Model studies of chromatin structure based on X-ray diffraction data. Model calculations are presented in order to interpret the X-ray diffraction diagrams given by chromatin gels. It is shown that by taking into account the hydration of chromatin subunits, the problem of calculating the interference function in concentrated gels is greatly simplified. In this way it is spossible to fully interpret the influence of concentration on the position and intensity of the various rings present in the X-ray diffraction patterns. The possibilities and limitations of models based on spherical symmetry are also discussed. It is concluded that each chromatin subunit most likely contains three turns of DNA in each 200 base pairs segment surrounding a central protein core. With the method presented here it is possible to test if other models of chromatin based on different kinds of evidence are compatible with the X-ray diffraction data.


Physical and functional heterogeneity in TYMV RNA: evidence for the existence of an independent messenger coding for coat protein. Turnip yellow mosaic virus RNA can be separated into two distinct components of 2 times 10(6) and 300 000 daltons molecular weight after moderate heat treatment in the presence of SDS or EDTA. The two species cannot have arisen by accidental in vitro degradation of a larger RNA, as they both possess capped 5' ends. Analysis of the newly synthesized proteins resulting from translation of each RNA by a wheat germ extract shows that the 300 000 molecular weight RNA can be translated very efficiently into coat protein. When translated in vitro the longer RNA gave a series of high molecular weight polypeptides but only very small amounts of a polypeptide having about the same mass as the coat protein. Thus our results suggest that the small RNA is the functional messenger for coat protein synthesis in infected cells.


Bone marrow ribonucleic acid polymerase. Effect of testosterone on nucleotide incorporation into nuclear RNA. The incorporation of 3H-UTP into RNA by isolated rat bone marrow nuclei is stimulated by testosterone. This effect is hormone and tissue specific. Using alpha-amanitine and different ionic strength conditions it was found that testosterone enhances preferentially RNA polymerase I activity. The sedimentation pattern of RNA isolated from bone marrow nuclei shows that the synthesis of RNA species within the 14-30 S range is mainly stimulated by the hormone.


The use of terminal blocking groups for the specific joining of oligonucleotides in RNA ligase reactions containing equimolar concentrations of acceptor and donor molecules. Under the conditions that RNA ligase converts the tetranucleotide, pA-A2-A, to larger polynucleotides, no such polymerization can be detected with the derivative, pA-A2-A(MeOEt), that possesses a terminal 2'-0-(alpha-methoxyethyl) group. The protection against self condensation offered by the methoxyethyl group in this system allows the specific joining of donor and acceptor oligonucleotides in reaction mixtures containing equimolar concentrations of the two species. Thus, the enzyme, together with ATP, converts equimolar quantities of A-A2-A and pA-A2-A(MeOEt) to A-A6-A(MeOEt) in 55% yield, while a similar reaction with A-A2-A and pU-U2-U(MeOEt) results in a 40% yield of A-A3-U3-U(MeOEt). The intermediate in these ligations is a disubstituted pyrophosphate composed of the donor molecule and the adenylate moiety deriving from ATP. In the case of the intermediate arising from the blocked adenosine tetranucleotide, the assigned structure, A5'pp5'A-A2-A(MeOEt), has been confirmed by chemical synthesis. The pyrophosphate derivative is able to participate in joining reactions in the absence of ATP. These observations constitute an efficient approach to the synthesis of larger polynucleotides from a specific series of oligonucleotide blocks since (i), the methoxyethyl group can be easily introduced into each oligonucleotide using the single addition reaction catalyzed by polynucleotide phosphorylase in the presence of a 2'-0-(alpha-methoxyethyl)nucleoside 5'-diphosphate, and (ii), the blocking group may be readily removed under mild conditions after each successive ligation reaction. Two other octanucleotides, I-I2-A-U3-U and U-U2-C-I3-A, have also been synthesized by this method, and these molecules correspond (with I substituting for G) to sequences appearing near the 3' terminus of the 6S RNA transcribed from phage lambda DNA. The terminal 3'-phosphate group serves equally well as a blocking group for specific ligation reactions in that the ligase converts equimolar amounts of A-A2-A and pA-A2-Ap to A-A6-Ap in 50% yield.


A restriction endonuclease from Staphylococcus aureus. A specific endonuclease, Sau 3AI, has been partially purified from Staphylococcus aureus strain 3A by DEAE-cellulose chromatography. The enzyme cleaves adenovirus type 5 DNA many times, SV40 DNA eight times but does not cleave double-stranded phi X174 DNA. It recognizes the sequence (see article) and cleaves as indicated by the arrows. Evidence is presented that this enzyme plays a role in the biological restriction-modification system of Staphylococcus aureus strain 3A.


Polynucleotides. XLII1. Limited addition of 2'O-onitrobenzyl nucleotides to the 3'-end of ribooligonucleotide with polynucleotide phosphorylase. 2'-O-o-Nitrobenzyluridine, -cytidine and -adenosine were phosphorylated with phosphoryl chloride to the corresponding 5'-phosphates and led to 5'-diphosphates by the method of Moffatt and Khorana. These 2'-O-oNB-nucleoside 5'-diphosphates were incubated with a primer CpApA and polynucleotide phosphorylase in the presence of Mn2+. Tetranucleotides CpApApU, CpApApC and CpApApA were obtained after photosensitive removal of oNB groups in yields of 54-70%.


Chromatin nu bodies: isolation, subfractionation and physical characterization. Monomer chromatin subunit particles (nu1) have been isolated in gram quantities by large-scale zonal centrifugation of micrococcal nuclease digests of chicken erythrocyte nuclei. nu1 can be stored, apparently indefinitely, frozen in 0.2 mM EDTA (pH 7.0) at less than or equal to 25 degrees C. Aliquots of the stored monomers have been subfractionated by dialysis against 0.1 M KCl buffers into a soluble fraction containing equimolar amounts of H4, H3, H2A, H2B associated with a DNA fragment of approximately 130-140 nucleotide pairs, and a precipitated fraction containing all of the histones including H5 and H1 associated with DNA fragments. The total nu1 and the KCl-soluble fraction of nu1 have been examined by sedimentation, diffusion, sedimentation equilibrium ultracentrifugation, low-angle X-ray diffraction, and electron microscopy. Physical parameters from all of these techniques are presented and correlated in this study.


Chromatin structure: a property of the higher structures of chromatin and in the time course of its formation during chromatin replication. The action of a number of enzymes and metals on one nuclear preparation were interpreted in terms of the existence of a fragile but highly DNAase-I resistant feature of chromatin superstructure. The generation of this DNAase-I resistance feature of chromatin was then followed during normal DNA synthesis in the regenerating rat liver by following the disappearance of a transitory DNAase-I susceptible state. This transitory, DNAase-I susceptible state appears to be extremely similar to the post-synthetic, DNAase-I susceptible state that has been described in He La32.


Infrared dichroism of the DNA-caffeine complex. A new method for determination of the ligand orientation. Infrared linear dichroism (LD) measurements on films of the DNA-caffeine complex in terms of the relative humidity (r.h.) show two main effects. Firstly, there is an insertion of caffeine molecules into the DNA double helix (B form), as evidenced by a very strong parallel LD behaviour of the 745 cm-1 band due to the C-H out-of-plane deformation vibration of caffeine. Furthermore, a high r.h. values a modified B form occurs in the complex similar to the B form recently reported by BRAHMS and coworkers for DNA-polypeptide complexes. The reversible B-A transition of the DNA in dependence of the r.h. is not affected in general in the presence of caffeine.


Recognition of polynucleotides by antibodies to poly(I), poly(C). The binding of anti poly(I). poly (C) Fab fragments to double or triple stranded polynucletides has been studied by fluorescence. Association constants were deduced from competition experiments. The comparison of the association constants leads to the conclusion that several atoms of the base residues do not interact with the amino acid residues of the binding site of Fab fragment while the hydroxyl groups of furanose rings interact. These results suggest that the Fab fragments do not bind to the major groove of the double stranded polynucleotides. An interaction between the C(2)O group of pyrimidine residues and Fab fragments cannot be excluded. Circular dichroism of poly(I). poly(C) or poly(I). poly(br5C)-Fab fragments complexes are very different from the circular dichroism of free polynucleotides which suggests a deformation of the polynucleotides bound to the Fab fragments.


A new synthesis of 5'-deoxy-8,5'-cyclo-adenosine and -inosine: conformationally-fixed purine nucleosides (nucleosides and nucleotides. XVI). A versatile method for the synthesis of 5'-deoxy-8,5'-cycloadenosine, a conformationally-fixed "anti" type of adenosine, was presented. Irradiation of 2', 3'-O-isopropylidene-5'-deoxy-5'-phenylthioadenosine with 60W Hg vapor lamp afforded 2',3'-O-isopropylidene-5'-deoxy-8,5'-cycloadenosine in high yield. The use of other 5'-alkylthio derivatives also gave the cycloadenosine, though the yields were rather poor. Deacetonation of the cyclocompound with 0.1N HCl gave 5'-deoxy-8,5'-cycloadenosine. The cycloinosine derivative was similarly prepared. The nmr, mass and CD spectra of 5'-deoxy-8,5'-cycloadenosine were given and discussed with the previously reported results.


End group of naturally terminated and UV lesion terminated T7 in vitro RNA. The 3' terminal nucleosides of RNA transcribed in vitro by E. coli RNA polymerase from T7 DNA and UV irradiated TN DNA were determined. The 3' terminal nucleoside of naturally terminated (t1 termination site) RNA cytidine. In the case of RNA terminated at UV lesions, it is cytidine in 0 per cent of the molecules and adenosine in the remaining 30 per cent. Cytidine trialcohols are labile in high concentrations of KOH and at high temperature and appear to convert to uridine.


On the character of the thermodynamic properties distribution in DNA molecules inside the melting interval. The variances of the distributions of DNA molecules over the degree of helicity and over the number of unwound regions inside the melting interval are calculated. The variance over the degree of helicity is expessed in terms of the values directly available from the experimental data. For the variance over the number of unwound regions a simple interpolation formula based on the machine calculations is proposed. Possible applications of the results obtained to interpolaation of the electron microscopic denaturation maps of DNA are discussed.


Nucleoside-3'-phosphotriesters as key intermediates for the oligoribonucleotide synthesis. III. An improved preparation of nucleoside 3'-phosphotriesters, their 1H NMR characterization and new conditions for removal of 2-cyanoethyl group. An improved procedure for the transformation of 5'-O-monomethoxytrityl-2'-O-acetyl-3'-phosphates of uridine la, inosine ib and 6-N-benzoyladenosine lc into corresponding 3'/2,2,2-trichloroethyl, 2-cyanoethyl/-phosphates iiaic is reported. H NMR characterization of nucleoside 3'-phosphotriesters is presented. New conditions i.e. anhydrous triethylamine-pyridine treatment have been found for the selective removal of 2-cyanoethyl group from nucleoside 3'-phosphotriesters in the presence of neighbouring 2'-O-acetyl one.


A acid-stable analogue of the 3-beta-D-ribofuranoside of Y-base. A cyclonucleoside analogue of Y(TU) riboside has been prepared and shown to be relatively stable in M-hydrochloric acid solution at room temperature.


Efficiency of in vivo labeling of red blood cells with 99mTc. The effectiveness of three commercial bone scintigraphic agents and freshly made stannous chloride in labeling erythrocytes with 99mTc was compared. Our results indicate that tin pyrophosphate is the agent of choice and that it is most effective when injected at least 15 minutes before the 99mTc-pertechnetate is administered. This technique of labeling red blood cells in vivo could be applied in performing blood pool studies.


[Determination of capillary permeability with labeled human albumin]. We propose a new test for measuring the "capillary permeability" with labeled albumin, with simpler methods, satisfactory results and good discrimination between normal subjects and pathological patients. In normal subjects, after the removal of the tourniquet, the radioactivity returns to former values (under 10% of this figure). In pathological patients, even after the 3 min following the removal of the tourniquet, there is no return to the former value (the retention of labeled albumin is always over 10%). It is in cyclic oedema that the test provides the most interesting results.


[Asymmetric brain perfusion in the aged?]. Between 1971 and 1975 we performed 1580 dynamic perfusion studies in 1411 patients. The patients were admitted to the nuclear medicine department for brain scanning from the medical, neurological and neurosurgical departments as well as directly by private family physicians. For dynamic brain studies we used the scintillation camera (Searle Radiographics) and a bolus of 99mTc-pertechnetate intravenously injected. The polaroid frames were exposed at 4 second intervals The results of the dynamic brain study were divided into five categories: normal, moderately diminished perfusion of one hemisphere, severe perfusion defect of one hemisphere, focal or multifocal hypervascular areas ("hot areas") and stenosis or occlusion of the carotid artery. In 1009 cases we found a normal perfusion of the tracer material without any side difference between the brain hemispheres. In 68 patients with motoric hemisyndrome of the right side and in 89 patients with hemisyndrome of the left side we were able to demonstrate a diminished perfusion of the contralateral hemisphere. In 65 patients with confirmed primary or metastatic brain tumors we observed a perfusion deficiency in 39 cases and focal "hot" areas in 26 cases. In 24 epileptic patients we found asymmetrical perfusion of the brain. In 109 patients without any neurological signs or symptoms we registered a "false positive" dynamic perfusion study with an asymmetrical initial transition of the injected tracer material. The left hemisphere showed a diminished perfusion in 86 cases, the right in 23 cases. The asymmetrical brain perfusion was not observed in patients under the age of twenty years. The incidence of "false positive" dynamic brain studies was found to be dependent on the age of the investigeted patients with a maximum of asymmetrical brain perfusion scans in the age group between 61 and 70 years. At present time we are not able to explain the reason of the "false positive" results. Because of this reason the investigation will be continued together with the neurologists and radiologists to find out a possible correlation between our study, the EEG-curves and results of the morphological brain investigations such as pneumoencephalography or ACT-scans.


[Is a dosage calculation for radio-iodine therapy possible?]. When trying a single-dose 131I therapy in thyrotoxic patients a dose calculation must be done to avoid an overtreatment raising the risk of posttherapeutic hypothyroidism. The calculation is based on the diagnostic 131I uptake, the thyroid weight, and the effective intrathyroidal halflife of the diagnostic 131I dose. In 46 thyrotoxic patients the radiation dose was calculated with 7000 R for small and 10 000 R for large (50--100 g) glands using the formula of Billion. Iodine-131 was given in a single dose. Therapeutic dose uptake was measured every day and the effective T 1/2 calculated using a least squares computer fitting to an monoexponential decrease. The radiation dose was then recalculated using the same formula. Small glands received 10 700 +/- 4300 R (SEM 1008 R) instead of calculated 7000 R; large glands 8600 +/- 4100 R (SEM 860) instead of 10 000 R. There was a significant correlation: the smaller the gland the higher the radiation dose. The smallest glands received 12 000 to 16 000 R. There might be such a great difference between calculated and received radiation dose than an individual prediction will be impossible. In our patients a careful calculation for the single-dose treatment was done; nevertheless in some cases an overtreatment of more than 100% was seen. A comparison of responding or overresponding to therapy with the radiation dose is only reliable using individual dosimetry with the therapeutic 131I dose.


Plasma and erythrocyte magnesium levels in patients with chronic renal failure. In 62 patients with chronic renal failure the concentration of total and ultrafiltrable magnesium in plasma water was significantly raised and showed a weak but significant correlation with the degree of renal failure expressed by serum creatinine concentration. Erythrocyte magnesium concentration increased significantly showing a more significant correlation with the degree of renal failure than the plasma magnesium level. The fluid used for dialysis contained 1.5 mEq/l of magnesium and this failed to prevent the rise of concentration of this electrolyte in the plasma and erythrocytes. A statistically significant positive correlation was demonstrated between the concentrations of magnesium and ultrafiltrable calcium in patients with creatinine concentration below 4 mg/100 ml.


Renal excretion of magnesium in chronic renal failure. In 42 patients with chronic renal insufficiency the 24-hour magnesium excretion decreased with the progress of renal failure and was independent of the total and intrafiltrable magnesium concentration in the plasma. At the same time the fractional excretion of this ion increased progressively probably as a result of increased osmotic load acting on individual nephrons and/or the action of the natriuretic factor. The high correlation between fractional excretion of magnesium and sodium, and magnesium and calcium may suggest an interrelationship between the transport mechanisms of these ions in the nephron.


Metabolic response to two-stage adrenalectomy ih patients with Cushing's disease. In 5 patients with Cushing's disease the balance of nitrogen, potassium, phosphorus, sodium and chlorides was determined during 5 days before, and 10 days after bilateral two-stage adrenalectomy. The patients received substitute treatment with hydrocortisone in mean doses of 112 mg/24 hours after the first stage and 203 mg/24 hours after the second stage. After removal of the first adrenal the metabolic response of the cell mass and extracellular space was within the normal range of moderately intense responses. After the second adrenalectomy the cumulative balance of the components of the cell mass was slightly negative and retention of sodium and chlorides was more pronounced than after the first operation.


Clinical value of urinary sodium and potassium content determinations in severely burned patients. In 15 severely burned patients the concentrations of sodium and potassium were determined in 605 urine samples. Concentrations of both electrolytes were reduced. A decrease in urinary sodium concentration below 10 mEq/l, persisting during several days, was an unfavorable prognostic sign. Low urinary potassium concentrations (below 10-20 mEq/24 hrs) were interpreted as an evidence of cellular potassium depletion.


Lymphonodular form of toxoplasmosis.

Lymphonodular form of toxoplasmosis. On the basis of 3 cases of lymphoglandular toxoplasmosis recognized after biopsy of lymph nodes the authors established the clinical and morphological syndrome of this disease entity. Attention is called to the possibility of erroneous histological evaluation of the examined lymph nodes owing to the similarity of glandular toxoplasmosis to other diseases of the lymphatic system.


Observations on behavior of platelet adhesiveness at the late stage of burn disease. Results of investigations on platelet adhesiveness in burned patients after the stage of shock were presented. In all cases studied (17 patients) the values of platelet adhesiveness were lower than in healthy subjects. Further investigations are required to explain this finding.


[Silicones for augmentation of soft tissues. Their properties following implantation]. The authors describe the results of 6-years' application of compositions based on liquid silicone rubber SKTN for cosmetic correction of pectus excavatum in 24 patients. The results of investigation of physico-mechanical properties of original allomaterials based on SKTN compared with the properties of soft tissues of living organism are shown. The effects of ageing of these allomaterials in the environment of the living tissues are presented.


[New polymers for transfusiology].

[New polymers for transfusiology]. The Institute of General and Inorganic Chemistry of the BSSR Academy of Sciences and the Byelorussian Research Institute of Blood Transfusion have developed and used in hospital practice a fundamentally new method of blood stabilization which does not require addition of alliens. Some part of calcium from blood plasma is extracted by filtrating the blood through layers of specially developed highly effective and biologically compatible fibrous sorbents of derivatives of cellulose (natural highpolymer). The blood may the used in all cases of homotransfusion and most expediently in extremely complicated cases, when direct blood transfusions are difficult. Stabilized blood may also be effectively used when large-quantity or exchange blood transfusions have to be quickly performed, to resuscitate patients from clinical death, to stop haemorrhage caused by disturbances in blood coagulation, to treat anaemia of different etiology, including radiation illness, and in case of sensitiveness to citrate solutions (serious affections of kidneys, liver and heart).


[Detection of pentachlorophenol in natural rubber latex]. The method of detection of pentachlorophenol in natural rubber latex is proposed. Pentachlorophenol is isolated from other nonrubber-like substances by thin-layer chromatography and identified by spectroscopic method in UV-light. Isolation of pentachlorophenol is carried out from water extracts obtained from the dry caoutchouc films, so the same method can be used for examination of the rubber articles designed for the medicinetoo.


Biological tolerance of copolymers of 2-hydroxyethyl methacrylate-vinylpyridine. The healing-in of implants of terpolymer gels having different chemical composition was studied in animals. Histological analysis showed that all polymers under investigation are healed-in in a similar way by encapsulation with collagen fibrous tissue. Neither cancerogenic effect nor calcification were observed within the interval studied.


[Respiratory function in chronic obstructions of the large pulmonary arteries (study of 30 cases]. If diagnosis of chronic thromboses of pulmonary arteries is usually easy at the stage of confirmed chronic pulmonary heart, it is not so when dysponea is the only symptom of the disease. The authors report 30 cases of chronic thrombosis and remark that if respiratory alkalosis is very frequent, hipoxemia is often missing. On the other hand they observe 27 times out of 28 an increase of CO2 alveoloarterial difference; measuring the CO2 difference appears a safe and reliable test for detecting chronic thrombosis. It should take place in every systematic complete examination of unexplained dyspnoea.


[Asthma and propranolol].

[Asthma and propranolol]. The authors report the results of a study of propranolol perfused intravenously at a dose of 1 mcg/kg/mn during 30 mn to 50 asthmatic patients. The VC decreased by 8.3 and by 10.9% in the middle and at the end of the perfusion. The FEV1 decreased by 18.3 and 23% concomitantly. Classifying patients in 4 groups according to the clinical severeness of the asthma showed that the response to propranolol increased with that severenesse. Exploration of obstructive bronchopneumopathies by propranolol provided valuable data or the differential diagnosis of asthma and chronic bronchitis.


[Comparative study of the ventilatory function during normal and whispered pronounciation of certain syllabes]. The study was done on 4 french speaking subjects: 2 men and 2 women. The pulmonary flow and volumes, aesophageal pressure and electromyography by needle of an internal intercostal were simultaneously recorded during normal and whispered pronounciation of 48 syllables These were made up of an occlusive consonant in a first position or not, followed by the vowel "A". The pneumotachographic tracing is reproducible both in normal and whispered voice, differing according to the mode of pronounciation. The aesophageal pressure and the electromyography of the internal intercostal are equally different. The comparative study of the ventilatory function in normal and whispered voices enabled the dissociation on pneumotachographic tracing of the variation of flow due to movements of the naso-bucco-pharyngeal articulations from those coming from movements of the vocal cords.


[Evaluation of functional repercussions of pulmonary tuberculosis sequelae. Apropos of 112 cases]. In a retrospective study of 112 observations, the authors studied the sequelae on respiratory function in pulmonary tuberculosis bacteriologically cured. With the help of a standardized clinical enquiry they defined three groups of patients: groupe I, 31 patients with parenchymatous sequelae but free of bronchopathy and parietal sequelae; groupe II, 45 patients presenting besides parenchymatous sequelae signs of chronic bronchopathy; group III, 36 patients with parietal sequelae. Complementary examinations confirmed the frequency and degree of functional respiratory alterations: --ventilatory handicap in 87% of cases; --scintigraphic lacunae much wider than the radiological images, in more than half of the cases; --hematosis disorders in 65% of the 73 patients tested; --pulmonary arterial hypertension, at least in effort, in 62% of the 58 patients examined by microcatheter. The study by groups showed the particular severeness of an association of tuberculosis sequelae with chronic bronchitis. The existence of parietal sequelae is an additional feature of severeness. The presence of functional deficiences, all the more serious that they are evaluated late; suggests a progressive worsening of these patients' respiratory condition.


[Epidemiologic study of chronic bronchitis in shipyard workers (selection of the most discriminating respiratory functional parameters)]. Out of 1106 subjects working in shipyards, either building or repairing, an epidemiological survey showed that 7.8% had chronic bronchitis. The ratio varied according to the age groups (4.1% to 9.4% from 35 to 55 years) and smoking habit (1.2% in non smokers against 13.6% in heavy smokers). The study of ventilatory parameters in 169 subjects taken at random showed that various tests (VC, FEV1, FEV1/VC, MMFR, RV, RV/TLC, V at 60% TLC, Raw, TCO) did not have a specific value. In an epidemiological study simple measures (VC, FEV1, FEV1/VC, MMFR) taken by strong plain apparatus would be enough.


[First cases of surgical pulmonary cryptococcosis in Vietnam]. Two cases of tumoral isolated pulmonary cryptococcosis are reported. The rarity of the facts explains that diagnosis is usually surgical, the inflammatory and necrotic pseudo-tumour swarming with yeast-like micro-organisms, easily recognizable by their thick gelatinous capsules.


[Myocardiopathy of progressive muscular dystrophy]. The authors have effected a clinical, radiological, electrocardiographic and apexocardiographic survey in 13 patients with progressive muscular distrophy (PMD) and in 6 healthy subjects belonging to families affected by the disease, in parallel with a group of 11 patients with severe myasthenia and 23 healthy subjects. Comparing the results with those found in the literature lead to the following results: 1) The ECG modifications and above all the abnormalities of the ventricular complex develop precociously in the PMD and express the pleiotropism of the myopathic gene. 2) The myocardial dyssynergia represents a link in the physiopathological chain of the cardiac distress. 3) The precociousness of electro and apexocardiographic modifications and their presence in healthy parents recommend these investigations in the genetic enquiry. 4) Clinical, histological and haemodynamic data individualize the myocardial distress as a true myocardiopathy.


[Primary interstitial pneumopathies].

[Primary interstitial pneumopathies]. Primitive interstitial pneumopathies are only a temporary classification. They seem to be due to an evolution for the worse of a "diffuse alveolar damage" of unknown origin. Evolution towards pulmonary fibrosis and respiratory insufficiency is their common risk. Etiopathogenic hypotheses would favour the immunological etiology. A diagnosis of primitive interstitial pneumopathy is reached by elmination when no known cause can be found. Liebow's classification remains valuable for pathology but is debatable where anatomo-clinical correlations, etiological hypotheses and the eventual effect of treatment are concerned. Today these primitive forms still represent 40% of the interstitial lung diseases, the causes of which are progressively discovered.


[Chronic mediastinitis].

[Chronic mediastinitis]. Although unfrequent, chronic mediastinites are not exceptional. Their clinical polymorphism results from diversity of the mediastinal content. The superior vena cava syndrome is the most frequent clinical sign. The essential examination is the angiopneumography. Mediastinitis can be associated to other fibrinogenous processes, particularly the retroperitoneal ones. Infectious processes (tuberculosis, various bacteria), parasitic or medicinal (methysergide), are found in the etiology of this affection. Very often the etiological research is negative: recurring lymphotropic respiratory infections appear responsible for these cryptogenetic chronic mediastinites. Surgery is debatable in case of a superior vena cava syndrome. Anti-tuberculous treatment is efficient against related affections.


[Clinical, functional and hemodynamic course in patients with chronic bronchitis at the stage of chronic cor pulmonale]. Twenty seven patients, almost all chronic bronchitic, and with a "chronic cor pulmonale" according to the E. C. G., were followed clinically, radiologically and for E. C. G. and pulmonary functions, and also for the hemodynamics, during a minimum of 3 years, the average length of observation period being about 5 years. Twelve patients died during this observation time. Periods of right heart failure (R. H. F.) were frequent : 3.6 +/- 3.0 in average, slightly more frequent in the deceased patients than in the others. The average delay between the onset R. H. F. and death was of 49.3 +/- 30.8 months ; the survivors on average lived another 54.6 +/- 30.8 months after their first R. H. F. The mean pulmonary arterial pressure (PAP) was quite stable, going from 27.5 +/- 7.0 to 31.2 +/- 9.6 torr (an unsignificicant difference); in only 9 cases did the PAP increase of more than 5 torr during the observation period (acute attacks excepted). The PAP evolution was not significantly different in the deceased and the survivors. PAP worsening by steps after a fit of R. H. F. was observed in only 4 cases. Chronological variations of PAP were well correlated with those of Pao2 during the same period : r = -- 0.68, P less than 0.001. The hemodynamic evolution (PAP), that of the E. C. G. and the volume of the heart were reasonably parallel to the overall clinical evolution ; the E. C. G. evolution had the closest match with the overall clinical evolution (78% of cases). The E. C. G. enables only a late diagnosis of CCP but its evolution is very valuable for prognosis. Hemodynamic tests have a double value initially for diagnosis and later for the evolution.


[Therapeutic survival beyond 5 years in medically treated primary bronchial cancer. Apropos of 9 cases]. The authors report 9 observations of bronchial carcinoma with a surviving time of 5 years or more. They insist on the various factors on which depends the surviving time: --histology: a differentiated epidermoid epithelioma has better results; --localization of the tumour: cancers of the apex or the trachea have a slow evolution but a very bad prognosis; --therapeutical methods: high energy radiotherapy at curative doses is the best medical treatment of bronchial cancer and chemotherapy is only its complement; --prolonged and regular check ups are a major point in this fighting of cancer. Beyond keeping watch on the general health, it enables early detection and treatment of any evolutive recurrence. Seven of their patients benefited from such repeated treatment.


[Mediastinal lymph node calcifications and Hodgkin's disease]. If mediastinal lymph-node calcifications are frequent, the "hodgkinian" origin of these calcified adenopathies is unusual; less than 30 cases are reported in the literature. A new observation is described here. These lymph-node calcifications occur most often after radiotherapy; exceptionally "hodgkinian" adenopathies can appear ready-calcified.


[Respiratory function tests in epidermoid cancers of the bronchi]. The results of functional tests are analyzed in 50 cases of epidermoid bronchial cancers. Severe disorders take place in almost every patient. In one patient out of two, there is an old distension already existing prior to the cancer; in other patients gas exchange disorders can be improved by the intervention. Moreover, from some results a spreading of cancer towards the mediastinum is to be feared.


High resolution polyacrylamide gradient gel electrophoresis. A method was developed for high resolution electrophoresis of proteins in linear gradient (3 to 30%) polyacrylamide gel rods in a neutral phosphate buffer containing 0.1% sodium dodecyl sulfate. Well-defined protein zones were observed and improved resolution was attained especially for low molecular weight proteins in preparations containing a variety of polypeptides, e.g. viruses that are often separated by continuous gel methods. Electropherograms of continuous (8%) and gradient (3 to 30%) gels were made of purified vesicular stomatitis virus, variola virus, Rickettsia rickettsii, and alpha and beta chains of hemoglobin in order to demonstrate the resolution of the gradient system.


A procedure for the bulk preparation of brain microsomes with low speed centrifugation. A method is described for the rapid isolation of microsomes from brains of various species. The method depends on the interaction of calcium with microsomes. The procedure is limited because calcium inhibits certain microsomal enzymes. Magnesium and manganese may be substituted for calcium. However, the substitutions decrease the reliability and efficiency of the procedure.


[Stimulating effect of vitamin A on the absorption and metabolism of zinc in chicks]. Zinc metabolism and absorption were examined in chicks of two groups that differed in vitamin A supply. Five week chicks that were given a diet without an addition of vitamin A showed overt symptoms of A-avitaminosis. The condition was followed by marked changes in the zinc metabolism and absorption in the intestine and by insignificant changes in the calcium metabolism. Vitamin A was administered per os at a dose of 24,000 i. u. (in oil) and 72 hours later zinc absorption in the ileum increased noticeably and zinc balance in the body became positive.


[In vitro biosynthesis of cholesterol and its precursors in the osseous tissue of rats]. By thin-layer chromatography compounds of sterol origin were isolated from the nonsaponified fraction of bone tissue of rats. The occurrence of squalene, lanosterol, cholesterol and incompletely identified Cdelta2427-sterol in the organic matrix of the bone was demonstrated by means of UV- and IR-spectrometry. Bone tissue incubation with 1,2-C14-aceticacid yielded C14-labeled lanosterol, C28, 29-sterols, cholesterol and squalene. The rate of cholesterol synthesis in the bone tissue was lower than that in the liver and intestine of rats.


[Obtaining complexes of thiamine with proteins]. The formation of thiamin complexes with different proteins--gluten, gliadin, edestin, albumin and casein--was studied. The reaction took place at pH varying from 1 to 10. The amount of protein--bound thiamin was measured by the thiochromic method. It was found that thiamin was complexed with proteins due to the reaction between sulphydryl groups of the thiol form of thiamin and disulphide groups of oxidized proteins. The optimum pH value for the formation of thiamin-protein complexes was 9. Calculation of the kinetic parameters of the process suggested that it was endothermic.


[Physico-chemical and structural changes gliadin and glutenin components of different qualities of gluten]. By gel-chromatography on Sephadex and electrophoresis in polyacrylamide gel the structure and composition of gliadin and glutenin compounds of gluten from the strong and weak varieties of Saratovskaya 29 and Akmolinskaya 1 wheats were investigated. It was shown that similar protein fractions of strong and week gluten differed in the content of certain amino acids, number of disulphide bonds, electrophoretic mobility, ratio of components made of one and several polypeptide chains, molecular weight of individual components and subunits, and the content of high molecular weight proteins.


[Amino acid composition of rice grain proteins]. The composition of the major reserve proteins of rice grain--globulins, prolamines and glutelins--was examined in four rice varieties (Dubovsky 129, Kuban 3, Alakul, Ushtobinsky). Globulins proved to be most heterogeneous whereas glutelins appeared to be least heterogeneous. In regards to the ratio of components globulins showed high variability and glutelins displayed high stability.


[Permeability of acetylcellulose ultrafiltration membranes with regard to biologically active substances]. The permeability of standard Soviet ultrafiltration membranes prepared from cellulose acetates was investigated with respect to biologically active substances (hemoglobin, trypsin, ribonuclease, vitamin B12, hydroxytetracycline) and inorganic salt (KH2PO4). The arrest of a substance by a membrane of a certain structure depended primarily on the size of the substance macromolecule in the solution. The filtration rate was related to the membrane type, pressure gradient and composition of the filtered solution. Potential use of the tested membranes is described.


[Pigment and antibiotic substance contained in the spores of Actinomyces streptomycini B-6]. The antibiotic activity and fractional composition of the supernatant of the homogenate of Actinomyces streptomycini B-6 spores were investigated. The homogenate supernatant was of yellow colour and showed antibiotic activity when used as the test-organism of the culture St. aureus 209. The antibiotic activity was associated not with the homogenate pigment but with the colourless substance referring to streptomycins which was contained in spores.


Variation in subglottic size in children. The incidence of variation in the subglottic size was investigated in 3304 infants and children. A mild degree of congenital subglottic stenosis was found in 0.91% and a moderate degree of stenosis in 0.06% of the patients. A mild degree of congenital subglottic enlargement was noted in 0.7% and moderate enlargement in 0.06% of the patients.


Locomotor activity and plasma, red blood cell and cerebral cortex lithium concentration in inbred mice given lithium carbonate. Inbred male C57 BALB, C3H and DBA mice received lithium carbonate in their food for 3 weeks. Their locomotor activity was measured by photocells and the concentration of lithium in their plasma, red blood cells and cerebral cortex was determined. The susceptibility of the inbred strains of mice to the activity-suppressant effect of lithium was C3H greater than DBA greater than BALB = C57. The concentration of lithium in plasma varied between 0.85-1.02 mEq 1. No relationship was found between lithium's pharmacokinetics and its effects on activity. The findings are consistent with the notion that genetic factors can influence the effects of lithium on behavior, but they do not support the hypothesis that genetic determination of lithium's uptake into cells is responsible for these effects.


The tryptolines: effect of intraventricular administration on spontaneous motor activity of rats. The pharmacologic properties of the tryptolines, hindered analogues of the tryptamines, were studied behaviorally in rats. Following intraventricular injections, it was found that spontaneous motor activity decreased markedly during the initial 25 mins when compared with saline. Since both the tryptolines and tryptamines have been shown to be inhibitors of 5-hydroxytryptamine uptake, it may be possible that these compounds are acting indirectly throught an effect on the serotonergic system.


Effect of tetraethyl lead on food and water intake in the rat. The effect of tetraethyl lead (TEL) on food and water intake in adult male albino rats was studied. Animals received 1, 4, 7, 10, or 13 mg/kg body weight of TELin peanut oil, or a peanut oil placebo, via either intragastric (IG) intubation or intraperitoneal (IP) injection. For food intake, route of administration was a significant factor and, compared to baseline levels, food intake was significantly depressed at dosage levels of 7, 10, and 13 mg/kg for both IP and IG administration. Further, the time course of food intake differed significantly across route of administration. Water intake was also significantly depressed at 7, 10, and 13 mg/kg, but route of administration was not a critical factor. Results were discussed in relation to clinical and experimental data on lead intoxication, and were viewed as severely limiting the utility of employing food and/or water as motivational variables in assessment of behavioral effects linked to TEL poisoning.


Secondary reinforcement property of a stimulus paired with morphine administration in the rat. Rats learned to run to the correct arm of a Y-maze. Correct responses were reinforced with morphine injection paired with a conditional tone stimulus. After the maze response was well established, extinction trials were run. During extinction half of the animals received neither morphine nor tone as a consequence of a correct response, while the other half received the tone but no morphine. Rats receiving the tone during extinction required significantly more trials to reach the extinction criteria than rats not receiving tone presentations. Extinction with the tone also facilitated relearning of the maze response. The results support the view that morphone is a potent reinforcer, and that stimuli paired with morphine administration acquire the properties of a secondary reinforcer.


Ethanol and delta-9-tetrahydrocannabinol: mechanism for cross-tolerance in mice. The pharmacological interaction between equipotent doses of ethanol (1.35 g/kg) and delta-9-tetrahydrocannabinol (THC, 17 mg/kg) was evaluated in mice using rotarod performance as a measure of drug action. Tolerance ot the effects of ethanol and THC as well as a symmetrical cross-tolerance between these two drugs was demonstrated. Ethanol elimination was not altered by previous treatment with either ethnaol or THC as determined by measuring blood ethanol concentrations with an enzymatic assay. THC metabolite ratios in blood, brain and liver tissues determined after a dose of 3H-THC demonstrated that THC treatment had no effect upon THC metabolism or disposition. Ethanol treatment altered the distribution of THC and also altered hepatic THC metabolism as evidence by the occurrence of increased proportions of polar THC metabolites. No treatment regimens produced lower whole brain levels of subsequent ethanol or THC suggesting that tolerance to ethanol or THC and cross-tolerance between these two drugs does not develop due to lower brain concentrations. A vehicle effect was shown when treatment with a mixture of propylene glycol and Tween-80 altered the metabolic and behavioral effects of subsequently administered THC.


Metrazol potentiated after-discharges: dose-response relationships and effects of selective lesions. In Experiment 1 the dose-response effects of pentylentetrazol (Metrazol) on photically evoked after-discharge (PhAD) parameters were examined. Metrazol potentiated PhAD activity by affecting all measured parameters - PhAD frequency, amplitude, burst duration and spindle composition - in particular PhAD burt duration and spindle composition. A mimimum effective dose of 10 mg/Kg of Metrazol was required for some statistically reliable potentiation. Metrazol dosage levels of 20 and 25 mg/Kg induced lengthy bouts of EEG spindling and spiking as well as near maximized PhAD component augmentation. In Experiment 2 stereotaxically oriented knife-cuts isolated the thalamus from cortical and/or midbrain and brainstem input. Such lesions did not block the capacity of Metrazol to potentiate PhADs, although the lesions altered evoked activity. These findings are discussed in terms of the current thought of Metrazol action and thalamic mechanisms in the control of after-discharge activity.


Noradrenaline synthesis from L-DOPA in rodents and its relationship to motor activity. Evidence has been obtained for an increase in noradrenaline (NA) turnover after administration of L0DOPA to rodents. Normal mice, and those pre-treated with either reserpine or alpha-methyl-p-tyrosine (AMPT) were given L-DOPA (200 mg/kg) plus MK 486 (alpha-methyldopahydrazine; 25 mg/kg). In all cases L-DOPA produced a rise in cerebral dopamine (DA) levels. Cerebral NA levels were increased by L-DOPA in reserpinised and AMPT-treated mice. The same dose of L-DOPA produced no change in NA in normal mice, although pre-treatment with the monoamine oxidase inhibitor pargyline (200 mg/kg) resulted in a greater rise in NA 1 hr after L-DOPA compared to animals receiving pargyline alone. This evidence suggests that NA is synthesized from- L-DOPA in all these situations. But whole brain 3-methoxy-4-hydroxyphenylglocol sulphate (MOPEG-SO4), a major metabolite of NA, measured after administration of the same dose of L-DOPA plus MK 486, was unaltered in normal and AMPT-treated rats, and was significantly decreased in reserpinised rats. However, an elevation of whole brain MOPEG-SO4 was found in reserpinised and AMPT-treated rats after a lower dose of L-DOPA (50 mg/kg). This discrepancy may be explained by high doses of L-DOPA causing inhibiton of catechol-O-methyl transferase (COMT), which is suggested by the observation that the forebrain homovanillic acid (HVA): 3,4-dihydroxyphenylacetic acid (DOPAC) ratio was significantly lower after the high dose of L-DOPA than in untreated mice. Such an inhibition would prevent formation of MOPEG-SO4. Pretreatment with dopamine-beta-hydroxylase inhibitor FLA (63(bis-(1-methyl-4-monopiperazinyl-thiocarbonyl)disulphide) prevented the increase in NA And MOPEG-SO4 formation observed following L-DOPA induced motor activity in these groups of animals suggesting the involvement of NA in the production of such behaviour.


Isolation and identification of two learning-induced brain peptides. Goldfish were trained either to avoid the blue compartment of a tank and swim into the green compartment or, conversely, to avoid green and prefer blue. Preliminary experiments indicated that acquisition of the avoidance behavior was associated with the presence in the brain of two peptides, one found in blue avoiding (BA), another in green avoiding (GA) fish. With the help of behavioral bioassays, the peptides were isolated and purified, and their structure was determined by ultrasmicroanalytical techniques. The sequence of the BA peptide, pglu-ile-gly-ala-val-phe-pro-leu-lys-tyr-gly-ser-lys-OH was reproduced by synthesis. Sequential analysis of the GA peptide gave two alternative structures, NAc-lys-gly-gln-ile-ala-val-phe-pro-leu-lys-tyr-gly-ser-OH or NAc-lys-gly-ala-val-gln-ile-phe-pro-lys-tyr-gly-ser-OH, both of which are being synthetized to be compared with the natural compound. Overlapping sequences between the BA and GA peptides suggest the existence of a family of peptides associated with behavior based on color discrimination.


Development of cholinergic inhibitory capacities in the hyperthyroid mouse. The ontogeny of behavioral arousal and inhibition, as measured by spontaneous locomotor activity, was compared in four experiments for controls and mice injected with thyroxine as neonates. Mice treated with thyroxine at 1-3 days of age had higher activity levels at 10-15 days of age than controls, suggesting potentiation of arousal systems by the hormone treatment. Although thyroxine-accelerated development had no reliable effect upon the age at which peak activity occurred, scopolamine injections increased activity as early as 15 days of age in thyroxine-treated mice, whereas saline-treated or unhandled controls did not show a similar increase until 16-17 days of age. The findings were interpreted as indicating both a potentiation of arousal and a compensatory acceleration of cholinergic inhibitory capacities as a result of the neonatal hyperthyroidism. In addition, the importance of the behaviorally suppressive effects of a novel injection experience in the neonatal mouse was demonstrated.


Effect of subcutaneous vs intraperitoneal administration of an anti-estrogen, CI-628, estradiol-and estradiol benzoate-stimulated lordosis in the ovariectomized rat. The anti-estrogen CI-628 (3 mg) inhibited estradiol (E, 150 mug, SC in oil)-stimulated lordosis in ovariectomized rats, when the anti-estrogen was given intraperitoneally (IP) at the time of E injection (Hr 0). No lordosis inhibition occurred after similar treatment, if the CI-628 was given subcutaneously. For estradiol benzoate (EB, 2 mug, SC in oil)-stimulated lordosis, CI-628 (Hr 0) had a substantial inhibitory effect whether it was given IP or SC, the greater percentage inhibition occurring after SC CI-628 (Experiment 1). All animals received sequential injections of estrogen and progesterone (500 = s,g, SC in oil) and were then tested to 10 mounts by an intact male. These results suggested that, after E injection, neural tissues mediating lordosis have a shorter period of sensitivity to the behavioral effects of CI-628 than after EB injection. Thus, inhibition of E-stimulated lordosis apparently required the more rapid onset of intracellular estrogen retention inhibition resulting from CI-628 given IP rather than SC. This was not the case for EB-stimulated lordosis, where a longer period of sensitivity to CI-628 seeemed likely. This hypothesis was supported by the data of Experiment 2, in which CI-628 (3 mg, IP) was first given 3 hr after E or EB treatment. In this paradigm, CI-628 no longer inhibited E-stimulated lordosis. In contrast, the anti-estrogen's effect on EB-stimulated lordosis was at least equal to the inhibition occurring after CI-628 (IP) given at Hr 0.


Role of noradrenergic and dopaminergic processes in amphetamine self-administration. Dogs were trained to intravenously self-administered d-amphetamine (0.05 mg/kg/infusion) until a stable intake per 4 hr daily session was achieved. When the dogs were given noncontingent infusions of d-amphetamine in varying amounts o% to 100% of the baseline intake) immediately prior to the session, they decreased their self-administration response rate appropriately so that total drug intake remained constant. However, there were not changes in subsequent responding for d-amphetamine following pretreatment with either the noradrenergic agonist methoxamine (0.5-2.0 mg/kg) or the noradrenergic antagonist phenoxybenzamine (1-8 mg/kg).  Additionally, responding was not maintained when methoxamine (0.05 mg/kg/infusion) was substituted for d-amphetamine. In contrast, pretreatment with either the dopaminergic antagonist pimozide (5-40 mug/kg) or chlorpromazine (0.25-2.0 mg/kg) produced dose-dependent increases in the number of self-administered d-amphetemine infustions. These data suggest that noradrenergic neurotransmission is not responsible for d-amphetamine self-administration, but an intact dopaminergic system does appear to be important.


Stimulation of food intake in horses by diazepam and promazine. In two adult horses doses of 0.02-0.03 mg/kg diazepam, intravenously, increased 1 hr intake 54-75% above control levels. Intake was stimulated when the diet was a high grain, calorically dense one and also when the diet was a high fiber, calorically dilute one. Two young rapidly growing weanling horses showed an even more pronounced stimulation of intake. Following diazepam 1 hr intake was increased 105-240% above control lelvels. Promazine at a dose of 0.5 mg/kg also stimulated intake in adult horses, but not as markedly as did diazepam. A transquilizer and a neuroleptic appear to have a stimulatory eff upon short-term intake in horses.


[Giant ulcers with rupture of the anterior tibial artery in a patient with calcinosis and hypercalcemia]. The authors report one case of giant varicose ulcer in a woman aged 85 years, who suffered from diffuse subcutaneous calcinosis, in which, after a period of shooting pain, spontaneous rupture of the anterior tibial artery occurred. Suture of this artery at the base of the ulcer did not hinder healing.


[The physiology of microcirculation].

[The physiology of microcirculation]. Since the work of Harvey and Malpighi, there have been more questions than answers in the physiology of the microcirculation. The microvessels and the interstitial connective tissue form a true functional and structural unit in which the capillary is only a passive feature. It is subject to the constraint of the connective tissue that surrounds it, is only a reflection of the hydraulic conditions above and below it and is a luxury metabolic pathway compared with the importance of the derivative or shortcircuit arteriovenous pathway in which the metarteriole is of major importance. Continual renewal, apparent vasomotor character, and extreme permeability sum up the physiology of the microcirculation. The cybernetics is dominated by the arteriolo-venular functioning and by chain rections. Stasis, the opening of arterio-venous anastomoses, and sludge are the main pathological features. Investigation of capillary function remains difficult under clinical conditions, since different methods give a global picture, that of the vascular-tissue unit.


[Scleroses of the junction of the internal and external saphenous veins. New approach]. Sclerotherapy of sapheno-femoral and sapheno-popliteal junctions has been accepted for many years. However, the author points out the present tendency to refer more and more of those cases to surgery on account of the inherent dangers of such injections and of the difficulty to achieve a solid and long lasting sclerosis. He describes present variations in technic of injection, explains how he discovered a more efficient method: introducing the needle some six cm below the junction and injecting while an assistant (or a free finger) compresses the junction. He describes its applications and enumerates short and long term advantages of this technical refinement.


[The planter neuroma (Morton's disease)]. This a metartarsalgia that is most often found in adult women. The diagnosis is based essentially on questioning the subject who complains of a painful episode: sudden pain, often very intense, occurring while walking, at any time of the day. The evolution takes the form of further episodes that occur at shorter and shorter intervals. Examination shows the pain to be located in an intermetatarsal space, typically the third sometimes the second, with radiation to the two adjacent toes. This syndrome must not be confused with rounded metatarsals where the pain is of a mechanical type and occurs in the heads of the metatarsals. Medical treatment (injections, special soles) is mainly a matter of diagnosis. Treatment of this benign lesion of the interosseous nerve is surgical: excision of the neuroma.


[Retrograde iliocavographie].

[Retrograde iliocavographie]. The authors describe a technique for retrograde phlebography of the lower limbs that involves introducing a Cournand catheter into the superior system via one pf the basilic veins so that it reaches the inferior vena cava, passing through the right atrium. The new feature of this method, which has been previously used by Dow and Gillot, is that the catheter may be passed fairly low into the iliac or femoral veins. Thus with a single catheter it is possible to carry out cavography, bilateral phlebography of the external iliac veins or even the internal iliacs, or bilateral femoral phlebography. The most suitable indications for the this technique include (1) the search for a residual cross after stripping, (2) the assessment of recent iliac thrombosis when there is an indication for surgery, (3) the assessment of a "swollen leg" when there is a doubt in diagnosis between lymphoedema and phleboedema, and (4) the study of deep repermeabilization in cases of post-phlebitic syndrome (before eventual surgery of the saphenous veins). This examination, which should be carried out in a vascular radiology unit; makes it possible to obtain films of good quality that are easy to interpret and that provide a very complete phlebographic assessment.


[Pulmonary embolism as seen by the phlebologist and the cardiologist]. In this article the author follows the fate of a clot from its venous origin, as is the rule--the domaine of the phlebologist--prevention of the different factors of thrombo-embolic disease, the fight against stasis, phlebological care, treatment to prevent platelet aggregation and anticoagulant treatment. The author also considers the point of view of the cardiologist, the diagnosis and treatment of the "pulmonary embolism heart". The phlebologist has the most important role which is preventive; when a cardiologist intervenes in cases of pulmonary heart, although his role may be curative, it is sometimes still disappointing from both the diagnostic and prognostic points of view.


[Quantitative research into vascular function in the lower limbs when these are affected by chronic venous insufficiency or lymphoedema]. Plethysmographic measurements of calf blood flow and venous muscle pump functions have been carried out in two groups of patients. In the first group of patients with chronic venous insufficiency the post ischaemic reactive hyperaemia decreased with the degree of clinical severity. In the other group of patients with primary lymphoedema no hyperfunctionning of the arterial system could be found. In this group the venous pump function was markedly reduced.


[Differential diagnosis of cerebral convulsive seizures in the tetanic syndrome]. An analysis of the types of attacks occurring in tetanus patients shows that epileptic attacks are a relatively frequent occurrence in such patients. In patients under anti-epileptic therapy it is readily possible for the clinical picture to be concealed, and this may then result in irreversible damage due to the disturbance of metabolism remaining uninfluenced. It is recommended that the treatment of patients with cerebral attacks should include measures aimed at preventing the occurrence in them of convulsions resulting from the particular metabolic situation in the case of tetanus. What is also pointed out by the authors in their present paper is that tetanus patients treated with anticonvulsives and particularly disposed sufferers from epilepsy may show a deterioration of the metabolic situation and a loss of stability of the vitamin D metabolism, respectively. Accordingly, it is advisable that regular clinical and paraclinical checks be made in the case of the two syndromes referred to above.


[Position of the delayed-action neuroleptic penfluridol (Longperidol/Janssen) in psychiatric therapy]. Longoperidol/Janssen, an orally administered neuroleptic with a five- to seven-day duration of effects, was clinically tested in six mental hospitals in the G.D.R. where the agent was administered to subjects of chronic to subacute schizophrenia. It was not possible for fully consistent results to be obtained in these tests. Workers at mental hospitals in Leipzig and Mühlhausen recommended that the drug should be imported, whereas those at the four other centers (Dresden, Halle, Jena, and Schwerin) did not consider the medication to be indispensable, although they were also able to observe the good effects of the agent.


[Definition and classification of neuroses]. The content of the concept of neurosis has been subject to repeated change in the course of scientific development, the collective term being still used to describe etiopathogenetically different disease pictures. Leading G.D.R. psychotherapists, in the interest of mutual understanding, have decided to narrow down the term "neurosis" and use it only to describe biographically derivable and psychoreactively produced and sustained disorders of the person-environment relation, thus acting in conformity with the present state of knowledge and following a recent international trend. Neuroses may, in principle, be classified according to different aspects. For the classification of individual forms of neurosis the author and his associates decided to select, as primary criteria, the main etiological factors believed to be chiefly responsible for the actual disease picture, and this was done under etiopathogenetic and at the same time diagnostic and therapeutic aspects. Accordingly, a distinction is drawn between the following four forms, of which two are in group 1 and two in group 2. 1. Neurotic reactions in the two subforms; affective reactions producing enduring effects; functionally fixed reactions; and 2. Neurotic developments in the form of primary and secondary maldevelopments. The above four forms of neurosis were exactly defined operationally, and they are, in general, easily distinguishable diagnostically, differ to a large extent in both course and prognosis, and require different therapeutic approaches.


[Influencing the lack of concentration in hyperkinetic school children with Aponeuron]. The authors, after typologically defining three etiopathogenetically different forms of lack of concentration power, report the therapeutic effects produced by Aponeuron administered to 38 eight- to thirteen-year-old hyperkinetic children lacking adequate concentration power but being of normal intelligence. The results reported in this paper are based upon comparative psychometric tests, valuation scales used by parents and teachers, and the grades received before and after a three- to six-month treatment. They provide statistical evidence of an increase in concentration power and a decrease in both fatigability and motor unrest. Obviously, objections frequently made to the treatment of encephalopathic children with centrally stimulating drugs are not justified providing indication is furnished expertly.


[Cyclothymic depression and performance. Comparison of the efficiency of agitated and non-agitated cyclothymic depression patients on a brief test of severe depression]. Agitated and non-agitated cyclothym depressive patients were compared relative to their results in a short achievement test for measuring degree of depression; the agitated patients worked significantly less slowly in two of the five subtests. These differences may exist premorbidly and can be explained by a theoretical concept of arousal. We propose to control the subject's activational states which -- besides the control of age and intelligence -- might possibly precise the test results relative to the depth of depression.


[Drug abuse and dependence of the amphetamine type with special regard to Amphetaminil (Aponeuron(R))]. In 1974 amphetaminil was included in the class of addictives or habit-forming drugs, although prescription of the drug is not requiring adherence to strict requirements. Whereas reports of abuse of, and addiction to, amphetaminil have been published in foreign countries since 1967, it was not considered a habit-forming drug in the G.D.R. Observations made by the author and his associates show that this may not be true; abuse of, and addiction to, this particular drug are possible in this country, too. The concern of this paper is to call the reader's attention to possible addiction to amphetamine type drugs. Prescription of amphetamines should always be with caution in order to prevent abuse. It is recommended that careful consideration be given to the question of limiting the amount of amphetaminil to be prescribed.


[Psychiatry and EDP. First experience with specialty-specific additional documentation-psychiatry with computer epicrisis]. A supplementary documentation on psychiatry, of which the purpose is to systematically collect certain predetermined patient data, was prepared as part of the electronic data processing project "Basic processes of patient-related information processing" which has been mapped out by workers at the Dresden Medical Academy. A psychiatric "computer-based epicrisis" has been formulated and introduced into daily psychiatric practice. A brief description of documents serving as vouchers is followed by a discussion of the advantages and disadvantages of such a method as well as the basic possibilities of development.


[Treatment of occlusive hydrocephalus with Torkilksen's drainage]. Seventy-three Torkildsen drainages are reported, of which 61 and 12 were performed on tumor patients and in the case of benign aqueduct occlusions due to congenital malformations or chronic inflammations, respectively. The results are quite satisfactory providing due consideration is given to both the basic ailment and the preoperative condition. The Torkildsen drain has proven extremely useful in the therapy of selected cases of occlusive hydrocephalus.


[Dissolutive and non-dissolutive elements in the phonetic disorders of aphasia patients]. The authors, by proceeding on the view that only part of the pathological phenomena may be satisfactorily explained by Jackson's theory of dissolution, have made an analysis of phonetic disorders (sound exchanges) for ten patients with sensory aphasia and mixed aphasia which is a mixture of motor and sensory aphasia. The results of preliminary studies of the ontogenetic occurrence of Bulgarian sounds in the development of the child's language were taken as a base for distinguishing dissolutive from non-dissolutive sound exchanges. It has been found that 36% and 64% of the sound exchanges were dissolutive and nondissolutive, respectively.


[Musical-rhythmic discrimination ability and recall in children with reading and spelling disorders]. Thirty 9- to 11-year-old children of normal intelligence, who are poor readers and spellers, were tested using shortened series of problems of the Seashore test of musical talents as well as Colured Progressive Matrices. Also, the children had to write from dictation using Kossakowski's table of words. All of the problems, with the exception of writing from dictation, were also presented to, and solved by, a correspondingly composed reference group of thirty normal schoolchildren. There were found considerable statistically significant group differences especially in respect of the ability to absorb successions of tones and distinguish between different tone colors and intensities of sound. The importance of these results to the development of methods of early diagnosis is discussed in detail.


[Etiology and pathogenesis of somnambulism]. The problem of somnambulism is discussed in this paper by reference to the present state of research in this field. A complex of conditions is assumed to underly sleep-walking and be triggered by various factors. Psychic or organic moments may trigger somnambulance if there exists a readiness for this form of reaction. The corpus striatum is assumed to control the overall coordination of stereotypic motor movements, which is made an independently functioning subsystem by certain states of tension in the central nervous system.


[Recurrent alternating cranial nerve paralysis as an unusual type of polyneuropathy predilection]. A case is described where relapsing alternating cerebral nerve pareses were frequently observed in the course of twelve years. The neurogenic character of the pareses could be demonstrated by electromyography. The extremities examined also showed signs of subclinical changes of the peripheral nervous system. The results of examinations suggest that the patient has an idiopathic form of polyneuropathy, the clinical manifestation of which is restricted to the cerebral nervous system. The literature on relapsing cerebral nerve pareses is discussed briefly.


Issues in the development of statistical and epidemiological data for mental health services research. The planning of health services consists of a process that generally involves the following steps: (a) situational analysis, or the description, definition and statement of the problem, its characteristics and dimensions in relation to population and time; (b) the formulation of alternative tactical approaches to the handling and solution of the problem; (c) decision analysis or the selection of a plan; (d) discussion and implementation of the plan selected; (e) evaluation of the results achieved in relation to the problem, situations or populations concerned. This paper discusses the content of a programme of mental health services research for collecting and analysing the information needed to apply these processes to the planning of mental health services, monitoring the manner in which the plan is being implemented, and assessing its effectiveness in achieving short-term and intermediate objectives and long-term goals. Statistical and epidemiological information play an important role in these processes, particularly in the situational analysis and the evaluation processes. Illustrations have been provided of types of data that are produced in the national mental health statistics programme in the United States. Difficulties in using such data to answer questions concerning the needs for mental health services, and manpower requirements for delivering services to meet these needs are discussed. In many instances, currently available data are quite inadequate for answering key issues such as these, plus others related to living arrangements of the population, the effect of services on the persons who receive them, their families and the communities in which they live. Thus, much still remains to be done to develop systematic, comparative morbidity statistics on the incidence, duration and prevalence of mental disorders in the general population, on the needs for mental health services, and on the effectiveness of our efforts to prevent disorders that can be prevented, and to reduce the amount of disability and distress caused by those that cannot be prevented or terminated. A series of problems have been identified, the solutions to which would assist materially in providing data that would narrow gaps between available knowledge and that which is needed. The importance of establishing well-staffed research units at the catchment area level with stable funding to accomplish this is underscored. It is a matter of the greatest urgency that adequate resources--financial, manpower, scientific and administrative--be made available to solve these problems. If this is not done, then effordts to document quantitatively the effectiveness of programmes to prevent and control mental disorders will continue to suffer from many of the same shortcomings that have impeded our past and continue to impede current efforts to accomplish this.


The coincidence of schizophrenia and Parkinsonism: some neurochemical implications. The hypothesis has recently been advanced that increased activity of central dopaminergic mechanisms underlies the symptomatology of the schizophrenias. The evidence that dopaminergic transmission in the corpus striatum is impaired in Parkinson's disease suggests that observations on the relationship between Parkinson's disease and  schizophrenia may illuminate the patholophysiology of the latter disease. Four cases are reported in which an illness with schizophrenic features developed in the setting of longstanding Parkinson's disease; attention is drawn to earlier reports of schizophrenic illnesses occurring as postencephalitic sequelae in the presence of a parkinsonian syndrome. These observations appear to conflict with the view that increased dopamine release in the striatum is necessary for the expression of schizophrenic psychopathology, but do not exclude the possibility that increased transmission may occur at other dopaminergic sites in the brain, for example the nucleus accumbens, tuberculum olfactorium or cerebral cortex. Similarly the dopamine receptor blockade hypothesis of the therapeutic effects of neuroleptic drugs cannot be maintained with respect to an action in the striatum in view of the differences between the actions of thioridazine and chlorpromazine in this structure, but may be tenable for actions at extra-straital sites.


Cerebrospinal fluid and plasma free cortisol concentrations in depression. Cerebrospinal fluid (CSF) cortisol levels were examined in a total group of 65 patients. Those who were not depressed (ND), and those suffering from depressive neuroses (DN) had marginally elevated values. Patients with unipolar depression (UD) and bipolar depression (BD) had levels twice as high as the ND and DN patients. Psychotic UD and BD patients had the highest values, three to four times as high as the ND and DN subjects. A significant reduction of CSF cortisol levels was observed following treatment and recovery. Manic patients had moderately elevated CSF cortisol values. The CSF results were in good agreement with plasma total cortisol levels and with urinary free cortisol excretion. Age and sex effects were not responsible for the observed differences; similar results were found in patient subgroups studied in Australia and in the United States. Preliminary equilibrium dialysis data are presented for plasma and CSF cortisol binding. CSF cortisol was 20% bound and 80% free. Plasma free cortisol levels were in good agreement with CSF free cortisol values. Depressed patients have increased tissue and central nervous system (CNS) exposure to free, physiologically active glucocorticoids. The appearance of severe depressive symptoms which manifest a diurnal rhythm may be determined in part by excesssve CNS exposure to glucocorticoids.


The influence of childbirth on psychiatric morbidity. The Camberwell Psychiatric Register was searched for contacts by the 2257 women resident in the register catchment area who were known to have had a child in 1970. Of these, 99 women (and 39 of their husbands) were found to have had a 'new episode' of psychiatric illness in the two years before or the two years after the birth of their child. The distribution of these 'new episodes' relative to the time of childbirth was then studied. In the women, both functional psychoses and depressive illnesses showed a sharp rise in the new episode rate in the three months immediately after delivery. There was also a suggestion of a secondary rise, less dramatic but more sustained, from the 10th to the 24th month after delivery. There was no comparable rise in the husbands. Women whose children were illegitimate had high new episode rates throughout the four-year study period, but not particularly so in the puerperium itself.


Cerebral function and the EEG in psychiatric disorder: a hypothesis. Independent studies which showed a difference between the EEG frequency spectra of test and control groups have been compared. Some of the test groups included schizophrenic patients, others comprised groups with dyslexia, reading disability and left preference. The EEG differences between the test and control groups are shown to be similar across the studies. It is suggested that the common attribute of the test groups relates to the functional organisation of the brain and that investigation of EEG correlates of this phenomenon may be of value to research into the biological basis of psychiatric illness.


The aetiology of childhood autism: a criticism of the Tinbergen's ethological theory. Kanner's descriptions of the children showing the abnormal behaviour pattern he observed and named "early infantile autism" are summarized. E.A. and N. Tinbergen's ethological theory of the aetiology of this syndrome is outlined and criticized. The major problem in evaluating this theory, apart from the absence of any evidence in its favour, is the lack of precision with which the Tinbergens use the terms "autism" and "Kanner's syndrome".


Symptoms of depression in two communities. Histories of depression-related symptoms were obtained from 3845 randomly selected adult residents of Kansas City, Missouri, and Washington County, Maryland. Depressed persons were slightly more common in Kansas City than in Washington County but within the latter area no urban-rural differences were observed. More depressed persons were found among blacks than among whites. Slightly more white females than males were depressed; no significant differences were found between black females and males. After adjustment for the effects of other independent variables, the probability of having symptoms of depression was highest among persons who were young adults, unmarried, not employed outside the home, poorly paid, and not well educated.


Psychiatric morbidity in general practice and the community. The "General Health Questionnaire" was used to assess the psychiatric morbidity among 365 consecutive attenders at a general practice and to compare this with a systematic random sample of 213 patients drawn from the lists of the same practice. Those attending a general practitioner are shown to be more psychiatrically disturbed than a random sample of the practice population, and this difference remains when those attending for psychological symptoms are discounted. Various social and demographic characteristics which distinguish between those who do and those who do not attend a doctor with a given set of psychological symptoms are described.


General practice aspects of self-poisoning and self-injury. A sample of individuals who had carried out acts of self-poisoning or self-injury were interviewed and information was also obtained from their general practitioners. More of both the men and the women had visited their general practitioners in the year before the acts than would have been predicted from national statistics, although this was not found to the same extent for persons aged 16-24. Thirty-six per cent of the sample had contacted their general practitioners during the week before the act and over 60% in the month beforehand. Sixty-three per cent had visited them for a variety of psychiatric and social reasons during the preceding year and had nearly all been prescribed psychotropic drugs, usually tranquillizers or sedatives. These were commonly the drugs taken in acts of self-poisoning. Methods of prevention are discussed.


An evaluation of an interview assessment of marriage. An interview assessment of marriage relationships is described. It is shown to have good inter-rater reliability, high consistency across the accounts of both marriage partners and to be resistant to methodologic bias. A four-year follow-up study demonstrated high predictive validity to later marriage breakdown. The marriage measure also showed a strong association with behavioural deviance in the children. The intercorrelations between individual measures of various aspects of the marriage and the summary are given. A shortened version of the interview is described and preliminary findings are given on its validity.


Observer variation and depressive phenomenology. An investigation into observer variation and depressive phenomenology is described. A group of 6 clinicians independently completed a 43-item sheet for 20 depressed patients at the same clinical interview. The coefficient of agreements on the items are given. Patient variables and observer variables did not have any influence on the degree of agreement. There was also an agreement in the subtyping of depression.


Systematic self-assessment by P.Q.R.S.T. (Personal Questionnaire Rapid Scaling Technique). This paper presents a Personal Questionnaire which is sufficiently simple for use in most clinical settings. Following a brief description of Personal Questionnaires, their origin and background are discussed and some subsequent developments delineated. The method involves the use of a general set of adjectives which can be used to qualify the symptoms experienced by any given patient. Successive measurements of the symptoms can be made so that changes in their subjective intensity can be monitored. The internal consistency of ratings of each symptom on each occasion is used as a measure of reliability. As with all previous Personal Questionnaires the symptoms which are measured are unique to the individual, but unlike other methods the format of this Questionnaire is predetermined, which ensures its simplicity and ease of use.


A method for decreasing patients' medication errors. Eighty anxious and eighty depressed patients were assigned randomly to receiving one of three versions of an information leaflet about their medication, or to receiving no leaflet at all. Mean medication errors were reduced from 15 to 4% by provision of suitably constructed leaflets. The results show the practical importance of informing patients about their medication and of paying attention to the difficulty level of any leaflets issued.


"Dieters" and "vomiters and purgers" in anorexia nervosa. Thirty-one females with primary anorexia nervosa were studied by means of a retrospective analysis of hospital notes. The patients were divided into 2 groups. The first group consisted of subjects who had become emaciated solely because of dieting, food refusal and excessive exercising ("dieters"); the second of those who had used additional means to bring about weight loss such, as habitual vomiting and the abuse of purgatives ("vomiters and purgers"). Most "dieters" were intense, introverted, socially withdrawan individuals whose anorexia behaviour had started in response to psychological stress. They had become completely preoccupied with thoughts of food, eating and losing weight. Several did well in treatment, and recovered fully from their anorexic symptoms. "Vomiters and purgers", on the other hand, were more outgoing in respect to personality. Most had previously been obese and, as they had been unable to keep themselves thin by simply abstaining from food, they had learnt to use other means to control their weight. These latter patients did less well in treatment. They continued to experience difficulty in controlling their weight, and the majority persisted with their abnormal behaviour.


Psychopathic personality: a conceptual problem. The concept of psychopathic personality is currently being called into question. Grendon prison has been established for the treatment of psychopaths. A recent study of Grendon prisoners enabled an examination of some characteristics commonly attributed to psychopaths to be carried out. It proved difficult to obtain good agreement in rating such phenomena as "conscientiousness", "sexual deviation", "impulsiveness". Of ten reliable variables including "personal relationships", "lying", "alcohol problem", only five bore a significant relationship one to another. It was concluded that whilst the term "psychopathic disorder" may be appropriate for a small handful of individuals the term is probably now used too widely and too loosely.


The learning of motor movements: a neurostatistical approach. From a factor analysis of data from a learning experiment evidence is presented which appears to support the Blomfield-Marr thesis that in the learning of motor actions the cerebellum operates by the turning off of incorrect movements rather than by the turning on of correct ones. The factor model employed is that due to Godfrey Thomson which gives a neurostatistical explanation of the origin of mental factors.


A technique for studying psychiatric morbidity in in-patient and out-patient series and in general population samples. Many surveys of general populations have suggested a high untreated psychiatric morbidity, vairously referred to as mental illness, pre-clinical neurosis, minor neurosis, untreated depression, etc. An Index of Definition psychiatric disorders is described which incorporates cut-off points on the basis of symptoms rated in the Present State Examination. Eight degrees of definition are specified. At the "borderline disorder" level and above, disorders are sufficiently well defined to apply the CATEGO program of clinical classification. This procedure enables in-patients, out-patients and samples of the general population to be compared. Data from surveys in south-east London are presented in order to illustrate the technique. The main conclusion at this stage is that it is possible to identify, by strictly defined and repeatable procedures, a substantial proportion of people in the general population who have "borderline disorders" that can be tentatively classified in terms of the ICD. Whether it is clinically useful to do so requires further investigation. It is also suggested that techniques of this kind can be scientifically useful in comparing the level of morbidity in various populations, both referred and non-referred, and in testing theories concerned with the causes and treatment of various types of psychiatric disorders.


The communication of affection between cancer patients and their spouses. Thirty-eight patients receiving chemotherapy for advanced cancer and 37 of their spouses were studied to assess changes since illness in the desire for affection (sexual, physical, and verbal) and changes in actual affectional behavior. Each participant in the study was interviewed and then completed the Beck Depression Inventory and an Affectional Needs and Behavior Scale. Results indicated that patients and spouses of both sexes experienced simultaneously an increase in the desire for physical closeness and a decrease in the desire for sexual intercourse. Women patients and their husbands were in greater agreement regarding the changes assessed than were men patients and their wives. In addition, women patients reported the highest level of depression, but were more likely than the other groups to have their affectional needs met. Interpretations of these findings and implications for the management of patients in advanced stages of life-threatening illness are discussed.


Newborn heart rate and blood pressure: relation to race and to socioeconomic class. The effect of race and of socioeconomic class upon heart rate and systolic blood pressure distributions was examined in 247 full-term, appropriate birth weight newborns. For each newborn, heart rate and blood pressure measurements obtained during all of the non-rapid-eye-movement (NREM) periods of sleep in a single test session were each averaged. Heart rate was significantly faster in black newborns than in white newborns, and this racial difference in heart rate was similar in upper socioeconomic class subjects as in lower socioeconomic class subjects. Newborn systolic blood pressure did not vary as a function of race or of socioeconomic class. Systolic blood pressure correlated positively with the number of feedings from birth, the total fluid intake from birth, and the total sodium ingested from birth.


Sexual life and sexual frigidity among women developing acute myocardial infarction. The various aspects of the sexual life of 100 female patients aged 40-60 with acute myocardial infarction were compared with those of a control group of 100 female patients of the same age, hospitalized for other diseases. Sexual frigidity and dissatisfaction were found among 65% of the coronary patients as compared with 24% of the controls. The commonest cause for sexual dissatisfaction was premature ejaculation or impotence in the husband. The incidence of premarital sexual relations was greater among the frigid patients when compared with those who achieved orgasm. The coronary patients had an earlier menopausal age than the controls. The number of coronary patients who underwent artificial abortions in the past was lower than in the control group. All these findings were statistically significant at a level of P less than 0.05. No connection was found between extramarital relations and sexual frigidity. There was no relation found between sexual frigidity and diabetes, essential hypertension, marital status, pathological gynecological findings, or localization of the infarction. Until now, sexual frigidity and dissatisfaction appear to have been a neglected aspect in the female coronary patient.


Estimating one's own systolic blood pressure: effects of feedback training. This study was aimed at discovering the ability of subjects to estimate absolute levels of systolic blood pressure after feedback of daily blood pressure information. Twenty-one subjects were studied who had shown a variation of at least +/- 20 mm Hg in systolic pressure during 8 days of base-line measurements. Subjects' estimates were found to be moderately accurate even before any specific blood pressure information feedback was given (mean error was +/- 12.4 mm Hg). Then during 15 days of information feedback, subjects' accuracy improved, e.g., for 10 subjects who were given correct information feedback the mean error was +/- 7.4 mm Hg, a highly significant improvement. This is a high degree of accuracy-especially in comparison with the mean variation of +/- 5.8 mm Hg from 1 min to the next in their systolic blood pressure. The learning of one's range of blood pressures appeared to be the principal component of the improvement. Range information had been provided by giving the subject his range of fluctuation for the 8-day base-line period, and by daily blood pressure information feedback immediately after each estimate. Two types of estimators were distinguished: Those who were relatively accurate versus those who were inaccurate in estimating at their own extremes of blood pressure. Those who were inaccurate at their own extremes (1) paid less attention to the feedback of information they were provided with as well as to the internal cues from their own blood pressure and (2) were more field independent.


Clinical, biological and pathogenic features of the syndrome of inappropriate secretion of antidiuretic hormone. A review of 26 cases with marked hyponatraemia. Twenty-six patients with the syndrome of inappropriate secretion of antidiuretic hormone were reviewed. The underlying diseases were bronchogenic carcinoma (12 cases); myxoedema (five cases); diseases of the nervous system (five cases); bronchopneumonia, carcinoma of the oesophagus, acute intermittent porphria and chlorpropamide therapy (each one case). Serum sodium levels ranged between 104 and 125 mEq per litre. Eighteen patients presented neurological manifestations, which in 14 were considered to be due to hyponatraemia. Neurological signs included disorders of consciousness (stage I and II coma), extrapyramidal signs, asterixis and epileptic seizures. An hyponatraemic coma was the first manifestation of the syndrome in five cases. In all cases where the EEG was recorded it showed non-specific signs of metabolic coma. The fundi never showed signs of intracranial hypertension. Blood urea and creatinine levels were invariably low in the euthyroid patients; these values were normal or elevated in patients with myxoedema and hyponatraemia. Hypokalaemia was frequent, and hypocalcaemia constant. In eleven cases an excess of water intake revealed the clinical syndrome: six patients were excessive beer drinkers and five had received extensive intravenous infusions. In one case the deleterious effect of diuretics was evident, and in another, the syndrome became evident during radiotherapy of an oesophageal tumour. Treatment of the syndrome was successful in all cases. A review of the literature concerning the various pathogenic mechanisms corresponding to the different underlying diseases is presented. The concept of aberrant hormonal production by a tumour is illustrated by an electron microscopic study.


Paraquat poisoning: new aspects of therapy. Clinical, laboratory, and pulmonary physiologic features of three fatal cases of paraquat poisoning are presented. Experimental investigations and clinical experience would suggest several possible means of modifying paraquat toxicity. The following specific therapeutic interventions, several of which had previously been applied only in experimental circumstances, were used: (1) inhibition of absorption of paraquat with Fuller's Earth and catharsis by magnesium sulfate, (2) elimination of absorbed paraquat by hemodialysis with ultrafiltration and forced diuresis, (3) competition by d-propranolol for tissue binding sites, (4) modification of direct pulmonary tissue effects of paraquat by hypoxic breathing mixtures, superoxide dismutase, and corticosteroids. Treatment was unsuccessful. However, our clinical experience and data concerning paraquat concentration in body and dialysis fluids suggest a therapeutic approach aimed at preventing early and progressive tissue damage. A combination of Fuller's Earth and magnesium sulphate should be used immediately and in frequently repeated doses to prevent absorption. Diuresis and haemodialysis should be instituted as soon as possible to increase excretion. Hypoxic atomspheres should be created urgently to produce a PaO2 of 40-45 mmHg, and the use of superoxide dismutase be further investigated. It is hoped that the high mortality of paraquat poisoning will be modified by this combined approach of early and intensive treatment.


Familial aspects of coeliac disease.

Familial aspects of coeliac disease. The incidence of coeliac disease amongst first-degree relatives of 115 patients with coeliac disease aged between nine and 75 years has been studied. Of 689 relatives 526 were living of whom 324 were willing to be investigated. One hundred and eighty-two relatives underwent jujunal biopsy. Forty-one were considered to have coeliac disease, 22 per cent of those biopsied, or 11-2 per cent of the available relatives. One-third of the relatives discovered to have coeliac disease were asymptomatic but all had at least one abnormal result amongst the laboratory indices used. Twenty-two per cent of the relatives with haemoglobin less than 13-0 g, 43 per cent with serum folate less than 3-0 pg/ml, 24 per cent with serum albumin less than 4-0 g/100 ml, with serum iron less than 60 mug/100 ml or with serum alkaline phosphatase above 13 K.A. units had coeliac disease. Less than 5 per cent of relatives with H.L.A. antigens other than H.L.A. 8 had coeliac disease compared with one in four of those with H.L.A. 8. The high percentage of relatives with H.L.A. 8 antigens or with anticonnective tissue antibodies, amongst those with non-specific biopsy appearances suggests that these groups also contain a number of relatives with varying degrees of gluten intolerance.


Pneumococcal meningitis: a clinical and laboratory study. Forty-two patients who were admitted consecutively with pneumococcal meningitis during an 18-month period were studied in Ahmadu Bello University Hospital, Zaria, Nigeria. The disease was seen most frequently in older children and young adults. A predisposing condition was found in only four patients. Counter-current immunoelectrophoresis was found to be a rapid and effective method of diagnosis: pneumococcal polysaccharide antigen was found in the initial cerebrospinal fluid (CSF) sample from all but one of the patients. Detailed physiological studies carried out in two patients showed profound disturbances of cerebral carbohydrate metabolism and an increase in cerebral vascular resistance. Twenty patients died (48 per cent) in spite of treatment with large doses of penicillin. A fatal outcome was associated with impairment of consciousness on admission, a low CSF white cell count and a high CSF antigen titre. It is suggested that marked changes in cerebral carbohydrate metabolism, and perhaps vascular damage, play important roles in producing severe brain damage in patients with pneumococcal meningitis and that defective CSF polymorphoneutrophil leukocyte function may contribute to the failure of the infection to respond satisfactorily to antibiotic therapy.