A study in general practice of the symptoms and delay patterns in the diagnosis of gastrointestinal cancer.

GASTROINTESTINAL CANCER WAS CLASSIFIED INTO FOUR GROUPS ACCORDING TO THE SITE: stomach, caecum and ascending and transverse colon, sigmoid colon and rectum. The incidence of these cancers in general practice is as rare as three per 10,000 consultations. I report on a study in general practice of the symptoms and delays in diagnosis in 150 patients with gastrointestinal cancer. There was an interval of many weeks between the onset of symptoms and diagnosis in the majority of cases. In approximately 50 per cent of cases there was an interval of weeks between the patient consulting the general practitioner and being referred for hospital investigation. No association was demonstrated between delay and social class, age, physical isolation, or the regular consulting rate of the patient. There was evidence that the consulting rate of some patients with gastrointestinal cancer increased in the 12 months before diagnosis because of the presence of symptoms not specific to the gastrointestinal tract.Much more knowledge of the early symptoms of these cancers is required if the general practitioner is to be able to identify those patients with a high probability of early cancer from others who have symptoms which are common both to non life-threatening conditions and to cancer lesions.


An audit of ENT referrals assessing training needs for general practice trainees.

Over 500 ENT diagnoses made by general practitioners when referring patients to one ENT department were examined and compared with the diagnoses by the specialist department. A broad grouping of the categories of referral was made and topics highlighted which seemed particularly appropriate for further postgraduate training for general practitioners.We believe the amount of postgraduate training in ENT currently available to trainees in the UK may be too low and ought to be increased and that this approach offers a logical starting point for constructing educational objectives for such training.


A randomized controlled trial of geriatric screening and surveillance in general practice.

A randomized controlled trial of geriatric screening and surveillance was undertaken on a practice population of 295 patients aged 70 years or more over a two-year period. In the screened group (145 patients) many social problems were found and a total of 380 medical conditions were reported during the study period, 144 (38 per cent) of which were previously undetected. Conditions found most frequently involved the circulatory, musculoskeletal and nervous systems; 67 per cent of the conditions found were manageable, half being improved and the remainder resolved completely.The screening programme was found to increase the use of social and health services but it did also decrease the expected duration of stay in hospital.Independent assessment of patients in the study and control groups at the end of the two-year period showed that the screening programme had made no significant impact on the prevalence of socio-economic, functional, and medical disorders affecting health.We formed the firm impression that the study patients were made more comfortable (by control of pain) and less disabled, although there was no unequivocal objective evidence of this. They were, however, kept independent for longer.The findings are discussed and a model of geriatric care is suggested combining conventional management on demand with comprehensive screening to identify the high-risk patients on whom care might need to be focussed.


Surgical emergencies in general practice.

Two thousand and thirty patients were seen in their own homes between 19.00 hours and 07.00 hours during a 14-month period. Twenty-nine per cent of these visits were for surgical conditions and a detailed analysis of this group is presented. An attempt to assess the necessity of the visit by grading them into minor, intermediate, and severe is also made. No attempt is made to discuss the treatment of individual conditions. The high admission rate to hospital probably reflects the uncertainty of further home follow-up.


Oxazepam esters. 1. Correlation between hydrolysis rates and brain appearance of oxazepam.

Esters of the centrally acting oxazepam were investigated to find quantitative correlations between the pharmacokinetics of the parent drug and in vitro biotransformation rates and physicochemical properties of its prodrugs. The 14C-labeled aliphatic and omega-phenyl-substituted esters were administered intravenously to mice. Brain levels of the esters and oxazepam were determined and the latter was fitted to a simplified exponential equation. In vitro hydrolysis rate of the esters catalyzed by the hepatic microsomal fraction was measured with a pH stat. Pharmacokinetic constants characterizing the rising part of oxazepam brain levels correlate well with the chromatographic RM values and with in vitro maximal hydrolysis rates of the esters. The hydrolysis is capacity limited in the liver. In a closely related set of aliphatic esters, oxazepam brain penetration also correlates with the steric constant (ES) of its esters.


Oxazepam esters. 2. Correlation of hydrophobicity with serum binding, brain penetration, and excretion.

Pharmacokinetics of a series of prodrug-type oxazepam esters were studied in mice. The effect of hydrophobicity was investigated in relation to serum binding, brain penetration, tissue storage, and excretion. Binding to mouse serum and to human serum albumin was measured by equilibrium dialysis, and the changes in binding free energy were correlated with RM values. Brain-blood partition of the esters did not change parallel with their serum binding. An indirect correlation exists between RM of the esters and oxazepam brain accrual. Brain-blood concentration ratios of oxazepam prove that hydrolysis precedes brain penetration and hydrophobicity might primarily influence the hydrolysis rate. The amount of tissue storage and total excretion rates also correlate with hydrophobicity.


Potential antiinflammatory compounds. 1. Antiinflammatory phenylpiperidine derivatives.

The syntheses of a number of amines and their derivatives, based on the phenylpiperidine nucleus, are described. Their activities on the rat paw carrageenan test are also reported. Activities comparable to that of phenylbutazone were obtained for some of the amines, notably 4-piperidino-beta-methylphenethylamine.


Potential antiinflammatory compounds. 3. Compounds derived from acenaphthene and indan.

Compounds having acenaphthene and indan as their parent nuclei were synthesized for antiinflammatory testing. Compounds which showed activity were 1-phenyl-5-acenaphthenylacetic acid and its alpha-methyl derivative (carrageenan rat paw edema) and the same alpha-methylacenaphthenylacetic acid and 2-(4-chlorobenzylidene)-3-oxo-5-indanacetic acid and its alpha-methyl derivative (rat adjuvant arthritis). None of the compounds was more active than the control compounds phenylbutazone and indomethacin.


[3-(1,4-Cyclohexadienyl)-L-alanine,8-lysine]vasopressin: synthesis and some pharmacological properties.

[3-(1,4-Cyclohexadienyl)-L-alanine,8-lysine]vasopressin, otherwise known as [3-(2,5-dihydrophenylalanine),8-lysine]vasopressin or [DiHPhe3]lysine-vasopressin, has been synthesized in an attempt to utilize 2,5-dihydrophenylalanine (DiHPhe) to evaluate the contribution of aromaticity in position 3 to biological activity. The analogue has the same primary structure as lysine-vasopressin, except that two additional hydrogen atoms are present on the ring moiety of the phenylalanine residue in position 3. The key intermediate was the protected nonapeptide N-carbobenzoxy-S-benzyl-L-cysteinyl-L-tyrosyldihydrophenyl-L-alanyl-L-glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-N epsilon-tosyl-L-lysylglycinamide that was synthesized stepwise by the solid-phase technique. Deprotection with sodium in liquid ammonia was followed by sulfhydryl oxidation with I2 to give the hormone analogue. [DiHPhe3]lysine-vasopressin exhibited 125--130 units/mg of antidiuretic, 129--132 units/mg of rat pressor, and 6 units/mg of rat uterus contracting activity. To confirm the presence of DiHPhe in the analogue, an enzymatic procedure employing Aspergillus oryzae was developed that liberates in high yield the amino acid residue in position 3 of the posterior pituitary hormone structure. This study should be applicable to other biologically active peptides.


Synthesis and antihypertensive activity of 2-benzamido-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizines.

The synthesis and antihypertensive activity of a series of 2-benzamido-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]-quinolizines are reported. A number of these compounds exhibit extremely potent hypotensive properties (e.g., N-methylbenzamides 42, 48, and 50 and N-ethylbenzamide 53 cause drops of 110, 103, 79, and 83 mmHg, respectively, in systolic blood pressure in the spontaneous hypertensive rat at the screening dose of 50 mg/kg po). Structure-activity relationships for the entire series are discussed.


Diels-Alder adducts of fulvenes and halogenated dienes. Synthesis and insecticidal activity.

A series of eight adducts (1--8) of substituted fulvenes and polychlorinated cyclodienes was synthesized by Diels-Alder cyclization. The products isolated were the endo bicyclo adducts as determined by detailed 1H and 13C NMR spectral analysis. Steric hindrance of end-product bridge substituents coupled with bulky substituents at C6 of the fulvenes led to one isomeric product in most cases. Compounds 1--8 demonstrated weak insecticidal action in Musca domestica as determined by topical LD50 and oral LC50 assays.


Antiestrogens and antiestrogen metabolites: preparation of tritium-labeled (+/-)-cis-3-[p-(1,2,3,4-tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxyl]-1,2-propanediol (U-23469) and characterization and synthesis of a biologically important metabolite.

The Upjohn antiestrogen (+/-)-cis-3-[p-(1,2,3,4-tetrahydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]-1,2-propanediol (2b, U 23469) has been prepared in tritium-labeled form by reduction of an unsaturated dihydronaphthalene precursor with carrier-free tritium gas over a palladium catalyst followed by alkylation with 3-iodo-1,2-propanediol. After extensive chromatographic purification, the final material was obtained with a specific activity of 13 Ci/mmol and a radiochemical purity of 94%. In vivo studies with immature rats show that [3H]2b is slowly converted to a more polar metabolite that is selectively accumulated in the nuclear fraction of the uterus where it is bound to the estrogen receptor. Chromatographic comparisons indicate that this metabolite is the demethylated analogue 2c, a compound that has an affinity for estrogen receptor more than 300 times greater than that of 2b. These studies suggest that the demethylated analogue 2c may be a biologically important metabolite of 2b that is involved in the action of this antiestrogen.


Synthesis of 4'- and 5'-hydroxyoxprenolol:pharmacologically active ring-hydroxylated metabolites of oxprenolol.

Synthesis and preliminary pharmacological activity data for 4'- and 5'-hydroxyoxprenolol (2 and 3) are reported. The synthetic routes make use of the isomeric 2-pyranyl monoether derivatives of 4-hydroxysalicylaldehyde and 2,5-dihydroxyacetophenone. The corresponding O-allyl ethers were converted to substituted phenols by Baeyer-Villiger oxidation and the propanolamine side chain elaborated using epichlorohydrin, followed by oxirane ring opening with isopropylamine. Each of the hydroxylated metabolites is about ten times less potent than oxprenolol as an antagonist to the isoproterenol-induced relaxation of guinea pig tracheal strips.


Synthesis and estrogenic properties of 17-epi-ethynylestradiol and its ether derivatives epimestranol and epiquinestrol.

The synthesis of 17-epi-ethynylestradiol (10), the 17 beta-ethynyl-17 alpha-ol epimer of the well-known orally active estrogen, ethynylestradiol (1), was achieved by LiA1H4 reduction of epoxide 9, as well as by demethylating epimestranol (11) with CH3MgI. Compound 11 was obtained by the unusual 17 beta-ethynylation of estrone 3-methyl ether 22 under equilibrating conditions. The in vitro estrogen receptor-binding affinity and the oral estrogenicity in the rat for the 17-epi compounds 10, 11 and 20 (epiquinestrol) was evaluated. Despite moderate estrogen receptor-binding affinity, compound 10 was devoid of measurable estrogenicity at 10 mg/kg or antiestrogenicity at 3 mg/kg.


Dimerization of coralyne and its propyl analogue and their association with DNA.

Dimerization of coralyne, Ia, and its propyl analogue Ic has been analyzed at neutral pH as a function of ionic strength. Even at low ionic strength (I = 0.02) dimerization constants (molar units) for both compounds are 10(5) or greater, which is considerably larger than values obtained for similar intercalating molecules. Coralyne seems to undergo association to higher aggregates somewhat easier than Ic, which could be due to the fact that the propyl group on Ic provides some steric hinderance in forming higher aggregates. Both compounds readily associate with DNA. At high ratios of ligand to DNA, the spectra for Ia or Ic are similar to that of a highly aggregated complex. At low ratios of ligand to DNA, the spectra for both compounds approach a limit, which is relatively independent of ionic strength and concentration, and can be identified with the intercalated species. The slight differences between Ia and Ic in dimerization or in association with DNA do not seem capable of explaining the significant differences in antileukemic activity of these compounds.


Potential antiinflammatory compounds. 2. Acidic antiinflammatory 1,2-benzisoxazoles.

A number of 1,2-benzisoxazoles, substituted in the 3 position with 4-substituted phenyl groups and in the 5--7 positions with acetic and propionic acid residues, have been synthesized and tested in the rat carrageenan foot edema assay. Activity has been found in the 6- and 7-substituted acids.


Genetic control of severe pre-eclampsia.

A genetic analysis has been made of published and new data on the familial occurrence of severe pre-eclampsia in primigravid women. This has shown that the condition may be largely a Mendelian recessive one. Bcause the condition occurs only in pregnancy, and because susceptible women cannot otherwise be identified, it is difficult to decide whether the genotype of the parent or of the offspring carried in utero leads to the condition. Data on the incidence of severe pre-eclampsia in the relatives of women who have suffered eclampsia support the maternal genotype hypothesis, while similar data, in which the index cases were women who had had severe pre-eclampsia, are more compatible with the fetal genotype hypothesis. Data on the incidence of the condition in blood relatives of index cases compared to the incidence in their corresponding in-laws are now required. Such a comparison would allow a choice to be made between the two hypotheses if one or the other were correct, or would assess the contribution of each if a genotype X genotype interaction were involved. Recurrent severe pre-eclampsia seems to have the same genetic basis as the more common primigravid type. However, mild, that is non-proteinuric, pre-eclampsia usually seems to be inherited independently of the severe form.


Association of glucose-6-phosphate dehydrogenase deficiency with diabetes mellitus in ethnic groups of Singapore.

Six hundred and nine male patients suffering from maturity onset diabetes mellitus, comprising 422 Chinese, 66 Malays, and 121 Indians, were investigated to determine the incidence of G6PD deficiency, ABO blood groups, and haemoglobin types, and these were compared with normal healthy controls. A positive association with a higher incidence of G6PD deficiency in diabetics was observed in Chinese and Indian patients. There was no significant difference in the frequencies of ABO blood groups and haemoglobin types between the patients and the controls in any of the ethnic groups studied.


Autosomal recessive lipid storage myopathy (probable carnitine deficiency).

Two sisters died at the age of 17 and 19, respectively, of a myopathy with exacerbations and remissions characterised by pain and weakness of muscles which ended fatally with lactic acidosis and respiratory failure. The clinical picture was very similar to that described in some cases of carnitine deficiency and the histochemical finding of many lipid-filled vacuoles in muscle fibres and the electron microscopical findings were identical to those reported in that disease. The finding of affected sisters supports autosomal recessive mode of inheritance.


Congenital hypothyroidism in Klinefelter's syndrome.

Congenital hypothyroidism has been found in four patients with Klinefelter's syndrome. It is likely that this reflects more than chance concurrence of these conditions.


Hereditary neurocutaneous angioma: a new genetic entity?

A family pedigree with a possible new genetic syndrome characterised by the presence of angiomas, systemic in nature, affecting particularly the skin and the central nervous system, is described. Angiomas of the CNS seem to have a marked tendency to bleed. The condition shows a clearly dominant mode of transmission, four subjects in three generations being affected. Differentiation from other conditions belonging to the vascular abnormalities subgroup of phakomatoses is presented.


Familial infantile scoliosis associated with bilateral paralysis of conjugate gaze.

A family with two sibs suffering from idiopathic infantile scoliosis associated with bilateral paralysis of conjugate gaze is reported. Although the parental consanguinity and the involvement of patients of both sexes in this family are suggestive of an autosomal recessive mode of inheritance, a dominant or multifactorial pattern remains a possibility.


Partial monosomy 7 with interstitial deletions in two infants with differing congenital abnormalities.

Two cases of interstitial deletion of chromosome 7 are presented, one involving the short arm and the other the long arm. The cytogenetic, dermatoglyphic, and clinical findings are compared with previously reported cases of chromosome 7 deletion. The patient with a short arm deletion differs clinically from the previously reported cases but, in common with a least one previous case, has a low total finger ridge count. His interstitial deletion involving the 7p13 leads to 7p21 region also differs from 7p deletions reported in earlier cases. The patient with a long arm deletion has an interstitial loss of the region between 7q11 and 7q21, corresponding to one of three groups of 7q deletion that have been recognised. The phenotypic changes in this group are less well defined than in the other two and the patient presented here differs clinically from the previously reported cases, apart from one phenotypically normal mosaic case, in lacking morphological abnormalities. He shares with one previous case both epilepsy and a high intensity of dermal ridge patterns.


Familial partial 7q monosomy resulting from segregation of an insertional chromosome rearrangement.

A family with an insertional type of chromosome rearrangement involving chromosomes 7 and 13 is reported. An interstitial deletion of a segment of chromosome 7 (7q32 leads to 34) had been inserted into the long arm of chromosome 13 at breakpoint q32. Segregation of this chromosome rearrangement gave rise to three subjects who were monosomic for the involved segment of chromosome 7. The karyotypes were: 46,XX, or XY,der(7)ins(13;7) (q32;q32q34). All three subjects were mentally retarded and had minor dysmorphic features. The Kidd, Colton, and Kell blood group systems were investigated, but were not informative.


Prolonged P-R interval in a male with 47,XYY karyotype.

A 47,XYY male with an extremely prolonged P-R interval (0.42 sec) on the electrocardiograph is described. There was also a secondary R wave in lead V1. He had no past history of heart disease and no cardiac abnormality on physical examination.


A further case of a new syndrome including midface retraction, hypertrichosis, and skeletal anomalies.

The clinical and radiological features of a male child with multiple malformations are described. He appears to be an example of a new syndrome recently described by Schinzel and Giedion (1978).


Roberts's syndrome and clonidine.

A child is described with features of Robert's syndrome. The mother took clonidine during pregnancy. The question of a relationship between the child's abnormalities and clonidine is raised.


A longitudinal study of circulating immune complexes, dna antibodies and complement in patients with systemic lupus erythematosus: an analysis of their relationship to disease activity.

The relationship between immune complex, DNA binding and complement levels and disease activity was studied in twenty-seven patients with systemic lupus erythematosus. Detailed longitudinal studies revealed a good correlation between immune complex levels and disease activity. In addition, a good correlation was obtained, in general, between immune complex and DNA binding values, and an inverse correlation between these values and the haemolytic activity of C1, C2 and C4. CH50 and C3 measurements, on the other hand, were found to be less consistent at reflecting short term fluctuations in disease activity. Statistical analysis of IC, DNA binding and complement values revealed a higher incidence and mean value of immune complexex in active disease compared with inactive disease. These high levels of immune complexes were associated with elevated values of DNA binding and low values of CH50 and C3. The highest values of immune complexes were found in samples with concomitantly abnormal values of DNA binding, CH50 and C3. It is concluded that the measurement of immune complexes in SLE patients is a useful procedure, not only in aiding diagnosis, but also in monitoring disease activity and response to therapy. The results also indicate that serial studies of immune complexes, DNA binding and complement can be of value in the long term management of individual patients.


Inhibition of mitogen induced blast transformation by a multiple sclerosis serum factor.

A factor in the sera of multiple sclerosis patients inhibits RNA, protein and DNA synthesis in actively metabolizing mitogen stimulated lymphocytes. Inhibition of macromolecular synthesis precedes cell death by 24 to 36 hours. The factor is effective on cells which are already committed to transformation by previous exposure to mitogen and cells which are simultaneously exposed to the factor and mitogen. Previous exposure of unstimulated cells to the factor does not alter their subsequent response to mitogen. The factor does not inhibit RNA synthesis of unstimulated lymphocytes isolated on a Ficoll-Hypaque gradient, nor is it toxic to these cells.


Detection of soluble immune complexes by the technique of ADCC inhibition in human diseases.

Soluble immune complexes were detected using inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC) in sera of patients with various diseases. Results were positive in 32/41 patients with rheumatoid arthritis (78%), in 27/38 systemic lupus erythematosus patients (71%), in 7/10 cutaneous lupus erythematosus patients (70%), in 6/8 mixed connective tissue disease patients (75%), in 11/26 membranous glomerulonephritis patients (42%), in 6/20 membranoproliferative glomerulonephritis patients (30%) and in 3/12 multiple sclerosis patients (25%). ADCC inhibition was compared with PEG precipitation technique and was found to be more sensitive for detecting soluble immune complexes. Various pitfalls are discussed.


Human thymus cells: effects of glucocorticoids in vitro.

The level of glucocorticoid receptors and the effects of dexamethasone on 3H-Uridine and 3H-Thymidine incorporation have been determined in normal human thymus cells. Under the experimental conditions employed human thymocytes appear more steroid-sensitive in vitro than human circulating lymphocytes.


The effect of in vitro irradiation on PHA-mediated cytotoxicity and lymphocytes with receptors for the Fc part of Ig.

In vitro irradiation of purified human lymphocytes reduced PHA-mediated cytotoxicity (MICC) against chicken erythrocytes in a dose-dependent fashion. Lymphocytes with receptors for IgG present in both unfractionated and T-cell enriched cell preparations were depleted after X-ray exposure. T-cells with IgM-receptors, however, appeared to be more resistant. Different lymphocyte subpopulations seem to cooperate in MICC, and shifts of their proportions may be one explanation of the reduction of MICC after X-ray exposure.


Strongyloidiasis in an infant orangutan (Pongo pygmaeus).

Necropsy of a 15-month-old male orangutan (Pongo pygmaeus) showed multiple nodular elevations of the mucosa of the colon, petechial hemorrhages in both lungs, and mucosal ulcerations in the cecum, appendix, and proximal colon. Light microscopy revealed filariform larvae of Strongyloides in the lung, colon, and mesenteric lymph nodes. Rhabditiform larvae were also observed in sections of colon.


Determination of reflection coefficients for various ions and neutral molecules in sarcoplasmic reticulum vesicles through osmotic volume change studied by stopped flow technique.

Osmotic volume change of sarcoplasmic reticulum vesicles was studied by following the change in light-scattering intensity using a stopped flow apparatus. From the analysis of the initial rate of scattering change, reflection coefficients for various ions and neutral molecules were determined. The following are typical results: K+, 0.72; Tris+, 0.98; choline 1; NO3-, 0.32; Cl-, 0.46; methanesulfonate, 0.62; gluconate, 0.96; glycerol, 0.86; and glucose, 1. When the K+ permeability was increased in the presence of 10(-6) g valinomycin/ml, the reflection coefficient for K+ changed from 0.72 to 0.31. It was found that there was a close relationship between the reflection coefficients and the permeabilities of the solutes. Hydraulic conductivity was also determined from the initial rate of light scattering change and was not different for the different solutes. The water permeability was estimated to be 2.1 x 10(-3) cm/sec at 23 degrees C.


Ion and water transport by isolated cockroach salivary glands.

When the isolated salivary glands of the cockroach Nauphoeta cinerea Oliver are stimulated by dopamine, the putative neurotransmitter, they secrete a fluid containing (mM):Na, 121; K, 47; Cl, 143. Stimulation of glands by 5-hydroxytryptamine or the neuro-transmitter evokes a secretion identical in Na composition to this. Dopamine-evoked secretion is abolished in the absence of extracellular Na. The relationship between the rates of fluid secretion and Na transport is linear. However, at very low rates of secretion the Na concentration falls. Calcium, K and Cl ions can be removed from the bathing solution without abolishing fluid secretion. Our evidence suggests that (i) the primary secretion is formed by active transport of Na in the acini, and (ii) the ionic composition of this secretion is modified by re-absorption of Na and an independent secretion of K in the ducts.


The Börjeson-Forssman-Lehmann syndrome: a new case.

A new case of the Borjeson-Forssman-Lehmann syndrome is described with details of anthropometry, dermatoglyphs, endocrine function studies and mental state. Comparisons are made with the five previously reported cases. The diagnosis is based on the clinical appearance. Endocrine studies gave normal results and the patient's short stature is not due to growth hormone deficiency. There is no evidence for primary hypogonadism.


On the analysis of repeated measures over time in medical, pharmacological, and behavioral research.

Studies comparing different treatments over time using repeated measures on a wide variety of outcome variables are very common in the research literature. Unfortunately, they are rarely analyzed appropriately, at least from the standpoint of controlling the type 2 error rate (false rejection of the null hypothesis). As a consequence, many of the positive findings reported in such studies may be incapable of replication. The present article reviews the logical and statistical problems involved, emphasizes the importance of controlling the experimentwise error rate regardless of the research design employed, and presents an integrated, multivariate strategy for dealing with the several issues raised. Resolution of these issues is essential if the "fictional" content of research journals is to be kept within reasonable bounds.


Effects of certain training parameters on detection of simulated breast cancer.

Forty-two female subjects, constituting 14 groups, palpated a silicone breast model in a lump detection task. Three variables, number of trials (amount of practice), search pattern requirement (restricted vs. unrestricted), and the presence or absence of lumps, were manipulated according to 3 x 2 x 2 design. The effect of all modes of practice on detection performance in posttest 1 was evidenced by an increase in percent of lumps detected and a decrease in detection threshold, but no form of practice was superior to the others. Following posttest 1 a brief search-training procedure was administered to 39 subjects which further lowered detection threshold, increased percent of lumps detected, and increased trial duration in posttest 2. The results indicate the effectiveness of the training procedure for improving detection ability and suggest the need for a more complex model to determine more specifically the effects of the practice models employed.


Psychological response of children to isolation in a protected environment.

A behavioral observation study of 14 children with cancer treated in a laminar airflow protected environment (PE) unit was done over a period of 2 years. A total of 3629 observations were completed, and results related to perception, sleep, intellectual functioning, physical discomfort, mood, management problems, activity patterns, social-communicative behavior, and sedation are reported. In general, despite evidence from the literature that sensory deprivation and social isolation can cause severe disturbance of the sensory apparatus, no debilitating or long-term psychological effects related to prolonged PE treatment were noted. The differences between PE and deprivation-isolation contexts are discussed, and the need for psychosocial support of these patients is emphasized.


A canonical correlation analysis of the Alcohol-Use Inventory and the Human Service Scale.

The responses of 312 persons with alcoholism to the Alcohol-Use Inventory and Human Service Scale were subjected to canonical correlation analysis. Results indicate that the relationship between alcohol-use constructs and psychological need satisfaction can be explained by two axes: a personal security--social dimension and a personal stress--environmental dimension. Microanalysis of the variates indicated that emotional need satisfaction was differentially influenced by social and physiological variables.


Irritable bowel syndrome: a test of the colonic hyperalgesia hypothesis.

This study tested the hypothesis that, patients with irritable bowel syndrome (IBS), there is a primary hyperalgesia of the colon. Previous work, which examined these patients and normals, has not included subjects who provide a control for relevant psychological characteristics. We compared ratings of pain, following varying degrees of distension of the sigmoid colon, in normals, patients with IBS, and patients who were psychologically disturbed but without bowel symptoms. Psychological characteristics were assessed by a psychiatric interview and psychometric inventories; response to distension was tested by placing a tube in the rectosigmoid colon and successively inflating a nd deflating a balloon at its tip at 10 cm3 increments up to 50 cm3. Ratings of pain were recorded at each volume. The results indicated that the two patient groups were psychologically similar and both were more disturbed than normals. A linear relation was found between reports of pain and volume of distension in all three groups. There were no significant differences between the proportions of subjects experiencing pain in each group or the average of the ratings. There were no significant associations between the pain ratings and measures of anxiety, depression, neuroticism, and extraversion. The data do not support the hypothesis that colonic hyperalgesia is an important contributory factor in the etiology of the irritable bowel syndrome.


An investigation of apparent mass psychogenic illness in an electronics plant.

An investigation of a case of apparent mass psychogenic illness was undertaken in a midwestern electronics assembly plant. The plant employed 500 workers, of whom 80% were female. The illness outbreak involved a total of 90 female first shift workers who reported a variety of nonspecific symptoms such as headache, dizziness, and lightheadedness in response to a strange odor in the workplace. Although environmental testing revealed some localized concentrations of a few airbone contaminants, no environmental toxins were discovered that could account for the continuing outbreaks of illness. An ad hoc sample of affected and nonaffected workers was surveyed to assess the influence of psychological, sociological, and work environment factors in the outbreak. Analysis of the data revealed that affected workers reported more physical discomfort (temperature variations, poor lighting) in the workplace as well as psychological job stress (increase in workload, conflicts with supervisors) than did nonaffected workers. Moreover, affected workers scored significantly higher than nonaffected workers on personality tests measuring extraversion and hysteria traits.


A comparative study of the differentiation and involution of the Mullerian duct and Wolffian duct in the male and female fetal mouse.

The present investigation has examined the ultrastructural differentiation of the genital ducts of both sexes of fetal mice. The emphasis of observations was placed on the phenomenon of morphogenetic cytolysis, particularly during the critical periods of Wolffian duct stabilization and Mullerian duct involution. Both developing and regressing genital ducts evidence extensive cytolysis. Autophagy appears to be the mechanism of morphogenetic changes in the developing male Wolffian duct. Autophagy, heterophagy, and degeneration in situ are all prominent cytolytic activities in female Wollfian duct involution. The developing female Mullerian duct undergoes extensive morphogenetic remodeling by the mechanisms of autophagy, heterophagy, and degeneration in situ. In the male Mullerian duct, autophagy, heterophagy, and degeneration in situ are also prominent. In addition, whole degenerated epithelial cells are extruded from the duct early in regression which may be realted to the transformation of periductal mesenchymal cells into an "epithelioid cell cuff" which does not form around the regressing Wolffian duct. The formation of this mesenchymal condensation surrounding the duct is also accompanied by the protrusion  of Mullerian epithelial cell cytoplasm into the mesenchymal cells. These observations may evidence a complex epithelial-mesenchymal interaction occurring during male Mullerian duct involution.


Comprehensive schemata on the histology of the liver with consequences in terminology.

New schemata of the liver are presented to discuss the combination of the three kinds of liver lobules known until today in a chalk-talk-manner. Terminology is also discussed. Further investigations are needed involving the construction and the vascular pattern of compound lobules of the three individial lobules of the liver in different species.


The structural organization of the pineal complex in the domestic goose.

The light and electron microscopic structure of the pineal complex of the domestic goose was studied. The complex is tubulofollicular but there is no direct connection between the constituent system of ducts and the third ventricle of the brain. Within the pineal, blood vessels accompanied by sympathetic nerve bundles are confined to the connective tissue. Other nerve fibers and occasional nerve cell bodies, however, do occur among the pineal cells. Threee basic pineal cell types were distinguished: (1) elongate epithelial cells which are arranged around follicles and ducts and resemble degenerate photoreceptor cells; (2) intramural supportive cells which are interspersed with elongate epithelial and intramural supportive cells; and (3) small supportive cells which lie between the bases of the elongate epithelial and intramural supportive cells. The follicular structure, vascularization, presence of secretory granules, and the nature of the elongate epithelial cells indicate that the pineal complex is primarily endocrine through a possible photoreceptive function cannot be ignored. Vesicles, 100-300 and 40-100 nm wide, were found with;n nerves and intramural supportive cells. The larger vesicles, present in pineals collected in the night, probably contain peptidic hormones. The smaller vesicles present in both day and night samples probably contain aminergic hormones.


The morphogenesis of the thigh of the mouse with special reference to tetrapod muscle homologies.

In order to provide an ontogenetic basis for the establishment of tetrapod muscle homologies and for the analysis of complex mammalian muscle states, a descriptive analysis of the morphogenesis of the thigh of Mus musculus has been made. The pattern and sequence of muscle cleavage and the migrations of individual muscle primordia are characterized from the eleventh day of gestation, when cleavage begins, through early neonatal stages. Observations on skeletal differentiation and lumbosacral plexus formation are also included. Thigh muscle morphogenesis is compared to that in the lizard, Lacerta, (Romer, '42) and the chick (Romer, '27) and homologies identified. An onogenetic basis for the definition of ancestral and derived muscle states is provided in muscles that are morphologically variable in mammals. These include the gluteus minimus, gracilis, adductor brevis and several hamstring muscles. Certain muscles that show variable innervation patterns in adult mammals, i.e., pectineus, quadratus and adductor magnus, typically develop from premuscle regions that separate muscle anlagen innervated by different nerves. Two muscle anlagen appear in the embryonic mouse thigh and then disappear late in prenatal or early postnatal development. Comparisons with other  mammals, especially the marsupial, Marmosa, reveal that these muscles are phylogenetic vestiges that degenerate before maturity. A sartorius vestige is identifiable through the thirteenth day of gestation. A tenuissimus anlage is present until shortly after birth and is clearly innervated by a branch of the peroneal nerve.


Cyanamide mediated synthesis under plausible primitive earth conditions. VI. The synthesis of glycerol and glycerophosphates.

The formation of glycerol occurs when a solution of DL-glyceraldehyde is heated in the presence of hydrogen sulfide at room temperature. DL-glyceraldehyde and dihydroxyacetone treated with hydrazine, as well as DL-glyceraldehyde incubated with formaldehyde are also partially converted to glycerol. The yields of the above reactions are from approximately 1% to about 3%. The formation of glycerophosphates occurs when glycerol is heated with ammonium dihydrogen phosphate and either urea or cyanamide. The yield of glycerophosphates is about 30%, most of which is sn-glycero-1 (3)-phosphate. These findings indicate that glycerol and sn-glycero-3-phosphate, which are moieties of glycerolipids, could have been formed under conditions which may have prevailed on the primitive Earth.


Self-condensation of activated dinucleotides on polynucleotide templates with alternating sequences.

We have prepared substantial quantities of the alternating polymers poly(U-G) and poly(C-A) and have used them as templates for the self-condensation of ImpApC, ImpCpA, ImpGpU and ImpG. We find that the condensation of ImpGpU and ImpUpG on poly(C-A) is efficient, the condensation of ImpCpA on poly(U-G) is moderately efficient, while the condensation of ImpApC on poly(U-C) proceeds poorly. In many cases, the product is predominantly 3'-5'-linked. These reactions demonstrate unequivocally, for the first time, that template-directed reactions occur in double-helical structures. Furthermore, they describe for the first time a pair of reactions in which each of two complementary polymers facilitates the synthesis of the other. The prebiotic significance of these findings is discussed.


Characterization of the myoglobin of the lamprey Petromyzon marinus.

Myoglobin has been identified in the myocardium of the lamprey Petromyzon marinus, one of the most primitive of all vertebrates. This protein was isolated by ammonium sulphate fractionation and purified by successive chromatography on Ultrogel AcA 54, DEAE-Sephadex and CM-23 cellulose. The molecule differs substantially from the monomeric hemoglobins found in the lamprey as evidenced by its elution profile on DEAE-Sephadex and the fingerprint pattern of its enzymically-produced peptides. The functional significance of this protein in Agnatha is discussed.


Insect lysozymes from three species of Lepidoptera: their structural relatedness to the C (chicken) type lysozyme.

Sequence studies of the N-terminal halves of the lysozymes isolated from Bombyx mori, Gallera mellonella and Spodoptera littoralis (Lepidoptera) allow us to classify these enzymes among the c (chicken) type lysozymes.


Selection and recombination in populations containing tandem multiplet genes.

Computer simulation for selective conditions that may apply in nature yielded three generalizations for prokaryotic organisms with recombinant mechanisms. (1) Selective forces can suffice to maintain a tandem gene family with the nearly optimum number of genes with little variance within the population. (2) Tandem genes will occur within the population unless the population is frequently cloned or unless the function due to a single copy is capable of over-providing the needs of the organism. (3) Even when there is no selective advantage or disadvantage due to extra gene copies, the population distribution becomes more skewed with time; and organisms with only single copies of the gene comprise a progressively larger fraction of the total. This may be the case with genes that function under strong cellular regulation. Evolutionary implications of these calculations are that the occurrence of unequal recombination of tandem genes would greatly slow evolution via duplication of genetic material. This difficulty and its possible resolutions are discussed.


Evolution of methionine initiator and phenylalanine transfer RNAs.

Sequence data from methionine initiator and phenylalanine transfer RNAs were used to construct phylogenetic trees by the maximum parsimony method. Although eukaryotes, prokaryotes and chloroplasts appear related to a common ancestor, no firm conclusion can be drawn at this time about mitochondrial-coded transfer RNAs. tRNA evolution is not appropriately described by random hit models, since the various regions of the molecule differ sharply in their mutational fixation rates. "Hot" mutational spots are identified in the Tpsic, the amino acceptor and the upper anticodon stems; the D arm and the loop areas on the other hand are highly conserved. Crucial tertiary interactions are thus essentially preserved while most of the double helical domain undergoes base pair interchange. Transitions are about half as costly as transversions, suggesting that base pair interchanges proceed mostly through G-U and A-C intermediates. There is a preponderance of replacements starting from G and C but this bias appears to follow the high G + C content of the easily mutated base paired regions.


Frequent mistakes made with black patients in psychotherapy.

This report reflects some insights derived from a decade of supervising psychiatric residents who engaged in dynamic psychotherapy with black patients. Of major interest was giving particular attention to what was said by black patients while remaining alert to the responses given by the therapist. From these observations some common mistakes have been identified and the conclusion is that rapport between patient and therapist was dependent upon a genuine regard for the patient's race, culture, and life-style.


Is there a doctor in the house?

When it is realized that American universities award nearly 50,000 different kinds of doctorates annually, it is little wonder that some should ask, "What is a real doctor?" This paper explores briefly the view which holds that the term "doctor" should be reserved for those whose long years of intensive study and practice in the field of medicine entitles them to this special designation. Attention is also given to the opposing view which argues that the phenomenon of doctoring, in the broad and generic sense, properly encompasses, not alone the field of medicine, but a number of disciplines that seek "to restore to good condition."


The ghetto emergency room.

A study of Emergency Room use by members of the Southside Community Health Plan was conducted to assess patterns and economies affected in health care delivery to the population. An analysis of the 141 patient visits is presented.


Mental illness in blacks: an overview, and treatment approaches.

Provisions for inner city mental health services must recognize the association between poverty, discrimination, and related social and physical conditions and disproportionately high rates of severe mental disorder-a transcultural phenomenon.Program emphasis should therefore be on the prevention, early recognition, prompt and effective treatment and rehabilitative care of psychosis. The total spectrum of psychiatric services is required for this, and thus an opportunity is afforded for necessary training and research.Poverty has negative impact on general health and cognitive development as well as on self-esteem, self-care, and the ability to utilize medical and health services. This contributes to a vicious, intergenerational poverty cycle.Primary prevention of mental illness, where possible, depends at present on socioeconomic change. Secondary prevention, ie, timely, appropriate treatment, is effective, but requires patient access to and acceptance of all indicated modalities of care.


Ultrasonic evaluation of the gallbladder in sickle cell disease.

The gallbladder is frequently diseased in sickle cell anemia. The distinction between cholecystitis and the abdominal crisis of sickle cell disease is difficult to make. Ultrasonography permits a rapid evaluation of the gallbladder in sickle cell disease.


Perinatal asphyxia I: Pathogenesis of multisystemic sequelae.

This paper describes the clinical and pathologic sequelae of perinatal asphyxia manifested by 17 neonates treated at Howard University Hospital over an 18-month period. Multiple systemic complications, occurring in 76.5 percent of the patients, were the rule rather than the exception. All vital organs were involved, singly or in combination. Understanding the pathogenesis and extent of these complications is of utmost importance not only to those rendering health care to acutely ill newborns, but also to those responsible for prenatal and maternal intrapartum care.


Hematocrit levels and race: an argument against the adoption of separate standards in screening for anemia.

The average hematocrit levels of black children have been widely reported to be about two to three percent lower than those of white children. Until recently, the relative contributions of economic, nutritional, and genetic factors to these differences have been unspecified. Based on new evidence and reanalysis of past data, however, some investigators now argue that genetic differences exist which transcend economic status. Separate screening standards are thus recommended for black children-standards which would define fewer as anemic. The present paper discusses methodological inadequacies in the evidence supporting the separate standards argument, focusing on the skewed economic distributions by race which suggest economic disparities within the racial subgroups compared. Findings are presented from a study of children in Washington, DC, to illustrate the role of particular risk factors known to be differentially distributed by income (eg, multiparity, birthweight, source of medical care). These factors are associated with varying hematocrit levels, even among blacks, and they also appear to account for a large part of the black-white hematocrit differentials. Study findings cast doubt on conclusions about the genetic basis of hematocrit differences and suggest that, without better evidence, it would be inappropriate to adopt lower standards for blacks in screening for anemia.


Malignant salivary gland tumors: role of radiation therapy.

Malignant salivary gland tumors are rare. They represent less than one percent of all head and neck tumors. Approximately three fourths of all salivary gland tumors occur in the major salivary glands.Traditionally, the treatment of choice for these tumors is surgery. The majority of these tumors reoccur after curative surgical procedures. Local recurrence rate following surgery varies with the histology, grade, and extent of the disease.In spite of high local recurrence rate following curative surgical treatment of these tumors, radiotherapy has seldom been used as an adjuvant to surgery. The value of elective postoperative radiation therapy for subclinical microscopic disease was not recognized. Review of the literature supports the improved local control rate with the use of immediate postoperative radiotherapy. Radiation therapy proved to be effective as an adjuvant to surgery. A local control rate of better than 40 percent can be achieved by radiation therapy as a sole modality in inoperable and locally advanced cases. Radiation therapy provides an excellent palliation for locally advanced tumors or symptomatic metastases.


Scimitar syndrome with associated Morgagni hernia in a Nigerian infant.

A Nigerian infant with symptoms of moderate respiratory dysfunction since birth is described. The diagnosis of the scimitar syndrome was made intraoperatively. The clinical and roentgenographic features with which the patient presented are outlined together with anatomical observations. The presence of an associated foramen of Morgagni hernia has not been reported previously.The relevant literature is reviewed, with emphasis on the preoperative diagnostic investigations essential in planning and executing appropriate surgical therapy.


Carcinoembryonic antigen in a black hospital population.

Sixteen normal individuals and 100 hospital patients, all black, were tested for abnormal carcinoembryonic antigen (CEA) levels. Male and female subjects (smokers and non-smokers) were tested. The results of the tests are discussed. For normal subjects, the CEA values ranged from 0.0 ng/ml to 2.6 ng/ml. Among hospital patients with neoplastic disease, male patients with lung disease showed elevated CEA titers but their female counterparts did not. On the other hand, female patients with breast cancer, in contrast to their male counterparts, had raised values of CEA. The clinical indices for laboratory tests of sensitivity, specificity, and predictive value were calculated and determined to be 71.5, 56, and 47.5 percent, respectively.


Testicular torsion and epididymitis demonstrated by radionuclide angiograms and static imaging.

Radionuclide testicular angiography and static images were performed using technetium 99m sodium pertechnetate in an effort to differentiate between testicular torsion and acute epididymitis in 12 patients. The diagnosis of testicular torsion was made in four cases that were confirmed at surgery. Acute epididymitis or acute epididymo-orchitis was diagnosed six times. These patients were treated with broad-spectrum antibiotics leading to a subsidence of their clinical symptomatology during therapy with no sequelae. The radionuclide angiogram and static image changes of chronic epididymitis are also discussed.Radionuclide testicular angiograms and static images can be significant benefits in addition to the clinical and physical findings to distinguish between testicular torsion and acute and chronic epididymitis.


The fortune of a capacious spinal canal.

Injury to the spine may be either osseous, neural, or both. The neurological deficit may or may not be a reflection of the severity of the osseous injury. Patients having wide canals are more likely to have less neurological dysfunction than those having narrow canals.


Viruses and human cancer.

The etiologic role of viruses in a great variety of animal tumors has been demonstrated beyond doubt. There is, however, no firm evidence that any malignant disease of man is caused by viruses. Data accumulated on the association of viruses with human cancer are reviewed.


Appendicitis in a tropical African population.

Acute appendicitis was once thought to be rare among rural blacks. It is now known that appendicitis is relatively common among Africans and in Africa. At the University College Hospital, Ibadan, Nigeria, appendicitis is the most common cause of acute abdomen on the surgical service.One hundred and eighty-one cases of appendicitis were operated on in a two-year period from June 1975 to June 1977. A retrospective analysis of 47 fully documented cases showed that wrong diagnosis occurred more often in females than in males. There was a high incidence of perforation (31.9 percent) in this series. Deaths occurred in perforated cases and cases complicated by typhoid perforation of the terminal ileum. Parasites and their ova were often present in the lumen of some appendices.The age group most affected was 16 to 20 years. This disease affected low, middle and upper income groups in our society. Chronic, recurrent appendicitis was frequently diagnosed (31.9 percent) and history of recurrent right lower quadrant pain as far back as three months was often elicited from these patients.


Effects of methylmercuric chloride intoxication on the intracellular activity of lysosomal enzymes in rat liver and brain.

The activity of the lysosomal enzymes of rat liver after a single intraperitoneal injection of methylmercuric chloride (5.0 mg/kg) was enhanced in the nuclear fraction during early post-injection (2 hr to 7 days), while it decreased in the mitochondrial fraction and increased in the lysosomal fraction during late post-injection (14 days). Rat brain activity, however, was reduced in the nuclear, mitochondrial and lysosomal fractions during late post-injection (14 days). A high accumulation of total mercury was observed in the liver during early post-injection (36 hr and 7 days) while similar accumulation in the brain occured during late post-injection (7 days and 14 days). Both the mercury burdens and the enzyme activities of the rat liver and brain returned to normal levels within 30 days.


Studies on the toxicity of coal-tar dyes II. Examination of the biological reaction of coal-tar dyes to vital body.

The toxicity of xanthene dyes were studied by various interaction between the dyes and the components in vital body. (1) An increase in the amount of Rose Bengale adsorbed on the gill of fish was followed by the increase in red corpuscle number, and it was assumed that the death of fish in xanthene dye solution was due to anoxemia. (2) Binding capacity of xanthene dyes with bovine serum albumin decreased in the following; Rose Bengale, Phloxine, Erythrosine, Eosine and Uranine. This order was quite coincident with the toxicity compared by TLm values. (3) From the results of rec-assay test by use of Bacillus subtilis, it was confirmed that Phloxine and Rose Bengale had DNA-damaging capacity related to the mutagenecity.


Studies on the metabolism and toxicity of dinitrotoluenes. Toxicological study of 2,4-dinitrotoluene (2, 4-DNT) in rats in long term feeding.

2, 4-Dinitrotoluene (2, 4-DNT) was incorporated at the level of 0.5% in a standard commercial diet and fed ad lib. to male rate for 6 months. Significant changes were noted in the body weight, organ weight, behavior, mortality, and biochemical analysis of blood and serum of rats ingesting 2, 4-DNT. Furthermore, it was found that the ingestion of 2, 4-DNT affected on the activities of drug metabolizing enzymes in liver microsomes.


Seasonal dimensions to rural porverty: analysis and practical implications.

This paper reports on a conference on seasonal dimensions to rural poverty. Presentations included specialised papers on climate, energy balance, vital events, individual tropical diseases, nutrition, rural economy, and women, and also multi-disciplinary case studies of tropical rural areas from the Gambia, Nigeria, Mali, Kenya, Tanzania, India and Bangladesh. While care is needed in generalising, the evidence suggested that for agriculturalists in the tropics, the worst times of year are the wet seasons, typically marked by a concurrence of food shortages, high demands for agricultural work, high exposure to infection especially diarrhoeas, malaria, and skin diseases, loss of body weight, low birth weights, high neonatal mortality, poor child care, malnutrition, sickness and indebtedness. In this season, poor and weak people, especially women, are vulnerable to deprivation and to becoming poorer and weaker. Seasonal analysis is easily left out in rural planning. When applied, it suggests priorities in research, and indicates practical policy measures for health, for the family, for agriculture, and for government planning and administration.


A case of paracoccidioidal granuloma in norther Nigeria.

A case of Paracoccidioidal granuloma in Northern Nigeria is presented. The fungus could be cultured and identified as Paracoccidioides brasiliensis. Histology revealed a fungal lesion due to a yeast like organism. The patient responded to long acting Sulphormethoxine (Fanasil). A variation from the classic histopathological description and association of pustular psoriasiform lesions on the soles with a possibility of 'Id' reaction to the fungus are discussed.


[Reconsideration of transureteral cutaneous ureterostomy: Y-shaped cutaneous ureterostomy (author's transl)].

After reviewing the history and technique used for transureteral cutaneous ureterostomy, the authors describe 5 cases treated by this method during the 3-year period, 1975--1977. This prodecure has many advantages when compared to the transintestinal cutaneous ureterostomy as described by Bricker, uteterosigmoidoscopy, and "double-barreleed" cutaneous ureterostomy. The authors conclude that transureteral cutaneous ureterostomy should be performed in cases of ureteropyelocalicial distention with renal failure from operable or inoperable bladder cancer, in women with inoperable or recurrent tumors of the genital organs and vesicovaginal, vesicourethrovaginal or vesicorectovaginal fistulae, and in patients with a neurological bladder. They propose that this surgical technique be known as "Y-shaped cutaneous ureterostomy" instead of transureteral cutaneous ureterostomy because of its similarity to the method of Roux for Y-shaped digestive tract anastomoses, and because this new terminology is simpler and describes the operative procedure in a clearer manner.


[The value of posterior iliac osteotomy in the treatment of ectopia vesicae. Two-cases (author's transl)].

The authors emphasise the value of bilateral posterior iliac oestotomy in facilitating aponeurotic and cutaneous closure of ectopia vesicae. The osteotomy cuts the wing of the iliac bone above the greater sciatic notch 2 cms lateral to the sacroiliac joint. The new point made by the author is the use of an external fixation device the pins of which are implanted only in the iliac crest in the still young child, whilst in the adolescent a more solid method of fixation involves in insertion of additional pins in the pubis (taking care to avoid the femoral vessels). The recommended operative schedule is as follows: 1) Simple posterior iliac osteotomy. 2) Bed rest for 8 to 15 days until cutaneous healing of the iliac incisions. 3) Urological phase (which for the author consists of excision of the plaque with ureterocolic implantation) with aponeurotic closure (using eliptical strips fashioned from the rectus sheath) and simple cutaneous closure without any traction because of the osteotomies. 4) Insertion of external fixation device at the end of the urological phase. This is supported by 2 cases reports with and uncomplicated postoperative course from both a urological and orthopaedic standpoint.


[The technique of ureteric advancement in vesico-ureteric reflux (author's transl)].

The authors, anxious about the crossed position of the ureteric meatuses after transverse submucosal advancement of the ureters, prefer descending submucosal advancement. They emphasise the widely open nature of the hiatus of penetration of the ureter into the bladder. Tightening of this orifice, distal to the orifice left free for the penetration of the ureter, participates in elongation backwards of the muscular layer upon which the submucosal advancement will take place. If necessary, if the trigone is too short, the vesical muscularis layer is slit in a proximal direction, uretero-vesical penetration withdrawn by an equal amount and suture of the muscular breach behand the ureter elongates a submucosal course which, without the use of this technique, would be too short. The authors have collected a series of 63 ureters. No stenosis, 3 residual reflux and at the time of follow up cystoscopy where applicable, the new meatus is easy to locate and to catheterise.


[Fluorine content in the urine and in the serum of hydrofluoric acid workers as an index of health administration (author's transl)].

The behavior of fluoride ion level in the urine and in the serum was measured as an index for health care of workers exposed to hydrofluoric acid, the effect of fluorine-containing foodstuff intake by the workers being considered at the same time. For this study, 250 hydrofluoric acid workers and as a control group 1,600 non-hydrofluoric-acid workers were examined. All workers, ranging in age from 15 to 59 years old, came from the same electronics factory. Fluorides in the biological fluids were measured by using the fluoride ion-specific electrode method and the electrode potential recording method concurrently. The fluoride ion levels (geometric mean) in the urine and in the serum of the non-hydrofluoric-acid workers were determined to be 0.59 ppm and 12 ppb, respectively. Among the influences of fluorine-containing foodstuff on fluoride content in the biological fluids, the effect of black tea and/or green tea intake was particularly remarkable. In the case of the non-hydrofluoric-acid workers, the concentration increased to about double of the control value. Similarly in a diet test on volunteers, the concentration increased about six times. As for the response to tea intake with the lapse of time, the concentration in the urine specimen (spot urine, S.G. corrected: 1.024) reached the maximum value three hours after the intake. In the case of the serum specimen, the maximum value was recorded one hour after the intake, and the influence of the intake continued for several hours. These results suggest that, in the medical examination of hydrofluroic acid workers, restriction of intake of tea and in some cases even a fasting program would have to be introduced as necessary pre-conditions. Upon observation of fluorine concentration in the urine with the lapse of time of hydrofluoric acid workers restricting tea intake, it was confirmed that the trend of the day-to-day variation was small. But that of the in-a-day variation, namely, an increase in the concentration toward the end of daily working hours was obvious. By introduction of these well-regulated methods, it has become possible to properly evaluate even the influence of hydrofluoric acid on the workers irregularly exposed to a hydrofluoric acid environment having a lower concentration than that of the threshold limit value (3 ppm). However, in view of ease of collection and measurement of specimens, speed, and degree of response to the exposure, it can be concluded that the measurement of fluorine content in the urine is more advantageous as an index for the health care than that in the serum. For this reason it is desirable that the former method should be given priority from the view point of prevailing industrial hygiene laws and regulations.


[Experimental studies of long-term aerosol inhalation. An inhalation apparatus for long-term exposure with concentration regulation facilities (author's transl)].

A "multipurpose" inhalation system for long-term experiments was developed to study health effects of the exposure to various kinds of aerosols appearing in general working environments as well as in the ambient atmosphere. In order to carry out a continuous inhalation study on animals for their life-span, at least two essential conditions should continuously be fulfilled. (1) Steady maintenance of the appropriate sanitary conditions for the animals placed in the inhalation box. (2) Constant feeding of aerosol at an appropriately regulated concentration level. The developed system described in the present paper has been proved to be satisfactory from the above viewpoints. This inhalation system was applied to an experimental study attempting to simulate the polluted lungs in the urban dwellers. Heavy oil combustion products were chosen as the inhalation material, which were made to be inhaled by the male rats of SD-JCL strain for their life-span. The present report is mainly concerned with the construction of the inhalation system including a newly devised regulation facility of the aerosol concentration. Operating characteristics and actual data obtained are described. Details of the exposure conditions and pathological findings obtained will be described in the succeeding reports.


[Accumulation kinetics of trichloroethylene and its metabolites during multiple exposures. A theoretical study (author's transl)].

In attempting to establish an excretory TLV for trichloroethylene, the rates at which trichloroethylene and its metabolites accumulate in the body with increasing number of exposures and their plateau values attained after repetition of an infinite number of exposures were estimated theoretically with a mathematical model. After a single inhalation exposure to trichloroethylene is over, its concentration in the blood, x, and the amount of its urinary metabolites, [D]to, as a function of time t are expressed as a sum of three exponentials: (formula: see text). where A1-A3 and D1-D3 are constants depending on the inhaled air concentration of trichloroethylene, and alpha 1-alpha 2 and kA-K3 rate constants. When the same degree of exposure is repeated for n consecutive days, the blood concentration, t hours after the nth day's exposure, becomes (formula: see text). From the experimental results of a single human exposure reported previously, the concentration of trichloroethylene in the blood was predicted to change only to a negligible degree after repetition of an infinitive number of exposures, whereas the amount of total urinary metabolites was predicted to increase by twice as much as that excreted after the single exposure.


[On the leptospirosis occurred in a worker under construction of World Ocean Exposition in Okinawa Prefecture (author's transl)].

A male worker, 29 years old, was engaged in construction work of World Ocean Exposition in Okinawa Perfecture, and was diagnosed as suffering from leptospirosis in September 1973. The leptospirosis was an acute infection caused by Leptospira hebdomadis. The parasite seemed to be transmitted to him by ingestion of food and drink contaminated with the urine and excreta of the reservoir animals in the unsanitary workshop and living environment in Okinawa district. This leptospirosis was determined as an occupational disease.


Effect of ethacrynic acid on guinea pig ileum.

The effect of ethacrynic acid on the motor function of guinea pig ileum was studied in vitro. Ethacrynic acid produced dose-related (5-160 microgram/ml) contractions in this tissue. Morphine, tetrodotoxin and sodium-free medium prevented the contractions while hexamethonium, diphenhydramine, methysergide or indomethacin did not. Atropine in a high concentration (0.1 microgram/ml) only inhibited the contractions. Ethacrynic acid inhibited the contraction of ileum induced by electrical stimulation of intramural nerves. This was not prevented by pretreatment with reserpine. Repeated exposure to ethyacrynic acid developed tachyphylaxis in contractile response. Inhibition of electrically elicited contraction of guinea pig ileum also diminished with repeated treatment. Ethacrynic acid (80-160 micrograms/ml) inhibited the peristaltic reflex of the guinea pig ileum. It is concluded that the excitatory effect of ethacrynic acid is most probably mediated by the release of neurotransmitter, however, the mechanism of the inhibitory effect remains to be elucidated.


Enhancement of dopamine-induced stimulation of pancreatic secretion by 5-dimethyldithiocarbamylpicolinic acid (YP-279), a dopamine beta-hydroxylase inhibitor.

Effect of 5-dimethyldithiocarbamylpicolinic acid (YP-279), a dopamine beta-hydroxylase inhibitor, on the secretion of pancreatic juice induced by dopamine was investigated in preparations of the isolated blood-perfused canine pancreas. Either a single injection (300 micrograms) or an infusion (100 micrograms/min) of YP-279 intra-arterially (i.a.) caused no change in the outflow of the pancreatic juice, but the secretagogue effect of dopamine (1-10 micrograms, i.a.) was enhanced by the infusion of YP-279 (100 micrograms/min, i.a.) for 60 min. The previous conclusion obtained with fusaric acid was confirmed as follows; the dopamine beta-hydroxylase activity controls the dopaminergic mechanism of the pancreatic secretion.


Comparative studies with 5-hydroxytryptamine and its derivatives in isolated, blood-perfused small intestine and ileum strip of the rat.

The mode of actions of 5-hydroxytryptamine (5-HT) and its derivatives, tryptophan (TP), 5-hydroxytryptophan (5-HTP) and 5-hydroxyindole acetic acid (5-HIAA) was studied on the isolated, blood-perfused small intestine and isolated ileum strip of rats. In the isolated, blood-perfused intestinal preparations, 5-HT and 5-HTP injected into the superior mesenteric artery caused a monophasic fast contraction, while TP and 5-HIAA had no effects on the intestine. The contractile responses to 5-HT and 5-HTP were abolished by tetrodotoxin (TTX), hexamethonium (C6) and morphine, but were resistant to blockade of either atropine, methysergide or phentolamine. On the other hand, in the ileum strip preparations, 5-HT contracted the ileum, but its derivatives had no effects on the ileum. TTX, C6, morphine and atropine failed to prevent the contractile response to 5-HT, whereas methysergide effectively antagonized the response. The present results indicate that 5-HT acts by exciting intramural neuronal elements or by directly contracting the smooth muscle of the intestine. 5-HTP seems to act in the same manner as 5-HT.


A possible purinergic mechanism for reactive ischemia in isolated, cross-circulated rat kidney.

The isolated kidney of the recipient rat was perfused at a fixed flow rate with blood from a donor by a cross-circulation technique. The renal vasculature responded to the release of arterial occlusion with vasoconstriction, the magnitude of which was increased with increase in the duration of occlusion. ATP, ADP, AMP, adenosine, noradrenaline and 5-HT injected into the renal artery induced a prominent vasoconstriction; IMP and inosine had only a weak vasoconstrictor effect even in large doses. Theophylline reduced the vasoconstriction in response to arterial occlusion and to ATP and adenosine but did not affect that produced by noradrenaline or 5-HT. This suggests that adenine compounds, particularly adenosine, may play a role in the genesis of reactive vasoconstriction after arterial occlusion in the isolated rat kidney.


Femoral vascular responses to purine and pyrimidine derivatives: release of 5-hydroxytryptamine by purine derivatives in isolated, cross-circulated rat hindlimb.

The mode of actions of the purines, adenosine, adenosine-5'-triphosphate (ATP), guanosine and guanosine-5'-triphosphate (GTP), and the pyrimidines, cytidine, cytidine-5'-triphosphate (CTP), thymidine, thymidine-5'-triphosphate (TTP), uridine and uridine-5'-triphosphate (UTP) was investigated in the isolated hindlimb preparation of the rat. A single injection of adenosine, ATP, GTP or UTP into the femoral artery induced a biphasic response, a prominent vasoconstriction preceded by a transient vasodilatation, whereas guanosine and uridine caused only a vasoconstriction. Cytidine, CTP, thymidine and TTP were almost ineffective on the vascular bed. The vasoconstrictor responses to adenosine, ATP, guanosine and GTP were effectively antagonized by either methysergide or reserpine, whereas those to uridine and UTP were not modified by either methysergide or phentolamine. Adenine, D-(-)-ribose and hypoxanthine had no effect on the vascular bed. The 5-hydroxytryptamine (5-HT) release from the hindlimb was fluorometrically determined. The present results provide direct evidence that the vasoconstriction caused by ATP, adenosine, GTP and guanosine is attributed to the release of 5-HT from their stores and that purine nucleotides and nucleosides are capable of releasing 5-HT.


Decreasing effects of glycerol-fractions extracted from ox diaphragm muscles on acetylcholine-induced contractions of smooth muscles.

Extracts of 5% glycerol obtained from ox diaphragm muscles were fractionated into four (A, B, C and D) with (NH4)2SO4. The activity as acetylcholine (ACh) receptor-like substance containing fraction was evidenced as follows; the ACh-induced contraction of tracheal muscles decreased with addition of the fraction, and such could not be attributed to the reaction with ACh receptors of tracheal smooth muscles. Fraction D had the most potent activity in the presence of neostigmine. This reaction induced by fraction D was reversed by addition of d-tubocurarine (d-TC). Fraction D was fractionated into three (I, II and III) by gel filtration on Sephadex G-75 with 50 mM phosphate buffer (pH 7.5). The purified fraction III was identified by electrophoresis, UV and visible absorption spectrum, and ion-exchange chromatography to be myoglobin. Pure myoglobin also proved to have a decreasing effect on ACh-induced contraction.


Fatty acid composition of cholesteryl esters in cholesterol-fed rabbits treated with lipid-lowering agent (ethyl 2-(p-chlorophenoxy) isobutyrate).

Regression mechanism of Ethyl 2-(p-chlorophenoxy) isobutyrate (CPIB) in the arterial wall was studied for elucidation in terms of fatty acid-compositional change in cholesterol-fed rabbits. The following evidence was obtained: (1) The amount of cholesterol and cholesteryl ester in the atheromatous aorta were reduced after CPIB treatment. (2) CPIB resulted in a significant increase in the ratio of linoleate to oleate in both the arterial wall and serum after withdrawal of the cholesterol diet. It is suggested that there is a preferential hydrolysis of linoleate-rich cholesteryl ester in both the arterial wall and the serum.


Effects of surugatoxin on adrenergically innervated tissues.

Effects of surugatoxin (SGTX), a new ganglionic blocking agent on adrenergically innervated tissues: guinea pig isolated atria and vas deferens were investigated. SGTX (1, 10 muM) markedly reduced the cardiostimulatory response of the atria to nicotine and also partially the response to 1,1-dimethyl-4-phenylpiperazinium (DMPP) and 5-hydroxytryptamine, without affecting responses to noradrenaline, tyramine and histamine. The contractile response of the vas deferens to nicotine, DMPP and hypogastric nerve stimulation was markedly reduced by SGTX (1, 10 muM), whereas that to noradrenaline, acetylcholine and transmural stimulation was not affected. These results indicate that SGTX has an antagonistic action on nicotinic receptors in these tissues as well as in sympathetic ganglia and in guinea pig ileum.


Effects of Panax Ginseng root on acquisition of sound discrimination behaviour in rats.

Pole-climbing and shuttle-avoidance tests were employed to study the acquisition of conditioned avoidance response (CAR) and discrimination behaviour (DB) in male Wistar rats which had been given extracts from Panax Ginseng root intraperitoneally or orally. Neither a lipid soluble fraction (GNo. 5) nor a ginsenoside Rg fraction (GRg) produced significant changes in the acquisition of CAR. GRg given intraperitoneally produced a significant acceleration in the acquisition of DB between a 500 Hz signal sound followed by an electric shock (SD) and a 1000 Hz signal sound without a shock (S delta) in rats which had learned to avoid the shock following SD at a rate of over 95%. Small doses of GNo. 5 produced a significant depression in the acquisition of DB.


Divalent cation transport in kidney slices. I. Properties of calcium transport in slices of rat kidney cortex and the effects of diuretics.

Correlative studies on transports of Ca2+ and Na+ and the properties of Ca2+ transport were carried out in rat kidney cortex slices. Ouabain had no effect on the Ca2+ transport but did inhibit the Na+ transport extensively. With addition of 2,4-dinitrophenol to the incubation medium, or under the anaerobic conditions, the effluxes of Ca2+ and Na+ were inhibited while the Ca2+ influx was enhanced significantly. Sulfhydryl inhibitors such as ethacrynic acid, mersalyl and p-chloromercuribenzoic acid suppressed Ca2+ efflux and stimulated Ca2+ influx. When the slices of kidney cortex were treated with these inhibitors, there was a reduction in the content of cellular ATP. The present results suggest that Ca2+ transport may be partly independent of Na+ transport, and that Ca2+ efflux may require energy-yielding processes.


Involvement of the cholinergic mechanism in depression of the caudate spindle.

Involvement of the cholinergic and catecholaminergic mechanisms in the caudate spindle recorded from the anterior and posterior sigmoid gyri was examined in cats. Physostigmine (0.01 to 0.1 mg/kg i.v.) abolished the appearance of the caudate spindle. These inhibitory effects were antagonized by the administration of atropine (0.25 to 1 mg/kg i.v.). The caudate spindle was inhibited by high frequency stimulation of the mesencephalic reticular formation: This inhibitory effect was antagonized by atropine. On the other hand, L-DOPA (25 to 50 mg/kg, i.v.), L-DOPA + MAO inhibitor and methamphetamine (0.5 to 5 mg/kg i.v.) did not influence the caudate spindle. These results suggest an involvement of cholinergic mechanism in depression of the caudate spindle.


Effects of pentylenetetrazol, pentobarbital and lidocaine on pallidal unit activities in rats.

In anesthetized immobilized rats, pallidal unit activities were recorded extracellularly through glass microelectrodes. Spontaneous activities were converted to an interspike interval histogram and an autocorrelogram by a medical computer and a correlator. Following pentylenetetrazol injection (20 mg/kg i.v.), burst discharges increased remarkably and the bursts tended to synchronize with repetitive spikes in electrocardiogram. Following administration of liocaine (5 mg/kg i.v.) the bursts increased by pentylenetetrazol were facilitated in approximately 70% neurons, whereas pentobarbital showed obvious reduction of the bursts in 80% neurons, although both drugs reduced the firing rate. Facilitation of burst discharges was also observed with high doses of lidocaine alone. These results indicate that lidocaine, as compared with pentobarbital, may block more easily inhibitory rather than excitatory neurons.


Partial purification and immunological aspects of carboxylesterase from rat liver microsomes.

Carboxylesterase (CEase) was solubilized from rat liver microsomes by autolysis followed by cholate treatment and then purified by the combination of ammonium sulfate fractionation, gel filtration, chromatography on DEAE Sephadex A-50 and hydroxyapatite and preparative Disc electrophoresis. The overall purification was 25-fold with a yield of 6% of the original enzyme activity. Analytical Disc electrophoresis of the final enzyme preparation showed a single band. However, SDS polyacrylamide gel electrophoresis revealed one main band of 93% and three other minor bands. To investigate the interaction between CEases of rat, monkey, pig and rabbit liver microsomes, rabbit antibody to the above enzyme preparation was prepared and immunological analyses, i.e., Ouchterlony's test and immunoelectrophoresis, were performed. In the comparative double diffusion test, the partial fusion of precipitation line between anti-rat CEase and the enzymes of other species was observed. In the second analysis, sharp arc precipitation lines also could be seen in all specimens and, furthermore, mobilities of each enzyme were different. These observations suggest that rat liver CEase seems to be immunologically related in part but not completely identical with the CEases of other species and the charge difference may exist in these specimens.


Increase of brain taurine contents of E1 mice by physiological stimulation.

We determined the effect of physiological stimulation on taurine contents in three regions (cerebral cortex, brain stem and cerebellum) of the brain of E1 mice, a genetically epileptic strain. Taurine contents in all regions of the brain increased significantly at the onset of convulsions, as induced by tossing the animals up many times. Levels in the cerebral cortex and cerebellum increased markedly in the early stage of the stimulation, yet convulsion did not occur. Taurine contents in the cerebral cortex and brain stem returned to the resting level with 30 min after the onset of convulsions, while levels in the cerebellum remained high for 3 hr. Concentration of taurine in the plasma also increased with the onset of convulsions. On the other hand, taurine administration increased the threshold of convulsion by the stimulation in E1 mice.


Anti-inflammatory action of progesterone on carrageenin-induced inflammation in rats.

Effect of progesterone (1 mg/kg) on the inflammation in rats induced by carrageenin was studied. Progesterone inhibited the vascular permeability and the formation of granulation tissue in the early phase of the inflammation. In the chronic proliferative phase, progesterone suppressed the vascular permeability and there was an active resorption of the granulation tissue. Increased degradation of noncollagen protein was observed in the treated group without apparent influence on the metabolism of collagen or on the synthesis of noncollagen protein. The mode of action of progesterone was compared with that of a potent anti-inflammatory steroid, hydrocortisone acetate.


Effects of 1-(2-chloro-4-hydroxyphenyl)-t-butylaminoethanol (HOKU-81), a new bronchodilator, on isolated trachea and atria of guinea pig.

Effects of 1-(2-chloro-4-hydroxyphenyl)-2-t-butylaminoethanol hydrochloride (HOKU-81), one of the metabolites of tulobuterol, on isolated trachea and atria of guinea pigs were compared with those of various bronchodilators. All test drugs abolished the resting tone of tracheal muscle completely. The potencies of test drugs which induced relaxation were in the order of: trimetoquinol greater than HOKU-81 greater than or equal to isoproterenol greater than salbutamol greater than terbutaline greater than or equal to tulobuterol greater than metaproterenol greater than clorprenaline. In acetylcholine-, histamine- or potassium-stimulated preparations, the intrinsic activities of 2-chlorophenyl derivatives were less than those of 3,4- or 3,5-dihydroxyphenyl derivatives and that of HOKU-81, 2-chloro-4-hydroxyphenyl derivative, lay between two groups. HOKU-81 showed weak positive chronotropic and inotropic actions and the potency ratio of HOKU-81 to isoproterenol was about 3/100 and less than 3/1000, respectively. Both chronotropic and inotropic actions of 2-chlorophenyl derivatives, including HOKU-81, were weak and the inotropic actions of drugs with N-t-butylamino radical were weaker than chronotropic actions. Effects of test drugs on trachea and atria were antagonized by propranolol 1 x 10(-6) or 1 x 10(-7) M. HOKU-81 appears to be a potent and selective beta 2-stimulant with a slight inotropic action.


Responsiveness and high-energy phosphate metabolism of isolated dog coronary arteries.

The relationship between responsiveness and high-energy phosphate metabolism was observed in isolated dog coronary arterial strips before and after equilibration, under aerobic conditions. The strips responded slowly to potassium, norepinephrine, isoproterenol and 5-hydroxytryptamine before being equilibrated but did respond quickly to these drugs after being equilibrated for 1 hour under aerobic conditions. The contents of ATP, creatine phosphate (CP) and lactate were not significantly altered before and after equilibration for 1 hr. It is proposed that, before being equilibrated under aerobic conditions, coronary arteries may be unable to utilize ATP and CP due to injury of contractile or relaxant mechanisms resulting in a weak vascular responsiveness.


Altered bile acid metabolism in alloxan diabetic rats.

Changes of cholesterol, phospholipid, triglyceride or bile acid levels in serum liver, bile and feces after the treatment with alloxan were examined in Wistar strain male rats. Serum cholesterol, phospholipid and triglyceride levels and liver cholesterol level markedly increased but liver phospholipid and triglyceride levels remained unchanged. The lipid levels in serum very low density and low density lipoproteins were elevated but those in high density lipoprotein were not. Bile flow was not changed but biliary secretion of cholesterol, phospholipid and bile acids markedly increased. Among the biliary bile acid components, cholic acid markedly increased but the amount of chenodeoxycholic acid was similar to that of normal rats. Fecal excretion of deoxycholic acid increased but that of lithocholic and hyodeoxycholic acids decreased, and alpha, beta- and omega-muricholic acids did not change, thus, the total amount of fecal bile acids remained unchanged. Hepatic cholesterol synthesis was markedly depressed, while cholesterol 7 alpha-hydroxylase activity did not change and cytochrome P-450 content was elevated by about 40%. From such evidence, it was apparent that synthesis of cholic acid increased while that of chenodeoxycholic acid decreased and the total amount of bile acids synthesized did not change in the diabetic rats. Furthermore, marked increase of the pool size of cholic acid and hepatic secretion of cholic acid stimulated the absorption of lipids and produced a hyperlipidemia in the diabetic rats.


Pharmacological studies of lycorenine, an alkaloid of Lycoris radiata Herb.: Vasodepressor mechanism in rats.

Vasodepressor mechanism of lycorenine (an alkaloid of Lycoris radiata Herb.) was investigated in anesthetized rats. Lycorenine (1--10 mg/kg i.v.) produced dose-related decreases in blood pressure and heart rate and tachyphylaxis developed with repeated injections. In the blood-perfused rat hindquarters, lycorenine (62.5--500 micrograms i.a.) produced dose-related decreases both in mean blood pressure and in perfusion pressure, and the lycorenine-induced decrease in perfusion pressure was abolished by phenoxybenzamine or hexamethonium. Lycorenine (more than 1 mg/kg i.v.) blocked the pressor response to sympathetic nerve stimulation, but failed to block the tachycardia induced by sympathetic nerve stimulation. Lycorenine (7.5 or 15 mg/kg i.v.) reduced the spontaneous splanchnic nerve activity. Lycorenine when given intracerebroventricularly produced decreases in blood pressure and heart rate only in large doses (over 500 micrograms). The maximal bradycardia induced by lycorenine was abolished by bilateral vagotomy. It is suggested that lycorenine may produce a decrease in blood pressure as the result of alpha-adrenergic blockade in conjunction with the reduction of the spontaneous sympathetic nerve activity, and produce bradycardia by modifying vagal activity.


Effects of angiotensin II and 1-sar., 8-isoleu. angiotensin II on electrical and mechanical properties of the portal vein from rats of different ages.

The effects of angiotensin II (Ag-11) and 1-sar., 8-isoleu. angiotensin 11 (anti-Ag-11) on the membrane and mechanical properties of smooth muscle cells of the rat portal vein were investigated in three different age groups (6--8 weeks, immature rat; 3--5 months old, young rat and 13--15 months old, adult rat). Application of Ag-11 (10(-10) g/ml) did not depolarize the membrane, but did increase the spike frequency and potentiated the frequency and amplitude of twitch contraction. In a concentration of more than 10(-9) g/ml Ag-II, the membrane was depolarized and a phasic contracture was developed in three age groups. Depolarization of the membrane produced by Ag-II could be classified into two components, i.e. phasic and tonic depolarizations. In adult rats, Ag-II produced the highest amplitude of the depolarization in three age groups but tonic depolarization showed nearly the same amplitude of smooth muscle cell membrane to Ag-II increases with age up to 3--5 months and that an increased sensitivity is accompanied by a generation of desensitization. Tachyphylaxis to Ag-II was also observed by repetitive applications, but the appearance depended on the stimulus conditions. Anti-Ag-II, itself slightly increased the spike frequency and the amplitude of twitch contraction. However, under pretreatment with anti-Ag-II (10(-9) or 10(-7) g/ml), the actions of Ag-II on the electrical and mechanical activities were markedly suppressed in the three age groups. When the dose-response curve was obtained from the mechanical response produced by Ag-II, the relation shifted to the right in the presence of anti-Ag-II in all age groups. In the presence of 10(-7) g/ml anti-Ag-II, no contracture was evoked by application of 10(-6) g/ml Ag-II in three age groups. Anti-Ag-II seems to possess a higher affinity to the angiotensin receptor than does Ag-II.


Effect of intra-uterine administration of indomethacin on ovarian steroids.

Proteolytic enzymes increase the sensitivity of the bronchial system against acetylcholine when inhaled as aerosols. These experiments were performed on 33 dogs in order to localize the area of sensitivity in the bronchial system responsible for bronchoconstriction. Pronase given in a small dosage as proteolytic enzyme aerosol only to the upper part of the airtract sensitises the lower part of the airways against acetylcholine. Pronase aerosol given to the lower part of the airways needs higher dosages for sensitization to acetylcholine. This effect assumes an interaction between the upper sensoric part in the reflex way of airway obstruction and the lower airways. Changes caused by proteolytic enzymes in the upper part of the airtract can cause increased reactivity of the lower airways.


Effect of verapamil on the calcium and magnesium transports of rat kidney cortex mitochondria.

The effect of verapamil on Ca2+ and Mg2+ accumulation was investigated in isolated rat kidney cortex mitochondria. For the 50% inhibition of Ca2+ accumulation, 2 x 10(-4) M verapamil concentration was required in the presence of ATP (2 mM) and phosphate (5 mM). Omission of phosphate from the medium increased the inhibitory effect of verapamil on Ca2+ accumulation. Verapamil had no effect on Ca2+ accumulation in the presence of both ATP and succinate (7.8 mM), but further addition of phosphate resulted in a significant inhibition of Ca2+ accumulation by verapamil. Mg2+ accumulation of mitochondria was similarly depressed by verapamil. The same tendency was found as for the modification of verapamil effect by acetate in mitochondrial Ca2+ and Mg2+ accumulation. Succinate oxidation of mitochondria was not affected by verapamil in the absence of phosphate, but was inhibited by verapamil in the presence of phosphate. Therefore, it seemed reasonable to assume that the depression of Ca2+ and Mg2+ transport of mitochondria by verapamil is modulated by permeant anions.


The mechanism of aggravation of indomethacin-induced gastric ulcers by adrenalectomy in the rat.

Bilateral adrenalectomy markedly aggravated gastric ulcers in rats induced by 5 or 20 mg/kg of indomethacin. The degree of aggravation was much the same in experiments done 1 and 14 days after operation. Pretreatment with prednisolone 10 mg/kg or cortisone acetate 10 mg/kg given subcutaneously significantly suppressed the aggravated ulceration in response to 20 mg/kg of indomethacin in these adrenalectomized rats. Desoxycorticosterone acetate 10 mg/kg, however, had no effect on the aggravation of indomethacin-induced ulcers. Epinephrine 0.1 or 1 mg/kg given subcutaneously markedly suppressed the indomethacin-induced ulcers in adrenalectomized rats. Removal of the adrenal medulla alone did not appreciably influence the development of indomethacin-induced ulcers. These results indicate that the adrenal cortex, particularly the area containing glucocorticoids, plays an important role in suppression of the noxious effect of indomethacin on the rat gastric mucosa.


Structure-activity relationship of 5-hydroxykynurenamine analogues in isolated dog cerebral arteries.

In helically-cut strips of cerebral arteries isolated from dogs, analogues of 5-hydroxykynurenamine (5-HK), including 2-(3'-aminopropyl)-aniline (Cpd. I), 2'-amino-3-dimethylamino-3'-hydroxypropiophenone(CPD. II), 2'-amino-3-dimethylamino-5'-hydroxypropiophenone (Cpd. III) and 2',3-diamino-propiophenone (kynurenamine), caused a dose-related contraction which was antagonized by treatment with methysergide. The potency for inducing contractions was in the order of 5-hydroxytryptamine greater than 5-HK greater than Cpd. III greater than kynurenamine, Cpd. I and Cpd. II. Treatment with the 5-HK analogues antagonized the contractile response to 5-hydroxytryptamine in a dose-dependent manner, the antagonistic potency being in the order of 5-HK greater than Cpd. III greater than kynurenamine, Cpd. II greater than Cpd. I. Alterations in the hydroxy group on the benzene ring and/or radicals of long side chain of 5-HK attenuated the agonistic and antagonistic actions of 5-HK; however, the attenuation of these actions differed. Thus, the radicals appear to be involved in the agonistic and antagonistic actions to a different extent.


[The development of the simple-sentence processing in Japanese children (author's transl)].

The present paper deals with the development of the simple-sentence processing in Japanese children. Subjects were 2-, 3-, 4- and 5-year-olds. Experiment I exemplified the hypothesis that in children's processing of the simple sentence there is some span with the phrase as a unit. This was found to develop in parallel with the increase of short-term memory span for words, being about one unit larger than the latter at all age levels. Although sentence length is dominant, structural differences in the sentence of the same length was found to have some effects on the processing in Experiment II. The sentence itself becomes a chunk as early as the age of three.


Characterisation of post exercise pressure response curves in the pedal arteries of patients with peripheral vascular disease.

The response of the systolic pressure in the pedal arteries to the stress of exercise is one of several ways of assessing the severity of peripheral vascular disease. We have examined 2607 such pressure response curves in an attempt to produce a simple method of response classification. Regression analysis of the curves has shown that errors are least when the regression used is the same order as the number of data points. We conclude that post exercise response curves can be adequately classified from three data points, one obtained within two minutes of the cessation of exercise, a second obtained between 4 and 6 minutes from the end of exercise and a third taken 10 minutes after exercise. The use of a response curve indexed to systemic systolic pressure was not found to produce a better correlation between full and three point curves, though the absolute classification differed slightly from that obtained from the non-indexed curve. Neither classification system proved significantly superior in relating to the degree of arterial disease.


Early diagnosis of multiple sclerosis by combined multimodal evoked potentials: results and practical considerations.

It is shown that using four combined types of evoked potentials one can disclose new localisations in 62.5% of as yet undiagnosed M.S. patients. Brainstem auditory EP recordings must be considered in detail to avoid missing slight anomalies. Blink reflexes yielding bilateral R1 seem to bear the same significance as an augmented latency with respect to the problem of disclosing new localisations.


An analytical investigation into possible mechanical causes of bone remodelling.

Three-dimensional finite element analyses were carried out on idealisations of two situations where bone remodelling has been reported clinically viz. the malaligned femur and a maxillary central incisor under orthodontic loading. The mechanical responses, i.e. stress, strain and change of curvature, in various directions, are presented. They are compared with the biological response, either bone resorption or bone deposition. The results are discussed in relation to three current theories of bone remodelling.


A combined transcutaneous pulse-echo and Doppler ultrasonic technique for the measurement of brachial artery peak velocity.

The Parks Model 806 Doppler blood velocity meter was shown to have a linear voltage output with respect to input frequencies of up to 5kHz. It was linear and accurate to velocities of 70 cms-1 at angles of 50 degrees and 60 degrees to the flow, on a steady flow rig, and shown to have a linear frequency response to 9Hz. A combined pulse echo and Doppler transducer system has been developed allowing quantitation of arterial peak velocity.