[The use of gentamicin-polymethylmethacrylate chains for the treatment of soft-tissue wounds in the region of the urinary tract (author's transl)]. Bactericidal concentrations of gentamicin can be attained by implanting at the site of the infection pellet chains of gentamicin-polymethylmethacrylate (PMMA) that permit the protracted release of the antibiotic for several weeks. Satisfactory healing of the wound was achieved in two cases of extensively infected soft-tissue wounds in the region of the urinary tract after temporary implantation of gentamicin-PMMA chains.


[Transvenous perfusion, a new technique of regional renal hypothermia (author's transl)]. An experimental study demonstrates the feasibility of local renal hypothermia by transvenous perfusion. The method is technically simple and provides continuous renal cooling within a range of 15-19 degrees C, optimally protecting the ischemic kidney. Thromobosis at the site of venous puncture was not observed.


Arteriolar nephrosclerosis in the Syrian hamster. Syrian hamsters developed spontaneous renal lesions that resembled those of arteriolar nephrosclerosis in man, and differed from other spontaneously occurring or virus-induced renal diseases in other rodent species. Morphologic changes were mainly degenerative with little cellular exudation and were associated with histologic changes in the intrarenal vasculature. The renal lesions were progressive, often fatal and sometimes were complicated by glomerular amyloidosis with the nephrotic syndrome and uremia. Endstage kidneys often had fibrinoid necrosis of intrarenal arterioles and thus resembled lesions characteristic of the malignant phase of human essential hypertension. Fibrinoid necrosis of small arterioles was common in the uterus, ovaries or testes of affected animals; it was less frequent in mesenteric or coronary vessels. Cardiac thrombosis, often involving the left atrium or left atrioventricular valves, also was common. Changes occurred earlier and often were more severe in females than in males. This disease was a major cause of morbidity and mortality and hampered life-span studies.


Fish oil-induced yellow fat disease in rats. I. Histological changes. Yellow fat disease was induced in young rats given a vitamin E-deficient diet supplemented with 15% fish oil. The changes in adipose tissue of this oil-induced disorder were different from those of natural yellow fat disease in horse, pig and mink. In the natural disease all fat depots had the early stage of yellow fat disease with interstitial lipofuscin-laden macrophages exclusively. In the rat, however, this change was seen only in the subcutaneous fat depot. Moreover, affected adipose tissue of animals with natural disease had extensive fibrosis, but in the rat fibrosis was always absent. Rats with fish oil-induced yellow fat disease had degenerative changes in various fat depots that occurred at various times but in the horse, pig and mink fat depots were affected simultaneously. Lipofuscin accumulated in the reticuloendothelial system in rats. Accumulation in spleen and liver was dependent on vitamin E deficiency, but only the accumulation in the Kupffer cells was correlated with yellow fat disease. Lipofuscin accumulation in the mesenteric lymph node did not depend on vitamin E deficiency.


Cryptosporidiosis in immunodeficient Arabian foals. Five of six immunodeficient Arabian foals that died of adenoviral infection were found to be infected with an intestinal coccidian of the genus Cryptosporidium. Various developmental stages of the organism were found in the microvillous border of the intestinal mucosa. The foals had diarrhea but it was not possible to separate the effects of the cryptosporidial infection from those of the concomitant adenoviral enteritis.


Fish oil-induced yellow fat disease in rats. II. Enzyme histochemistry of adipose tissue. Adipose tissue in various stages of fish oil-induced yellow fat disease in the rat had the same acid phosphatase and 5-nucleotidase activity pattern as similar stages of the disorder in mink and pig. A weak acid phosphatase and 5-nucleotidase activity was seen in interstitial lipofuscin-laden macrophages in "stage M" yellow fat disease without fat cell degeneration. Activity of these macrophagic enzymes increased when there was fat cell degeneration ("stage S" and "stage E" yellow fat disease). This different phosphatase activity in the same cell type may result from phagocytosis of substrates with variable digestibility. Macrophages directly surrounding affected fat cells in steatitis areas ("stage S" and "stage E") had strong acid phosphatase and 5-nucleotidase activity. As in the pig, increased 5-nucleotidase activity was found in affected fat cells, which probably indicates plasma membrane damage. Increased nonspecific esterase activity occurred around affected fat cells. Only a small part of this esterase activity originated from inflammatory cells. This indicates that an increase of esterase activity in degenerating adipose tissue may be an endogeneous process in this tissue.


Primary neoplasms of the nasal cavity, paranasal sinuses and nasopharynx in the dog. A report of 16 cases from the files of the AFIP. Sixteen cases of primary neoplasms of the nasal cavity, paranasal sinuses and nasopharynx in the dog were reviewed from the files of the Armed Forces Institute of Pathology (AFIP). The mean age of affected dogs was 9.5 years. The presenting clinical signs were epistaxis, nasal discharge or facial swelling. Eleven of the affected dogs were purebred. Three of these were Collies and two German Shepherds. The nasal cavity was involved most often. All neoplasms were malignant (11 carcinomas and five sarcomas), and there was invasion of the adjacent bony structures in most dogs. Tumors were classified according to prominent cell type and degree of differentiation into respiratory epithelial carcinoma (four), adenocarcinoma (one), squamous cell carcinoma (one), mucoepidermoid carcinoma (two), undifferentiated carcinoma (three), chondrosarcoma (three) and undifferentiated sarcoma (two).


Fatal strongyloidiasis in gibbons (Hylobates lar). A 6-year retrospective study of necropsy material from a colony of 200 gibbons showed strongyloidiasis to be the most frequent cause of death (24 cases). Clinical signs included diarrhea, constipation, weight loss, paralytic ileus and dyspnea. Lesions were most frequent in the gastrointestinal tract and lungs. In the gut there were erosive and ulcerative enteritis associated with adult female parasites and rhabditiform larvae and acute and granulomatous enterocolitis associated with invading filariform larvae. There was severe multifocal or diffuse hemorrhage associated with migrating larvae in the lungs of 23 gibbons. Filariform larvae and the lesions they caused also occurred in various tissues; this was commensurate with the wide distribution of these larvae when hyperinfection occurred.


Intimal changes in the coronary arteries of Indian water buffaloes (Bubalus bubalis). Of 75 Indian water buffaloes (Bubalus bubalis) examined, 14 6-year-old or older buffaloes had early atherosclerotic lesions in the coronary arteries. These lesions resembled fatty streaks seen in man. Ageing changes and gross and microscopic features of the fatty streaks in the vessels resembled those described in the corresponding arteries of man.


Mediastinal parathyroid adenocarcinoma in a dog. A tumor in the anterior mediastinum was found in an adult male German Shorthaired Pointer. The dog presented with hypercalcemia that varied with the removal and recurrence of the tumor. The neoplasm was characterized by an encapsulated multilobed grey-white soft mass with stroma, and the recurrent tumor infiltrated veins and the heart. The tumor consisted of groups of clear cells with well outlined cytoplasmic boundaries separated by thin vascular stroma. These cells had few organelles, scattered clumps of glycogen, clear cytosol and prominent infolding and interdigitating plasma membranes and desmosomes. The clinical, light and electron microscopic features were consistent with a functional neoplasm of parathyroid tissue origin.


Transmissible congenital demyelinating encephalopathy of lambs. Twenty-two fetal lambs were inoculated in utero with tissue suspension prepared from lambs born with weakness, incoordination and clonic tremor. Clinically, affected newborn lambs had clonic tremor, were generally weak and had abnormally pigmented hairy fleece. The inoculation resulted in a disseminated encephalomyelitis with secondary teratologic changes in a significant number of fetuses. The mononuclear inflammatory changes were most obvious 14 days after inoculation, after which there was rapid resolution. Changes seen at birth were chronic astrocytosis with neuron loss in the spinal cord and cerebellar dysplasia. Single radioimmunodiffusion studies showed consistently low IgG in infected fetuses and high IgG in lambs at birth.


Diagnostic clues in metastatic lesions of endocarditis in addicts. Gram stains and cultures of multiple extravascular sites showed the infecting organisms in 17 of 26 heroin addicts with endocarditis. In addition to routine blood cultures, the etiologic agent was cultured from Osler nodes and Janeway lesions in ten patients, subcutaneous abscesses in eight, pleural fluids in eight, joint aspirates in three, spinal fluids in three, pericardial fluids in two, muscle abscesses in two and endometrium in one patient. Gram-positive cocci were found in extravascular lesions in 11 of 12 patients with staphy-lococcal endocarditis and from as many as four different sites. In contrast, no Gram-positive cocci were seen in extravascular sites in any of eight patients with enterococcal endocarditis although six of them had peripheral lesions. Gram stain and culture of multiple extravascular sites appears to provide a valuable early clue to the nature of the etiologic agent in addict endocarditis.


Splenic subcapsular hematoma--ultrasonic diagnosis. In five patients with varying histories of blunt abdominal trauma, examinations were carried out with ultrasonography and other imaging modalities. In all five patients, large, fluid-filled masses were noted in the left upper quadrant. Two patients had nonpalpable hematomas, but examinations were done because of history and vague clinical symptoms. Three patients had palpable masses. In all five patients there was surgical confirmation of the ultrasonic findings, and all recovered without complications. Ultrasonic tomography offers a convenient noninvasive method for assessing suspected splenic hematoma and can also exclude the possibility in a careful examination.


Factors influencing the location of rural general practitioners. A study in Washington state. Data on (1) personal background, (2) place of medical education and training, (3) reasons for selecting the present place of practice and (4) previous practice location were gathered and analyzed from 41 general practitioners in rural Washington state. The analysis was done to isolate factors influencing the choice of location by physicians. Results show that most of the physicians had spent at least some of their preadulthood years in small communities and that most had some exposure to the state of Washington before establishing their practices in the state. In addition to the apparent importance of previous exposure to small communities and Washington state, the physicians were also influenced in their locational choice by (1) the professional advantages or appeal of the community, (2) recruitment efforts by persons within the community and (3) economic reasons. The physicians were rather immobile. Most had never practiced in another community and only two of the 41 physicians planned to move to another community.


Medical school graduates who leave California. A study at the University of California, San Francisco. A follow-up survey of 1,087 physicians who had graduated from the University of California, San Francisco, School of Medicine from 1951 through 1971 was completed in 1977. A total of 307 (28.2 percent) of these persons were found to have left California. Comparison of the 307 who left with the 780 who remained showed only slight and statistically insignificant differences on most variables, such as sex, academic performance in premedical and medical education, educational level and social class of parents, age at entry into medical school, ratings by admissions interviewers, choice of specialty and a wide variety of personality inventory measures. Among the variables that did differentiate were place of birth, location and prestige of premedical college, preferences for subjects in the sciences and the humanities, and the Medical College Admission Test (MCAT) scores for quantitative ability and general information. However, attempts to combine these individual differentiators into clusters or equations from which to forecast emigration from California were unsuccessful.


Unprofessional physicians--some correlative data. In the background of those physicians who have problems in medical practice serious enough to attract attention by the licensing body, there are factors that apparently can help predict such behavior. As a candidate for medical school the applicant more likely to have future problems has the following profile: (1) older than the average applicant with a lower grade point average; (2) more likely to have used tobacco; (3) did not receive a baccalaureate degree; (4) no military service; (5) turned in a sloppy handwritten application form, and (6) received a less than ideal character reference by the college from which applying. Furthermore, after admission to medical school the person more prone to future problems tends to be a poorer student than his peers and to receive a poorer rating in his first postgraduate year. The Loma Linda University graduate who has had such problems is also more likely to have settled in Southern California and to be in general practice.


Thoracic outlet syndrome.

Thoracic outlet syndrome. Soft tissue cervical injuries are among the most common posttrauma problems faced by general practitioners, orthopedists and neurosurgeons. The development of the thoracic outlet syndrome (TOS) following such injuries is more frequent than is generally recognized. Conservative treatment with physiotherapy, muscle relaxants, anti-inflammatory drugs and percutaneous electrostimulation usually proves effective in relieving TOS. In this series of 1,958 soft tissue cervical injuries, 459 patients (23 percent) were diagnosed as having TOS. Of these patients, 185 (41 percent) failed to respond to all conservative measures and consequently surgical operation in the form of a supraclavicular neurovascular decompression became necessary to relieve not only the symptoms of the neck-shoulder-arm syndrome but also to relieve a frequently unrecognized (72 percent) vertebrobasilar artery syndrome. The latter is most definitely an integral part of TOS. The most common misdiagnoses were cervical disc syndrome (42 percent) and cervical strain (42 percent). A long-term follow-up (average of seven years) of 90 patients showed that the results were judged good in 75 percent, fair in 11 percent and poor in 14 percent.


[Poisoning in childhood--an information centre report (author's transl)]. The Poison Control Centre in Vienna registered 4018 inquires regarding possible poisoning in children over a two-year period. The peak incidence occurred in the age group between 2 and 3 years and poisoning chiefly took place in the mornings and in the afternoons, the most frequently ingested substances being household chemicals and drugs. A study in 100 households showed ignorance and carelessness in dealing with chemical substances. An analysis of inquiries concerning medicines revealed the influence of packaging and external characteristics on the frequency of poisoning with these substances. Possibilities which might be of value in the prevention of poisoning in children are discussed.


[Changes in mortality of low birth weight infants after the introduction of newborn intensive care (author's transl)]. The Newborn Intensive Care Centre at the Landeskinderkrankenhaus Linz is the referral centre serving an area in which 20% of births in Austria occur. During a 4-year period ending 1976, after the facilities for intensive care had been introduced, the overall mortality of low birth weight infants (LBWI) was reduced by 44% (from 26% to 14%), whilst the mortality of LBWI born at the Landes-Frauenklinik Linz, which works in close collaboration with the Landeskinderkrankenhaus, went down by 60% (from 24% to 9%). The chances of survival decreased with increasing transportation distance and suboptimum standards of obstetrical care, in spite of intensive treatment after referral. It is suggested that the improved methods of perinatal care applied at the obstetrical and neonatal units are the cause of this remarkable improvement in survival rate of LBWI. These improvements in neonatal survival rate contributed considerably to the 40% decline in infant mortality in Upper Austria from 26.7% in 1973 to 16.2% in 1976..


[The occurrence of nappy rash at a children's hospital and its treatment with Canesten (author's transl)]. An unselected, mycologically-controlled trial was conducted at the University Children's Hospital of Graz on the treatment of nappy rash by the topical application of Canesten (clotrimazole), a broad-spectrum mycotic in the form of a 1% cream. 56 children, ranging in age from 3 weeks to 41/2 years, were treated for thrush, principally located in the genital area. Only some of the children were admitted primarily on account of the oral and/or perianal moniliasis. The majority of the children were hospitalized for some other reason and thrush was diagnosed as an accompanying condition. Candida albicans proved to be the most frequent pathogenic organism. The results of therapy were judged according to mycological and clinical criteria. The mycological findings became negative in 54 out of the 56 children. Clinical improvement was apparent in all cases between the 5th and 10th day of therapy; complete recovery occurred between the 5th and 25th day, depending on the extent and localization of the moniliasis. One child showed improvement in, but not recovery from the disease, because therapy was interrupted on premature discharge from hospital. Therapy was unsuccessful in the remaining child, although slight improvement occurred. Tolerance was good in all patients on application of Canesten cream thrice daily.


[Heroin withdrawal syndrome in a newborn infant (author's transl)]. The case of a newborn infant showing heroin withdrawal syndrome is reported. Symptoms of neonatal drug withdrawal syndrome, together with the complex problem of maternal drug addiction and pregnancy are briefly discussed.


[Ring chromosome 15 in a child (author's transl)]. A report is given of the occurrence of a ring chromosome 15 in a 5.6 year-old girl. The features of this case are mental retardation, small stature, microcephaly, malformation of the kidney, congenital heart disease and congenital dislocation of the hips. The features of this syndrome are very variable. Only 4 cases have been described up to 1975.


[A comparison of Ultrax, Diazil, Bactrim and Spiramycin in experimental toxoplasmosis in mice (author's transl)]. White mice infected intraperitoneally with the RH-strain of Toxoplasma gondii (inoculum size 50,000 to 100,000 free protozoans per mouse) received treatment between the second and eighth day after infection with sulphamethazine-pyrimethamine, sulphamethoxy-diazine-pyrimethamine, trimethoprim-sulphamethoxazole or spiramycin subcutaneously. All untreated controls and all mice of the trimethoprim-sulphamethoxazole and spiramycin-treated groups died during the acute stage (except two mice in the latter group on the 15th day). The mean survival times were 6.5, 7.5 and 7.6 days, respectively. The best results were obtained in the sulphamethazine-pyrimethamine-treated mice; 18 out of 27 survived the 30-day observation period (5 cured), in contrast to only 9 out of 40 sulphamethoxydiazine-pyrimethamine-treated mice. Considering the high pathogenicity of the RH-strain, the differences in immunological defence mechanisms in mice (absence of antibody-activating "accessory factor") and the late commencement of treatment of the infected mice, one can state that the combination of sulphamethoxydiazine-pyrimethamine should also be capable of overcoming acute human toxoplasmosis in pregnancy. Spiramycin, by contrast, should be given only in cases where sulphonamide intolerance exists and must then be given in high doses until delivery. The combination of sulphamethoxazole-trimethoprim cannot be recommended.


[Mumps meningitis and mumps vaccination (author's transl)]. Mumps meningitis (MM) is the most frequent inflammatory disease of the central nervous system in children. It occurs twice as often in boys as in girls. Usually it is mild; encephalitic signs are found only in 2-3% of the cases. Even here persistent neurological signs are rare, but psychological alterations are found in about 20% of the cases. 40% of all MM cases occur in children of school age necessitating absence from school for four weeks at last. The frequency of MM makes it a financial problem too. In Viennese hospitals 4.2 million Austrian Schillings were spent yearly for hospitalization of children with MM, on average, during the years 1971-1975. The vaccination of all Viennese children born in a single year (18,000) against mumps would require an outlay of only 2.8 million Austrian Schillings. Wide-spread routine vaccination against mumps is indicated, therefore, not only for medical, but for social and economic reasons as well.


[Results achieved on metabolic treatment of 90 pregnant women with manifest diabetes (author's transl)]. This paper concerns the treatment schedules employed and their outcome in 90 pregnancies in women with insulin-dependent clinical diabetes between 1962 and 1977. During the period 1962 to 1970, during which time diabetic control was still mostly carried out externally, the perinatal mortality rate (pnm) was 23.8%. As from 1971 the patients were put under control by the clinic as soon as possible on an interdisciplinary basis and the pnm dropped to 4.1%. The case history of these patients revealed that the pnm in previous pregnancies supervized elsewhere was 65%. No correlation was found between the pnm and the severity and duration of diabetes according to White's classification. Rigorous metabolic control is essential for an improvment in the pnm. This involves striving for mean blood glucose levels of under 100 mg% during the last trimester. Fetal weight gain above normal levels was sometimes detected by ultrasonic methods in spite of satisfactory metabolic regulation. The daily intake of carbohydrates should be reduced in these cases from 150-200 g to 100 g. Other important aspects include treatment of frequently-occurring complications (toxaemia, urinary infection, etc.), as well as measures to lower the rate of premature birth. The date of delivery was flexible and dependent on the response to metabolic control and the appearance of critical situations. On average, delivery took place at the end of the 38th week of gestation.


[Results of an interdisciplinary study on the value of contact thermography in the diagnosis of breast disease (author's transl)]. An interdisciplinary study was carried out to determine the accuracy of contact thermography in the detection of breast cancer. 200 patients were examined in form of a blind test, the mammographic and clinical findings being listed separately and inaccessible to the thermography team. The findings obtained on contact thermography also were listed separately and afterwards compared with the clinical and mammographic findings. 50 out of these 200 cases required histological clarification, which revealed 24 carcinomas and 26 benign conditions of the breast. Mammography and contact thermography both failed to detect 3 out of the 24 carcinomas, clinical examination gave a false negative result in 2 cases. Therefore, in the present case material, the accuracy of mammography and contact thermography is equal and enables us to state that the combination of clinical examination and contact thermography of the breast is of high accuracy and suited for routine mass screening programmes to enable the detection of breast disease without radiation exposure.


[Subanaesthetic doses of ketamine for obstetric delivery (author's transl)]. Twenty five parturients were anaesthetized by administration of 0.3 mg ketamine per kg body weight intravenously before emergence of the head of the newborn infant. 20 patients had complete amnesia for the time of delivery, but most of them remained cooperative, nevertheless. Of the other 5 patients, 3 recounted that they recalled the birth of their child like remembering a dream, but they did not remember pain. The method proved a failure in the case of two patients. The main advantage of this technique lies in keeping most of the parturients cooperative and able to help with pushing, while offering them amnesia and analgesia for this period. Comparison with thiopental and propanidide is discussed.


[Clinical evaluation of the antioestrogenic agent tamoxifen in the treatment of metastatic breast cancer (author's transl)]. The endocrine management of advanced breast cancer is of great clinical importance. Apart from the known therapeutic approach with oestrogens, androgens, gestagens and steroids, the oestrogen antagonist, tamoxifen appears to be a promising therapeutic agent. In this study from October 1st, 1975, to October 1st, 1976, the value of tamoxifen was examined in a controlled clinical trial. An objective remission after 3 months' treatment was achieved in 41% of the cases. The criteria of Karnofsky were used to evaluate clinical success. The median time of remission was 5,5 months. The determination of oestrogen receptors could provide a better selection of patients and, hence, help to achieve an increase in the remission rate. An interesting observation was a probably immunostimulative effect, but further investigations are necessary. The side-effects of treatment are detailed and the indications for the use of tamoxifen are discussed. More astonishing than the objective remission was the subjective improvement with relief of pain due to generalized bone metastases. On the basis of our observations it is concluded, that the use of the oestrogen antagonist, tamoxifen presents a potent alternative in the treatment of advanced and incurable breast cancer, especially in postmenopausal patients.


[Ideal application of computer tomography in the field of radiotherapeutic planning (author's transl)]. The value of computerized radiotherapeutic planning is illustrated by the case report of a patient with an extensive pelvic wall metastasis of a carcinoma of the uterine cervix diagnosed by conventional methods. The exact topography is delineated by computer tomography and enables optimum dosimetric radiotherapeutic planning.


Techniques for assessment of biliary excretion and enterohepatic circulation in the rat. 1. A surgical technique is described which enables biliary excretion studies to be performed in conscious unrestrained rats. 2. Bile is continuously collected in a glass vessel implanted into the peritoneal cavity. 3. Assessment of enterohepatic circulation is made by a modification of the technique. 4. The application of these techniques to both metabolic and pharmacokinetic studies is described briefly.


Metabolism of methylmercuric chloride by the gastro-intestinal flora of the rat. 1. The contents of the caecum and small intestine of the rat metabolized methylmercuric chloride in vitro to a volatile product over a period of 3 to 4 days. The bacterial flora of the gut were responsible for the metabolism. 2. in the presence of caecal contents methylmercury was reduced to metallic mercury. 3. The contents of the small intestine metabolized methylmercuric chloride indirectly, as a result of prior synthesis of H2S to a volatile sulphur derivative of methylmercury.


The fate of [103Ru]ruthenocene in mice and rats. 1. The metabolic fate, rate of excretion and organ distribution of [103Ru]ruthenocene, administered to mice intravenously, intraperitoneally and orally, were investigated. 2. Most of the 103Ru was eliminated from the body in 24 h; the remainder was located mostly in liver, gastro-intestinal tract and fat and was slowly excreted. 3. The 103Ru was excreted in the bile and urine as ruthenocene-O-glucuronide, as shown by enzymic hydrolysis and mass spectrum of the permethylated metabolite.


A comparison of drug-metabolizing capability in isolated viable rat hepatocytes and renal tubule fragments. 1. The metabolism of a number of xenobiotics has been investigated in isolated viable rat hepatocytes and kidney tubule fragments in suspension. 2. The level of Phase I metabolism was very low in the kidney cells although such cells possess appreciable Phase II metabolic capacity. 3. These findings are discussed in relation to the physiological role of cytochrome P-450 and the conjugating enzymes, and the value of intact cells systems in assessing inter-organ differences in xenobiotic metabolism.


Metabolism of alpha-methylfluorene-2-acetic acid (cicloprofen): isolation and identification of metabolites from rat urine. 1. Four metabolites of alpha-methylfluorene-2-acetic acid (cicloprofen) have been isolated from rat urine and identified as the 7-hydroxy, 9-hydroxy, 7,9-dihydroxy and 9-hydroxy-9-methoxy derivatives of cicloprofen. 2. 7-Hydroxy cicloprofen was the major metabolite, contributing 47% of the total radioactivity excreted in rat urine. The other three metabolites each contributed approx. 10% of the radioactivity in urine. There was little unchanged drug excreted in urine (2-6%); at least three other minor metabolites have not been identified. 3. A metabolic pathway for the formation of the 9-hydroxy-9-methoxy metabolite of cicloprofen is proposed.


Effect of polycyclic aromatic hydrocarbons on hepatic microsomal enzymes and disposition of methylnaphthalene in rainbow trout in vivo. 1. The effects of 3-methylcholanthrene, 2,3-benzanthracene and beta-naphthoflavone on xenobiotic metabolism in rainbow trout were studied. 2. These three polycyclic aromatic hydrocarbons increase hepatic arylhydrocarbon (benzo[alpha]pyrene) hydroxylase activity without altering glucuronyl transferase activity. 3. All three polycyclic aromatic hydrocarbons increased hepatic microsomal cytochrome P-450 levels by approximately 50%. 4. Pretreatment of trout with 2,3-benzanthracene resulted in an increase in the metabolism and biliary excretion of 2-methylnaphthalene in vivo. 5. These studies demonstrate that the induction of mono-oxygenation by polycyclic aromatic hydrocarbons can result in significant effects upon the metabolism and excretion of xenobiotics by fish in vivo.


Stereochemistry of the metabolic incorporation of oxygen into (+)- and (-)-N-benzylamphetamine. 1. Both (+)- and (-)-N-benzylamphetamine undergo alpha-carbon and N-oxidation to form N-dealkylated, deaminated and N-oxidized metabolites during incubation with fortified rabbit liver homogenates. 2. Quantitative determination of the metabolites based on specific g.l.c. procedures showed that all activities are localized in the microsomal fraction of rabbit liver. 3. N-Dealkylation, deamination and nitrone and secondary hydroxylamine formation are stereoselective. 4. The characteristics of the enzyme-substrate interactions for both isomers of N-benzylamphetamine indicate that at least two distinct enzyme systems are involved in the N-oxidation and alpha-carbon processes, or a single enzyme possessing an active site with differing conformational requirements for the two oxidative processes.


The stereoselective metabolism of ethylamphetamine with fortified rabbit liver homogenates. 1. The liver enzyme systems of rabbits involved in the oxidative metabolism of ethylamphetamine were shown to be localized in the microsomal fraction. 2. The effect of substrate concentration, incubation period and storage of the microsomal preparations at 4 degrees was investigated. 3. The results indicate the involvement of at least two stereoselective enzyme systems or different conformations of binding of different substrates to the same enzyme system. R-(-)-Ethylamphetamine is the preferred substrate for N-oxidation and dealkylation, whereas the S-(+)-isomer is preferred for deamination. When racemic ethyl amphetamine is metabolized, the enantiomers act as independent compounds and compete for the enzymes. 4. Neither alpha-C- nor N-oxidation is induced by pre-treatment with phenobarbitone or 3-methylcholanthrene.


[Special aspects of basaliomas (pigmentation, stroma, glucosaminoglycan capillary patterns)]. 1. 47 out of 61 basalcellepithelomas (BCE) contained melanocytes, but only 16 contained melanin; melanin was found predominantly in cystic BCE. 2. In contrast to malignant melanoma the proliferative activity in the stroma of BCE is low, since proliferating lymphocytes are lacking. Leukocytes and mast cells may be numerous, and are also Dopa-positive. 3. Our findings suggest that BCE produces a partially metachromatic substance, which apparently influences the stroma. 4. A well differentiated BCE has a distinct capillary pattern like a network, related to and similar to the capillary net of the pilosebaceous unit and especially to that of the sebaceous glands. 10% of the BCEs reveal at least a partial double-layered network resembling that of the hair follicle.


[Methods for determination of vitamins by means of high performance liquid chromatography (HPLC). II. Determination of vitamin A (author's transl)]. A method is described for the rapid determination of vitamin A in vitamin-concentrates, precursors and mineral supplements. After saponification of the sample, the vitamin A is extracted with petroleum-ether. In this extract the vitamin A is determined spectrophotometrically by HPLC without further clean-up.


[Spectral-photometric determination of L-ascorbic acid with N-bromsuccinimide and starch iodide (author's transl)]. A new spectrophotometric method for the determination of L-ascorbic acid (AS) with N-bromosuccinimide (NBS) and starch iodide as an indicator was developed. The questions of pH-dependence, sensitivity and specificity of the oxidation-reduction process were investigated. The method is suitable for the determination of AS in acid solutions; the best pH was 2.6. The specificity of the method for AS cannot be considered as definitely better than other methods. Its sensitivity, however, is higher than when using 2.6-dichlorophenol-indophenol (DIP). When applied the method usually yielded results close to the DIP method and due to its high sensitivity AS determinations in very dilute and hazy solutions are possible.


[Copper and zinc contents in milk and plasma of cows after high nutritional copper supplements]. In three feeding trials with dairy cows over periods of six weeks each, it was studied whether very high nutritional supplements of copper alter the copper and zinc levels of milk and plasma. The supplemented groups with an average milk yield of 20 kg were given CuSO4 X 5H2O at levels varying from 250 to 550 mg copper per cow and day over and above the amount supplied by the commercial winter ration (300 mg copper and 1200 mg zinc). There was no significant influence of the copper supplementation on the copper and zinc contents of milk compared with the untreated control animals. On the average for all experimental weeks, copper contents of 0.15--0.20 mg and zinc content of 4.0--4.6 mg/kg milk were recorded for the various experimental groups. The mean copper contents in plasma varied from 1.00 to 1.18 microgram/ml in the copper-supplemented groups and from 0.93 to 1.09 mircogram/ml in the control groups. The corresponding mean values for zinc ranged from 0.93 to 1.18 microgram/ml. Analysis of variance did not show any significant differences between the experimental groups nor any interactions between the copper and zinc contents. These results were discussed in relation to the dietary supply status.


[Residue analysis of plant material for organophosphorus pesticides with thioether groups including their sulphoxides and sulphones (author's transl)]. Residue analysis of food of plant origin for organophosphorus pesticides containing thioether groups should include the corresponding sulphoxide and sulphone metabolites. A method is proposed, consisting of a simple clean-up step for extracts from plant material and subsequent oxidation with potassium permanganate. The sulphones formed are detected and determined by gas-liquid chromatography with alkali flame thermionic detection.


[Surgical treatment of ureterocele].

[Surgical treatment of ureterocele]. From 1971 the authors operated on 6 patients with ureterocoele type B (Uson), using a modified Hutch-Chisholm method. Following the removal of the ureterocoele and reconstruction of the detrusor muscle, the hiatus of the ureter and the vesicular wall, the ureter is placed on the reconstructed muscle whereas its free end is fixed to the trigone. Covering the ureter with vesical mucosa is not necessary; in cases with large ureterocoeles that is not even possible. The regenerative capacity of the vesical mucosa is great and rapid and covers the intravesicular part of the ureter without causing damage to the ureteral orifice or to its valvular function. In all 6 patients the results were good at the control examination 3 to 6 years postoperatively.


[Acute gangrenous acalculous cholecystitis in a 6-year-old boy]. Acute cholecystitis in children and adolescents is unusally rare especialy the gangrenous inflammation. Only a few cases are reported in medical literature and each publication of such a case is a contribution to the further understanding of the clinical picture and diagnosis of this rare childhood disease. Special attention must be given to the early discovery of acute cholecystitis and early surgical intervention because if the pocess gains a foothold it can cause complications which can be life threatening. The treatment consists of an early cholecystectomy in which case the prognosis is good and the mortality rate is very low.


[Drug therapy of chronic tissue ischemia with improvement of microcirculation]. In this study the experience in treating 213 patients suffering from chronic ischemia with improvement of the microcirculation has been discussed. Medicamental treatment of chronic ischemia in patients with various pathologiic alterations of the circulation is indicated in cases which do not indicate reconstructive surgery. In the abundance of measures adopted in the treatment of these pathologic conditions the authors summarize their experience with the use of Pentoxyphyllin (Trental). During 1976 theyy treated 213 patients with this drug: 142 patients with pathologically altereed arterial circulation 51 patients with pathologically altered venous circulation 20 patienst on whom transplantations using various tissue transplants were used. The plan of administration of the drug, its undesireable side effects and the manifesting vasoactive effects of trental at the microcirculatory level especially on the microcirculation in tissue with pathologicaly altered perfusions has been discussed. Based on the shortlasting and limeted experiences the authors conclude that this drug can be recommended in therapy for various conditions of pathologicaly altered tissues circulation.


[Advantages and hazards of the intraoperative control of endocardial electrode pacemakers]. Discussed in this study are the authors' experiences with electrostimulation of the heart. The study is based on 276 pacemaker operations performed in the past 7 years. The authors remain partial to the transvenously introduced endocardial pacemakers monitored by X-raj. When radiation symptoms manifested themselves in 2 team members, a revision was made in the procedure. As a result, the means by which one may be exposed to uncontrolled and, prolenged stron radiotion were cited. Such radiation can result in pathologic changes in the blood, damage to the skin, nails, germinative epithelium and bone marrow. To prevent such an outcome, certain precautionary measures are taken which protect both the patient and surgical team. Also mentioned is that the surgical personnel should have the same benefits as radiologists.


Volume displacement of the tympanic membrane at stapedius reflex activity in different postures. Studies on variations in perilymphatic pressure. With the microflow method the volume displacement of the tympanic membrane and its direction of movement can be recorded at stapedius reflex contraction. There is an outward or inward movement of the tympanic membrane, which is affected by changes in posture. The results indicate that the perilymphatic pressure in man varies with the posture and that these variations can be measured indirectly outside the tympanic membrane. This can only be done, however, on condition that there are no pressure variations across the tympanic membrane. This method opens up new ways of studying possible pressure changes in the inner ear in acute diseases.


The effects of the vacuum on vascular permeability of the middle ear. Following local application of various degrees of negative pressure to the middle ear, the authors observed changes in vascular permeability in guinea pigs, using Majno's vascular labelling technique. Increased permeability and effusions were seen in all experimental middle ears. Any pressure below -5 mm of mercury induced middle ear effusions. Accordingly, a decrease in pressure developed in the middle ear cavity may cause transdation of serum drawn from the submucosal vessels, resulting in fluids in the middle ear of aero-otitis. In such a circumstance, mast cells which are easily influenced by atmospheric pressure may be involved in increasing vascular permeability.


The influence of cigarette smoke on the pharyngeal mucosa. The influence of cigarette smoke on the pharyngeal mucosa was investigated in a clinical study and in an experiment on animals. Histologic reports were evaluated according to the Kambic-Lenart classification of hyperplastic aberrations of the throat mucosa. A close dependence of the degree of hyperplasia and the number of cigarettes smoked was revealed. The more cigarettes the patients smoked every day, the more evident were changes on the mucosa, more clearly manifested in male than in female smokers. It was observed that the changes related to the hyperplasia atypica were more evident the longer the patients smoked. They were also more intense the younger the smokers were when they started smoking. In the experiment on animals, a number of factors with additionally noxious influence on the pharyngeal mucosa were excluded. A great interdependence was observed between the number of daily inhaled cigaretes and the changes on the pharyngeal mucosa.


Bilateral nasal vascular responses to unilateral sympathetic stimulation. Unilateral preganglionic cervical sympathetic stimulation in the anaesthetized cat evoked vasoconstriction in both nasal cavities, dependent on stimulation frequency. Vasoconstriction in the contralateral cavity was 15--20% of that of the stimulated side. Similar findings were obtained on unilateral Vidian nerve stimulation. Vasoconstriction evoked in the sympathectomized nasal cavity by stimulating the opposite cervical chain was reduced but not abolished by sectioning the posterior nasal and ethmoidal nerves of the stimulated side. It is suggested that vasoconstrictor fibres reach the opposite cavity either in these nerves or by way of blood vessels, but more likely that sympathetic fibres from these pathways innervate blood vessels which supply both nasal cavities.


Comparative measurements of the mucosal blood flow in the human maxillary sinus by plethysmography and by xenon. Two different methods, one plethysmographic and one where the elimination of radioactive inert gas was measured, have been used to calculate the blood flow in the mucosa of the maxillary sinus in living man. A total of 5 persons were investigated and the mean values of the blood flow in the two methods showed a close correlation. Plethysmography is more easily performed and is therefore the preferable method to be used in studies on the physiology of the maxillary sinus.


Congenital hypothyroidism in Sweden. Incidence and age at diagnosis. A total number of 112 children with congenital hypothyroidism were diagnosed in all Children's Hospitals and Pediatric Wards in Sweden during the 7-year period 1969-1975. Since it may be assumed that all cases of congenital hypothyroidism, which were diagnosed during that period were seen in one of these hospitals, the incidence of congenital hypothyroidism in Sweden can be calculated to be 1:6900 live births. In spite of an efficient National Health Care Program for infants the diagnosis was delayed until after an age of three months in 52% of the cases. This fact supports the view that mass screening of newborns for congenital hypothyroidism has to be introduced in Sweden. However, the beneficial effects of such a program cannot be fully elucidated until it has been considered whether earlier instituted treatment would have improved the outcome of children in whom a diagnosis was made after 3 months of age.


Labyrinthine and somatosensory convergence upon vestibulo-ocular units. The vestibular nuclei were investigated in 18 adult cats. Vestibulo-oculo-motor neurons were identified by antidromic stimulation of the ascending medial longitudinal fasciculus (MLF). The neurons were subjected to various stimuli: vestibular, neck, forelimb and hindlimb nerve stimulation on both sides. The recording was extracellular with micropipettes containing Fast Green. Only the medial and the superior vestibular nuclei were found to project to the MLF. All projecting units had input from the labyrinths. Excitatory response latencies to ipsilateral labyrinth stimulation never exceeded 3 msec. Both excitatory and inhibitory response latencies could be distributed into different categories. The majority of the neurons did not receive a somatosensory input, and surprisingly few convergent units could be seen. Peripheral somatosensory information apparently plays a minor role in vestibulo-ocular relations.


Deletion short arm 18 and Silver-Russell syndrome. A 14-year-old boy presented with physical signs of the Silver-Russell syndrome. He further had low-set, large protruding ears, ptosis, broad nasal base, thick protruding lips, pronounced caried, malaligment of teeth, micrognathia and mental retardation. Chromosome examination showed deletion of the short arms of chromosome No. 18. It is concluded that considering the previous findings of chromosome No. 18 aberrations in some patients with Silver-Russell syndrome such patients should always have chromosome examination made.


The size of the middle ear and the mastoid air cell. The total volume for the middle ear and mastoid air cells was measured in 55 temporal bones with normal ear drums from a Norwegian post-mortem material. The measurements were made by an acoustic method and checked by means of fluid filling induced by vacuum pumping. As a measuring fluid X-ray contrast medium was employed so that the degree of filling could be examined by X-ray. The volume varied between approximately 2--22 cm3 with an average round 6,5 cm3.


Cytolytic activity of tonsil cells.

Cytolytic activity of tonsil cells. The ability of normal canine tonsil cells, and that of humans with chronic tonsillitis, to lyse heteroerythrocytes in vitro is shown. Heterologous erythrocyte destruction by tonsil cells is markedly increased after immunization of the animal. Tonsil cells of patients with chronic tonsillitis lyse the erythrocytes coated with streptococcus and staphylococcus antigens more actively. An experimental tonsillitis increases the ability of tonsils to lyse erythrocytes. Since cytolytic activity of tonsil cells is not altered by the removal of phagocytes and treatment with antiglobulin serum, one can presume that it is caused by T-lymphocytes.


Peliosis hepatis in a child.

Peliosis hepatis in a child. A boy is described with peliosis hepatis. He suffered from a Fanconi anaemia and was treated with prednisolone, dianabol and methyltestosterone. A review of the clinical and pathological aspects of the condition is given.


Ultrasonic irradiation of the guinea pig labyrinth. Correlation of morphology and intralabyrinthine temperature. The effects of high frequency ultrasound on the inner ear structures after irradiation of the lateral semicircular canal have been analysed by means of light-and electronmicroscopy. Sudden as well as gradual morphological changes in the vestibular sensory epithelium are described. Damage to the connective tissue stroma, blood vessels and nerve fibres characterized the chronic phase. Both cochlear morphology and hearing remained normal after irradiation of some behaviorally conditioned animals. The temperature rise in the labyrinth during continuous irradiation was studied. The experiments indicated that the mechanical effects may be more significant than the thermal in explaining the structural changes of the inner ear of guinea pigs. The results are compared with previous extensive experience of ultrasound treatment of patients with Meniere's disease.


Immunosuppressive measles encephalopathy. A case of measles infection without a rash, which was followed by a severe encephalopathy after two months, is described in a 2 1/2 year old boy. At the age of 8 months he had been irradiated for an inoperable intrathoracic neuroblastoma, and at the time of exposure to measles he was being treated with cyclophosphamide and vincristine. This case closely resembles other cases recently described and termed immunosuppressive measles encephalopathy. The syndrome is believed to represent the effect of measles virus in patients with deficient cellular immunity induced by antineoplastic treatment. The importance of protecting children on immunosuppressive treatment for contracting measles is stressed.


The effects of mercurial poisoning on the vestibular system. The sensory epithelium with adjacent nerve endings and the secretory epithelium may both become damaged following mercury chloride intoxication. Peripheral myelinated nerve fibres in the crista ampullaris showed signs of degeneration following chronic poisonins. Ultrastructural alterations of the vestibular hair cells initially occurred in animals free from clinical signs of intoxication. The sensory epithelium and occasionally the secretory cells were affected before signs of ultrastructural damage could be detected in the myelinated nerves.


Function and dimensions of the circulatory system in anorexia nervosa. The functional and dimensional components of the oxygen transporting system was studied in 17 female and 11 male patients suffering from anorexia nervosa. Both groups were 14.9 years old, on average, and had lost about 25% of their weight. Measurements at rest included blood and heart volume, heart rate, blood pressure, oxygen uptake (VO2), RQ, blood lactate (LA) and in 6 of the patients cardiac output. During bicycle ergometry the determinations of heart rate, blood pressure, LA, VO2 and cardiac output were repeated and maximal aerobic power was determined. A low metabolic rate with bradycardia and hypotension was apparent at rest. Blood and heart volume was decreased proportionally to the weight loss. On a given work load VO2 was lowered to the same extent as the resting metabolic rate. At maximal effort VO2 was reduced out of proportion to the circulatory dimensions and maximal heart rate was low. During exercise cardiac output was normally related to VO2 and stroke volume was maintained, indicating a normokinetic circulation and an unimpaired myocardial function. The main cause of the low maximal aerobic power seems to be the reduced muscle mass.


Reliability of Békésy threshold tracing in identification of carriers of genes for an X-linked disease with deafness. Seven identified carriers and 20 potential carriers of Norris's disease have been examined by pure tone octave audiometry and Békésy audiometry. The investigation supports earlier results of Békésy threshold tracings performed in heterozygote carriers of genes for recessive hearing impairment. The sensitivity of the method is poor. The specificity of the Békésy threshold tracing is high, meaning that an absent dip cannot exclude the possibility of a subject being a carrier, whereas a present dip can be regarded as an indication of carrier. When comparing conventional octave audiometry and Békésy threshold tracing, the latter method is found to be more subtle in finding carriers of genes for recessive deafness. Therefore, Békésy threshold tracing may be of help in the genetic counselling of potential carriers of genes for recessive deafness.


Farber's disease as a ceramidosis: clinical, radiological and biochemical aspects. A case of Farber's disease associated with athyreosis is reported in a Belgian infant born from consanguineous parents. A detailed clinical observation made from the early onset of symptoms until death of the patient at age of 22 months, together with radiological, morphological and biochemical data confirmed the diagnosis of Farber's disease and its specific storage process. Cultured fibroblast studies disclosed an abnormal catabolism of ceramides, presumably related to the deficiency in lysosomal ceramidase. Family history confirms that the disease is inherited as an autosomal recessive trait.


The effect of preceding tilt on the perceived vertical. Hysteresis in perception of the vertical. The subjective vertical (SV) was measured at various positions of roll-tilt (R). Positions R90-right, R 45-right, R0, R45-left, R90-left were reached either in clockwise sequence (i.e. starting with R 90-left) or in counterclockwise sequence (starting with R90-right); position R135-right was attained from R 110-right or R 160-right. The SV was affected by the preceding tilt (hysteresis). Clockwise position sequence produced, for example, a counterclockwise SV deviation (from the medium value at the obtained position) as though indicating a more advanced tilt position (Fig. 5). It is concluded that the aftereffects and hysteresis differences in perception of position and of SV depend on adaptational processes in the somatoreception system which interacts with the labyrinth posture-receptors.


Bilateral renal asplasia without Potter's syndrome. A newborn infant with bilateral aplasia of kidneys and ureters and a rudimentary bladder is reported. Other manifestations of Potter's syndrome (oligohydramnios, lung hypoplasia and an abnormal face) were missing as were other congenital malformations. Deviations from the full picture of Potter's syndrome seem to be rare. This case, however, shows that bilateral renal aplasia cannot be excluded as a cause of anuria in a newborn infant, even if all other manifestations of Potter's syndrome are missing.


Seasonal variations in weight of children attending an under-fives clinic in Lesotho. The incidence of weight loss between successive visits, prevalence of under centile 3 weight-for-age and over centile 97, showed a marked bimodal annual variation for 1243 children attending an under-fives clinic. 9949 weighings on 661 boys and 682 girls over a five year period, contributed to the database. Season of birth also significantly influenced the centile distributions of weight-attained-for-age. Children over 1 1/2 years old showed considerably higher rates of weight loss (about 1 in 5 children attending in their fifth year of life), than children younger than the mean age of weaning. The rates of weight loss, together with seasonal variation, was considerably higher for a group of 'Regular Attenders' to the clinic, than for a group of 'Low Attenders'. Seasonal influences on growth need to be taken into accounts in evaluating the quality of care and outcome produced by under-fives clinics.


Relative underweight in cystic fibrosis and its prognostic value. On the basis of observations in 117 children with cystic fibrosis, seen from January 1956 to June 1976, it is demonstrated that the relative underweight (weight loss corrected for height) is most pronounced in children with predominantly pulmonary sypmtoms. The degree of underweight closely correlates inversely with survival. Because of its prognostic value, it is recommended that this clinical parameter be included in the checkups which are periodically carried out on children suffering from cystic fibrosis.


Cardiovascular impairment and physical working capacity in children with chronic renal failure. Forty children with chronic renal failure (CRF) on conservative treatment, on hemodialysis, or after renal transplantation and 22 children respresenting a non-uremic control group were subjected to repeated cardiologic examinations by ECG, PCG, chest X-rays and cycle ergometer exercise tests to monitor signs of uremic heart disease and to evaluate physical working capacity (W170). In the CRF group a progressive impairment of W170 was found, starting at an early stage of the disease. Exercise tolerance was inversely related to the degree of CRF. A correlation was also found between W170 and renal anemia. After starting dialysis, W170 failed to increase significantly. Immediately after dialysis an acute drop in W170 occurred. Renal anemia was found to be the main pathogenetic factor of uremic heart disease in children. In some cases hypercirculation following arteriovenous fistulae became equally important as a cause of reduced myocardial performance. Physical rehabilitation, as measured by exercise tolerance tests, was better in transplanted than in dialysed children.


Lipolytic activity in milk from mothers of unjaundiced infants. Lipoprotein lipase activity and free fatty acid concentrations are measured in samples of milk collected from 50 mothers of infants without prolonged neonatal jaundice; in many samples the values are in the same high range as observed in all samples collected from nine mothers of jaundiced infants. These findings are discussed with relevance to the problems of breast-milk jaundice and factors controlling the milk secretion.


Factor VIII activity and antigen in sick newborns with pathological proteolysis in blood. Factor VIII clotting activity (VII:C) and factor VIII related antigen (VIII:R:AG) were determined in 12 sick newborn infants with pathological proteolysis in their circulation. A marked discrepancy was noted between VIII:R:AG and VIII:C, the ratio in sick infants being, on average, 2:1, while no discrepancy was seen in healthy newborns. The finding in the sick infants resembled a low grade plasminogen activation, which was studied experimentally. It is concluded that demonstration of a marked discrepancy between VIII:R:AG and VIII:C is a useful indication of pathologic proteolysis in sick newborns.


Electrolytes in nails analysed by X-ray microanalysis in electron microscopy. Considerations on a new method for the diagnosis of cystic fibrosis. Patients with cystic fibrosis (CF) have an increased concentration of sodium in their nails. Hitherto, only neutron activation analysis has been considered for the diagnosis of cystic fibrosis by analysis of electrolytes in nails. It has been thoroughly tested methodologically and clinically. However, the intrinsic advantages of X-ray microanalysis and the results obtained in this study suggest that this method, after further testing, may be a useful diagnostic acid for cystic fibrosis. In comparison with neutron activation analysis, X-ray microanalysis has the advantage of simultaneously giving the concentrations of several elements and may be accessible at any hospital with an electron microscope fitted with the necessary equipment. Nails of CF-patients are here shown to have increased concentrations of Na, K and Cl, which will make the diagnosis of cystic fibrosis more reliable. The possibility of using sulphur as a reference element may eliminate the weighing procedure necessary in neutron activation analysis.


The influence of amphetamine addiction on pregnancy and the newborn infant. The influence of amphetamine addiction on pregnancy and the newborn infant has been studied retrospectively in 23 cases. Six of the mothers claimed to have discontinued their abuse in early pregnancy, while the remaining 17 mothers continued throughout. In comparison with the average number of visits by pregnant Swedish women to maternal health centres, the 17 women who continued their abuse made significantly fewer visits, although there was a wide variation. Complications related to pregnancy and delivery were few, however. One child with a myelomeningocele was stillborn. Six children were preterm and three small for gestational age. Two full-term children were extremely drowsy and in need of tube feeding, symptoms that might be due to the maternal abuse. Eight of the ten mothers, who had previous children placed in foster homes by the Social Welfare Department, left the hospital with their newborn infant in their care as well as all the eleven primiparae.


The incidence of diabetes mellitus in Swedish children 1970--1975. We report a retrospective study of diabetic children, 0--14 years of age, from seven Swedish departments of paediatrics. There were 359 new cases in the years 1970--1975. Notification suggested that there was a mean yearly incidence of 19.6 cases per 100 000 with a year to year variation of 10.0--26.4 per 100 000. Consequently about 330 new cases of childhood diabetes would be expected in Sweden every year. Incidence varied considerably between different geographical areas. The age distribution was bimodal with a main peak at about 12 years and another peak at about 7 years. There was some evidence for clustering of new cases in January and the autumn. The mean prevalence of childhood diabetes in the seven districts was 1.3 per 1 000.


Serum cholesterol and triglyceride levels in Norwegian adolescent school children. The frequency distribution of serum cholesterol and triglycerides in 172 boys and 232 girls, 13--16 years, from four elementary schools in Oslo has been determined. The cholesterol values were significantly higher for girls 15--16 years than for boys of the same age group. In the case of triglycerides boys 15--16 years had significantly higher values than boys 13--14 years. Otherwise no statistically significant differences with regard to sex and age were observed. The 85th percentiles have been suggested as appropriate upper normal limits. In all groups the 85th percentile for plasma cholesterol was slightly below 6 mmol/l. The corresponding plasma triglyceride value was below 2 mmol/l.


Brain-typical creatinekinase in the serum of newborn infants with perinatal brain damage. The normal values of serum-CK-activity in healthy newborns varied greatly (95% range: 4--165 U/l; 257 probands) and the borderline to pathological values was not sharp. Brain-typical CK-isoenzyme (CK-BB) could be detected in serum of 6 of 8 infants with perinatal brain damage by means of agar gel electrophoresis. The combination of neuropathological symptoms, increased total-serum-CK-activity, and significant amount of CK-BB in serum seemed to be a sure sign of severe CNS-damage in newborns.


Ano-rectal manometry in the diagnosis of Hirschsprung's disease in infants. Manometric recordings of internal sphincter activity were performed during distension of the rectum in 10 healthy control infants and in 9 infants with clinical signs of Hirschsprung's disease. In 8 of the healthy infants relaxations of the internal sphincter were obtained, which were maximal 4 to 7 secs after rectal distension. This was also the case in 5 of the patients who were later proven not to have Hirschsprung's disease. In 3 patients no relaxations of the internal sphincter could be recorded. Subsequent rectal biopsy revealed absence of ganglion cells, confirming the diagnosis Hirschsprung's disease. The remaining 3 infants (2 controls and 1 patient) could not be calmed during the examination and the results were inconclusive. It is concluded that ano-rectal manometry is a valuable method of examination in the diagnosis of Hirschsprung's disease in infants. No false results were obtained in this study. Furthermore, it is an easy procedure without risk or discomfort for the patient.


Phenobarbital metabolism in adults and in newborn infants. Two adult volunteers and four newborn infants were given a single dose of phenobarbital. The output in the urine o f unchanged phenobartital and of the two main metabolites p-hydroxy phenobarbital and conjugated p-hydroxy phenobarbital was followed during 8 days in the newborns and during 2 or 4 weeks in the adults. The plasma levels were also determined and some pharmacokinetic constants calculated. It was found that the newborn patients excreted unchanged phenobartibal and p-hydroxy phenobarbital in the same proportions relative to dose as did the adult volunteers, 2.e. 16--17% unchanged drug and 9--10% of the metabolite during the first 8 days after administration. On the other hand, there was a clear-cut age difference in output of conjugated metabolite where the newborns excreted only 5% of the given dose during the 8-day observation period. The corresponding value for the adults was 15%. It is concluded that a poor conjugating capacity in the newborn may not have any serious consequences with a drug like phenobarbital where major alternative routes of excretion exist (unchanged drug and unconjugated metabolite). The clinical significance of immature drug metabolites and of unchanged drug is taken into consideration.


Renal function in anorexia nervosa.

Renal function in anorexia nervosa. Renal function was examined in twelve patients, eight girls and four boys, with anorexia nervosa (AN) ranging in age from 12.6 to 18.2 years. The weight loss at the time of the study averaged 26%. Determinations were made of glomerular filtration rate (GFR), PAH clearance (CPAH) and urinary concentrating capacity. For references the same studies were also carried out in five healthy teenagers. Both GFR and CPAH were generally CPAH as shown by a significantly lower filtration fraction (FF) in AN. Indirect evidence suggests that the low FF could be attributed to reduced water permeability of the glomerular capillary. The urinary concentrating capacity following fluid deprivation was moderately depressed both before and after the administration of vasopressin. The concentrating defect in AN must therefore be primary of renal origin.


Limb circulation in anorexia nervosa.

Limb circulation in anorexia nervosa. Blood flow, skin temperature and blood pressure of the lower limbs and the effect of indirect, radiant heat on calf blood flow and leg skin temperature was determined in sixteen children with anorexia nervosa (group A) and fourteen healthy children (group H) of the same age and body height. Calf blood flow as measured by venous occlusion plethysmography. Arm blood pressure was obtained by tourniquet and toe pressure and digital plethysmograms by a strain-gauge. Skin temperature was measured with a thermocouple. In group A calf blood flow was about 50--60% lower than the mean values observed in group H and a marked difference was maintained after the heat load. Skin temperature of the knees and toes were higher in group H. Systolic arm blood pressure and toe pressure were on the average 20 mmHg and 13 mmHg lower in group A. It is suggested that there is a heat-conserving, selective peripheral vasoconstriction in the anorexic patients.


Total body potassium fat free weight and maximal aerobic power in children with anorexia nervosa. Body composition and aerobic work performance have been studied in 5 boys and 10 girls suffering from anorexia nervosa. The average ages of the two groups of children were 15.4 (boys) and 15.2 (girls) years respectively. Measurements of body composition included height, weight (W), body potassium (40K), skinfold thickness (SFT) at triceps and subscapularis, blood volume (BV) and femoral condylar and radioulnar breadths. From these measurements estimates of fat free weight (FFW), skeletal weight (S) and lean body mass (LBM) were made. Work performance was assessed by measurement of the maximal aerobic power (VO2 max). The patients had lost on average 26% of their former body weight. The boys had on average greater than 7% of their body weight as fat compared with greater than 9% in the girls. However, the loss of weight was not solely due to loss of body fat, but could also be ascribed to a decrease in soft fatfree tissue. LBM or FFW could be estimated as well from SFT as from 40k. vo2 max averaged 1.43 1/min (35.1 ml/kg/min) in the anorexic boys and 1.24 l/min (33.2 ml/kg/min) in the girls and was associated with FFW and LBM. However, VO2 max was lower in relation to LBM than in healthy children of the same age. Thus it was suggested that the emaciation in anorexia is directly attributable to loss of both fat and muscle and accounts in part for the reduction of aerobic power observed. However, an important factor may be the debilitating effect of starvation on the patient, particularly in its advanced and later stages, which reduces his/her level of habitual physical activity.


Pseudohypoaldosteronism. Clinical, biochemical and morphological studies in a long-term follow-up. A boy with pseudohypoaldosteronism was followed from birth to the age of 7 years. Failure to thrive, vomiting, dehydration, hyponatraemia and urinary sodium loss were prominent findings. Urinary excretion of corticosteroid metabolites was normal. Before treatment, excessively high plasma renin concentration was found, associated with a marked activation of aldosterone secretion. A renal biopsy showed  pronounced hypertrophy of the juxtaglomerular apparatus. Persisting metabolic acidosis and an insufficient urinary acidifying capacity suggested the presence of distal renal tubular acidosis. Treatment with sodium bicarbonate and sodium chloride from 19 to 31 months of age resulted in normal growth and normal physical and mental development. The plasma electrolytes were normalized but a pronounced activation of the renin-aldosterone system persisted after therapy, and on sodium restriction this system responded with a considerable further activation.


Fall in choline acetyltransferase activity in the ventricles of the rat heart after treatment with a ganglion blocking drug. The choline acetyltransferase activity was found to be 27% lower in the ventricles of rats which had been given the ganglion blocking drug chlorisondamine than in those of untreated rats. Since the weight of the ventricles were also lower in the treated rats than in the untreated ones, it was wondered whether a change in the muscle mass as such affected the activity of the enzyme: isoprenaline treatment was found to cause the weight to increase markedly, while it left the enzyme activity unchanged. The decrease in enzyme activity observed after the prolonged ganglion blockade is interpreted as being the consequence of a reduced traffic of impulses along the postganglionic parasympathetic nerves of the ventricles. Thus, the results of the present investigation give further support for the ideal of a vagal innervation of this part of the heart.


On the neuromuscular effects of pindolol and sotalol in the rat. The effects of pindolol and sotalol on neuromusclar transmission were tested using intracellular microelectrode recording of resting membrane potentials, miniature end-plate potentials and end-plate potentials, and recording of muscle contractions upon nerve stimulation of rat phrenic nerve-hemidaphragm preparations. Both pindolol and sotalol reduced the amplitudes of miniature end-plate potentials and end-plate potentials in a dose-dependent manner without significantly affecting their time-courses. Pindolol, but not sotalol, also increased the frequency of the miniature end-plate potentials and decreased th number of acetylcholine quanta released by nerve impulses. Neither of the drugs significantly affected resting membrane potentials of the muscle fibres or excitability of the motor nerve to electric stimulation.


Ultrastructure of synaptosomes from fetal rat brain. The crude mitochondrial fraction P2 and subfractions of P2 were prepared from the brain stem, hemispheres and whole brain of 19-day-old fetal rats. Samples were fixed in glutaraldehyde-osmium, NaMnO4 or by Tranzer's triple fixation method (aldehydr-chromate-dichromate-osmium) and examined by electron microscopy. The C-fraction from whole brain was the main synaptosome fraction, containing 3.2% presynaptic terminals as counted from all membrane bound particles. The brain stem showed more presynaptic terminals than the hemisphere (2.8% versus 0.9%) suggesting a caudal-rostral maturation gradient for synaptogenesis. The maturity of the nerve endings obtained was very variable in contrast to the rather uniform synaptosomes derived from adult tissue. They varied from profiles without any substructures to mature synaptosomes displaying asymmetric synaptic junctions. Monoamine synaptosomes containing small granular vesicles were not detected in the present study, suggesting immaturity of the granular monoamine pool at this stage of development.


Effect of chronic hypoxia on hepatic triacylglycerol concentration and mitochondrial fatty acid oxidizing capacity in liver and heart. The effect of moderated hypoxia (50.5 kPa air) and severe hypoxia (40.8 kPa air) in vivo liver and heart triglyceride concentration and mitochondrial respiration rates was studied. Liver triglyceride concentrations increased in severe hypoxia from 7.3 mumol/g wet weight to 23.3 mumol/g wet weight over 7 days. After the period of seven days in severe hypoxia, the palmitate, octanoate and palmitoylcarnitine oxidation rates of mitochondrial suspensions were significantly reduced when the citric acid cycle was operative. No decrease in the fatty acid, fatty acyl-CoA or carnitine derivative oxidation was observed when only the beta oxidation system was studied. Mitochondria isolated from the heart or liver after seven days in severe hypoxia showed reduced respiratory control ratios, the decrease being from the normal 4.9 to 1.9 in the liver mitochondria using succinate as substrate. The reduction in respiratory control was mainly due to lowered State 3 respiration rates. Some reduction in the ratio was also observed in the fasting controls, from 5.8 to 3.4 with succinate. The respiratory control ratio could be partially normalized by the addition of albumin to the isolation medium for the liver mitochondria after severe hypoxia. Under these conditions, however, the State 4 respiration of the mitochondria from the hypoxic animals was higher than that for the controls.


Efflux of phenylalanine and troptophan from cerebral cortex slices of adult and 7-day-old rats. An equation of two exponential terms was found to adequately describe the efflux of phenylalanine and tryptophan from cerebral cortex slices of adult and 7-day-old rats. These exponential terms described two forms (components) of efflux taking place at different rates. The fast component of efflux was more prominent in the slices from young rats than in those from adults. In both age groups the contribution of the fast component increased with an increasing amino acid concentration in the superfusate, but there were no changes in the rate constants. The rate constants of the fast components were equal in all experimental conditions in both age groups. The rate constants for the slow components of both amino acids were lower in the slices from adult rats than in those from young rats. The reason for efflux occurring at two different rates is discussed. The fast component probably consisted of the amino acid originating from the extracellular space of the slices and of the intracellular amino acid released by exchange. The slow component consisted of the amino acid released from the cells by other mechanisms, e.g. by diffusion through the membranes or by some active efflux processes. The cerebral cortex slices from adult rats have greater ability to concentrate aromatic amino acids than the slices from young rats. This may partly be dependent on the more effective influx and partly on the slower efflux of amino acids in the slices from adults.


The function of baroreceptor C fibres in the rabbit's aortic nerve. The participation of aortic nerve C fibers in the baroreflex was investigated by recording changes in renal nerve activity in response to acute increases in arterial pressure, in two experimental situations: with the A and C fibres of the aortic nerve intact, and with the A fibres temporarily blocked by a hyperpolarizing current (anodal block). Pressure was increased by manual inflation of an intra-aortic balloon, and interference from other barorecptor areas was avoided by carotid occlusion and sectioning of the right aortic nerve. Rises in mean arterial pressure exceeding 20 mmHg, to levels above 110 mmHg, were needed to trigger sympathetic inhibition via C fibres. A rise of 45 mmHg caused 50% reduction in sympathetic activity, equal to that obtained by stimulation of aortic nerve C fibres at about 3 Hz. In contrast, a rise of 20-30 mmHg evoked more than 60% reduction in sympathetic activity when the A fibres were operative. Judged by these studies of peak reflex responses to brief pressure rises, baroreceptors with C fibres in the aortic nerve have a much higher threshold to pressure than their myelinated counterpart; the C fibres contribute to the baroreflex inhibition sympathetic discharge only when pressure is increased well above normal resting levels.


Tissue osmolality in intestinal villi during luminal perfusion with isotonic electrolyte solutions. A cryoscoptic technique has been developed that makes it possible to determine tissue osmolality in the core of the intestinal villi. During absorption from an isotonic electrolyte solution containing glucose an osmolality gradient was demonstrated from tip to base of the villi in both the jejunum and the ileum. The tissue osmolality at the villous tips was measured to 1 000-1 200 mOsm/kg H2O while the osmolality at the villous base was approximately isotonic with plasma. Increasing intestinal blood flow by i.a. administration of a vasodilator drug, or making the intestine ischemic by clamping the intestinal vascular supply while supplying the mucosa with oxygen, markedly decreased tissue osmolality. Substituting all sodium ions with choline in the luminal perfusate abolished almost completely the tissue hyperosmolality and the intestine became a secretory organ. These observations are consistent with the view that the observed villous tissue hyperosmolality was created by a countercurrent multiplication of sodium chloride. The physiological implications of this mechanism is discussed and it is, among other things, proposed that the hyperosmolar region represents the hyperosmotic compartment necessary for explaining intestinal water absorption.


Kidney volume expansion and prostaglandin release by bradykinin. The effect of indomethacin pretreatment. 100 ng/kg/min bradykinin was infused into the left renal artery in anaesthetized dogs which were loaded with 10% mannitol in saline to produce a diuresis of approximately 1 ml/min. Bradykinin initially increased renal blood flow (70%), kidney volume (20%). Kidney volume, diuresis and urine osmolarity remained equally changed during continuous kinin infusion, while other parameters subsided toward the control levels. When renal blood flow was maintained constant during the infusion of bradykinin, urine PG-excretion increased (330%), the glomerular filtration decreased (60%) and this was accompanied by decreased kidney volume, diuresis/natriuresis with unchanged urine osmolarity. Indomethacin treatment (2.5 mg/kg i.v.) decreased renal blood flow (35%) and inhibited urine PG-excretion. Bradykinin after indomethacin showed effects which were very similar to those observed before indomethacin treatment. It is concluded that increased intratubular volume is a main determinant of bradykinin induced increase of whole kidney volume. The accompanying increase of intrarenal pressure does not apparently contribute to the kinin induced PG-release. The vasodilation by bradykinin seems independent of released prostaglandins. The diuresis/natriuresis and decreased urine osmolarity are probably of hemodynamic origin.


Indirect vascular actions of (Gln4)-neurotensin in canine adipose tissue. The vasoconstrictor action of the tridecapeptide (Gln4)-neurotensin has been studied in subcutaneous adipose tissue in the inquinal region of anesthetized dogs. Close intra-arterial infusion of (Gln4)-neurotensin, 30--120 pmol X kg-1 b.wt. X min-1, elicited similar vasoconstrictions in the adipose tissue on the infusion side and on the contralateral side. This suggests that (Gln4)-neurotensin must enter the general circulation before it can elicit vasoconstriction. Removal of parts of the gastrointestinal tract did not change the vasoconstrictor response. Thus, there is no indication of release of vasoactive substances from the gastrointestinal tract by (Gln4)-neurotensin. Infusion into the portal vein elicited the same vasoconstriction in adipose tissue as the same dose administered i.v. It is suggested that the vasoconstrictor action in adipose tissue is not caused by (Gln4)-neurotensin per se. Instead, vasoactive substance(s) may be formed from (Gln4)-neurotensin.


The effects of cholera toxin on intramural blood flow distribution and capillary hydraulic conductivity in the cat small intestine. Blood flow distribution to the mucosa-submucosa and to the muscularis in the cat small intestine was investigated with a 85Kr elimination technique before and after exposing the intestinal mucosa for 30 min to cholera enterotoxin. In all experiments the toxin induced an intestinal secretion. Concomitantly, total intestinal blood flow was increased to a level 50 per cent above control 3 h after exposure. This vasodilatation reflected a doubling of mean blood flow in the mucosa--submucosa while muscularis blood flow remained unchanged. In another series of experiments the effect of cholera toxin on intestinal capillary hydraulic conductivity was investigated by determining the capillary filtration coefficient (CFC). A slight increase in CFC was noted during the 3 h observation period but this was not more pronounced than would have been expected from the concomitant vasodilatation. It is concluded that hemodynamic changes in the intestinal mucosa may be one of the several factors that probably are involved in the pathogenesis of cholera.


Effect of adenosine, adenosine analogues and drugs inhibiting adenosine inactivation on lipolysis in rat fat cells. It has been suggested that adenosine may be a physiologically important modulator of lipolysis. In the present study it was found that adenosine inhibited lipolysis stimulated by low (0.03 micrometer) concentrations of noradrenaline (NA). Lipolysis stimulated by higher concentrations (0.3 and 3 micrometer) of NA was inhibited to a minor degree or not at all. Theophylline (1 micromete)-induced lipolysis was inhibited by adenosine (IC50 approximately 10 micrometer). Inhibition of theophylline-induced lipolysis was tested for several analogues of adenosine. Some N6-substituted adenosine analogues and 2-Cl-adenosine were more potent inhibitors. Adenine-nucleotides (ATP, ADP, AMP) were about equipotent with adenosine. Several adenosine analogues, including its breakdown products were considerably less potent or ineffective. None of the analogues tested inhibited the action of adenosine. Dipyridamol, dilazep and papaverine, which inhibit the uptake of adenosine into cells, caused only a slight enhancement of the antilipolytic effect of adenosine. None of the analogues inhibited the effect of adenosine. It is concluded that adenosine can inhibit lipolysis due to low, "physiological" concentrations of noradrenaline and of low concentration of theophylline via an action on a receptor structure on the cell surface which exhibits structural specificity.


Prostaglandin-mediated inhibition of noradrenaline release: II. Dual mechanism behind its frequency-dependence. Sympathetically innervated, isolated rabbit hearts were perfusated according to Langendorff and the nerves were stimulated at 2, 5 or 10 Hz by equally long trains of pulses. The outflows of prostaglandin-like substances (PLS) and of noradrenaline (NA), induced by the nerve stimulations, were followed. The sensitivity of the process of NA release to exogenous PGE1 (2--6 X 10--8 M) at 2, 5 and 10 Hz was assayed. The outflow of PLS was found to be frequency-dependent, being greater at 2 Hz than at higher discharge rates, while the outflow of NA was similar at the different frequencies. The inhibitory action of PGE1 on the NA release process was more pronounced at 2 than at 10 Hz. It is concluded that the frequency-dependence of the endogenous PGE-mediated inhibition of the release of NA from discharging sympathetic nerves is based on 2 independent, frequency-related mechanisms: a) a higher synthesis rate of PLS/impulse, and b) a more pronounced sensitivity of the process of NA release, at low compared to higher impulse frequences.


The spatial distribution of odour induced potentials in the olfactory bulb of char and trout (Salmonidae). Monopolar DC-recordings were made of the gross responses from the olfactory bulb of char (Salvelinus alpinus syn. Salmo alpinsus L.) and trout (Salmo trutta L.) during stimulation with different odours. The response features studied were: the magnitude and polarity of the slow potential shift, the amplitude of the induced waves and their asymmetrical waveform. Amino acids elicited the largest responses in the lateral part of the bulb. Water containing "crude fish odour" caused the largest response in the rostral and medial parts. The results demonstrate odour specific differences in the localization of the bulb responses and the separate origin of the slow potential and the induced waves.


Neuroeffector maturity of portal veins from newborn rats, rabbits, cats and guinea pigs. Isolated portal veins from newborn and adult rats, rabbits, cats and guinea pigs were studied isometrically. Spontaneous activity and induced responses to transmural nerve stimulation (NS), noradrenaline, tyramine, acetylcholine and BaCl2 were quantitated. In agreement with our previous observations the portal veins of the newborn rat was found to lack spontaneous activity and responsiveness to applied stimuli whereas the newborn rabbit's portal vein showed inconsistent and weak responses. In the neonatal cat and guinea pig portal veins the pattern of the spontaneous activity and induced responses resembled those found in vessels from adult animals. It is concluded that the portal vein maturity at birth in several respects dramatic neuroeffector development of the portal vein during the postnatal period in the rat corresponds to prenatal events in cats and guinea pigs which are more highly developed at birth. Consequently, the lack of responsiveness of the portal vein during the first week of life does not seem to be secondary to the hormonal and hemodynamic adjustments during the neonatal period. Rather, the postnatal development of the rat portal vein occurs according to a genetically predetermined schedule, possible in parallel with the ontogenesis of vascular control in general.


Characteristics of static and dynamic regulatory mechanisms in myogenic microvascular control. The recently described static and dynamic components in myogenic microvascular control (Grände, Lundvall and Mellander 1977) were analysed in this study with regard to their stimulus-effector characteristics. Total and microvascular resistance responses in the sympathectomized vascular bed of skeletal muscle were analysed during graded changes of vascular transmural pressure (PT) applied at different rates (dPT/dt) in the range from +7.5 to -7.5 mmHg/s. The dynamic microvascular resistance responses, developing during the phase of changing PT, were pronounced and distinctly graded in relation to the magnitude of the dPT/dt stimulus, both with regard to amplitude of resistance response and rate of resistance change per unit time (dRmicro/dt). The static responses, revealed in the steady state phase of constant increased PT, were comparatively small and graded in relation to the amplitude of the PT increase. Rate-sensitivity in microvascular myogenic control was bi-directional, eliciting excitatory effects (constriction) in response to positive, and inhibitor effects (dilation) in response to negative, values of dPT/dt. The dynamic constrictor response to a given dPT/dt stimulus increased with increasing amplitude of PT and, thereby, increased duration of the dynamic stimulus. This effect might be explained by successive activation of myogenic "receptor units" with different thresholds. The described rate-sensitivity in the myogenic control system seems to increase its rapidity, stability, and sensitivity and thereby can contribute efficiently to well-adapted and refined microvascular adjustments.


Absorption and elimination of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): comparison between young and elderly subjects. The single-dose kinetics of D-propoxyphene, acetyl salicylic acid and phenazone, given in a combination tablet (Doleron), were compared in young and elderly subjects. Serial blood samples were taken 0--48 hours after administration. The plasma concentrations of propoxyphene and of its major metabolite, norporpoxyphene, were assessed by mass fragmentography, those of phenazone by gas chromatography, and those of acetyl salicylic acid plus salicylic acid by spectrofluorometry. Neither for propoxyphene, norpropoxyphene, acetyl salicylic acid nor phenazone did the areas under the concentration curves or the elimination half-lives differ between young and elderly subjects. These data do not provide pharmacokinetic support for a general reduction of the Doleron dosage in elderly subjects.


Platelet aggregation in diabetes mellitus. Thirty-eight patients with juvenile diabetes mellitus, aged 21-77, were tested for platelet aggregation in vitro. Vascular complications were found in 20 patients with diabetic retinopathy in 16 of these. All patients received their usual dose of insulin in the morning on the day of the examinations, where were carried out shortly before a 2--3 hours after lunch. Ninety normal controls were tested at the same time of day. The aggregation was estimated turbidometrically and defined by the threshold concentration of adenosine diphosphate or adrenaline that produced a secondary aggregation with a light transmission not less than 80% of that given by the platelet-poor plasma. No significant differences could be demonstrated in platelet aggregation between the normal controls and the patients with diabetes mellitus or any subgroup of these. No correlation was found between the threshold concentrations and the plasma levels of glucose or beta-hydroxybutyric acid.


Electrocardiographic changes during total energy deprivation (fasting). The effect of 10 days of total energy deprivation (fasting) on ECG reactions was evaluated in 14 healthy normal-weight males. The heart rate and the ratios between QRS and T wave amplitudes in leads I and II decreased significantly, as did body weight and blood glucose levels. The urinary excretion of adrenaline increased. It is concluded that other hormonal (e.g. thyroidal), neural and metabolic mechanisms are of greater significance for the heart than the sympatho-adreno-medullary activity during fasting. T wave abnormality without an abnormal Q wave and without other clinical symptoms was noted in one subject on the 8th day of starvation and remained abnormal for more than a year.


Prognosis for juvenile diabetics with nephropathy and failing renal function. A total of 157 consecutive patients with juvenile diabetes (onset before the 31st birthday), diabetic nephropathy, and impaired renal function were followed up until 1.1.1976. All the patients had been admitted to the Steno Memorial Hospital, Copenhagen, between 1934 and 1972. Independently of the patients' age at onset of diabetes, it was found that persistent proteinuria appeared after an average of 19 years, and that death ensued 5--6 years thereafter. Division of the patients into two groups, according to whether the diabetes had set in before or after 1940, showed no signs of an improved prognosis during the past few decades. Once the serum creatinine has started to rise, the prognosis is very grave. Only 50% were alive 21 months after serum creatinine levels of 2--5 mg/100 ml had been ascertained. Among patients whose serum creatinine exceeded 5 mg/100 ml, 50% succumbed in 9 months. It is concluded that renal transplantation, if it is to be done, should be instituted early.


Overweight in women--metabolic aspects. The population study of women in Göteborg 1968--1969. In a population sample of 1462 women aged 38--60 years, those with overweight were studied separately and compared with the women in the total population sample. Overweight was defined as the upper 5% of a weight index in the various ages studied and the weight index as (formula: see text). Significant differences, with higher values in the overweight women, were found for serum triglycerides, serum uric acid and arterial BP. Smoking was significantly less common in the overweight women. Serum cholesterol was similar in overweight women and in women in the total sample. Higher values for some risk factors for ischaemic heart disease in the overweight group of women thus seemed to be compensated to some extent by a lower number of smokers in this group.


Electroencephalographic prediction of anoxic brain damage after resuscitation from cardiac arrest in patients with acute myocardial infarction. The short-term prognostic value of routine electroencephalography (EEG), carried out on the days after cardiac arrest, was evaluated in a consecutive study of 185 patients with acute myocardial infarction together with an episode of clinical cardiac arrest. The individual EEGs were classified on a 5-grade scale. Of the 89 patients who survived, 18 had signs of anoxic brain damage; 96 patients died, 76 as a result of cerebral anoxia. Only 2 patients survived out of the total of 72 for whom the first EEG was classified as grades III--V. The EEGs of both these patients were recorded within a few hours after the cardiac arrest. None of the patients with an EEG of grade I died of cerebral anoxia, while all degrees of brain damage were otherwise observed in connection with EEGs of both grades I and II. It is concluded that an EEG of grades III--V indicates a fatal outcome, provided it has been recorded more than 24 hours after the cardiac arrest. A grade III--V EEG that is recorded within 24 hours after a cardiac arrest should be repeated some days later. It is not possible, on the basis of a single EEG, to predict the extent of the anoxic brain damage.


Third degree atrioventricular block, chronic progressive external ophthalmoplegia and pigmentary degeneration of retina. Case report and survey of the literature. A woman was noted to have chronic progressive external ophthalmoplegia, pigmentary degeneration of retina and third degree AV block. She was admitted to hospital because of syncopes and was successfully treated with a permanent pacemaker. Since 1958, 12 similar cases have been noted. Three of 7 patients without pacemaker treatment died, and 5 were successfully treated with pacemaker. The disturbances in AV-conduction are not thought to be a mere coincidence to the ocular disorder. Cardiomyopathy has been suggested.


Increased serum levels of immunoglobulins in untreated and treated essential hypertension. I. Relation to blood pressure. In 164 consecutive patients with essential hypertension, serum immunoglobulin (Ig) levels of IgA, IgG, and IgM classes were determined, using single radial diffusion techniques, and compared with 80 healthy normotensive subjects without any family history of hypertension. Of 80 untreated and 84 treated patients, IgA and/or IgG were significantly increased in 40% and 37%, respectively. IgG correlated positively to BP in untreated patients (p less than 0.0008), as well as in insufficienctly treated males (p less than 0.004). No correlations were found between Ig and duration of hypertension. The increase in Ig was not associated with any particular drugs. A family history of hypertension was found in 19.6% of the patients with elevated Ig and in 9.7% of those with normal Ig (p less than 0.10). The study provides further evidence for involvement of immune mechanisms in essential hypertension, and suggests a possible genetic predisposition.


The effect of hemodialysis on neutrophil chemotactic responsiveness. After several hemodialysis treatments, neutrophil chemotactic responsiveness is commonly depressed. The median chemotactic index of 34 patients was 21, compared with 47 for 21 controls tested simultaneously. The depressed chemotactic responsiveness was not restored to normal when leukocytes were washed and resuspended in normal plasma, neither did plasma from patients with depressed chemotaxis affect control neutrophils.


Embolism in sinoatrial disease.

Embolism in sinoatrial disease. Among a series of consecutive patients treated with permanent pacemaker between 1965 and 1976, 43 had sinoatrial disease with paroxysmal tachycardia (group A), 30 sinoatrial disease without tachycardia (group B) and 165 atrioventricular block (group C). A retrospective study showed systemic vascular events compatible with embolism in 35%, 7% and 10% in groups A, B and C, respectively. The groups were comparable as regards age, other diseases and duration of pacemaker therapy. Because of the high incidence of embolism in group A, anticoagulant therapy should be evaluated in patients with the brady-tachycardia syndrome.