clinical euthyroid state. Enlarged thyroid gland was found in 369 children (23.1%). Goiter OB was diagnosed in 271 children, I degree in 85, II degrees in 11, III degrees in 2. Enlargement of thyroid gland occurred significantly more often in rural areas (36.8%) than in towns (14.8%). The lowest percentage of goiter was found in 3-year-olds. These results point out that the province is an endemic area of mild goiter. Emphasis was put on the necessity to increase goiter prevention in the Rzeszów district.


[Endemic goiter in the area of Mielec].

[Endemic goiter in the area of Mielec]. The scope of this report is the incidence of goiter in school children living in Mielec and neighbouring villages. We examined a group of 3537 children aged 6-14. The enlargement of thyroid gland was observed in 49.3% of the population. Judging by the results of the research this region can be regarded as endemic. There might be several reasons for a high incidence of goiter in this region. The most important are: insufficient iodine prophylaxis, pollution of the environment including the pollution with radioiodine after the damage of the Chernobyl reactor.


[Diagnostic criteria, physiopathology and etiology of intra-alveolar hemorrhage]. In the first part of this article the clinical and paraclinical criteria of intra-alveolar haemorrhages are reviewed. The principal signs and symptoms are dyspnoea, haemoptysis, anaemia and bilateral alveolar and interstitial opacities. Computerized tomography of the chest shows a non-systematized alveolar filling. In the second part, the cytological and histological criteria are considered; they are provided by examination of the alveolar lavage fluid and by lung biopsy. Finally, the main elements in the physiopathology and causes of these haemorrhages are successively described.


[External resistances and dyspnea. Value of the study of flow-volume loops]. Breathlessness induced by external resistances (diaphragms with orifice size of 20, 15, 10, 7.5 and 5 mm) introduced in the ventilatory circuit of a spirometer and the corresponding parameters of a maximal flow-volume loop have been studied. 10 healthy subjects (5 men, 5 women), free from any acute or chronic cardiorespiratory disease, volunteered for this study. The results showed that the breathlessness (severe or moderate) was especially correlated with the decrease in peak flows, peak inspiratory flow (PIF) more than peak expiratory flow (PEF): when breathlessness was moderate, PIF was more decreased than PEF, -35% and -28% respectively; when breathlessness became severe, PIF also decreased more than PEF, -60% and -50% respectively; forced vital capacity (FVC) never changed and maximal expiratory flows at 50% and 25% of FVC were only slightly modified despite obvious breathlessness. The increase in diaphragmatic activity seemed more implicated than the activation of expiratory muscles in the genesis of breathlessness. PIF more than the commoner PEF could be a useful marker of the breathlessness perceived by the patient during acute bronchial obstruction (asthma).


[Extrapleural hematoma: emergency diagnostic pitfall. Value of computerized x-ray tomography]. A case of extrapleural haematoma consecutive to a chest injury is reported. This is a rare site of blood effusion since such injuries usually result in haemothorax. These two diagnosis can be distinguished not only by exploratory thoracotomy but also by computerized tomography which shows a characteristic subpleural fat-like ribbon.


["Soft" parameters and invisible resuscitation]. Caring for a patient implies performing technical interventions and caring for the whole person, recognising his/her personal life, habits, family, wills. The working experience of an intensive care unit of Bellinzona is described: the theoretical framework that led the health team to start this new approach to intensive care patients and its translation in everyday practice. Verbal and non verbal communication skills (with the patient and the team) are pivotal in this approach; relatives are considered partners in the care of the patient and an essential element of the caring environment. Nurses identified meaningful data (soft data) related to living experience of the patient, to the interaction with the healing environment, his/her patterns of communication, and their use in the intensive care unit is described.


[To live death in the hospital. The Lendinara School of Nursing]. Issues related to death and dying are important subjects in the educational curriculum of nursing students; in the nursing school of Lendinara this subjects were discussed analysing practical and emotional experience of nursing students. An anonymous questionnaire was distributed to the 74 second and third year students (67 returned) to explore emotional experience and 52 terminal patients were observed during a 3 month period, to obtain data on the care of these patients in the hospital. Data were analysed by nursing students as part of their practical training. Some of the results are presented; results were discussed in the classroom and presented and commented in an open meeting with caring personnel (nurses, doctors, volunteers) involved in the care of dying patients.


[The results of nursing interventions: is an evaluation possible?]. The growing interest in measuring patients outcomes of nursing is argued has been occasioned by economic pressures and professionalizing thrust of the nursing profession. Problems in defining what a nursing intervention is and what can be considered an outcome are critically appraised. Ascertaining whether nursing care makes a difference by using outcome measures raises methodological as well as professional issues, for instance that of separating nursing from inputs of other professional groups. Opportunities and challenges posed to nurses by patient outcomes research are addressed, together with priorities for future nursing research in the field.


[A window on the past: are women more adapted to care of the sick?]. The issue of nurse and nursing as feminine concepts and profession was widely debated at the beginning of the century by various professional and political groups and female associations. One of the most accepted positions even among nurses was that women by nature are more patient and kind, therefore born to care for men. Women supported this position because saw in the nursing profession the possibility to have a job and economical independence, but the role of mother and nurse were considered conflicting. Doctors strongly favoured a female nurse, from middle class well educated women but the idea behind this position was to keep separate and subordinate roles. With the first World War, when lack of theoretical knowledge and organization of Italian nurses, especially compared with foreign countries, were evidenced, National Council of Italian Women proposed a nursing curriculum only for female nurses and with very strict requirements. Nurses Federation succeeded in 1920 in opening nursing education to both men and women but, with the advent of fascism, in 1925 a Regio Decreto Legge, with the establishment of Scuole Convitto only for female nurses was definitely approved.


[Nursing research methods and instruments: an analysis of some articles]. Research papers published on some of the most well known foreign nursing journals are presented and discussed. The main aim of the contribution, which opens a new arena for discussion on the Rivista dell'Infermiere is to critically appraise published research works focusing both on strengths and novelty and weaknesses in the hypothesis formulation, methods and instruments used, discussion of results. A critical analysis should enable nurses to start to learn to read and eventually write a research protocol, possibly avoiding some common mistakes.


Clinical pathology for preclinical safety assessment: current global guidelines. Regulatory guidelines for preclinical safety assessment studies of new drugs, chemicals, and food additives exist in many large industrial countries. Current guidelines include recommendations or requirements for clinical pathology testing. Many of the testing requirements are similar for every country, but others are not. The similarities and differences among several of the guidelines are discussed, and specific instances of ambiguous or inappropriate testing requirements are cited.


Interpreting clinical laboratory data in safety assessment studies. Traditionally, clinical laboratory data in safety assessment studies have been analyzed statistically to determine potential treatment-related effects. This has often led to inappropriate and/or controversial conclusions about clinical laboratory findings that are statistically significant but considered biologically unimportant. To overcome these problems, a decision-making process that integrates statistical analyses and sound medical judgement is required. Understanding the reasons why false-positive and false-negative results occur is the first step toward both better test selection and more accurate decisions on test material effects.


Clinical pathology in the National Toxicology Program. The National Toxicology Program (NTP) developed a standard approach for clinical pathology investigations that was integrated into most toxicity studies designed and conducted after 1986. Protocols for these studies include specific hematology and clinical chemistry analyses at 3 selected time points in 13-wk studies. Requirements concerning the anesthetization of animals, collection and analysis of samples, and reporting of results have been established to control sources of variability within and between contract laboratories that perform these studies for the NTP. Laboratories must meet minimum standards to be approved for participation in the Program. Important areas of consideration for these laboratories to perform clinical pathology investigations include the facility, equipment, personnel, performance, and quality control procedures. Clinical pathology results from approximately 60 13-wk studies that have been conducted by the NTP in 7 laboratories since 1987 are being analyzed to generate a database of control values for the Fischer rat and B6C3F1 mouse and to identify sources of variability. Experimental data from these studies are being analyzed and correlated with histopathologic findings to evaluate the contribution of clinical pathology to the characterization of toxicity and to examine the appropriateness of the current approach. Efforts such as these will provide for the evolution and continued relevance of clinical pathology in toxicity testing.


Clinical pathology: preanalytical variation in preclinical safety assessment studies--effect on predictive value of analyte tests. Significant differences in concentrations of analytes in samples may be introduced before samples enter analyzers. These differences are known as preanalytical variation and are part of the overall variation in analytical data. Preanalytical variation is caused by factors that operate during animal preparation prior to sampling, sample collection, sample processing, and sample storage prior to measurement. Preanalytical variation is important because it detracts from the predictive value of analyte measurements. Preanalytical variation may permanently damage data. Because its effects are difficult to quantitate it should be minimized in safety assessment studies. Sources of preanalytical variation are actions performed on animals prior to sample collection and actions performed on the specimen prior to analysis. Preanalytical variation produces a range of artefacts in experimental data. Consequences of preanalytical variation are loss of confidence in the data, obfuscation of real test article effects, false effects, and possibly the expense of repeating a study. To limit preanalytical variation, its sources must be identified, the effects documented, and measures devised to eliminate its sources. Predictive value (likelihood of actual disease) of appropriate clinical pathology tests in toxicology is inversely dependent on preanalytical variation: uncontrolled variation produces data with low predictive values, and controlled variation produces data with high predictive values.


Enzymology in preclinical safety evaluation. This short paper will briefly discuss the merits of determining plasma enzyme activities in pre-clinical safety evaluation. Emphasis is placed on the value of selecting the appropriate enzymes and collecting blood samples at the appropriate times during the study, so as to gain the maximum amount of diagnostic information. Examples of actual results will be cited to illustrate some of the points. These examples are drawn from the 2 commonly used toxicology species--the laboratory white rat and the beagle--and serve to demonstrate the importance of enzymology in monitoring the progress or resolution of an adverse drug effect.


Regulatory concerns of the United States Environmental Protection Agency. The US Environmental Protection Agency, under 2 of its legislative mandates, has the authority to require the testing of industrial and pesticide chemicals. Among the testing requirements, particularly in chronic studies, are those relating to hematology, clinical chemistry, and urinalysis. Some of these requirements will be discussed in detail. Comments on the usefulness of the current requirements and recommendations for changes will be solicited from the meeting participants.


Present status of animal clinical pathology examinations in the Japanese Pharmaceutical Manufacturers Association. This paper will review the current status of animal clinical pathology in Japan using data obtained during a survey conducted by the Japanese Pharmaceutical Manufacturers Association (JPMA). I am presenting this information as a representative of the Non-Clinical Evaluation Committee of the JPMA. Two co-workers, Dr. Nomura of Daiichi Pharmaceutical Co., Ltd., and Dr. Unno of Kanebo Co., Ltd., are also involved in this effort. Investigating and discussing the various problems concerning animal clinical pathology is timely and truly heartening, and we expect this information exchange in the animal clinical pathology field to continue.


Clinical pathology testing regulatory concerns. In toxicity testing, each animal may have to be viewed as a surrogate for millions of people and should be examined as thoroughly as a human patient. However, there are many differences between human diagnosis and animal toxicity testing. Human diagnosis is primarily based on anamnesis, symptoms, and utilization of a huge database of diseases. However, in animal toxicity testing, clinical and anatomical pathology data are usually a primary source of toxicity information, even though the positive endpoints are generally not known in advance and the number of positive toxicity endpoints may be numerous. This situation will generate at least 2 practical problems in clinical pathology testing: (1) how to preselect test items without precise knowledge of toxicity endpoints and (2) how to handle multiple data sets for toxicity detection. The latter includes issues of inflation of the overall false-positive rate and multicomparison problems. A "disease" called "significantosis" and a concept of integrated interpretation of multiple biologically related items to avoid false-positive judgments and unnecessary censoring of meaningful outlier data are briefly discussed. In general, toxicity tests are quite exploratory and the endpoints are unknown and multiple, so the procedures for data interpretation should be determined on a case-by-case basis. Construction of toxicity entity-oriented databases may be a requirement for further refinement of toxicity study interpretation.


Clinical pathology testing recommendations for nonclinical toxicity and safety studies. AACC-DACC/ASVCP Joint Task Force. Clinical pathology testing in nonclinical toxicity and safety studies is an important part of safety assessment. In recent years, clinical laboratory testing has rapidly expanded and improved. Some government regulatory agencies provide guidelines for clinical pathology testing in nonclinical toxicity and safety studies. To improve these testing guidelines and the resultant safety assessments, the American Association for Clinical Chemistry's Division of Animal Clinical Chemistry and the American Society for Veterinary Clinical Pathology formed a joint committee to provide expert recommendations for clinical pathology testing of laboratory species involved in subchronic and chronic nonclinical toxicity and safety studies. These recommendations include technical recommendations on blood collection techniques and hematology, serum chemistry, and urinalysis tests.


[Physiopathology of intestinal Salmonella infection]. Following a long period during which studies on the pathogenesis of salmonellosis and typhoid fever have been exclusively based on careful evaluation of clinicopathological data in infected patients and experimental infection in mice, the new tools that are now offered by molecular genetics and cell biology allow more systematic and analytical approaches. Numerous mutants have been obtained that can be assayed in selected cell assay systems such as in vitro-cultivated epithelial cells or macrophages, thus allowing to identify and characterize key virulence bacterial products as well as their eucaryotic receptors and effectors. Significant contributions have recently been made in the analysis of the mechanisms allowing invasion of the intestinal epithelium and survival and multiplication of bacteria within macrophages. However, many unsolved questions remain. It is still unclear what produces diarrhea during salmonellosis and studies on the pathogenesis of typhoid fever are still impaired by the lack of a proper animal model.


[Resistance of Salmonella].

[Resistance of Salmonella]. The emergence and the increase of antibiotic resistant Salmonella particularly in non-typhi species has occurred in recent years. Beside plasmid mediated resistance, new resistance mechanisms like alterations of permeability have been identified. Factors associated with resistance are the use of antibiotics in human and animals. These findings have important public health implications. It seems necessary to define a more adapted policy in human and veterinary use in order to avoid the rapid emergence of drug-resistance among regularly active antibiotics like fluoroquinolones.


[Epidemiology of minor salmonellosis].

[Epidemiology of minor salmonellosis]. Epidemiological data concerning non Typhi salmonella infections in France and other industrialized countries are characterized by the important increase of S. enteritidis salmonellosis due to raw or insufficiently cooked eggs products since 1987, increase of salmonellosis among immunosuppressed patients, particularly patients with AIDS. There is a new interest for non typhi salmonellosis instead of typhoid fever which is regularly declining in industrialized countries.


[Clinical aspects of salmonellosis].

[Clinical aspects of salmonellosis]. Salmonellosis includes two groups of diseases: typhoid fever and non-typhic infections. Epidemiological and clinical features are different in each group. Typhoid fever is a major health problem in developing countries. It realizes septicemia and endotoxinic symptoms, and has not to be forgotten when the patient is back from travelling. Non-typhic infections in most cases produce acute feverish diarrhea, conforming with collective food toxi-infection. Non digestive localizations are usually the fact of underlying diseases, and are able to kill the patient.


[Non-typhoid salmonellosis in HIV infection]. Non-typhoid Salmonella infections associated with HIV infection are 20 times more frequent than those observed in the general population. Drug addicts and homosexuals are equally infected. Concerning physiopathology, a deficit in gastric acid secretion has been blamed as an etiological factor, together with T-cell deficit, except for reduction in the number of CD4 cells. This type of infection usually presents as fever; diarrhea is noted in only 20% of the cases. Several viscera can be involved. The best treatment seems to be fluoroquinones administered during 3 weeks, and several months in case of relapse. Patients under AZT therapy are less often affected with salmonellosis due to the antibiotic activity of this anti-retrovirus agent.


[Salmonellosis: therapeutic aspects].

[Salmonellosis: therapeutic aspects]. The antibiotic therapy of salmonellosis has changed during the last decade, due to the development of resistance to classical drugs and also to increased knowledge in the conditions of in vitro and in vivo efficacy of new compounds. These new informations led to clinical studies of efficacy and tolerance of fluoroquinolones in the treatment of acute diarrhea or chronic carriage due to Salmonella, or against typhoid fever. These drugs appeared very efficacious and able to significantly shorten the duration of treatment. However, two potential pitfalls have to be kept in mind deserving additional informations: selection of resistant mutants and increased risk of persistent carriage.


[Anti-typhoid vaccines].

[Anti-typhoid vaccines]. There are three commercially available vaccines against typhoid fever: parenteral inactivated whole cell vaccine, oral live attenuated (strain ty21a), parenteral polysaccharide vaccine (capsular antigen-Vi). Their protective efficacy is 50 to 88% (inactivated vaccine), 50 to 96% (live attenuated vaccine) and 75 to 80% (polysaccharide vaccine). The frequency of notable adverse reactions with the inactivated vaccine justifies the use of the new vaccines.


[Phenylketonuria yesterday and today. Evaluation of the work of systematic neonatal screening]. Phenylketonuria is due in the very great majority of cases to a deficiency in phenylalanine hydroxylase, an enzyme whose cofactor is biopterin. Prenatal screening consists in measuring the concentration of phenylalanine in a sample of dried blood taken after birth (levels are already raised by day 3). Screening, organized by the Association française pour le dépistage et la prévention des handicaps de l'enfant, is very thorough (cover greater than 99%). Treatment involves observance of dietary restriction for at least five years. Results are good. Questions concerning the useful duration of dietary treatment, the level of phenylalanine that should not be exceeded, and the future of girls with PKU remain controversial. When adult, such girls may give birth to retarded children if they do not resume dietary restriction before becoming pregnant. Now that problems of screening, its organization, and the management of diet have been solved, these questions are the new challenge that faces us.


[Epidemiology of asthma].

[Epidemiology of asthma]. Asthma epidemiology aims to provide answers to the following questions: what is the prevalence? what are the consequences? what are the risk factors of asthma? Questionnaires indicate that asthma prevalence averages 6 to 8% whereas assessment of bronchial reactivity reveals that approximately 15% of the population exhibit bronchial hyperesponsiveness; these figures have been increasing in many western countries. Asthma is an important cause of impairment in children physical development, school-related problems along with increased number and duration of hospitalizations. Asthma mortality averages 3/100,000 in France and is mainly focused on people more than 50 years old; its increase is very likely in some countries, but is still controversial in France. Environmental and socio-economic factors play a major role in the development of asthma and genetic factors are now under investigation. Although both understanding and drug treatment of asthma have dramatically improved in the recent past, no positive change has been observed so far in terms of morbidity and mortality. Nevertheless, knowledge of factors specific to France requires further investigations.


[Physiopathology of asthma].

[Physiopathology of asthma]. Asthma is a multifactorial disease where genetic predisposition, environmental factors (allergens and pollutants) and endogenous factors intervene to varying degrees. Among the disturbances involved in the physiopathology of asthma dysfunction of the autonomic nervous system and development of bronchial inflammation are now known to play the major roles. From the adrenergic system, the role of which is now controverted, the attention of pharmacologists has shifted to the cholinergic central nervous system responsible for bronchial tone and the non adrenergic non cholinergic (NANC) nervous system. The more recently known NANC system is complex and mediated by neuropeptides, and it can alternately induce bronchodilatation and bronchoconstriction, as well as vasoconstriction and vasodilatation. The inhibitory NANC system acts through the bronchodilator VIP. The excitatory NANC system is mediated by tachykinins as which are potent bronchoconstrictors. Interaction of this system with the inflammatory cells induces a "neurogenic inflammation". Local inflammatory reaction is an almost constant element of asthma, irrespective of the cause of the disease. Although mast cells are the initial cells of the inflammatory reaction, there are important and complex cellular interactions with eosinophils, macrophages, lymphocytes and epithelial cells. Owing to their direct cytotoxic actions on the bronchial epithelium, eosinophils play a key-role in the inflammatory reaction. Cytokines secreted by alveolar macrophages, lymphocytes and mast cells amplify and maintain the inflammatory process.


[From asthmatic crisis to severe acute asthma]. Life-threatening acute attacks constitute the major complication of asthma. These attacks develop progressively or abruptly, within minutes. They are responsible for a mortality rate which in France has been estimated at 3 in 100,000 inhabitants. Most of the deaths occur before any medical assistance is given. Such deaths in serious attacks are caused by bronchial obstruction and not by possible cardiovascular complications. Since inflammation of the bronchi is now thought to be the primum movens of these near-fatal to fatal attacks, nothing but an early and prolonged anti-inflammatory treatment can prevent them. Because no precise profile of subjects at risk can be drawn, it is necessary to supervise with the utmost attention all patients who suffer from attacks of acute asthma which, unless proven otherwise, should be regarded as potentially serious: signs of severity must be systematically looked for, and strict therapeutic and monitoring measures must be taken.


[Pseudo-asthma and asthma with hypereosinophilia]. Despite of its high prevalence, asthma is not the sole cause of wheezing dyspnea: the obstruction of the principal airways, some diffuse bronchial diseases may present as pseudoasthma. The diagnosis of some behavioral dyspneas as well as functional laryngeal obstruction is sometimes highly difficult. The finding of a marked hypereosinophilia prompts the clinician to research a parasitic infection as a cause of pseudo-asthma, allergic bronchopulmonary aspergillosis complicating asthma, or an idiopathic hypereosinophilic disorder of which asthma is a component (as in Churg and Strauss syndrome).


[Characteristics of allergic asthma].

[Characteristics of allergic asthma]. The frequency of extrinsic (or allergic) asthma varies with age and sex. An inborn tendency to atopy, shown by a positive Phadiatop test or by skin tests positive to air-borne allergens, is found in 50% of asthmatic patients. The arguments in favour of the allergic origin of asthma are primarily clinical: same time and place of symptoms in the typical form, frequent bouts of acute rhinitis, history of familial or personal atopy. The responsible allergen is often easily identified by questioning, and its nature can be confirmed by positive skin tests. The allergens most frequently involved are air-borne allergens, notably house dust mites furs or feathers of domesticated animals, and pollens. Compared with intrinsic asthma, extrinsic asthma has the following features: it begins at an earlier age, it is less severe, it seldom evolves towards chronic ventilatory impairment and, by definition, it implies that an allergen is responsible for the onset or worsening of the symptoms.


[Asthma with permanent obstructive ventilation disorder]. Asthma accompanied by chronic airways obstruction (CAO) is frequent and raises difficult clinical problems. Persistent inflammation of the airways is the main factor responsible for obstruction. There are no symptoms that distinguish this form of asthma from non-asthmatic chronic obstructive lung disease, and only respiratory function tests can confirm the diagnosis of CAO. Pharmacological tests with bronchodilators evaluate the bronchomotor part of CAO which is substantial in asthma as opposed to other causes of obstructive lung diseases. A negative test cannot exclude the diagnosis and suggests that the obstructive component due to bronchial inflammation is predominant. In such case a reversibility test performed with corticosteroids is of considerable interest as it reduces the partly reversible inflammatory part of the obstruction. Peak flow curves provide more precise date on the evolutive type of CAO and therefore contribute to a great extent to the monitoring and education of patients. Severe chronic asthma with high annual systemic corticosteroid consumption requires special care and justifies the current attempts made to replace corticosteroids by other anti-inflammatory drugs.


[Non-allergen bronchial hyperexcitability and asthma: single and serial measurement]. Non-specific bronchial hyperresponsiveness (NSBH) is an essential characteristic of asthma. Its absence in a symptomatic individual virtually excludes asthma. Its presence is not synonymous with asthma although, in the absence of other obstructive or restrictive pulmonary conditions, it strongly suggests the diagnosis. The severity of NSBH is related to the degree of bronchial inflammation. Changes in NSBH are more frequent, although not constant, in late asthmatic reactions. The measurement of NSBH is useful in confirming or excluding a clinical diagnosis of asthma. It can also help in assessing the need for medication. Serial assessment of NSBH can be a useful tool in the follow-up of an asthmatic subject or in a subject investigated for occupational asthma although figures for sensitivity and specificity are low and preclude its routine use in these circumstances.


[The asthmatic child].

[The asthmatic child]. Asthma is the most frequent chronic pediatric disease. Management is based on assessment of severity and should normalize lifestyle as well as pulmonary function. Mild asthma is treated with intermittent beta-2-agonists. Moderate asthma should receive non-steroids prophylactic anti-inflammatory drugs. Immunotherapy should be considered. Severe asthma requires inhaled steroids. At each stage inhaled medications should be preferred. Therefore inhalation delivery system must be adapted for children of different ages and degree of dyspnea. The importance of environment control is well recognized. Establishing a partnership with the child and its family and with the medical staff and with the child's school is always necessary.


[Occupational asthma].

[Occupational asthma]. The diagnosis of occupational asthma requires the integration of a multiplicity of data; the history, cutaneous skin tests, biological tests, respiratory function tests and non-specific tests of bronchial hyperreactivity and specific bronchial provocation test. The history search for the presence of an atopic state, the occurrence of similar disorders in members of the same firm and also the timing of symptoms in relation to the occupational activities. Cutaneous tests are particularly helpful in IgE-mediated asthma in relation to the inhalation of animal or vegetable materials of glycoprotein origin. For haptens, the need for their prior coupling to a protein carrier causes problems which have not been entirely resolved. Laboratory tests run into the same snags. Respiratory function and non-specific bronchial provocation tests, confirm the diagnosis of asthma and enable the medium and long term prognostic to be assessed. Specific bronchial provocation tests are the most appropriate tests to establish an aetiological diagnosis in occupational asthma. Different technical methods are possible: quantitative administration of allergen aerosols, realistic tests, and tests using exposure chambers to achieve true test doses. The products responsible for occupational asthma are multiple. The different substances are characterised in a simplified manner: first animal matter (mammalian and arthropod allergens), secondly substances of vegetable origin (roots, leaves, flowers, grain and flour, wood and its derivates) and finally chemical products. The chemical products are primarily from the pharmaceutical and metal industries and above all from the plastics industry.


[Drugs for asthmatic crisis].

[Drugs for asthmatic crisis]. The drugs used in asthmatic attacks must act on the two major mechanisms of the disease: bronchial obstruction and inflammation of the airways. Two main classes of drugs are available to reach these targets: bronchodilators, headed by beta 2-stimulants, and anti-inflammatory drugs of the corticosteroid family. Bronchodilatation obtained with beta 2-stimulants is the first and most effective treatment of the attack. These drugs are usually administered by inhalation: metered-dose aerosols with or without inhalation chambers, or nebulization for severe attacks. Very high doses can be used without fear of side-effects, the principal objective of this treatment being to relieve bronchial obstruction. In the absence of rapid and lasting improvement bronchodilators must always be combined with corticosteroids. In all cases medical supervision immediately after the attacks is necessary and the patient should subsequently be put under care of pneumologists.


[Treatment of bronchial inflammation].

[Treatment of bronchial inflammation]. Inflammation is a general defence mechanism. It is constant in asthma where it is characterized by the presence of eosinophils in sputum and blood. Treatment of bronchial inflammation is one of the master pieces of therapeutic strategy and relies on inhaled corticosteroids in most cases. These drugs are remarkably effective and can be used for long periods with little or no side-effects, but compliance with treatment must be checked regularly. In all cases, even when corticosteroids are the mainstay of maintenance treatment, bronchodilators must be used simultaneously. The triggering factors must be taken into account and re-evaluated according to the course of the disease. In the short-term all efforts must concentrate on educating the patients and making sure that they comply with their treatment. In the mid-term new, more effective steroids with even less side-effects than the others can be tried. In the long-term anti-inflammatory agents might multiply and be prescribed in combinations for successful cure of a multifactorial syndrome.


[Therapeutic strategy].

[Therapeutic strategy]. The clinical manifestations of bronchial asthma fall into two categories: acute asthma which consists of asthmatic attacks and their variants, and chronic asthma. The treatment of acute asthma is now well established, while that of chronic asthma, more difficult to organize, is part of a true therapeutic strategy which has two aspects: 1. A more global approach to the treatment must be developed. This means full management of asthmatic patients who must be instructed and considered as active partners in the prevention of acute attacks, the evaluation of the severity of their disease and the application of the treatment prescribed. 2. An asthma severity scale must be devised and a specific therapeutic programme must be offered for each stage of the disease. The general principle, beside treatment of acute asthma, is to pay much attention to the intercritical situation and, in particular, to treat effectively the bronchial inflammation.


Simulation of B-scan images from two-dimensional transducer arrays: Part I--Methods and quantitative contrast measurements. Recently, theoretical investigations of the beamforming capability of two-dimensional (2-D) transducer arrays have characterized the array parameters required to steer a symmetrically focused ultrasound beam up to 45 degrees off-axis. These investigations have also shown that the number of elements in a steered 2-D array can be dramatically reduced by using a sparse set of elements, randomly distributed throughout the aperture of the transducer. The penalty paid for the use of a sparse array is the development of a "pedestal" sidelobe in the beam profile, the amplitude of which increases as the number of elements in the array decreases. In this paper the potential of 2-D arrays for medical imaging is assessed by simulating B-scan images of spherical lesions, both cystic and scattering, embedded in a large random scattering volume. Similar contrast characteristics over a range of cyst sizes are demonstrated for a dense 2-D array and a sparse array with 1/8th the number of elements, both operating at 5 MHz. A 32nd order sparse array is shown to perform at a reduced level, producing unacceptable artifactual echoes within images of cysts. The 8th order sparse array pattern has been fabricated on a fixed-focus poly(vinylidene difluoride) transducer using photolithographic techniques. Experimental images from this transducer are used to verify some of the theoretical predictions made in this paper. Comparisons between simulated B-scan images from linear and 2-D phased arrays are presented in a companion paper.


Simulation of B-scan images from two-dimensional transducer arrays: Part II--Comparisons between linear and two-dimensional phased arrays. Two-dimensional (2-D) arrays have been proposed as a solution to the degradation in medical ultrasound image quality occurring as a result of asymmetric focusing properties of linear phased array transducers. The 2-D phased transducer array is also capable of electronically steering the symmetrically focused ultrasound beam throughout a three-dimensional volume. In a companion paper the potential of 2-D transducer arrays for medical imaging has been investigated using simulated B-scan images. In this paper, the advantages of 2-D over linear transducer arrays is demonstrated by simulating images of spherical cysts embedded in a large scattering volume. The large elevation beamwidth in the nearfield of a 5 MHz linear phased transducer array results in a severe reduction in the image contrast measured between a 4 mm diameter cyst and the surrounding scattering media. By employing a 2-D array with symmetric focusing, the contrast between the cyst and surrounding scatterers is significantly improved. The use of additional elements in the elevation direction of a linear array is also investigated. In this case the additional elements are included only to focus, but not to steer the ultrasound beam. Using the contrast characteristics of a 4 mm diameter cyst, it is shown that relatively few elevation elements are required to significantly improve the nearfield imaging capability of the linear array.


Synthetic aperture imaging using a Lagrange based filtering technique. Synthetic aperture imaging using a catheter based, circular phased array providing high resolution, dynamic focusing has been explored. Due to the high input impedance and low signal-to-noise ratio (SNR) of a classic single element synthetic aperture system, multi-element synthetic aperture processing has been proposed with SNR improvement of about 8 dB for a 33 element aperture. Reconstruction in this case uses an optimal filtering approach based on minimizing the mean square error between filter output and desired beam pattern. This approach, however, does not directly control both mainlobe beamwidth and sidelobe levels. To overcome this problem, a Lagrange based filter design technique has been developed that not only satisfies the minimum energy criterion, but also constrains sidelobe levels under a certain threshold. The new technique provides better spatial and contrast resolution. Both the mathematical formulation and simulation results are presented.


A comparison method for mean frequency estimators for Doppler ultrasound. Mean frequency estimators as used in pulsed Doppler ultrasound equipment should provide an accurate (quality) and consistent (robustness) estimate over a wide range of signal conditions. In a simplified signal model, the main parameters to consider are the noise level, mean frequency, bandwidth and power of both the Doppler signal and the stationary component over a given time window. It may be expected that one estimator for a given parameter combination exhibits a good performance while another estimator for the same parameter combination behaves poorly. To allow direct comparison between different types of frequency estimators, a method is introduced to evaluate the quality and robustness of estimators for a common signal space covering a wide range of realistic parameter combinations. The method is illustrated using three different mean frequency estimators: (1) a first order autoregressive estimator in combination with a stationary echo filter; (2) a second order autoregressive estimator; and (3) a complex linear regression estimator in combination with a stationary echo filter. It is concluded that, for the parameter combination considered, the complex linear regression estimator exhibits the best quality (low variance and bias of the estimate) and robustness (consistent quality for all parameter combinations).


A discussion of two wavefront aberration correction procedures. This review paper discusses the basic properties of two adaptive signal processing procedures for dealing with weak scattering in a phased array transducer system. A fundamental improvement in the lateral resolution of ultrasonic echo scanners will result if the weight vector of a large phased array transducer can be modified to account for distortion in the propagation medium. Lateral resolution in most tissue is limited to a few mm by wavefront-distortion-induced sound-speed variations. One important wavefront-distortion source is scattering from local speed variations within large and reasonably homogeneous tissue beds such as the liver. Scattering disperses some energy from the beam and perturbs the wavefront, thereby distorting the image and limiting the resolution to the scale of the distortion. Often, such scattering is weak, meaning that most of the energy in the beam is unscattered. The total field at the receiving transducer is the vector sum of the unscattered and scattered fields. In weak scattering the unscattered field is dominant and the resultant field can be treated as the unscattered field plus a perturbation. The net effect is primarily a distorted phasefront, while the amplitude or modulus of the wavefront remains reasonably intact. Refraction and strong scattering effect the wavefront more severely and are less responsive to these algorithms.


Two dimensional ultrasonic beam distortion in the breast: in vivo measurements and effects. Two dimensional arrival time data was obtained for the propagation of ultrasound across the breasts of 7 female volunteers. These profiles were extracted through the use of cross-correlation measurements and a simulated annealing process that maintained phase closure while aligning the data. The phase aberration measured in two dimensions had a larger magnitude than previously reported phase aberration measured in one dimension in the breast. A point spread function generation computer program was used to demonstrate the system response degrading effects of the measured phase aberration and the usefulness of current one dimensional phase aberration correction techniques. The results indicate that two dimensional correction algorithms are necessary to restore the system performance losses due to phase aberration.


[Pathogenesis of myocardial ischemia and acute coronary syndromes]. Since the seventies, and in particular the eighties of this century, findings on pathogenetic mechanisms of ischaemic heart disease are expanding markedly and are becoming more accurate. This makes it possible to know and understand better factors which influence the genesis and development of myocardial ischaemia including the most serious clinical forms (unstable angina pectoris, acute myocardial infarction and sudden cardiac death). Diminution of the cardiac flow and/or increased oxygen demands of the heart muscle are not the only determinants of myocardial ischaemia which is influenced markedly also by neurohumoral, metabolic, prothrombotic (proaggregation and procoagulation) factors as well as antithrombotic and haemodynamic factors. Acute coronary syndromes have as a rule, in particular in patients with out severe atherosclerotic stenosis of the coronary arteries, a common pathophysiological mechanism of fissuration of the atherosclerotic plaque followed by different grades of dynamic coronary occlusion depending on vasoconstriction--spasm of the coronary arteries and thrombus formation. The coronary arteries, usually affected with atherosclerosis, may be due to the comprehensive action of various factors temporarily, intermittently or permanently occluded. In case of the development of acute coronary syndromes thrombosis plays a key role. Better knowledge of pathogenetic mechanism of IHD markedly changes views on treatment and management of patients with IHD in particular patients with acute coronary syndromes. The authors emphasize strategies focused (also preventively) on preventing progression of the disease with the aim to improve survival and the short-term and long-term prognosis.


[Present views on unstable forms of ischemic coronary disease]. The term unstable angina pectoris covers several forms of ischemic heart disease with heterogeneous pathophysiology, different clinical presentation and non-uniform prognosis. Recent results of angiographic, angioscopic and autoptic observations on the nature of unstable coronary plaque rendered possible a better understanding of clinical symptoms of the unstable myocardial ischemia. Holter ECG monitoring of patients with unstable angina pectoris showed, that myocardial ischemia may persist despite the medical control of angina pectoris. It seems therefore more appropriate to use the terms unstable myocardial ischemia or unstable coronary syndromes rather than unstable angina pectoris. Coronary angiography in patients with unstable angina pectoris demonstrated eccentric narrowing with irregular or overhanging edges or intraluminal filling defects in 71-73% of vessels responsible for unstable myocardial ischemia. Autoptic studies showed, that thrombus usually develops on plaque with fissures, ulcerations and hemorrhage. The common pathway for all unstable coronary syndromes is an impairment of plaque integrity with subsequent activation of platelets, development of thrombosis and coronary spasm. Subsequent fate of coronary thrombus determines the clinical course with ischemic episodes lasting from several minutes to several hours. Medical therapy, PTCA or coronary bypass surgery are used to stabilise the patient, however, myocardial infarction or sudden death may occur.


[Modern cardiac pacing. I. Dual-chamber pacemakers: 10 years' experience]. Dual chamber cardiac pacemakers restoring an impaired atrioventricular synchrony meet a demand of contemporary so-called physiologic cardiac pacing. 39 dual chamber (DDD) pacers were implanted in 1982-1991 in our center. They improved both well-being and hemodynamic values (doppler echocardiography) more distinctly than common ventricular demand devices did. P-wave driven ventricular pacing in normal sinus node function (in 40 per cent of our DDD patients) made a frequency response in physical exercise possible. A short atrioventricular delay in DDD pacing proved to be helpful in the treatment for reentry tachycardias refractory to antiarrhythmic drug administration. Demanding implant, high price, lengthy programming as well as a higher incidence of complications (30.7 per cent) as compared to ventricular pacemakers (7.6 per cent) were the main problems of DDD ones.


[Modern cardiac pacing. II. Rate responsive pacemakers: clinical experience]. Rate responsive cardiac pacemakers adapting their pacing frequency according to physical effort are able to solve not only a bradycardia, but a chronotropic incompetence too. 23 rate responsive pulse generators, implanted in 1987-1991 in our center, simulated the physiological conditions and in this way they significantly improved both working capacity in bicycle stress test (p < 0.0001) and well-being in comparison with ordinary demand pacers. The incidence of complications did not exceed that in simple common pacemakers, but the rate adaptive ones were expensive and their programming was time consuming. In all three rate adaptive principles used their non-specific response revealed some imperfection of sensor driven devices. In addition, both in QT and in respiratory dependent systems their pretty proportional frequency response was delayed, while the irregular pacing rate in body activity sensor was not very proportionate to the physical exercise. The non-specific sensor response may be reduced by a combination of biologic sensors.


[Relation between creatinine clearance and glomerular filtration in various stages of chronic renal disease]. The relationship between creatinine clearance (Ccr) and inulin (C(in)) was investigated in 20 healthy subjects (group A) and 54 subjects with chronic renal disease (C(in): 10-80 ml/min/1.73 m2) treated conservatively (group B) and in 10 subjects with regular dialyzation treatment and a preserved residual diuresis (more than 1000 ml/24 h) (group C). In subjects from group B the Ccr/C(in) values were significantly higher than in healthy subjects (p < 0.01). In subjects of group C the values of Ccr/C(in) before dialysis did not differ significantly from values recorded in healthy subjects. Twelve hours after dialysis a marked increase of C(in)/Ccr occurred (p < 0.001). The findings are consistent with the idea that the increase of tubular creatinine secretion in patients with chronic renal disease is associated with a rise of its plasma concentration. In terminal stages in chronic renal failure there is, however, again a drop of tubular creatinine secretion which is reversible and rises after dialysis. These changes in tubular creatinine secretion could be explained by the fact that in chronic renal failure substances cumulate in the organism which inhibit tubular creatinine secretion. Due to haemodialysis the concentration of these inhibitors of creatinine secretion declines and after dialysis this process increases again temporarily. The findings suggest that the residual Ccr value assessed before dialysis is closer to the real value of glomerular filtration than values assessed during dialysis.


[The effect of erythropoietin therapy on biocompatibility in hemodialysis]. In order to evaluate the treatment with erythropoietin (EPO) on selected indicators of biocompatibility the authors examined 8 patients dialyzed for prolonged periods before treatment (HTK = 0.23, median), during EPO treatment (Recormon, administered by the s.c. route, HTK = 0.28) in the course of 4-hour haemodialysis on dialyzers with a Cuprophan membrane. The examination before and during treatment was made under equal conditions. Heparinization was also equal despite the fact that during EPO in four patients the residual blood volume in the dialyzer was increased. Comparison of the results before treatment and during EPO treatment did not reveal at any of the collection times (before dialysis, during the 15th, 10th, 60th and 235th minute of the procedure significant differences in the number of leucocytes, plasma concentrations of the C5a complement component, number of thrombocytes and activated coagulation times. Plasma concentrations of the thrombin-antithrombin III complex were in EPO during the 60th minute of haemodialysis significantly lower (p < 0.05) than before EPO. The authors conclude that EPO treatment does not have a significant effect on changes in the number of leucocytes in blood during haemodialysis nor on the activation of complement by an alternative way. EPO does not lead to a greater activation of the coagulation system during haemodialysis; the lower concentration of the thrombin-antithrombin III complex suggests the opposite. Explanation of this finding, similarly as detection of the cause of the increased residual blood volume in some patients, calls for further investigation.


[Increased levels of noradrenaline in hypothyroidism and its association with cardiovascular system function]. In a group of 10 athyroid subjects treated with thyroxine and triiodothyronine discontinuation of both hormones induced hypothyroidism. During its development on the 7th, 14th, 21st and 28th day systolic time intervals, the heart rate, blood pressure and noradrenaline and adrenaline plasma level were assessed. On the 7th day of hypothyroidism an increased index of the preejection time was recorded, and its value continued to rise throughout the investigation period. A reduction of the index value of the ejection time was also observed on the 7th day and during the subsequent period the value did not change any more. A decline of the heart rate was observed on the 7th day and subsequently the frequency was stable. The index of electromechanical systole was protracted on the 28th day. The systolic blood pressure declined on the 14th day and did not change afterwards. The diastolic pressure rose on the 28th day. The noradrenaline plasma level was elevated from the 21st day of hypothyroidism, the adrenaline level did not change during the decline of thyroid function. The authors discuss the mutual relationship of changes and evaluate the impact of the rise of the noradrenaline level in hypothyroid subjects.


[Significance of laboratory examinations in the diagnosis of iron-deficiency anemia in older persons]. In order to assess the effectiveness of selected laboratory examinations in the differential diagnosis of anaemias in elderly patients the authors examined 170 patients aged 65-93 years. Depending on the cause of anaemia, they divided the group into five sub-groups. Analysis revealed that for the diagnosis of iron-deficiency anaemia the mean corpuscular volume and red cell haemoglobin level have a relatively low sensitivity (63 and 65.6%) and specificity (76.7 and 72.4%), serum iron has a very low specificity (37%) and the total iron binding capacity has a low sensitivity (31.3%). Serum ferritin (sF) has at the lower borderline of the reference interval 30 micrograms/l a 48% sensitivity and 100% specificity; when the value is 65 micrograms/l the respective values are 80 and 99%. Using routine parameters, it is not possible differentiate reliably in this group iron deficiency anaemia during chronic inflammations, infectious diseases and malignant diseases. Examination of SF when the lower borderline of the reference is raised improves the effectiveness of laboratory diagnosis in elderly patient.


[Smoking habits of male and female physicians in the Czech Republic]. The results of questionnaires given to 673 male and female physicians, pertaining to smoking habits, were compared with the Czech population with a similar age distribution according to results of the MONICA study. Male doctors smoke less frequently than men of the Czech population (24.2% vs. 44.9%). Female doctors smoke more frequently than male doctors, and what is worse, more frequently than women in the Czech population (27.4% vs. 26.6%). Specialists in internal medicine smoke least frequently (17.4%), surgeons smoke most frequently (32.3%). Partners of male and female smokers smoke more frequently than partners of non-smokers. Husbands more frequently than wives. Smokers are more frequently ignorant of their other risk factors. The authors present also data from some European and overseas countries. In countries where the number of smokers among medical doctors declines, there is also a decline of smoking in the general population. In the USA, Great Britain, Switzerland, Norway and Sweden smoking habits declined among physicians during the past 30 years 3-6x.


[Treatment of congestive heart failure using angiotensin I convertase inhibitors]. The authors describe the case of a 70-year-old female patient with ischaemic heart disease with an implanted pacemaker on account of sick-sinus syndrome, who after classical treatment with diuretics and cardiotonics suffered from frequent relapses of global decompensation of the circulation. After administration of the ACE inhibitor--Tensiomin--within a very short time (days) normalization of all indicators of previously severe congestion was found. During the subsequent follow up no relapse of decompensation occurred. The patient was shifted from stage IV to stage II in the functional classification of ischaemic heart disease according to NYHA.


[Adult-onset Still's disease--the effect of methylprednisolone pulse therapy]. The authors describe in a 40-year-old woman Still's disease with an adult onset. The activity of the disease was not controlled by large Prednisone doses and therefore pulsed treatment with methylprednisolone with very favourable results was used. The authors discuss the use of pulsed treatment with methylprednisolone in this disease.


[The effect of linseed oil on the fatty acid composition of blood plasma low- and very low-density lipoproteins and cholesterol in diabetics]. Twenty patients with compensated diabetes mellitus of 10-15-year duration took polyunsaturated fatty acids omega-3 (30 g of flax oil a day) in addition to their routine food. This led to an insignificant lowering in total cholesterol and elevation of cholesterol in high density lipoproteins. A significant rise in the level of omega-3 polyunsaturated fatty acids in lipoproteins occurred in 6 patients only. Minor effect of the diet oil may be due to low delta-6-desaturic activity in the majority of the examinees. The findings point to necessity to use other sources of omega-3 acids in diet therapy of diabetics, fish oil, in particular.


[The effect of omega-3 polyunsaturated fatty acids on the clinico-biochemical indices and kidney nitrogen-excreting function in patients with chronic kidney failure]. The addition of fish oil (20 g for 3 weeks) to diets of 7 patients with chronic renal failure (CRF) contributed to correction of metabolic derangement and nitrogen release, to alleviation of clinical symptoms. The most pronounced positive shifts were reported in early CRF. This gives evidence for a preventive value of diets supplemented with fish oil which secure delay of terminal CRF.


[The use of monosodium glutamate in the combined therapy of patients with atrophic gastritis]. Monosodium glutamate (MSG) taken per os has been found to stimulate gastric secretion provoked by pentagastrin. MSG gave rise to a marked elevation of endogenic gastrin levels both in experimental animals and atrophic gastritis patients. Thirty-six patients with secretory gastric insufficiency received MSG as an additive to their food during combined therapy of their disease. The preparation proved to be well-tolerated, good stimulant of gastric secretion, efficient in digestion improvement. MSG is recommended as an adjuvant in combined therapy of atrophic gastritis.


[The vitamin C, B12 and folate allowances of pregnant women in Moscow]. A dietary supply of vitamins was studied in 212 pregnant women for 11 months. Mean blood levels of vitamins were found subnormal, the percentage of the women with vitamin deficiency increased. Especially inadequate was supply of folate followed by vitamin C. Intake of 1 dragee a day of polyvitamins "Gendevitum" improved the vitamin status of the examinees with the best results obtained in the first trimester. Folate and B12 levels decreased with advance of pregnancy irrespective of polyvitamins administration. Vitamin C supply was better in summer and autumn, folate levels were higher in winter and spring. It is suggested that vitamins C, B12 and folate deficiency observed in pregnancy should be corrected.


[The vitamin allowance of the pupils in a rural vocational and technical school and their prophylactic vitaminization]. The actual nutrition and providing with vitamins C and B1 was studied in boys aged 16-17 years, students of a rural trade school (Volsk of Saratov Province). Although the caloric value of their ration was high enough the content of animal proteins was only 42-48 g/day. The content of ascorbic acid in the ration comprised 48%, in the spring of 1987 it was 17%, and of 1988-29% of the recommended standard, vitamin B1 levels did not show seasonal differences. Vitamin C and B1 deficiencies in the spring were proved by their low excretion levels in urine, and by a low concentration of vitamin C and decreased activity of B1-dependent enzyme transketolase in the blood. Intake of "Undevitum" (1 dragee/day) during 4 months was conductive to the improvement of the student providing with vitamins.


[The evaluation of the efficacy of a 6-month vitaminization of schoolchildren in grades 1 to 8 in the city of Baku]. Investigations were conducted in 110 schoolchildren aged 7-10 and 11-14 years. They had received insufficiently balanced traditional nutrition deficient in animal proteins, vegetable oils, calcium, and, especially, in vitamins. Excretion of ascorbic acid, thiamine, riboflavine, N1-HA was decreased as compared to the lower standard limits 3.5-1.9 times in 85-90% of schoolchildren aged 7-14 years, microsymptoms of vitamin deficiency (including polyvitamin deficiency) were noted in 33-53% of the children. Administration of varying doses of "Undevitum" (0.5, 1 and 1.5 dragees/day) has shown that for normalization of vitamin status, decreasing morbidity rate and improvement of their mental capacity, the schoolchildren of 1-4 forms should receive 1 dragee and those of 5-8 forms--1.5 dragee of "Undevitum"/day as an optimum dose.


[The effect of milk consumption on the activity of the formaldehyde detoxification system in sensitization to this compound]. The activity of formaldehyde dehydrogenase (FDG) and total nonspecific formaldehyde oxidative activity of nasal mucosa and liver and the amount of reduced glutathione in the liver were measured in guinea pig subjected to epicutaneous or inhalative action of formaldehyde and additionally fed with cow milk. Glutathione-deficient animals demonstrated an increase in FDG activity following formaldehyde sensitization both in the liver and in nasal mucosa, whereas FDG activity in glutathione-supplied animals did not change significantly. The concentration of formaldehyde in the internal environment is supposed to be controlled by the levels of coenzyme (reduced glutathione) and FDG activity.


[The level of available methionine and the biological value of fish protein]. Food value of fish protein in fish canning was evaluated biologically and chemically (by available methionine). High-temperature sterilization (126 degrees) proved the least adequate for it causes the greatest loss in the protein food value. The chemical method by available methionine showing close correlation with biological techniques (NPU and PER rates) is thought demonstrative and convenient for technological control in fish processing industry.


[The comparative activity of natural and synthetic enterosorbents in experimental hyperlipidemia]. In-vitro experiments have shown that dietary fibre microcrystalline cellulose and lignin (polyphepan) possess high activity in binding sodium salt of cholic acid. This action is comparable with that of pectin and metamucile. Hypolipidemic effect of microcrystalline cellulose, polyphepan and synthetic enterosorbents carbonates was also seen in hyperlipidemic rats. It is concluded that microcrystalline cellulose and polyphepan hold promise as a dietary supplement for hyperlipidemic patients.


[Triacylglycerols in human milk and milk mixtures for infant feeding]. High-performance liquid chromatography and computer program for identification of individual triacylglycerols (TAG) were employed for investigation of TAG composition of mature breast milk and 8 specimens of dry milk food for infants. The comparison was made by 15 molecular types of breast milk TAG using methods "close neighbour" and "star symbol plot" (Statgraphics). The composition appeared quite different. The design of artificial nutrition for infants basing on identity of fatty acids is believed inadequate as it cannot reproduce Tag composition of natural breast milk.


[The use of ferrocyanides for obtaining pure meat production in contaminated areas following the accident at the Chernobyl Atomic Electric Power Station]. The paper reports a new technique of obtaining radioactive Cs-free meat in the regions contaminated with radionuclides as a result of Chernobyl accident. The method is based on specific digestion features of ruminant animals. Ferriferrocyanide compounds are proposed as sorbents. Ferrocene is most efficient when introduced into mixed feed (1-3 g/day for sheep, 3-5 g/day for calves and young bulls) once a day. After that the animals can be fed radioactively contaminated forage and graze on contaminated land.


[The nitrate reductase activity of human saliva]. Investigations of human saliva reductase activity report the enzyme inactivation in 5-min heating at 50 degrees C, its maximal activity in neutral medium, reduced specific activity in the saliva dilution. Routine centrifugation inactivated nitrate reductase in supernatant, its activity in the precipitate hardly reached 10%. Combination of supernatant with precipitate recovered the baseline activity completely. Nitrates reduction into nitrites requires donor electrons. The latter are suggested to be present in the supernatant. Dehydrogenases substrates (lactate, pyruvate, malate, etc.) may act as donor electrons for nitrate reductase reaction. The addition of lithium lactate instead of supernatant to the precipitate partially recovered nitrate reductase activity. Biological role of salivary nitrate reductase is considered.


[Overt and latent restlessness and the awareness of the meaning of life in patients with valvular heart disease]. By means of R. B. Cattell Self-Knowledge Sheet and Crumbough and Miholick Scale of the Awareness of the Meaning of Life, 25 patients were examined, prepared for surgical correction of valvular heart disease. By means of R.B. Cattell Self-Knowledge Sheet a group was isolated of patients showing high overt restlessness (OR) and high latent restlessness (LR). It was shown that the personalities of these two groups of patients demonstrated numerous common features, but very significant differences also existed. The patients with high latent restlessness (LR) demonstrated strong emotional tension caused by frustration, feeling of inferiority with low self-estimation, as well as many conflicts at super ego level, but they had strong defensive mechanisms of own personality. The patients with high overt restlessness (OR) revealed high degree of intensification of the feeling of isolation, loneliness, and existential emptiness resulting from the lost feeling of the meaning of further existence with the progress of disease. The results of our studies are guidelines for the choice of psychotherapeutic management of patients qualified for operation of valvular heart disease.


[Arteriovenous fistula with subcutaneous displacement of basilic vein in children left in a program of repeated hemodialysis]. In the paper 15 children are presented with terminal renal insufficiency in whom 17 arteriovenous fistulas were created between brachial artery and basilic vein displaced subcutaneously within the arm. Operational technique and obtained results are discussed with particular stress put on the usefulness of this type of fistula for children requiring treatment with haemodialysis.


[Appearance of circulating immune complexes in patients with Hodgkin's disease and the etiology of this disease]. The serum of 47 previously untreated patients with Hodgkin disease (HD) was subjected to analysis for the presence and level of circulating immune complexes (IC) detected by the tests of inhibition of EA and EAC rosette formation. The control group included 100 healthy persons, health service workers. Significantly higher incidence and levels were demonstrated of EA IC and EAC IC in the serum of patients in relation to the control group (p < 0.001). No correlation, however, was found between the appearance of EA IC and EAC IC and the degree of clinical progression of the disease, and the presence or absence of systemic symptoms. The presence of IC in the serum of patients with HD is one link in the whole chain of various immunological disturbances existing in this disease, the starting point of which can be a pathologically changed cell of the lymphatic system.


[The effect of diet on the concentration of fructosamine in the serum of obese people]. The influence was studied of slimming diet on the concentration of fructosamine in the serum of obese persons with normal glucose tolerance. It was found that the reduction of carbohydrate supply, apart from body weight reduction, led to normalization of the raised fructosamine level.


[Ultrasonographic criteria of diagnosing tubal pregnancy]. The results were subjected to analysis of USG examination of 11 patients with tubal pregnancy, verifying the found echographic anomalies with the intraoperative assessment done shortly after the USG examination. Of greatest usefulness for the preoperative diagnosis of tubal pregnancy is, according to the authors' opinion, coexistence of the following sonographic signs: enlargement of the uterus without echographic sing of pregnancy in the uterine cavity;-a mass of irregular outline, cystic-solid appearance, and axial dimension of above 50 mm, situated near the uterus;-fluid in the Douglas pouch. The experience of the authors shows that ultrasonography is a valuable supplementation of clinical examination and laboratory analysis in the diagnosis of tubal pregnancy, on condition of using objective criteria for sonogram interpretation.


[Functional and morphologic changes of left ventricular myocardium in the course of aortic valve disease]. The mortality of patients with aortic valve disease is growing significantly from the time of manifestation of features of left ventricular heart failure. Probably, the causes of that situation are the irreversible changes in the myocardium. During the first, asymptomatic stage of aortic valve disease, the increase of preload and afterload is compensated by myocardial hypertrophy, concentric or eccentric respectively. The global heart function as a pump remains normal, in spite of decreased contractility of individual sarcomeres. Valve replacement at that stage of the disease gives the best effects, being the causal treatment. After having used up the compensation possibilities, of the myocardium, the features develop of left ventricular heart failure. The mortality of patients operated on in that stage of the disease is high. Valve replacement is often a palliative method.


[Sudden death--aspects of epidemiology and prophylaxis]. The survey of literature is presented from the last over ten years, pertinent to the ever present problem--sudden death. The paper presents mainly the problems of epidemiology, and the possibilities and methods of preventing sudden death, as well as the organizational activities increasing the chances of resuscitation of patients with sudden cardiac arrest.


[Genetic counseling in the case of carrier state with reciprocal chromosome translocations]. The principles are presented of genetic counselling for families with carrier state of reciprocal chromosome translocations (RCT). RCTs are the risk factor for the occurrence of reproduction disturbances, such as infertility, spontaneous abortion, congenital anomalies in the offsprings, and the degree of risk depends to a large extent on which chromosome segments are in the state of imbalance in the offsprings, due to various mechanisms of abnormal meiotic segregation. The uniqueness of chromosome translocations with respect to the type of chromosomes involved in translocations, and the location of breaking sites is the reason for the necessity of construing large pedigrees for the evaluation of the degree of risk. The newest Stene and Stengel-Rutkowski model makes possible the combination of smaller pedigrees in translocation groups of the so-called single risk of imbalance and determination of the individual risk of birth of children with anomalies. A number of psychological determinants are important for the possibility of genetic investigations in the affected families, and the decision about procreation may be influenced by a number of determinants other than the result of genetic counsel.


[Difficulties diagnosing type I distal tubular acidosis in a 10-year old girl]. A case is presented of type I distal tubular acidosis in a 10-year-old girl. The characteristic features of the disease are discussed together with related difficulties in the diagnosis of this case. The attention is paid to the age of diagnosis establishing, and to the clinical consequences resulting from the administered appropriate treatment.


[A case of functional hyperprolactinemia]. A case is presented of a 27-year-old woman in whom galactorrhoea and amenorrhoea occurred simultaneously with the signs of acute neurosis. The determination of prolactin concentration after the administration of metoclopramide made possible the diagnosis of functional hyperprolactinaemia. Other causes of hyperprolactinaemia were excluded. The signs and symptoms regressed completely after several months of treatment with parlodel. Control investigation done after 18 months showed that the concentration of prolactin after administration of metoclopramide was slightly lower than before, but was still high.


[Duodenal neurofibroma as a cause of chronic bleeding from the gastrointestinal tract]. A rare case of chronic exacerbating gastrointestinal tract bleeding is reported which was caused by duodenal neurofibroma. The patient was successfully treated surgically.


["I want to join my Peterle". Anthropological and ethical considerations of sexuality and suicidal behavior in the elderly]. Sexuality and suicidality express man being competent to shape his/her own life. From the bioethical point of view both phenomena are connected by shortening and fulfilling as well as autonomy. Considerations are provided for the physician to assist the aged being competent. Adequate framework is related to a concept of values guide living together. Thus tenderness and communication are appropriate levels of sexuality. Therefore they are to be integrated into the physician's concept of sexuality. For suicidality that means not to rescue life in a biological sense, but helping the elderly people making their life fulfilled and determining their life competent.


[Sexuality and suicidal behavior. Ethical considerations from the viewpoint of geriatrics]. The alternative "restriction" or "fulfillment" characterizes as age as geriatrics. Necessarily geriatric medicine has to realize not only a holistic concept of medicine but also to deal with the ethic questions and tasks risen by this quest. In both regards completion of awareness of the patient and his background is central. Especially concerning sexuality and suicidality geriatric and ethic interest must focus on the patient and his subjectivity and not start abstractly from principles and norms.


[Hermeneutics of the quality of life concept]. Medicine looks for reasonable criteria solving the problem of fair allocation of resources, assessing risks or discontinuing treatment. Further a reasonable measure is required for treating or accepting life in a reduced stage. The term "quality of life" seems to be like that. But it is generated by social politics and its problem, i.e. what people need for living, and does not ask whether a special treatment is useful for a patient. Thus the term should be used as follows: 1) only from patient's perspective, 2) as an undefinable term related to an "anthropologia negativa", and 3) reconstructing patient's preferences.


[The quality-of-life doctrine and the sanctity of life]. The term "quality of life" might be used to qualify external circumstances with regard to the life of human beings (A). It also can be used to define the quality of a human life itself (B). Then it replaces the idea of "sanctity of life" by an eugenic idea that can be abused as a notion of discrimination. The B-position implies that life is only an instrument in order to serve a separable purpose (i.e. "the quality of being a person"). This specific quality articulates itself in so-called "indicators of humanhood/personhood". In consequence this "quality" is an eugenic expression including a dangerous power of definition and a selective anthropology that does not seem to be convincing theoretically and that can never serve as the basis of a reasonable and good social life of man.


[Quality of life and fate].

[Quality of life and fate]. While the term "happiness of life", the "eudaimonia" of the greek philosophers, includes the good as such and therefore a metaphysical and moral component, the modern term of the "quality of life" is wholly defined by the criteria of a person's functional capacity and subjective wellbeing. The doctor's orientation by these criteria meets its limits, where he is confronted with fatality. This shows that we cannot really comprehend the quality of life without man's fundamental task of mastering his fate.


[Quality of life--demands and reality as a medical parameter versus quality of life as individual reality]. Quality of life (QL) is a term, whose definition extends beyond scientific methods. Even the most accurate description will only be able to represent a part of the reality due to the proviso of only a limited view. For that reason the abandonment of this term, described as "utopical" and "principally remaining in dissent", was called for. This could be countered by the possibilities to use QL as a therapeutic aim, as well as an aid towards finding an individual indication. Alone the demand staged by QL, to take the individuality seriously, and to be the motor for patient oriented medicine, make this term valuable. The definition itself will remain a called instruments have been developed and tuned, their evaluation has not yet been concluded. The acceptance of QL-registration within clinical studies is low, since the individual integration of values compared to the biometric difficulties can hardly be generalized. The aims of QL-research are: the individual focus on the field of projection of QL; a motivation-oriented mode of record; the involvement of QL-registration in form of information and accompaniment; adequate modular techniques including dialogical methods (nondirective interviews); the establishment of a QL-anamnesis towards an extension of the clinical picture; the observance of a possible conflict of roles, the danger of linguistic inaccuracies and misunderstandings, the consideration of a person's privacy.


[Type I diabetes mellitus: quality of life as a subjective reality in the systemic context]. Quality of life of insulin-dependent diabetics seems to be redefinable because of new findings in diabetology, i.e. more flexible therapy-concepts. Objective quality of life--operationalized by metabolic parameters--stands against subjective assessment by the patient. A comprehensive model of subjective quality of life-assessment of type-I-diabetics is presented. Beside individual assessment-processes also systemic factors are integrated. Finally, consequences for diabetes-care are discussed.


[The "dialogic principle" as the force of the physician-patient relationship]. The discussion is opened with an analysis of the inherent problems of the concept of quality of life. Why must it be pressed into the straight jacket of a quantitative scheme? The second theme, the thesis that verbal contact and interviews in the doctor's office are an application of the philosophical programme of personalism and "dialogism", is also critically analyzed. Why must the physician (and the psychotherapist) aim so high? Is not the lack of symmetry between the physician and the patient typical of the verbal contact between the two? These factors are discussed, not-withstanding the valid insight that intense personal concern and contact are highly desirable in patient-oriented medicine.


[The dialogic principle in medical treatment]. Almost all kinds of medical therapy are based on a therapeutical dialogue. Some aspects of the dialogue principle in medical therapy are shown in this article. In addition the dialogue can open ways of communication to art-therapy (e.g. music therapy) and even to the arts itself.


The rise of private practice: a growing disquiet with public services? A survey of 325 national patients attending six private clinics in Port Moresby was carried out to determine the characteristics of those using private medical services. Most patients were employed in professional or clerical occupations. A sizeable proportion of private patients were from low and moderate income categories and over 40% of those interviewed said that they had to borrow the money to pay for the consultation. Education level was positively associated with both attending a private practitioner as first choice of treatment and enrollment in a medical insurance scheme. 15% of patients were medically insured, and they were more likely to choose a private practitioner as first treatment choice. The most common reason given for choosing private sector health care was that it was quicker, but a notable proportion, particularly amongst those who had previously attended government health services for the same complaint, thought that private clinics had better doctors or gave better medicine. The findings are discussed and contrasted with those from other developing countries. Conclusions are drawn regarding the significance of these findings both in relation to the upgrading of the public health services and the regulation and monitoring of private health services.


Factors affecting the use of immunization among urban settlement dwellers in Papua New Guinea. This paper examines the importance of selected social factors in the acceptance of childhood immunization in urban settlements in Port Moresby, Papua New Guinea. The study found that the provision of information to mothers on when to start immunization and how often the child should be immunized were key factors in determining immunization status. Maternal education was found to be positively associated with knowledge of immunization, but was not significantly associated with actual immunization practice. Over 70% of the women studied found out when to attend for immunization from the local maternal and child health (MCH) staff, hence emphasizing their importance in disseminating information. If coverage is to be increased further in urban settlements with mobile populations, maximal use must be made of local community organizations to disseminate the key immunization information and for follow-up of newborns and infants new to the community. Efforts to encourage mothers to deliver under supervision should also continue as this is an important point of first contact for immunization.


Precipitation of asthma attacks in Melanesian adults by sodium metabisulphite. Seven Melanesian asthmatic patients were challenged with substances that have been shown to precipitate asthma attacks in asthma patients in developed countries. Patients were challenged in a double-blind fashion using placebo and active substances. The active substances were tartrazine, sodium metabisulphite, aspirin and betel nut. All 7 patients were challenged with tartrazine and sodium metabisulphite; 5 were challenged with aspirin also, but only 2 were challenged with betel nut. Asthma attacks were precipitated by sodium metabisulphite in 3 patients. No other substances precipitated asthma. As sodium metabisulphite is a common food additive, these results suggest that processed foods introduced into developing countries may have an important role in precipitating asthma attacks in susceptible persons.


The 'longlong' population of Ialibu District, Southern Highlands Province, Papua New Guinea: contact with health services and care in the village. The aim of the study was to describe the general behaviour, living arrangements and level of health services contact of the mentally ill population of a health district in Papua New Guinea. The immediate relatives of 31 'longlong' people living in Ialibu District were interviewed. About half of the mentally ill subjects were able to cook and look after a garden. Just over half had engaged in physical violence or stolen and one-fifth had been physically restrained. Almost all were living in their own village although not all were living with their own families. Just over half had had contact with health services and this contact had usually been brief and, in the relatives' eyes, unsatisfactory.


Determining drug dosages by height: applying a model made for coastal children in Papua New Guinea to children from the highlands. A height scale for the determination of drug dosages in children of the Madang area was applied to children from the Nipa area of the Papua New Guinea highlands. In only 13 out of 1314 children (1.0%) did the use of the height scale result in drug doses below the recommended minimum dose per kilogram of bodyweight. The scale can therefore be used safely for highlands children in areas where facilities for accurate weighing are not available.


Markers of hepatitis B infection in Tari District, Southern Highlands Province, Papua New Guinea. Serum samples collected from two groups in the Tari District of Southern Highlands Province were assayed for markers of hepatitis B virus (HBV) infection. 85% of women of childbearing age were found to have markers of HBV infection; 37% were positive for HBV surface antigen (HBsAg), indicative of the chronic carrier state, and 6.6% were positive for HBV e antigen (HBeAg), indicating the presence of actively replicating virus. 75% of women negative for HBsAg were positive for antibody to HBV core antigen (HBcAb), a marker of past infection. A group of children aged 6 to 18 years showed a significantly lower prevalence of markers of infection (66%) but higher rates of HBsAg positivity (46%) and HBeAg positivity (30%). Only 37% of the HBsAg-negative children in this group were positive for HBcAb. The results from this serosurvey suggest that the major route of HBV transmission in this population is horizontal, between older children, though significant transmission also occurs during the neonatal period.


Gentamicin resistance in fatal Klebsiella septicaemia. The occurrence of antibiotic resistance in nosocomial infections is a common problem. This case details a fatality associated with Klebsiella infection acquired as a hospital inpatient. The transfer of gentamicin resistance between gram-negative bacteria could present a considerable problem in Papua New Guinean hospitals.


Typhoid fever complicated by chloramphenicol toxicity, ataxia and psychosis. A case of typhoid fever complicated by pancytopenia, cerebellar signs and psychosis is described. The association of reversible marrow suppression with chloramphenicol treatment and its clinical features are outlined. The features of cerebellar dysfunction and of psychosis in patients with typhoid are described. Recommendations are made to help identify the problem of chloramphenicol-induced marrow suppression when it occurs.


[Multiple positional relationships of nerves arising from the sacral plexus to the piriformis muscle in humans]. The positional relationships between the piriformis muscle and the nerves which arise from the sacral nerve plexus were studied in 514 sides of 257 Japanese adults. These were classified into Types I-XIII and numerous subtypes based on: 1) the number of nerves perforating the piriformis muscle, 2) whether all or part of the nerve perforated the muscle, 3) the order of perforation and position in the muscle, and 4) communications between the nerves. In this paper, the multiple positional relations between the nerves and the piriformis muscle, the frequencies of the various types, and the order of priority concerning the perforation of nerves through the muscle are discussed. 1) The typical case, Type I, in which the piriformis muscle is not perforated by nerves except for a part of the superior gluteal nerve, was found in 309 (60%) of 514 sides. Types III-X, in which the muscle is perforated by additional nerves, were found in 195 sides (38%), and in 175 of these, all or part of the common peroneal nerve passed through the muscle. Types XI-XIII, in which the inferior gluteal nerve and other nerves pass above the piriformis muscle, were found in 10 sides (2%). Among all types, the following were generally seen: Type V, the piriformis muscle is perforated by both the inferior gluteal and common peroneal nerves; Type VII, the muscle is perforated by the two above-mentioned nerves and part of the posterior femoral cutaneous nerve (Fig. 16, Table 1). The common peroneal nerve followed two courses (a combination of over, through, and under the piriformis muscle) in 49 extremities. In the 4 cases of Type X (1%), the tibial nerve was divided into two components due to the intervention of the most caudal bundle of the piriformis or an unknown muscle. The dorsal component passed through the muscle, while the ventral component followed the typical course under the muscle (Figs. 9-11). Therefore, in the above-mentioned 53 cases as well as in other cases, the sacral nerve plexus cannot be divided into ventral and dorsal layers up to the sacral nerve roots, as in typical cases. Type II, in which the piriformis muscle is perforated by only a caudal branch of the superior gluteal nerve, was found in about 16% of 249 cases; this type was accompanied by some of the other types (Table 2). In the extraordinary case of Type XII with Type II, a branch of the superior gluteal nerve passed under the piriformis muscle (Fig. 13).(ABSTRACT TRUNCATED AT 400 WORDS)


[Study of the degree of pneumatization of the viscerocranium in man and pongidae]. The volumes of the paranasal sinuses of 41 adult skulls of humans, gorillas, chimpanzees and orangutans, were examined with use of a Computertomograph type SOMATOM DR. The percentage distribution of the volumes of the different paranasal sinuses showed that the maxillary sinus always had the greatest volume. The maxillary sinus of the humans showed the smallest volume percentage in comparison with the pongids. The typical differences between humans and pongids were observed in the ethmoidal cells and the sphenoidal sinus. The ethmoidal cells of the gorilla and the orangutan have to be defined as rudimentary. Those of the humans come to more than 20% of the total volume of the paranasal sinuses of all hominoids. Differing from the humans, the sphenoidal sinus of the pongids pneumatizes almost the whole sphenoid bone. This volume percentage of the pongids is twice as high as that of the humans. In addition, an index was calculated from the volume of the facial skeleton volume and the total volume of the paranasal sinuses and defined as the degree of pneumatization. We found that the gorilla has the highest degree of pneumatization followed by the chimpanzee, the orangutan, and the humans. The lowest degree of pneumatization of the humans may be related to the reduction of the jaws.


Variability of origin of serratus anterior muscle in Japanese. The observations on 567 male and 251 female Japanese cadavers revealed that there was a wide variation of the lowermost origin of the serratus anterior muscle ranging from the 6th to the 12th rib. The most frequent cases in males were of the 8th rib type (42.5%), whereas those in females were of the 9th rib type (43.3%). There was a statistically significant difference in the distribution of the muscle origin between the sexes. The observations also showed that bilateral symmetry of the muscle origin was preponderant over asymmetry, the symmetric cases forming about seven-tenths of all individuals without sex distinction.


Histogenesis of tunica media of the chick aorta. We investigated the formation of the aortic tunica media in developing chicks from Hamburger-Hamilton stage (st) 12 to 1-day after hatching. At st 12, some cells of the lateral plate and the somite adjacent to the aorta extended processes toward the aortic endothelial tube. This is the first sign of the tunica media formation of the aorta. Then, these cells detached from the lateral plate and the somite attached to the aortic endothelial tube and covered it almost entirely by st 18. At this stage, bundles of microfilaments and spots of dense material were found in the peripheral region of cells of the tunica media (media cells); suggesting the earliest differentiation of smooth muscle cells. Subsequently, the tunica media increased in the number of cell-layers, reaching approximately 20 layers at st 34 (8-day incubation). The outer layers of the tunica media consisted of undifferentiated cells, whereas typical smooth muscle cells were found within the inner 4 to 5 layers. Elastic fibers first appeared at this st 34. With there was an increase in the elastic component, the tunica media assumed the lamella structure consisting of the alternating myocytes and elastic laminae. The aortic media 1-day after hatching essentially exhibited the same mature state as seen in the adult chickens.


Defective response of plasma growth hormone to growth hormone releasing factor in growth hormone deficient children. In an attempt to establish the reference pattern and the plasma growth hormone (GH) response to growth hormone releasing factor (GRF) (1-29)NH2, 5 normal stature with single kidney children and 14 with idiopathic GH deficient dwarfism received intravenous injections of 1 microgram/kg GRF(1-29)NH2. Plasma GH levels were measured at 0, 15, 30, 45, 60, 90, and 120 min after injection. The results showed that, first, in normal stature with single kidney children, each plasma GH reached peak level (80.31 +/- 19.28 ng/ml) at 45 min after injection. Second, the majority of those with GH deficient dwarfism also obtained maximal GH levels (13.10 +/- 10.78 ng/ml) at 45 min after injection but at significantly lower levels than the normal children (P < 0.01). To compare with that obtained after the insulin-induced hypoglycemia test, the peak GH level after GRF was higher but there was no significant correlation between them. The maximal GH level after GRF(1-29)NH2 injection did not show significant correlation with either chronological age or bone age. Third, 3 of 14 (21.4%) with GH deficient dwarfism had half response to GRF(1-29)NH2. It is reasonable to assume that out of these patients' GH deficiency is of hypothalamic origin. Therefore, GRF test is a safe and useful test for differential diagnosis of defect level in GH deficiency and may become a therapeutic regimen.


Urinary N-acetyl-beta-glucosaminidase (NAG) in children receiving antiepileptic drugs. The activity of urinary N-acetyl-beta-glucosaminidase (NAG) was measured in random urines using the ratio (NAG index) of NAG to grams of urine creatinine in 102 epileptic children taking antiepileptic drugs (AEDs). A high urinary NAG index (2 SD or more above the mean for the age-matched control/normal subjects) was detected in 40 (39%, 40/102) epileptic children with AEDs. None of the 40 epileptic children with abnormal urinary NAG excretion had significant proteinuria. Among the 83 epileptic children under monotherapy, 29 cases (35%) had elevated urinary NAG excretion. Valproic acid presented the highest incidence of abnormal urinary NAG index (78%, 7/9 cases) within the monotherapy group, and the incidence was statistically significantly higher than that (26%, 14/55) in the carbamazepine group (p < 0.005). In the monotherapy group, no significant difference in serum levels of AEDs was found between children with normal urinary NAG excretion and those with abnormal. Nineteen epileptic children were treated with more than one AEDs. Eleven of them (58%, 11/19 cases) had a high urinary NAG index. The incidence of high urinary NAG index in the polytherapy group and that in monotherapy group was not significantly different (p > 0.05). This study suggests that AEDs may be potentially nephrotoxic and that urinary NAG may play a role in screening renal tubular injury in epileptic children under therapy of AEDs. Further investigation should be conducted to determine whether the effect of AEDs on renal tubular cells is or is not reversible.