The cryptonephridial system in the mealworm Tenebrio molitor: transport of radioactive potassium, thallium and sodium; a functional and structural study. Larvae of the mealworm Tenebrio molitor were injected with radioactive potassium, sodium or thallium solution. It was found that the rectal complex of the animal was labelled with potassium and thallium, but not with sodium. Potassium and thallium labelled the complex to the same level as if the two ions were tracers for each other. Ramsay has found that potassium is actively transported to the complex from the hemocoel and there are reasons to believe that T1+ follows the same pathway. Therefore animals injected with thallium were investigated both by light and electron microscopy. The results suggest that thallium spreads from the hemocoel through the leptophragma to the neighbouring ordinary tubular cells, and in moist mealworms thallium is further found in the perirectal space. Due to diffusion and washing out of thallium during fixation it can not be determined whether T1+ and K+ follow identical pathways, but it is possible to determine how far thallium has penetrated during the experiments.


The microfiber texture in a specialized plastic cuticle area within a sensillum field on the cockroach maxillary palp as revealed by freeze fracturing. A field of sensilla extends across the ventral surface of the terminal segment of the maxillary palps of Periplaneta americana. The sensilla project from a sheet of pliable cuticle. Ultrathin sections of the cuticle in this area reveal a clear-cut parabolic microfiber pattern. Microfibers can also be seen from freeze fracture faces running parallel to the cuticular surface. These microfibers have a diameter of 80 A and may consist of chitin crystallites surrounded by a matrix coat. The number of straight parallel microfibers visible in a fracture face increases the more closely parallel to the surface the fracture runs. This result suggests a helicoidal texture, as the model of Bouligand would demand. The layer-to-layer rotational displacement of the microfibers is about 12 degrees. This texture can be regarded as typical for flexible cuticles in general. Other structural properties such as the continuation of the epicuticular dense layer into deeper cuticular layers around the enveloping cells of sensilla can be interpreted as specializations connected with the function of the sensillum field.


Spermiogenesis in the teleost Gambusia affinis with particular reference to the role played by microtubules. During nuclear elongation in spermatids of Gambusia affinis, a deep fossa is formed at the base of the nucleus in which the centriolar complex and proximal portion of the flagellum reside. To stabilize the positional relationship between the nucleus and centriolar complex, while nuclear morphogenesis is taking place, a series of microtubules develop which emanate from the centriolar complex and extend to the nuclear envelope lining the fossa. Buttressing microtubules also develop within the nuclear fossa which both originate and insert along the nuclear envelope. These appear to stabilize nuclear shape prior to the time when chromatin condensation has proceeded to the stage where it could lend structural stability to nuclear form. Microtubules develop only after specific nuclear morphogenic events have taken place. It is therefore concluded that the spermatid nucleus is capable of "self-assembly" involving microtubules in a supportive role in addition to stabilizing the nuclear-flagellar relationship in G. affinis. The pattern of nuclear fossa-associated microtubules in G. affinis is significantly different from that observed in other poeciliid teleosts indicating a degree of species specificity with regard to both the timing of appearance and total number of microtubules.


Precocious differentiation of immature chief cells in fundic mucosa of infant rats induced by hydrocortisone. Injection of hydrocortisone into developing rats induced precocious increase in the potential peptic activity of pepsinogen in the fundic mucosa, change from the immature to the mature electrophoretic pattern of pepsinogen isozymes and morphological change from the immature to the mature chief cells. The continual presence of hydrocortisone was required for maintenance of mature chief cells.


Control of cell division and cell differentiation by deoxynucleotides in the early embryo of Xenopus laevis. It is proposed that the deoxyriboside triphosphates present in the egg of Xenopus laevis support the synchronous cell divisions occurring during the earliest phase of embryonic development and that, as long as synchrony prevails, the cells are prevented from undergoing differentiation. This hypothesis has been tested by injecting deoxyribonucleotides into fertilized eggs. The following effects were observed: 1) the duration of synchrony is prolonged, 2) the morphological development is suppressed, an effect which is greatest when four nucleotides are injected together and 3) the synthesis of all kinds of RNA is inhibited, including the mRNA required for differentiation to occur.


[Phosphoglyceridosis].

[Phosphoglyceridosis]. On the basis of a bioptic examination of the appendix, skin and a liver specimen, the diagnosis of phospholipidosis was made in a girl aged 27 months. In contrast to the Niemann-Pick's complex of sphingomyelinoses, phosphoglycerides were stored in larger amounts than spingomyelin. The disease should be undoubtedly included under one heading with the so-called "kephalinosis" [11] and with the cases described by Wiedemann et al. [10]. The terms "Type II phospholipidosis [Baar-Wiedemann's disease]" or, briefly, phosphoglyceridosis, appear to be most adequeate for designating the diseases in question. The disorder can be diagnosed on the basis of iron hematoxylin staining, visualizing all phospholipids. In Niemann-Pick's sfingomyelinosis, alkaline hydrolysis does not alter the colour, whereas in the phosphoglyceridosis under discussion the colour is substantially reduced or even desappears after alkaline hydrolysis.


[Jejunal mucosa in children with mucoviscidosis]. Thirty-eight specimens obtained by jejunal biopsy from 22 children suffering from mucoviscidosis were examined by histochemical techniques. In 27% of the patients the findings were within normal limits. In 18% of cases, associated coeliacal sprue was disclosed. The remaining cases displayed slight morphological abnormalities associated with trehalase and/or lactase deficiency, and in 41% there was hypersecretion of viscous mucus filling up dilated crypts and adhering to the surface of villi. The findings as observed in enterobiopsis are not pathognostic of mucoviscidosis. They however, should make one to think of it, particularly if trehalase and/or lactase deficiency is found associated with hypersecretion of viscous mucus and an almost normal morphological appearance. Neither normal findings nor that of coeliacal sprue exclude the diagnosis of mucoviscidosis. It appears that malabsorption in mucoviscidosis is not only pancreatogenic; the intestinal mucosa may be contributory to a various degree as well.


A simple method for the synthesis of cholesterol esters in high yield. A simple and convenient synthesis of cholesterol esters from cholesterol and fatty acid anhydrides is described. The high, reproducible yield of cholesterol ester and the small excess of fatty acid used makes this method attractive for the preparation of cholesterol esters using difficultly obtained fatty acids.


Conformational analysis of phosphatidylethanol-amine in multilayers by infrared dichroism. Built-up films of L-alpha-dipalmitoyl phosphatidylethanolamine were prepared. Infrared dichroism was measured for the sample and analysed by a new method. This method has been developed for the determination of the directions of transition moments in a film sample, in which there is an axis of symmetry of perpendicular to the film plane. The directions of transition moments were determined for the six vibrations assigned to the CH2 antisymmetric stretching, CH2 symmetric stretching, CH2 scissoring, C=O stretching, PO2- antisymmetric stretching, and C-C-N+ antisymmetric stretching modes. The results indicate that hydrocarbon chains are inclined at about 75 degrees to the film plane and the polar groups orient parallel to the plane in the builtup film. A structural model of the phosphatidylethanolamine in the built-up film is proposed.


Mass spectrometric analysis of permethylated glycosphingolipids I. Sequence analysis of two blood-group B active glycosphingolipids from human B erythrocyte membranes. Two blood group B active glycosphingolipids (B-I and B-II) formerly isolated and purified from human B erythrocytes (16) were investigated by mass spectrometry after permethylation. B-I yielded fragments up to m/e 1266 and B-II up to m/e 1495, showing the sequence of six and seven carbohydrate residues respectively. In combination with additional experimental evidence (18) the glycosphingolipids are demonstrated to be a gal-[ fuc ]-gal-glcNAc-gal-glc-ceramide (B-I) and a gal-[ fuc ]-gal-glcNAc-gal-glcNAc-gal-glc-ceramide (B-II). Mass spectrometric evidence for the ceramide residues are also obtained indicating besides spingosine C24-,C24:1-, and C22-fatty acids as main constituents.


Individual variation in inosine triphosphate accumulation in human erythrocytes. Erythrocytes from 5% of a normal population accumulated relatively high amounts of radioactive inosine triphosphate (i.e., greater than 70 nmoles/10(10) cells in 2 hr) when they were incubated with [14C]hypoxanthine. The incidence of this characteristic in a mentally retarded population was 16%. Inosine triphosphate was synthesized from [14C]hypoxanthine, but not from [14C]adenine or [14C]guanine. The metabolism of [14C]adenine and [14C]guanine was the same in erythrocytes that accumulated "normal" and "high" amounts of inosine triphosphate. Inosine triphosphate did not accumulate in leukocytes.


Urine vapor pattern for olivopontocerebellar degeneration. Autosomal dominant olivopontocerebellar degeneration was evaluated in a family numbering 414 living members. Urine samples were obtained from 5 affected and 5 unaffected not at-risk family members after 4 days on a synthetic diet. 159 urine vapor constituents were measured by gas-liquid and ion-exchange chromatography and a non-correlation index was calculated. 2 distinct populations of urine vapor patterns were identified which conformed to the normal and disease affected groups, thus a diagnostically useful pattern for this disease in this family has been demonstrated which will be helpful in genetic counselling and potential elimination of the disease.


Combined radioimmunoassay of four steroids in one ml of plasma: I. Progestins. Using partially specific antisera combined with a 1 step celite microcolumn chromatography, progesterone (P), 20alpha-hydroxypregn-4-ene-3-one (20alpha-P), 17-hydroxyprogesterone (17-P), and 16alpha-hydroxyprogesterone (16alpha-P) could be  measured in the same 1 ml aliquot of plasma. The chromatographic step removed known interfering steroids and conferred specificity to the assay. After correction for recovery the sensitivities, expressed as ng/ml of plasma, were respectively: 0.04 for P, 0.03 for 20alpha-P, 0.02 for 17P, and 0.01 for 16alpha-P. Recovery experiments, using steroid-free plasma to which various amounts of each steroid were added and then measured in the assay in 12 replicates, confirmed adequate accuracy and precision. The ability to measure multiple progestogens in small volumes of plasma should permit comprehensive evaluation of the role of these steroids in health and disease.


Combined radioimmunoassay of four steroids in one ml of plasma: II. Androgens. Using partially specific antisera combined with a 1 step celite microcolumn chromatography, androstenedione (A), 5alpha-dihydrotestosterone (DHT), testosterone (T), and androst-5-ene-3beta, 17beta-diol (delta 5-diol) could be measured in the same 1 ml aliquot of plasma. The chromatographic step removed known interfering steroids and conferred specificity to the assay. After correction for recovery the sensitivities, expressed as ng/ml of plasma, were respectively: 0.025 for A, 0.05 for DHT, 0.025 for T, and 0.1 for delta5-diol. Recovery experiments, using steroid-free plasma to which various amounts of each steroid were added and then measured in the assay in 12 replicates, confirmed adequate accuracy and precision. The ability to measure multiple androgens in small volumes of plasma should permit comprehensive evaluation of the role of these steroids in health and disease.


Scope and limitations of propionylthiocholinesterase in the characterisation of cholinesterase variants. 1. A manual procedure, using propionylthiocholine, for the determination of serum cholinesterase and its genetic variants has been assessed in respect of its precision and of its ability to classify the genetic variants of the enzyme. 2. It is shown that the propionylthiocholinesterase activity alone is a useful guide in identifying individuals who are likely to be sensitive to succinylcholine. 3. In phenotyping with dibucaine and fluoride, sera of phenotypes U and UF could not be distinguished from each other with confidence, but were distinguishable from sera of phenotype UA.


The In Common Laboratory, Toronto.

The In Common Laboratory, Toronto. 1. The history of the In Common Laboratory system has been described, together with some of the techniques developed to deal with the problems of a centralised hospital laboratory. 2. It is suggested that the growth and strengthening of such systems will provide a solution to some of the problems of providing a comprehensive clinical laboratory service in multi-hospital groupings, and that this resource may be extended readily to distant, less well-served areas.


The molecular heterogeneity and instability of radioiodinated human chorionic gonadotrophin. Gel chromatographic studies on radioiodinated HCG have shown that a polymer and fragmented materials are associated with the radiolabelled product which interfere in the RIA of HCG in serum. Scatchard plots of experimental data indicated that the polymer material (fraction I) has two species of antigenic determinants that recognize two species of binding sites on the anti-HCG-beta. The use of purified 125I-HCG (gel chromatographic fraction II) for radioligand improved the reliability of the RIA. It was further demonstrated that a labelled preparation of HCG could be used for RIA tests for periods of five weeks or longer provided that chromatographic purification was carried out immediately prior to the assay.


A system for reporting analytical results according to the actual level of the test's exactitude. The number of significant digits, or better the increment by which a result is increased to the next highest figure, has to be related to the precision of the analytic procedure. If the relative increment is much smaller than the precision, the last digits are meaningless, and if it is too large, information contained in the result is lost. A system based only on a determined number of digits in a report is inefficient as the relative increment varies within too wide a range of 10 to 1. In the proposed system, the increment and the range of values to which this increment applies are determined. The two limits of the range are set as fractions of the 95% limits of confidence so that at mid-range, half of the results have better precision and half less than the relative increment. A Table gives the increments to be used for various ranges of results between 0.001 and 1000 units and for precision between 2% and 12%. The system produces realistic reports for every level of analytical precision and its application is simple. It also permits to take into account changes of precision at the extremes of low or high values.


Immunological relationship between human placental and intestinal alkaline phosphatase. Crystalline human alkaline phosphatase from placenta and intestine was isolated by butanol extraction, acetone precipitation, a heat step (for the placental enzyme), ammonium sulfate precipitation, anion exchange chromatography, gel filtration and crystallisation with ammonium sulfate. Rabbit antibodies showed a partial cross-reaction between both enzymes in double diffusion, quantitative precipitation experiments and in serial precipitin curves. There was no reaction with human alkaline phosphatases from liver, kidney and bone. Three phenotypes of placental alkaline phosphatase with different electrophoretical mobility exhibited identical immunological reactions with their respective antisera. Monospecific antisera were obtained by absorption with crystalline intestinal or placental alkaline phosphatase. These monospecific antisera against the placental or the intestinal alkaline phosphatase can be used for an immunological determination of these two alkaline phosphatases without contamination by other alkaline phosphatases in human serum.


Acid proteinase and peroxidase activity in spielmeyer-Vogt's syndrome (Batten's syndrome-Stengel's syndrome). The acid proteinase and the peroxidase activity of peripheral leucocytes of respectively 12 and 13 patients suffering from Spielmeyer-Vogt's disease, alias Batten's disease, alias Stengel's disease was studied. Cathepsin D activity was found to be normal in the disease, but the cathepsin B activity was decreased by 24 percent. However, the decrease was insignificant. The peroxidase assay was made using Guajacol as well as p-phenylenediamine as substrate. When the assay was performed with p-phenylenediamine, the enzymic activities were significantly decreased (p less than or equal to 1%) compared to the activity of normal control leucocytes. Assaying peroxidase activity by means of Guajacol revealed a non-significant difference between the two groups. The data obtained indicate the syndrome under study to be due to hampered peroxidase activity. The defect found explains the occurrence of lipofuchsin in the nervous system previously demonstrated.


An examination of the age-related patterns of decay of the hexokinases of human red cells. A previous method for red cell fractionation by density gradient centrifugation, using a swing-out rotor, has been scaled up to deal with larger volumes of red cells. This method, involving the use of a zonal rotor, is described and has been applied to the study of the decay of hexokinase in the red cells of normal individuals. Hexokinase activity was seen to fall very rapidly in the young cells followed by a much more gradual decline in older cells. It is estimated that the mature red cell probably contains no more than 2-3% of the hexokinase activity originally present in the reticulocyte. An electrophoretic study showed a changing pattern of the isozymes HK1 and HK2 with increasing cell age. HK2 declines very rapidly in the early fractions whereas HK1 appears to decay more gradually.


Serum immunoglobulins in healthy children and adults. Levels of the five classes, expressed in international units per millilitre. Serum levels of IgM, IgG, IgA, IgD, and IgE were determined in serum samples of 270 healthy Dutch children (aged 4-13 years) and of 30 healthy Dutch adults, the amounts being expressed in International Units per millilitre. Special attention is given to the IgD and IgE results, since the IgM, IgG, and IgA levels in mg per 100 ml of these sera and their implications have already been reported. In the children's sera the occurrence of relatively high IgD and IgE levels was frequently observed, whereas the adult group did not show excessive variation in this respect. The mean IgD levels found for adult males and females are 21 I.U./ml and 24 I.U./ml, respectively; the mean IgE levels for the same groups are 68 I.U./ml and 88 I.U./ml, respectively. The mean IgD and IgE levels in the children of each year group were usually higher than those of each of the juvenile groups and the mean level of the adult group was not statistically significant. A statistically significant influence of sex and season on the IgD and IgE levels could not be demonstrated in this material either. Three of the 270 children's sera showed an exceptionally low IgA content. In two of these cases the serum was sampled and studied a second time after an interval of four years, when the IgA deficiency proved to be still present. The IgE levels in the sera of these healthy IgA-deficient children were normal, whereas the presence of IgD could not be demonstrated.


On the quantitative determination of liver ferritin in the rat. The measurement of liver ferritin is usually performed after homogenization of liver, heating the homogenate and centrifugation. Because ferritin is stable to 80 degrees this protein and its iron are recovered in the supernatant. We found that this procedure resulted in losses of ferritin so we developed a method to measure ferritin protein in the unheated homogenate. Total liver ferritin iron could be calculated with use of the ferritin protein and ferritin iron values as measured in the supernatant after heating the liver homogenate.


Validation of routine methods for serum progesterone determination using mass fragmentography. A mass fragmentographic reference method for determination of serum progesterone is described. A fixed amount of [4-14C]progesterone (usually 7.5 ng) is added to a fixed amount of serum (usually 1 ml) and extracted with hexane. The extract is purified by means of thin-layer chromatography. The purified progesterone is converted into the dienol heptafluorobutyrate derivative by treatment with heptafluorobutyric acid anhydride. The amount of unlabeled progesterone is determined from the ratio between the recordings at m/e 510 and m/e 512 obtained after analysis with a combined gas chromatograph-mass spectrometer equipped with a MID-unit (multiple ion detector). The two ions used correspond to the molecular peak in the mass spectrum of the dienol heptafluorobutyrate derivative of unlabeled and labeled progesterone, respectively. The relative standard deviation of the method was 3.7% provided that serum progesterone concentration was in the range 10-70 nM. Two radioimmunoassay techniques with commercial kits were compared with the mass fragmentographic method. The correlation coefficient obtained was 0.93 and 0.76 respectively, and the regression coefficient 0.93 and 1.05, respectively.


Measurement of renin concenration in human plasma using 125i-labelled sheep renin substrate. Sheep renin substrate was prepared 28% pure, labelled with 125I and then diluted in concentrated unlabelled sheep substrate. Ten percent of the 125I-label was released as a small fragment on incubation with excess human renin. Adequate separation of the labelled fragment from the parent protein was accomplished with charcoal precipitation or gel filtration. Renin concentration in human plasma was assayed by incubating the 125I-labelled substrate with plasma under zero-order kinetic conditions. Renin was assayed in plasma that had been either acidified or untreated. The acidification procedure was employed to activate inactive renin which accounted for more than half of the total plasma renin concentration. The results of this radiochemical assay correlated closely with the results of bioassay. Specificity of the method was established with antirenin. The assay was sufficiently sensitive to measure suppressed plasma renin levels. The iodinated substrate was stable on storage at -10 degrees C over a six-month period. Because of its high affinity for human renin, ease of purification and stability of the iodinated product, sheep substrate provides a convenient means for routine determination of plasma renin concentration by radiochemical assay.


The influence of viscosity on dilution methods. Its problems in the determination of serum sodium. Dilution with a roller-pump is a well known procedure in clinical chemistry. This method may be influenced by viscosity. A higher viscosity of the sample yields a lower sample output and consequently a larger dilution. If the substance to be determined in the diluted sample can be measured accurately, the influence of viscosity may be analysed easily. This was performed for serum sodium. It was shown that with extreme pathological viscosities (as are found e.g. in multiple myeloma and Waldenström's macroglobinemia) underestimations of more than 15% may occur. Especially for serum sodium, the physiological range of which is fairly small, this may provoke serious diagnostic and therapeutic problems. We propose to use viscosity independent dilution systems.


The erythrocyte protoporphyrin in chronic renal failure. The erythrocyte protoporphyrin concentration in 63 patients suffering from chronic renal failure was estimated and found to be significantly decreased when compared to healthy subjects. There was a negative correlation between the decrease of the erythrocyte protoporphyrin and the blood urea and haematocrit. Following haemodialysis the concentration of erythrocyte protoporphyrin was reduced but not significantly so. It is proposed that uraemia or insufficiency of erythropoietin could affect erythroblasts and young red cells impairing haem synthesis.


Synthesis of polymers of Bence-Jones protein for use as molecular weight markers for sodium dodecyl sulphate-polyacrylamide gel electrophoresis. A simple method is described of preparing a series of stable polymers of Bence-Jones protein, of known molecular weight, for use as molecular weight markers for sodium dodecyl sulphate (SDS) - polyacrylamide gel electrophoresis.


Influence of the myopia gene on brain development. Evaluation of the performance of 17-18-year-old high school students on standard intelligence tests confirms previous reports that nearsighted persons consistently achieve scores approximately eight I.O. points higher than non-myopes. Comparison of tests administered to the same students 10 years earlier suggests that the intellectual gain precedes the development of nearsightedness. Since there is convincing evidence from genetic studies that myopia is an inherited condition, probably transmitted as a recessive characteristic, it is concluded that the myopia gene has a stimulant action on the brain in addition to its effect on the eye. The high frequency of myopia in urbanized societies is explained in terms of an evolutionary adjustment, myopes probably having a survival advantage under conditions of industrialization.


The Nathalie syndrome. A new hereditary syndrome. Deafness, cataract, muscular atrophy, skeletal abnormalities, retardation of growth, underdeveloped secondary sexual characteristics, and electrocardiographic abnormalities are the features of a new, probably hereditary syndrome. Case reports are presented.


The 9p- deletion syndrome. Report of a patient with a 46, XX, 9P- constitution due to a paternal t(9p-;15+) translocation. A new case of the 9p- chromosome-deletion syndrome is described. The 9p-chromosome, identified by the G-, R-, Q- and G11-banding techniques, showed mainly a deletion of bands p23 and p24. Routine chromosome analysis and banding studies in the parents revealed normal chromosomes in the mother and a balanced t (9p-; 15q+) translocation in the father. The main clinical features of the proband are narrow cranium, prominent forehead, flat occiput, hyperteloris, flat bridge of the nose, long upper lip, micrognathia, low-set and abnormal ears, short, broad neck, wide-set nipples, systolic murmur, umbilical hernia, diastasis musculi recti, short arms and broad thumbs, equinovarus adductus, hypotonia and psychomotor retardation. These clinical findings are compared with those of the three 9p- cases found in the literature.


Origin of a small metacentric chromosome: familial and cytogenic evidence. A family is described in which the mother has an 18p- chromosome, one normal 18, and a probable i(18p). One of the daughters of this woman inherited the 18p- chromosome, and her phenotype resembles that of other 18p- cases. The other daughter inherited the presumed i(18p) chromosome, and her phenotype resembles that of some cases with extra, small metacentric chromosomes. The clinical, chromosomal, and familial evidence suggest that these abnormal chromosomes originated in the occurrence of one transverse break of the centromere and subsequent misdivision of a chromosome 18 in an earlier generation of this family. According to this interpretation, the mother is trisomic for 18p, one daughter is monosomic and the other daughter is tetrasomic for this chromosomal region.


Ring chromosome 6 in a malformed boy.

Ring chromosome 6 in a malformed boy. In a mentally retarded and malformed boy who died at 6 months of age a ring chromosome 6 was identified by G banding. Clinical, cytogenetical and post-mortem findings are discussed.


Hyperpipecolic acidemia associated with hepatomegaly, mental retardation, optic nerve dysplasia and progressive neurological disease. A male infant with hyperpipecolic acidemia is described. To our knowledge this is only the second report of this disorder. As with the previous case, our patient's course was characterized by persistent hepatomegaly, severe mental retardation, progressive loss of developmental milestones and diminished visual acuity associated with nystagmus, abnormal discs and retinal changes. Death occurred at 2 years of age, following a progressive loss of neurological function. Pipecolic acid was repeatedly present in the serum at a concentrattion of 4-5 mg %. Trace amounts of this compound were also detected in the urine. In addition, an adaption of the method of Piez et al. (1956) for the direct quantitation of pipecolic acid in serum was evaluated and found to be very useful for the biochemical diagnosis of this disorder.


Cryoglobulinaemia in patients with infectious endocarditis. Serum cryoglobulins were found in nineteen out of twenty patients with infectious endocarditis. The cryoglobulins were of the 'mixed type' consisting of IgG, IgM and IgA. C3 and fibrinogen were present in some specimens. The concentration of the cryoglobulins tended to fall with therapy and clinical improvement of the patients. Serum antibodies to the offending bacterial organism were not preferentially concentrated in the cryoglobulins. In contrast, IgM rheumatoid factor was present in the cryoglobulins, though undetectable in the corresponding serum. These findings are consistent with the view that cryoglobulins represent circulating immune complexes which may be important in the pathogenesis of immunological sequelae sometimes found in patients with infectious endocarditis.


Activation of the classical and alternate pathways of complement by Corynebacterium parvum. The immunological adjuvant Corynebacterium parvum has been to activate the alternate pathway of complement in human and guinea-pig serum. Human serum in addition contains anti-C. parvum antibodies leading to activation of the classical complement pathway. The possible role of a C. parvum derived polysaccharide in this activation is considered in relation to the biological effects of the micro-organism.


Cytotoxic activity against rubella-infected cells in the supernatants of human lymphocyte cultures stimulated by rubella virus. Supernatant fluids of lymphocyte cultures from rubella-seropositive donors, stimulated with inactivated rubella virus, showed cytotoxic activity against rubella-infected target cells (NYU 32 line of human embryonic fibroblasts) but not against uninfected fibroblasts. The time of appearance of cytotoxic activity in rubella-stimulated lymphocyte cultures correlated with increased rate of DNA synthesis as measured by thymidine uptake. No such cytotoxic activity became detectable in the supernatants of lymphocyte cultures from rubella-seronegative donors cultured in the presence of rubella virus, or in unstimulated lymphocyte cultures from seropositive or seronegative donors. The cytotoxic activity was lost at 60degreesC in 30 min. In contrast to this rubella virus-induced cytotoxic activity, cytotoxin produced in mitogen-stimulated lymphocyte cultures from rubella seropositive and seronegative donors was equally cytocidal against rubella-infected and uninfected human fibroblasts. Although the nature of cytotoxic activity remains to be characterized, it is suggested that it is associated with a lymphokine released immune-specifically from rubella virus-stimulated lymphocytes.


Depression of grass pollen-induced lymphocyte transformation by serum from hyposensitized patients. Serum from grass-sensitive patients who had received hyposensitization therapy was found able to depress the in vitro response to Holcus lanatus grass pollen extract of lymphocytes from untreated grass-sensitive individuals. The inhibitory activity could no longer be demonstrated at serum dilutions equal to or greater than 1/100 and was not seen when the cells were stimulated with PHA or unrelated antigens. It was contained in the precipitated fraction of 33% saturated ammonium sulphate-treated serum, segregated with the 7S peak of Sephadex G-200 and with the IgG fraction of DEAE-Sephadex-fractionated serum and could be removed by the absorption of the serum with the Holcus lanatus allergenic extract. These data suggest that the serum factor responsible for the depressed in vitro lymphocyte response to the allergen in hyposensitized patients was a 7S IgG antibody induced by immunotherapy.


Galactose oxidase-induced blastogenesis of human lymphocytes and the effect of macrophages on the reaction. Treatment of human lymphocytes with neuraminidase and galactose oxidase induced extensive blastogenesis. A less pronounced effect was observed after treatment of the cells with galactose oxidase alone. Macrophage-depleted human lymphocytes had a markedly reduced blastogenic response after treatment with neuraminidase and galactose oxidase. Incubation of the purified lymphocytes on macrophage monolayers markedly enhanced their response to neuraminidase and galactose oxidase. Furthermore, a stimulation of thymidine incorporation into purified untreated lymphocytes was noted after incubation of the cells on neuraminidase and galactose oxidase-treated macrophage monolayers.


Immunological studies in patients with chronic active hepatitis. Cytotoxic activity of lymphocytes to autochthonous liver cells grown in tissue culture. The cytotoxic activity of lymphocytes against autochthonous liver cells was studied in patients with chronic liver diseases and in controls. Cytotoxicity of lymphocytes was observed in eight of ten patients with chronic active hepatitis, two patients with chronic persistent hepatitis, one patient with primary biliary cirrhosis, one patient with alcoholic hepatitis and carcinoma of the pancreas, and in three of five patients with acute viral hepatitis, but not in seven patients without liver alteration or with miscellaneous liver diseases. Serum was not cytotoxic, but in three patients it decreased the cytotoxicity of lymphocytes. Cytotoxicity was seen in both HBAg-positive and HBAg-negative patients, appears to be influenced by therapy, and does not correlate with autoantibodies. These data support the hypothesis of an aggressive activity of lymphocytes in certain liver diseases.


The leucocyte migration technique as an assay of presensitization to human transplantation antigens. An assay of cell-mediated immunity, the leucocyte migration technique (LMT), has been compared with the commonly used assay of humoral immunity to transplantation antigens, the microlymphocytotoxicity test. Five recently multiply transfused patients and nineteen haemodialysis patients who had been potentially immunized against transplantation antigens were studied by both tests. All five transfused patients gave positive LMT results while only two gave a positive serological test. Sixteen out of nineteen dialysis patients gave positive LMT results compared with nine with known anti-HL-A antibodies and four showing positive serological direct cross-matches. There was no correlation between cell-mediated and humoral immunity as detected by these methods, although there was a tendency, which was not absolute, for positive direct cross-matches between patients' sera and the panel's lymphocytes, to be associated with positive LMT results. There was a significant correlation (P less than 0-05) between the number of blood transfusions received by the dialysis patients and the detection of cytotoxic antibodies but not with the LMT results. It is felt that some of these positive LMT results are due to reactivity with non-HL-A antigens, and that false negative results also occur. For this reason the technique is not of great value in determining presensitization against HL-A before transplantation.


The effect of anticomplementary substances on properdin in normal and C2-deficient sera. The effect of anticomplementary substances, including zymosan, cobra venom, endotoxin, inulin and immune complexes, on serum properdin concentration and immunoelectrophoretic mobility was studied. In normal serum, zymosan, inulin and immune complexes 'fixed' properdin, while in C2-deficient serum, only zymyosan 'fixed' properdin. Slowly migrating properdin (P) was detected in normal serum following activation by endotoxin and cobra venom but in C2-deficient serum only with cobra venom. Endotoxin did not activate the alternative pathway proteins studied in C2-deficient serum. Fast migrating properdin (P) represented activated properdin and occured as a result of activation of properdin in the Noble agar medium used for electrophoresis provided sufficient cofactors, including Mg2+, were present.


Cell-mediated immunity in idiopathic autoimmune haemolytic disease. Membrane antigens from autologous and from allogeneic red blood cells (RBC) induced migration inhibition of splenic leucocytes and transformation of peripheral blood lymphocytes from a patient with idiopathic autoimmune haemolytic disease (AHD). No migration inhibition occurred following stimulation of splenic leucocytes obtained during splenectomy from a patient with beta-thalassaemia major. Lymphocyte transformation did not occur when normal lymphocytes were stimulated by similar RBC membrane preparations. These findings indicate that autosensitization in AHD may be a function of both humoral and cellular immune mechanisms.


The different migratory characteristics of lymphocyte populations from a whole spleen transplant. Spleens from AS x BN donor rats labelled in vivo by multiple doses of [3H]thymidine were transplanted into syngeneic recipients by anastomosis to the abdominal great vessels. The recipients were killed 1-5 days after receiving the whole spleen transplants and the numbers and location of the [3H]thymidine-labelled cells which had migrated from the labelled donor spleen traced by means of autoradiographs of sections, imprints and smears of various recipient lymphoid tissues. These results were compared with the migration pattern of labelled dissociated spleen cell suspensions injected intravenously. The latter consists almost entirely of small lymphocytes which migrate to T or B areas of recipient spleen, lymph nodes and Peyer's patches. The labelled whole spleens also contained cells which migrated to the T and B areas of recipient lymphoid tissues, but in addition contained many lymphoid cells which migrated to the red pulp of the recipient spleen and to the lamina propria of the gut. These experiments showed, therefore, that the spleen contains mobile elements which have not been detected by transfer of spleen cell suspensions.


Experimental myositis in rats. II. The sensitivity of spleen cells to syngeneic muscle antigen. The transformation responses to a syngeneic muscle homogenate of spleen cells, lymph node cells and blood lymphocytes have been studied in rats with allergic myositis. Significantly increased responses to muscle were obtained only for spleen cells from rats which had received two or more immunizing injections of heterologous muscle with Freund's complete adjuvant. Other populations of lymphoid cells which had previously been shown to be capable of transferring the disease did not show significant transformation responses to muscle. Increased responses in spleen cells were obtained using a supernatant ultracentrifugal fraction as well as a whole muscle homogenate. Fractionation of the antigen showed blast stimulating activity to be present in fractions of differing molecular size, suggesting that the antigen(s) responsible may be present in polymeric form or may be bound to molecules of varying molecular size.


Hydantoin immunosuppression and carcinogenesis. The immunological response of mice submitted to hydantoin treatment was determined. Hydantoin reduced the absolute number of spleen cells in treated animals and did not modify spleen cells reactivity to concanavalin A, although the response to SRBC challenge, as measured by the Jerne plaque-forming cell technique, was significantly decreased. Following these findings, the influence of hydantoin on carcinogenesis was evaluated by using the model of urethane-induced lung adenomas in SWR mice. Treatment with hydantoin significantly reduced the incidence of the induced adenomas. We confirmed that hydantoin modifies the immune response of the host mainly by depressing its humoral function and we have shown that this effect was associated with an inhibitory effect on tumour induction.


Cytolysis of neuraminidase-treated autochthonous lymphoid cells by autologous serum. Rabbit lymph node cells treated with bacterial neuraminidase become susceptible to cytolysis by autologous antibody and complement. Cytolysis of cells can be prevented by absorbing out the antibodies, probably IgM antibodies, from the autologous serum using neuraminidase-treated autochthonous lymph node cells. The significance of this mechanism is discussed.


Suppressor cells in different types of unresponsiveness to DNCB contact sensitivity in guinea-pigs. Cyclophosphamide (CY) treatment known to enhance the normal cell-mediated immune response by selectively inhibiting the function of suppressor cells abrogates tolerance by pretreatment when tolerant animals are sensitized 3 days after the intraperitoneal injection of CY. The tolerance during the primary response is also reversed by CY treatment, indicating that in both these types of unresponsiveness suppressor cells may be operating. However, CY treatment did not influence the short-lasting unresponsiveness induced in already sensitized guinea-pigs by the intravenous injection of tolerogen. These findings corroborate the idea that the mechanism of desensitization is different from that of tolerance induced by pretreatment of during the primary response.


Immunoglobulin synthesis and antibody content in the small intestine of the rabbit. The concentration of immunoglobulin and specific antibody in the serum and the intestinal fluid and the rate of synthesis of immunoglobulin in the small intestine was measured in normal and immunized rabbits. IgA was found to be the predominant immunoglobulin in the intestinal fluid. IgA and IgG were secreted at rates of 4-3 mug/cm/hr and 1-3 mug/cm/hr respectively. Specific anti-Vibrio cholerae antibodies in the intestine were found mainly in the IgA class after oral immunization.


Reversal of experimental allergic thyroiditis in cyclophosphamide-treated rats. A 10-day course of cyclophosphamide completely reversed the histopathological manifestations of experimental allergic thyroiditis in Wistar rats. This therapeutic effect of cyclophosphamide was sustained, no recrudescence of thyroid inflammation being detected among rats examined 4 weeks after immunosuppressive therapy.


Immune reactions in acute viral hepatitis. Serial studies of PHA-induced lymphocyte transformation, serum autoantibodies, immunoglobulins and complement were performed in seventeen patients with hepatitis A and nine patients with hepatitis B. In both types of hepatitis PHA-induced transformation was markedly impaired during the 1st week after the onset of jaundice and there was less marked but prolonged impairment for a further period of 6-10 weeks. A group of eleven subjects with a previous history of hepatitis had values which were similar to those of healthy persons. Serum from patients with hepatitis A and hepatitis B contains an inhibitor of lymphocyte response to PHA. The inhibitor depresses the function of both patients' and normal lymphocytes and is only detectable during the acute phase of the illness. Washing lymphocytes free from autologous serum did not restore the PHA response to normal but the markedly impaired response present during the first 2 weeks of the illness was improved. A serum factor or factors may therefore be responsible for at least part of the impaired response of lymphocytes to PHA during the acute phase of hepatitis but does not appear to account for the more prolonged impairment of the PHA response. The protracted lymphocyte defect is possibly induced by hepatitis virus. The incidence of autoantibodies and the changes in immunoglobulin levels were similar to those reported by other workers.


Anti-reticulin antibody in jejunal juice in coeliac disease. Anti-reticulin antibody has been demonstrated in the jejunal juice of eight out of fourteen (57%) untreated coeliac patients, one out of twelve (8%) patients with normal jejunal biopsies and none of ten normal control subjects. The jejunal juice antibody was invariably of the IgA class. It is suggested that the presence of anti-reticulin antibody in the jejunal juice in coeliac disease supports the hypothesis that this antibody is secreted in response to reticulin antigens present in the diet.


Cytotoxicity of lymphocytes from healthy subjects and from melanoma patients against cultured melanoma cells. The in vitro cytotoxicity of lymphocytes from forty-seven melanoma patients and thirteen healthy subjects for cultured melanoma cells was studied using a 51Cr release assay. Two different melanoma cell lines were used as target cells: one cultured in suspension (SK Mel1) and one tissue culture line growing as a monolayer (NK I1). The lymphocytes from most healthy subjects were found to be cytotoxic for these cultured cells, with individual variations. These repeatable cytotoxic reactions could not be explained on the grounds of previous isoimmunization. The lymphocytes from melanoma patients were also cytotoxic for the melanoma cell lines, but the highest degree of cytotoxicity was found in patients with primitive and localized tumours, and not in patients with metastases.


L-tetramisole. Enhancement of human lymphocyte response to antigen. The anthelminthic drug L-Tetramisole enhanced in vitro lymphocyte transformation of normal young adults in the presence of PPD, Candida or measles antigen. This enhancement occurred regardless of evident pre-existing immunity to the antigen used. The increase in stimulation obtained by the drug and antigen combined, beyond that by antigen alone, varied between 1-25 and 5-99 for all three antigens in fourteen cell donors. Lymphocyte transformation was induced in seven individuals by the drug alone and suppressed in two. In levamisole dose--response tests, the optimum dose for this in vitro effect in six donors was similar for the three antigens.


Studies on the specificity of agglutinins against human erythrocytes modified by Newcastle disease virus. The specificity of agglutinins in human sera against human erythrocytes modified by Newcastle disease virus (NDV-O agglutinins) was studied with agglutination and agglutination inhibition techniques. Virus grown in both embryonic eggs and tissue culture was used in the experiments. The findings were compatible with the existence of four specificities of agglutinins. In some sera, including those from subjects recently inoculated with vaccines prepared in eggs, the agglutinins were directed against a component of the allantoic fluid. In high-titred infectious mononucleosis (IM sera the agglutinins were directed against antigenic groupings present in the Vic strain but not the B1 strain of NDV, whereas in certain other sera they were directed against antigens present in both of them. Finally, in some sera the agglutinins probably reacted with a red cell antigen uncovered by the viral neuraminidase.


Treatment of chronic glomerulonephritis with a combination of indomethacin and cyclophosphamide. 33 cases of chronic glomerulonephritis who responded unsatisfactorily to treatment with indomethacin alone were treated in addition with a low dose of cyclophosphamide. The five patients with focal glomerulosclerosis responded poorly. The remaining 28 patients showed a statistically significant improvement in renal function and proteinuria.


Complications of percutaneous renal biopsy: an analysis of 1,000 consecutive biopsies. In a series of 1,000 consecutive percutaneous renal biopsies, adequate tissue for diagnosis was obtained in 94.9%. The rate of complications was 8.1% and was directly related to 1. age of the patient, 2. presence of renal insufficiency, and 3. arterial hypertension. The use of fluoroscopic control for localization of the kidney did not affect the rate of complications, nor did it improve the success rate in obtaining adequate tissue.


Bone volume and mineral density of iliac crest spongiosa in uremia. Bone mass and bone mineral content were measured in non-dialyzed and dialyzed uremic patients. Bone mass, measured by micromorphometry and a gas displacement method, was higher in uremic than in age and sex matched control subjects (micromorphometry-U:25.8 +/- 8.24%; Co:15.6 +/- 4.38; gas displacement-U:211 +/- 66 mm3/cm3; Co:191 +/- 45). In hemodialyzed patients, bone mass was lower the longer the patients had been on dialysis (r = 0.38; P 0.05). Bone mineral content (specific weight) was diminished in uremia (1.82 +/- 0.095 g/ml; controls 1.854 +/- 0.0173). In hemodialyzed patients, specific weight was higher, as was Ca content of bone assessed by neutron activation analysis. It is concluded, that negative Ca balance was the major cause of bone loss and that bone loss is thus preventable.


Experimental crystal nephropathy (one year study in the pig). An acute crystal nephropathy was produced in pigs by feeding a mixture of guanine and allopurinol. The pathogenesis of the lesion produced was studied by serial histology and renal function tests over 12 months. Tubular blockage by the crystals produced erosion of the basement membrane and an accompanying interstitial nephritis. Tubular degeneration around the crystal mass transferred the crystals to the interstitium. Despite rapid subsequent disappearance of these crystals the interstitial nephritis was still evident nine months later. An early return of renal function to near normal was not sustained beyond nine months. It was shown that even brief periods of intratubular crystal deposition caused irreversible changes, resulting eventually in a reduction in kidney size, nephron population and renal function.


Experimental model for peritoneal dialysis in small laboratory animals. A simple method of performing peritoneal dialysis in rats and guinea-pigs for 48 hours is described. The method appears to be suitable for the experimental investigation of clinical problems although the long term problem of protein loss should not be forgotten when assessing the results of these short term experiments.


Quinine-induced alterations in drug disposition. In normal volunteers, chronic quinine administration shortened plasma antipyrine half-life and significantly increased the intraindividual correlation between the disposition of quinine and antipyrine. Decreased plasma antipyrine half-life appears to be due to a quinine-induced enhancement of antipyrine metabolism. A dose-dependent prolongation of plasma quinine half-life was observed and attributed primarily to an increased apparent volume of distribution of quinine, although our data did not permit separation of an effect on quinine metabolism from an effect on quinine distribution between the peripheral and central compartments. Plasma protein binding of quinine was similar at both the low and high doses of quinine. Studies in dogs given quinine intravenously revealed a biphasic plasma decay curve compatible with a 2-compartment open model for quinine disposition. Dose dependence of plasma quinine half-life in the dog after intravenous quinine eliminated altered gastrointestinal absorption of quinine as a cause for the dose dependence of plasma quinine half-life. These studies illustrate the importance of such conditions as dose and time of administration in determining the type and magnitude of interaction observed between drugs.


Effect of hemodialysis on kinetics of acetaminophen elimination by anephric patients. The pharmacokinetics of acetaminophen elimination were determined in 4 anephric patients during hemodialysis and on an interdialysis day. The biologic half-life of acetaminophen ranged from 119 to 147 min on an interdialysis day and was decreased by 42% to 53% during hemodialysis. Individual mean dialyzer extraction ratios, based on assay of plasma samples from blood flowing into and out of the dialysis unit, were 0.46 to 0.78 for acetaminophen, 0.53 to 0.57 for acetaminophen glucuronide, 0.13 to 0.60 for acetaminophen sulfate, and 0.70 to 0.87 for urea nitrogen. There was a strong correlation between the extraction ratios of acetaminophen and urea nitrogen. Hemodialysis was the major or sole routine of elimination of acetaminophen glucuronide and sulfate in the anephric patients.


Action of delta-9-tetrahydrocannabinol. An approach to the active metabolite hypothesis. The active metabolite hypothesis, that delta-9-tetrahydrocannabinol (THC) must be converted to its 11-hydroxy metabolite before it becomes active, was tested in a study of subjects chosen as rapid and slow hydroxylators of drugs on the basis of antipyrine and phenylbutazone plasma disappearance rates. Although the sample of subjects showed the customary wide variations in effects experienced after an intravenously administered dose of THC, it was impossible to correlate either the speed of onset, total intensity, or duration of these effects with speed of hydroxylation of drugs. Although 11-hydroxy-THC has unquestioned activity indistinguishable from THC itself, it need not necessarily be solely responsible for the pharmacologic activity of THC.


Clinical pharmacology of nabilone, a cannabinol derivative. Nabilone is a modified cannabinol derivative with central nervous system activity. Administration of nabilone in single doses of 1 to 5 mg results in dose-related pharmacologic effects in man. One and 2.5 mg doses of nabilone induced relaxant and sedative effects in all subjects. No euphoria, dry mouth, tachycardia, or postural hypotension was seen after 1 mg, minimal effects were seen after 2.5 mg, and marked effects were seen after 5 mg. Effects were evident within 60 to 90 min and persisted for 8 to 12 hr. Nabilone produced no significant tachycardia. There were no changes in supine blood pressure; however, marked postural hypotension occurred after the 5-mg dose. The administration of nabilone at doses of 1 mg or 2 mg two times daily resulted in euphoria and dry mouth during the first two days of drug; thereafter tolerance developed to these effects but there was no apparent decrease in relaxation. Subjects challenged with a single 5-mg dose of nabilone showed a 66% reduction in symptoms and signs after the 7-day drug period compared to that of the same dose after 1 wk of placebo. Comparison of nabilone with other cannabinol derivatives suggests that some of the undesirable pharmacologic effects can be separated within the group.


Phenytoin and phenobarbital concentrations in saliva and plasma measured by radioimmunoassay. Saliva and plasma levels of phenytoin (DPH) and phenobarbital (PB) in a series of epileptic patients were compared by means of a radioimmunoassat (RIA) that required only 10 mul of saliva or plasma. There was an excellent linear relation (r = 0.98) between the logarithms of the concentrations of DPH in the two fluids. The ratio saliva/plasma was remarkably constant at 0.10 and was unaffected by varying levels of PB. The ratio was close to the fraction of DPH reported unbound in plasma at 37 degrees. PB plasma and saliva levels were also closely related (r = 0.98 for logarithm of plasma and saliva levels). This relation was nonlinear [plasma ocncentration = 4.43 X (salivary concentration)0.86], but could be approximated by the ratio plasma/saliva = 3.4. The simplicity of sample collection and the sensitivity of the RIA procedure suggest that clinical monitoring of these anticonvulsant levels may be carried out by RIA on saliva samples.


Renal clearance of canrenoate in normal man. Potassium canrenoate was administered intravenously, twice at a 9-hr interval, to 3 apparently healthy male volunteers. No consistent changes in endogenous creatinine or PAH clearances were observed for 6 hr after the initial 200-mg dose of this aldosterone antagonist. The clearance of canrenone (the major gamma-lactone metabolite) exceeded by 70% the simultaneous clearance of creatinine from the second through the sixth hour. The excretion of canrenone amounted to 6.8 mg (3.4%) of the dose during the 6-hr clearance study, but was nearly absent (0.2 mg) during the ensuing 6- to 9-hr period. The cumulative excretion of the glucuronide conjugate of canrenone amounted to 4.6 and 2.8 mg (2.3% and 1.4%) of the dose during these respective periods. A sustained retention of K was observed in 1 subject. Otherwise, as was anticipated in the absence of hyperaldosteronism, urinary electrolyte levels were essentially unchanged. Circulating aldosterone and plasma renin activity levels were essentially unaltered.


Serial serum digoxin concentrations and quantitative electrocardiographic changes. Four elderly female patients in sinus rhythm and with mild congestive cardiac failure were treated with digoxin and studied over a 6-month period. There were significant linear correlations between serum digoxin concentrations and several quantitative electrocardiographic (ECG) parameters. T-wave amplitude was the most important ECG variable. ECG changes reverted to baseline values when digoxin was discontinued. These findings suggest that quantitative ECG changes are potentially useful in clinical and research situations involving digitalis glycosides.


The influence of potassium on the renal vasculature and the adrenal gland, and their responsiveness to angiotensin II in normal man. 1. The effect of modifying potassium intake on arterial plasma renin activity, angiotensin II and aldosterone concentrations, renal blood flow and their responses to exogenous angiotensin II has been assessed in twenty-six normal subjects. 2. Reduced potassium intake was associated with a significant increase in circulating renin activity and angiotensin II concentration and a significant reduction in renal blood flow. Conversely, a high potassium intake was associated with a significant increase in plasma aldosterone concentration and renal blood flow without alteration in plasma renin activity or angiotensin II concentration. 3. Reduced potassium intake decreased both the renal vascular and the adrenal response to infused angiotensin II. Conversely, an increased potassium intake enhanced the responsiveness of both systems. 4. The results suggest an important influence of potassium-induced renin-angiotensin system responses on both the renal vasculature and adrenal glomerulosa cell in normal man.


Potassium depletion induced by vasopressin and overhydration in the rabbit. 1. In order to study the effect of overhydration on body potassium, experiments were performed on pair-fed rabbits, one of which was maintained continuously on vasopressin and given extra water (60-90 ml day-1 kg-1) for 6-8 days, while the other served as control. 2. Overhydrated rabbits excreted significantly more potassium (53%) in their urine than control rabbits and accumulated a mean potassium deficit of 65-0 mmol, significantly higher than the mean value of 37-1 mmol in the control rabbits. 3. In the overhydrated rabbits, potassium fell significantly in both erythrocytes, from 266 to 173 mmol/kg of dry cells, and also in muscle, from 435 to 341 mmol/kg of fat-free dry solids. Neither changed significantly in the control animals. 4. Overhydration in the presence of vasopressin leads to potassium depletion in the rabbit and a similar phenomenon might be expected in man. Potassium depletion due to overhydration might account for the hypokalaemia and reduction in exchangeable potassium observed in some patients with the syndrome of inappropriate secretion of antidiuretic hormone.


I-cell disease (mucolipidosis II): resolution of N-acetyl-beta-D-glucosaminidase and alpha-L-fucosidase components by DEAE-cellulose chromatography. 1. In a patient with I-cell disease the activities of several acid hydrolases were elevated inplasma and reduced in cultured fibroblasts when compared with normal values. Normal activities for the enzymes were found in leucocytes. These findings agree with reports on other cases. 2. N-Acetyl-beta-D-glucosaminidase was resolved into its component forms by chromatography on microcolumns of DEAE-cellulose coupled with continuous automated assay of activity in the column effluent. Cultured skin fibroblasts from three patients showed a profound deficiency of glucosaminidase component A and a relative increase in the activity of a form eluted earlier than A. 3. In the one patient studied, the elution profile of plasma glucosaminidase was similar to that of normal plasma, but treatment with neuraminidase revealed a minor component which did not appear in control specimens. 4. Chromatographic resolution of glucosaminidase secreted by normal fibroblasts into the culture medium shoed that component A comprised two forms, a serum-type and a tissue-type, whereas only a serum-type was found in I-cell medium. 5. Different forma of alpha-L-fucosidase were shown to occur in normal plasma and fibroblasts. This is the second lysosomal hydrolase for which differences between intracellular and extracellular forms have been described and might reflect a general phenomenon. 6. The major acidic component of fucosidase from normal fibroblasts was not detected in I-cell fibroblasts. Elution profiles of fucosidase activity in normal and I-cell plasma were indistinguishable, both before and after treatment with neuraminidase. 7. On the basis of the above findings, we suggest that for several acid hydrolases there is a common biosynthetic reaction, which produces forms of these enzymes destined for incorporation into primary lysosomes rather than secretion by the cell. In cultured fibroblasts from patients with I-cell disease, the enzyme catalysing the reaction leading to the production of intracellular forms is deficient or defective, whereas the synthesis of precursor and secreted forms is unaffected.


The early effects of intravenous frusemide on central haemodynamics, venous tone and plasma renin activity. 1. Nine paatients with clinically unimportant heart disease or benign essential hypertension were given frusemide intravenously during right-heart catheterization. 2. Pressures in both atria decreased rapidly and in parallel. The magnitude of the pressure decrease was clearly related to decrease in plasma volume loss. 3. Plasma renin activity increased significantly after 5 min (P less than 0-01), but did not correlate with plasma volume loss. 4. Venous tone in the forearm was unchanged. 5. It is concluded that the pressure reduction was secondary to plasma volume depletion through diuresis and that increased plasma renin activity was mainly caused by intrarenal changes.


Systolic blood pressure variation during the first 6 days of life. 1. Systolic blood pressure was measured by a Doppler ultrasound technique in twenty normal babies on 6 successive days after the day of delivery. In three babies blood pressure was recorded every 15 min for 24 h. 2. Systolic blood pressure during the first 6 days of life was 95 (SEM = 2) mmHg. 3. Systolic blood pressure increased on average by 2 mmHg/day, but increased most between the second and third days of life. 4. Systolic blood pressure was 11 mmHg higher when awake than when the babies were asleep. 5. There was marked within-baby variation in the systolic blood pressure of neonates, which could not be accounted for by age or recognizable changes in level in consciousness.


Urinary concentration and dilution after unilateral nephrectomy in the rat. 1. The effects of unilateral nephrectomy on urinary concentration and dilution were studied in Sprague-Dawley rats. To exclude incomplete suppression of antidiuretic hormone, free water formation was also sutdied in rats with congenital diabetes insipidus (Brattleboro strain). 2. Urinary solute-free water formation was similar in Sprague-Dawley and Brattleboro rats. Uninephrectomized animals excreted a water load promptly and diluted their urine to the same degree as control rats. Maximal values for Cwater and TCwater per kidney were higher after nephrectomy, but were similar to those of control rats at comparable rates of fluid delivery to the distal nephron. Renal tissue osmolaity was similar in uninephrectomized and sham-operated animals, indicating that nonantidiuretic hormone-dependent backflux of filtrate was the same in the two groups. The only defect observed in uninephrectomized animals was a small reduction in maximal urine osmolaity. 3. These results demonstrate that free water formation and reabsorption are unaffected by unilateral nephrectomy and suggest that, in the remaining kidney, filtrate reabsorption along the entire nephron increases in proportion to the increment in glomerular filtration.


The meaning of dopamine beta-hydroxylase in essential hypertension. 1. Resting plasma dopamine beta-hydroxylase (DBH) activity and haemodynamic parameters were studied in untreated borderline (twenty-nine) and permanent (twenty-seven) essential hypertensive patients. DBH was also measured in sixty-three apparently healthy subjects. 2. Mean DBH values were not significantly different between the groups. 3. Cardiac output, cardiopulmonary blood volume and the cardiopulmonary blood volume/total blood volume ratio (CPBV/TBV) were significantly higher in borderline than in permanent hypertensive patients. 4. In borderline hypertensive patients, plasma DBH activity was directly correlated with diastolic arterial pressure and with values of cardiac output, cardiopulmonary blood volume and CPBV/TBV ratio. No such correlations could be observed in the permanent hypertensive group. 5. These results suggest that plasma DBH activities in borderline hypertension mainly depend on the sympathetic activity responsible for the haemodynamic variations. Contrariwise, plasma DBH activities in permanent essential hypertensive patients appear to reflect other factors.


Measurement of muscle protein synthetic rate from serial muscle biopsies and total body protein turnover in man by continuous intravenous infusion of L-(alpha-15N)lysine. 1. Five healthy male subjects were studied by continuous infusion of L-[alpha-15N]lysine over 20-30 h with timed blood and urine samples, and two or three percutaneous needle biopsies of vastus lateralis muscle. 2. A standard creatine-free diet, quantitatively related to body surface area, was given for 5 days before the infusion. The [15N]lysine was administered at a constant rate in  an amino acid solution with a nitrogen content of 0-96 mol/l, which constituted the sole source of exogenous nitrogen during the infusion. 3. A plateau level of plasma free [15N]lysine enrichment was achieved after infusion for 14 h. The total plasma lysine flux calculated from the plateau was 7-3 mmol/h (range 4-8-9-6). Total body protein turnover calculated from the lysine flux was 3-5 g day-1 kg body wt.-1 (range 2-5-5-0). 4. Muscle sarcoplasmic and myofibrillar fractions were separated, purified and the 15N enrichment was measured. The sarcoplasmic protein fractional synthetic rate was calculated as 3-8%/day (range 2-2-5-1). The myofibrillar protein synthetic rate was 1-46%/day (range 1-09-2-44). 5. Muscle mass, calculated from 24 h creatinine excretion, was 33-7 kg (range 28-8-37-4), which represented 50-0% of body weight (range 38-9-58-1). Total muscle protein synthesis was calculated to account for 53-2% (range 39-5-62-1) of total body protein syntehsis. 6. The advantages and limitations of using continuous infusion of [15N]lysine in human subjects are discussed.


Relation between hepatic alcohol dehydrogenase activity and the ascorbic acid in leucocytes of patients with liver disease. 1. Hepatic alcohol dehydrogenase activity and leucocyte ascorbic acid content was measured in thirty-five patients with liver disease and in ten control subjects with duodenal ulcer. The patients with liver disease were divided into three groups consisting of non-drinkers, moderate drinkers and alcoholic/heavy drinkers. 2. There was no significant difference in hepatic alcohol dehydrogenase activity between the groups with liver disease, but all patients had less than half the hepatic alcohol dehydrogenase activity of the control subjects (P less than 0-001). 3. The ascorbic acid in leucocytes was significantly lower in the alcoholic/heavy drinker group than that in the control subjects (P less than 0-02) when the Student's t-test was applied, but no significant difference was found when the Mann-Whitney U-test was used. 4. A correlation coefficient of r = 0-77 (P less than 0-001) was observed among the thirty-five patients with liver disease when hepatic alcohol dehydrogenase activity was compared with leucocyte ascorbic acid content. An insignificant correlation (r = 0-332) was found in the control subjects with no liver disease. 5. This comparison was also significant among non-drinkers with liver disease (r = 0-873; P less than 0-001), moderate drinkers (r = 0-739; P less than 0-02) and alcoholic/heavy drinkers (r = 0-702; P less than 0-005). 6. The addition of ascorbic acid in vitro (0-5-10 mmol/1) had no effect on the activity of alcohol dehydrogenase. 7. The relation between hepatic alcohol dehydrogenase activity and leucocyte ascorbic acid content is probably a consequence of liver disease, as opposed to any specific effect of ascorbic acid deficiency of alcohol consumption on alcohol dehydrogenase activity.


The stimulation of renin secretion by non-vasocontrictor infusions of adrenaline and noradrenaline in the isolated rat kidney. 1. The effect of adrenaline and noradrenaline on renin secretion in the isolated perfuseed rat kidney was examined. The doses of catecholamines used were such that renal vasoconstriction and therefore increases in renal perfusion pressure were avoided. Under these conditions adrenaline and noradrenaline significantly increased renin secretion rates, compared with control experiments in which no catecholamine was infused. 2. Mean renal perfusion pressure during both adrenaline and noradrenaline infusion paralleled the control study by showing a progressive fall. 3. Administration of phenoxybenzamine did not impair the stimulation of renin secretion by adrenaline whereas this was prevented by racemic propranolol. 4. These observations suggest that catecholamines stimulate renin secretion by an intrarenal effect which is largely independent of changes in renal perfusion pressure. It is postulated that the beta-adrenoceptors mediating renin secretion are an integral component of the renin-producing cell.


Plasma uric acid concentration related to the urinary excretion of aldosterone and of electrolytes in normal subjects. 1. The relations between the concentration of plasma uric acid and urinary excretion of aldosterone, sodium and potassium, were studied in ten healthy males on a diet containing 160 mmol of sodium and 90 mmol of potassium per day. 2. Plasma uric acid correlated positively with aldosterone excretion and this correlation was statistically independent of sodium and potassium excretion. 3. Plasma uric acid correlated positively with potassium excretion and negatively with the urinary sodium/potassium ratio. There was no significant simple correlation with sodium excretion but the partial correlation of plasma uric acid and sodium excretion was negative and significant when excretion of aldosterone and potassium were held constant.


The relationship between dietary fat composition and plasma cholesterol esterification in man. 1. Cholesterol esterification has been studied in the plasma of subjects on diets rich in saturated or polyunsaturated fat. 2. The diet rich in polyunsaturated fat was associated with lower rates of plasma cholesterol esterification in vitro. The data suggest that there was a reduction of plasma lecithin-cholesterol acyltransferase activity as well as decreased ability of the lipoprotein substrates of the enzyme to support esterification. 3. On this diet, there was no change in the proportion of the plasma cholesterol esterified but the plasma cholesterol and triglyceride concentrations were reduced.


Plasma squalene as an index of cholesterol synthesis. 1. Seven subjects were studied before and after the rate of cholesterol synthesis was altered with drugs or dietary cholesterol. 2. The rate at which plasma free cholesterol was formed from squalene during constant infusions of radioactive mevalonate increased with colestipol treatment, decreased with clofibrate treatment and decreased when cholesterol was added to the diet. The plasma squalene concentration showed corresponding changes, confirming that its measurement may qualitatively define changes in cholesterol synthesis. 3. The mean plasma squalene concentration in seven hypertriglyceridaemic, slightly overweight subjects was significantly higher than in six hypercholesterolaemic subjects, which is consistent with other evidence for increased cholesterol synthesis in hypertriglyceridaemia.


Plasma prostaglandin E during neurogenic hypertension in tetraplegic man. 1. Arterial blood pressure and heart rate were measured before, during and after cutaneous and visceral stimulation in subjects tetraplegic due to severe cervical spinal cord damage. Stimulation resulted in marked hypertension as a result of reflex sympathetic overactivity. 2. Mixed venous blood from a catheter situated in the right atrium was obtained before and after stimulation and plasma prostaglandin E and prostaglandin F were measured. A consistent and significant rise in plasma prostaglandin E, but not plasma prostaglandin F, accompanied the hypertension. 3. It is suggested that prostaglan ding E is released during this sympathetic nervous activity and may be related to neurogenic hypertension.


Linking planning with evaluation in community mental health. A suggested example of a systematic approach for linking planning with evaluation is presented. The proposed systematic processes would help deal with the ambiguities of the mental health field and provide a more objective way of planning and evaluating programs. Program evaluation can then be related to the predetermined effectiveness criteria of the planning processes. The planning and evaluation processes are described as a part of a 13-stage cycle of 18 months.


A nonobtrusive interview technique for drug abuse program follow-up. A follow-up study of 65 former clients in a drug abuse program employed paraprofessional street workers, indigenous to the area, as data gatherers. The interview was designed to appear to be a casual conversation. Interviewers were trained in the use of a mnemonic device which allowed them to guide the conversation over 46 items of factual information. The information was recorded later on a form. An alpha coefficient reliability estimate of additional subjective ratings on the 65 former clients was .923. An analysys of correlational associations between measures provides an interesting insight into the paraprofessional interviewers' perceptions of posttreatment functioning.


Teamwork and social worker advocacy: conflicts and possibilities. Consumer participation in mental health services has made professional activities, including teamwork, visible to increased examination of points of conflict that often focus on aspects of professional ehtics. Social workers are ethically bound to serve as client advocates, which implies an adversary process not provided for in assumptions about teamwork. Social work generally is based on a consensus model and occurs in the absence of legitimate standards to assess competence. These factors are likely to be a negative influence on social workers' contributions to teamwork. An interprofessional procedure focused on client rights is suggested to increase explicit attention to conflict in teamwork.


Special role and role expectation of black administrators of neighborhood mental health programs. This paper attempts to portray the role conflict and ambiguity of black administrators in community mental health programs. The paper is not about mental health programs themselves but rather focuses on the problems of blacks in leadership positions in such programs. The implication of this paper is that blacks cannot escape being black despite their professional position or training. They are regarded by their superiors, colleagues, staff, and the community as performing what Hughes called a "racial function." This function presents an interesting dilemma. On the one hand, the black administrators are recruited and employed out of the needs expressed by the black community. On the other hand, their white superiors determine whether they remain in those positions. To offend either group risks the loss of their position. The black community and white employer sometimes make conflicting demands on these black administrators. The result is that blacks find themselves unable to please either. Blacks have reacted by withdrawal from the black community or resignation from the organization. This paper attempts to explain these conflicts. Although the problems of black administrators are called special cases it does not mean that other ethnic groups have not experienced any or all of these problems. It is called a special case because the black community is undergoing a special and unique kind of socioeconomical transition. Black administrators in other types of public organizations will recognize some of the conflicts described in this paper.


Prior occupational experience and choice of alcoholism rehabilitation counselors. Although the use of recovering alcoholics as counselors in professional settings is increasing, there is little information on the factors important in selecting counselors. This study looks at previous occupational socialization as one such factor. On the basis of a study of alcoholism rehabilitation counselors and their supervisors in Indiana it has been concluded that such socialization is an important factor. It is recommended that prospective employers be wary of applicants without some experience in "bureaucratic" types of work experience, that is, who have not had experience in work settings or with work requirements somewhat analogous to those in the professional setting.


Citizens' boards for Philadelphia community mental health centers. Community participation is a frequently discussed and controversial aspect of the community mental health center program. To many professionals and lay people, the community mental health center concept includes a basic commitment to a participatory process of the community in the planning and implementation of the community mental health center program. However, this commitment is not readily evident in the federal and Pennsylvania regulations. This paper presents an approach taken by the Philadelphia Office of Mental Health and Mental Retardation to insure that its 13 centers and base service units have a meaningful partnership with their catchment area communities. Specifically the paper presents the community participation regulations developed by the Philadelphia office, as well as the conditions that led to the development of these regulations. A conclusion of the paper is that additional regulations are needed to insure that community participation becomes an integral part of the community mental health center program.


Following the Blackfoot Indians: toward democratic administration of a community mental health center. Community mental health centers have been held back by authoritarian administrative structures, inherited from the traditional medical model, from fulfilling their original promise of innovative approaches to mental health and responsiveness to the community. This is a 10-year case history of one mental health center's struggle "to put its own house in order" to further staff morale, productivity, more egalitarian attitudes toward clients, and a sense of partnership with each other and the community. The paper shows the development of democratic structures and processes, how line staff and administrators confronted their taboo on power, the traditional hierarchy among disciplines, staff participation in administration, and their vulnerability within the wider bureaucratic system.


Learning style preferences of community mental health professionals. Programs of continuing education in mental health are increasing at a rapid pace. This study examines-selected personal and occupational characteristics of enrollees in one such program and classifies the nature of enrollee motivation for participating in specialized programs of community mental health training. The learning-style preferences of these highly experienced professionals are also explored and recommendations are made concering the design of similar educational programs under development elsewhere.


Results of hospital rehabilitation of 1000 patients with myocardial infarction. Hospital rehabilitation of patients with myocardial infarction was conducted according to the model worked out by the Institute of Cardiology in Warsaw and modified at the Department of Cardiology of the Medical Academy in Lublin. According to their clinical condition, the patients were divided into 3 groups. Group A comprised patients with extensive myocardial infarction and complications; duration of hospital stay was 28 days. Group B included patients with extensive infarction without complications; hospital stay was 21 days. Group C included patients with limited myocardial necrosis and a mild course of the disease, and duration of stay of 14 days. Out of 1000 patients with myocardial infarction 134 (13.4%) died within the first 4 days after admission, i.e. before the beginning of rehabilitation treatment; 56 (5.6%) died during rehabilitation. The group of patients undergoing rehabilitation treatment comprised 866 patients (86.6%), including 382 (44.1%) in group A, 404 (46.6%) In group B, and 80 (9.3%) in group C. The mean duration of hospital stay of all patients with myocardial infarction was 24.3 days; in 80 cases (9.9%) it was 14 days, in 397 cases (49.0%) 21 days, and in 236 cases (29.1%) 28 days. In 97 cases (12.0%) hospitalization was longer than 28 days. Work was resumed by 30% of white and blue collar workers and 89.5% or farmers within the productive age groups.


Changes in the plasma kinin system in patients with myocardial infarction. The levels of kininogen, prekallikrein and kininase activity in the plasma of 54 patients with myocardial infarction were studied. It was demonstrated that in acute myocardial infarction (during the first two days after its onset) the level of kininogen and that of prekallikrein decreased simultaneously. After two weeks of the disease both these parameters returned to the values obtained in healthy controls. No correlation was observed between the degree of fall of kininogen and prekallikrein levels on the one hand, and the extent of myocardial infarction, on the other. Complications of myocardial infarction in the form of shock and pulmonary oedema affected only the level of kininogen which decreased, while they were without effect on prekallikrein. Kininase activity was reduced in all cases of myocardial infarction and did not change for two weeks. It seems likely that the biological activity of kinins in myocardial infarction may rise owing to their inadaequate breakdown by kininase.


Characteristic features of the differential sphygmogram in peripheral vascular dilation. Characteristic features of differential sphygmogram were investigated in persons in whom the radial circulation had been interrupted in order to produce a partial distension of muscular-type arteries and minute peripheral vessels. Eighteen subjects aged 20-35 years were examined. The differential and volume sphygmograms were recorded in the radial artery. After a five-minute stoppage of the circulation, the following characteristic features of the differential sphygmogram were observed: 1) the differential curve assumed the shape of a triangle with a broad base; 2) the amplitudes of all wave components decreased, the B wave disappeared, the V2 wave was minimal, and the t2 time considerably extended. The ratios V2/V1 and V2/(V1 +V2) were considerably diminished. These ratios may serve as fundamental criteria for the appraisal of vascular elastic properties in an intact organism.


Changes in microcirculation and oxygen pressure in the liver and kidneys in experimental traumatic shock. Changes in microcirculation and oxygen pressure in the liver and kidneys were studied in experiments on 42 rats in the course of experimental traumatic shock elicited by Cannon's methoicroscope with a microphoto adapter MFN-12. Oxygen pressure was recorded with the aid of active open hemispheric platinum electrodes with diameters of 150-200 mum. With advencing shock, considerable disturbances of microcirculation and PO2 occurred in hepatic and renal tissues. By the end of the torpid phase of the shock, the PO2 in the liver sank to 1/2.4, and in the kidneys, to less than 1/4 of the respective initial values. The changes in microcirculation were of an ischaemic, vasospastic type in the kidneys, and of a mosaic pattern in the liver: ischaemic segments alternated with areas fully supplied with blood. A severe and rapid course of shock was accompanied by more marked disturbances of PO2 and circulation in hepatic and renal terminal vessels.


Perceptual and linguistic factors in the language impairment of developmental dysphasics: an experimental investigation with the token test. Twelve developmental dysphasics and twelve control children were tested on De Renzi and Vignolo's Token Test. The performance of the dysphasics, though significantly poorer than that of the controls on Parts 2-5 of the test, seemed to follow a similar pattern. Both groups were errorless on the initial parts of the test. As the demand on auditory retention increased on subsequent parts of the test, the performance of both groups progressively deteriorated. However, the addition of grammatical complexity on Part 5, rather than causing even further deterioration in performance, actually served to improve the performance of both groups, though not significantly. Although the pattern of errors made by the two groups was similar, the quantity of errors made by the dysphasics, as compared to the normal control children, demonstrated the magnitude of the dysphasic children's receptive language impairment. Analysis of errors indicated that dysphasic children have greater difficulty with auditory retention and verbal memory than they do with the grammatical or structural complexity of language. It is suggested that the observed gross language impairment of developmentally dysphasic children does not result, at least primarily, from a specific inability to analyze the linguistic components of language. Rather, the language impairment of these children appears to reflect their primary inability to analyze the rapid stream of acoustic information which characterizes speech and is essential to normal speech perception and language development.


Effects of dichotically presented simulatneous synchronous and delayed auditory feedback on key tapping performance. A selective replication of Tsunoda's (1966) application of the DAF key tapping paradigm to the study of functional auditory asymmetry was conducted. Present findings do not offer confirmation of Tsunoda's assertion that most subjects will exhibit performance disruption at a lower intensity level when a vowel is delayed at the right ear and when a pure tone is delayed at the left ear. In the present study, it was found that no difference existed between the pure tone and the vowel delayed to the left ear conditions in terms of performance deterioration. The significant difference in performance disruption between the vowel delayed to the right ear condition and the pure tone delayed to the right ear condition was interpreted to be suggestive of functional auditory asymmetry.


Recognition thresholds in the central and lateral visual fields following temporal lobectomy. This study examined recognition thresholds for patients wtih unilateral left or right temporal lobectomy and for normal subjects. Material was projected tachistoscopically and successively to the center, left, and right visual fields. Stimuli were random designs and three-letter words oriented vertically. The recognition thresholds of the left temporal and normal groups were comparable, for both sets of stimuli. In contrast, the right temoral group was impaired in the recognition of words and random designs in the central and lateral fields. Results were seen to reflect the processing of units of visual information, whether in the form of letters or random designs, which at this elementary level relates to the right temporal lobe functioning.


Patterns of hand preference in a student population. The handedness of 1599 college students was assessed using a modification of Annett's (1967) inventory. The addition of a strength of preference scale makes the "mixed" classification a better indicator of ambidexterity than in the original inventory by eliminating from it subjects who show preference for the same hand for nearly all tasks. Contrary to previous reports, sex was not significantly related to handedness. It was found that a family history of left-handedness was significantly related to the handedness of the subject. The present form of the Annett inventory provides an easily scorable inventory for determining handedness of large groups as well as for use in individual testing situations. A further advantage of the present inventory is the ease with which data may be transferred by key-punch operators prior to special analysis or sorting procedures.


Aphasia with infarction in the territory of the anterior cerebral artery. Two right-handed patients with clinical evidence of major infarction in the territory of the left anterior cerebral artery developed a profound but transient aphasia characterized by (1) a striking dissociation between intact repetition and grossly disturbed spontaneous conversational speech, (2) an absence of phonemic paraphasia, (3) a lack of speech inhibition and (4) relative preservation of conformation naming and comprehension. Despite the initially profound motor aphasia, servicable spontaneous conversational speech returned in two to three months. However, more subtle changes in the form of lack of speech initiative and difficulties in narrating stories and describing complex pictures, remained many months after the onset. In these patients the major features of the disturbance could not be explained only on the basis of an interruption of the downgoing pathway from the dominant motor speech area, and in fact, may have been due to damage to the superior and mesial pre-motor area (particularly the supplementary motor region), an area that has been shown to play a role in processes which govern the initiation, continuation and inhibition of speech.


Incidence of laterality effects in mandibular and manual performance of dichoptic visual pursuit tracking. In dichotic pursuit auditory tracking tasks (PAT) subjects match a continuously varying pure tone presented to one ear with a second tone presented to the other ear and controlled by unidimensional movements of part of their motor system. In previous studies in which tonal frequency was varied, performance was significantly better when the tone controlled by a speech articulator (tongue, jaw) was presented to the right ear, rather than the left, but not if the tone was hand controlled. This study examined a visual analog of the PAT in which subjects matched the vertical position of a continually moving horizontal line (target) presented on one side of their point of fixation, with a second line (cursor) presented on the other side of their fixation point. Two predictions were confirmed for 12 right handed subjects: that there would be no significant laterality effect for articulatory (jaw) tracking because previous auditory tracking findings were speech related; and, that there would be a significant laterality effect (cursor right field-left hemisphere) for right hand tracking because of the development of a specialized sensorimotor integration mechanism for eye-right hand coordination in the left hemisphere. Alternative explanations for the right hand tracking results, and for the nonsignificant trend towards a laterality effect (cursor left field-right hemisphere) for left hand tracking, were discussed.


A tapping test in apraxia.

A tapping test in apraxia. An enigma in understanding the mechanism of motor apraxia is why patients with disease restricted to the left hemisphere cannot imitate motions with the left hand despite intact visual motor apparatus. Liepmann suggested that motor memories are stored in the left hemisphere and that in apraxia these engrams are either destroyed or separated from the right hemisphere. If Liepmann's hypothesis is correct, then, in addition to poor performance on commands and imitation, there should be poor performance in a motor task. To ascertain if there is a motor defect of the non-paretic hand of apraxic patients, twenty apraxic patients were given a rapid finger tapping test and their performance was compared with the left hand performance of aphasic right hemiparetic non-apraxic controls. The aptaxic group performed this task significantly slower than the control group, thereby giving support to Liepmann's hypothesis of apraxia.


Grammatical impairment in developmental aphasia. The language production of a 23 year old patient with developmental aphasia caused by birth injury was analyzed in detail within the framework of Chomsky's generative grammar. It was shown that different stages of grammatical development occur simultaneously, without the predominance of those grammatical forms which are identical with or close to adult grammar. Thus the language of this patient with developmental aphasia is quite comparable to the language of children from 3 to 6, and shares many features with grammatical impairment well known from agrammatism and paragrammatism in adult aphasia. It was suggested that in developmental aphasia incomplete linguistic generalizations are related to an incomplete maturation of inhibitory functions during language acquisition, whereas in adult aphasia comparable forms of less advanced grammars are set free by dissolution of function.


The lateralized effects of concurrent cognitive activity on a unimanual skill. Laterality studies have long been plagued by: (1) poor psychological methodology; (2) lack of specification of treatment parameters' and (3) exclusive use of left-hemisphere dependent measures. It was suspected that a recent study by Kinsbourne and Cook (1971) suffered from these faults. The present experimental findings confirm these original suspicions. Both spatial and verbal cognitive tasks were employed and comparisons made with performance during two control conditions. One was a mixed spatial-verbal activity, the other control required S to merely look at a blank card. While left-hand performance was enhanced under the verbal concurrent activities, when compared with performance under control (spatial-verbal) conditions, no other significant enhancement of performance occurred with any other concurrent activity condition. With the "No Activity Specified" control some support for the Kinsbourne study was found. However, the major finding, or implication, of this study was in demonstrating that the methodological problems outlined above cannot be ignored if worthwhile laterality studies are to be performed.


Advantages of the prone position for neurosurgical procedures on the upper cervical spine and posterior cranial fossa in children. The authors have reviewed the charts of 107 patients undergoing 119 surgical procedures in the prone position for posterior fossa or upper cervical lesions. The intraoperative complications encountered include cardiac arrhythmia, respiratory complications, cardiac arrest, hypothermia, air embolus and technical difficulties. In all but three children the problems were minor and easily remedied. The use of controlled ventilation appears to reduce blood loss, permits excellent relaxation of the exposed tissues and had some anesthetic advantages.


Extradural hematomas in children. 104 cases. The authors have studied the clinical features of 104 extradural hematomas in children. The frequency of this complication seems rather high and its severity undeniable. 17 cases were observed in newborns and 2 cases were localized in the posterior fossa. From a clinical point of view, 57% of the children had no disturbances in consciousness at the time of the injury, and 7% had no disturbances at anytime. A lucid interval was found in 68% of the cases, and this was less than 24 h in 60% of the cases. In 19% of the cases there was no skull fracture. Angiography allowed correct diagnosis and a better choice of the surgical technique. The hematoma was distinctly localized in 59 children, whereas it was widespread in 45, meaning that, excepting the coronal suture, the cranial sutures do not limit the spreading of an extradural hematoma. For treatment the authors prefer a bone flap with four or five holes (90 operations). The results are rather unsatisfactory. 18 patients died and in 21 (7.2%) the motor sequelae were the most important complications.


Schizencephaly: a clinical study and review. Schizencephaly is a rare malformation in which symmetrical portions of the cerebral mantle fail to develop. It should be differentiated by angiography and pneumography from the porencephalies that follow destructive lesions and from the prognostically more favorable subdural hematomas and effusions. If the diagnosis of this anomaly can be firmly established short of surgical exploration, operation or further treatment of any kind is not, in the authors opinion, warranted.