The British system for anticoagulant control.

The British system for anticoagulant control based on the use of a national reagent with a national system of reporting supported by national quality control using lyophilized plasma preparations appears to offer a model which many countries abroad seem interested in adopting to solve their own national problems. Good progress has already been made in this direction in some Commonwealth countries and in South Africa. At a symposium at the 3rd Mediterranean Congress on Thromboembolism in 1973 invited participants from all over the world agreed to set up an International Study Group to provide an international organisation for anticoagulant control, and an encouraging start has been made.


A simplified thromboplastin calibration procedure for standardization of anticoagulant control.

In thromboplastin calibration, the possibility of replacing fresh individual plasmas by pooled fresh plasmas (used immediately after preparation or after storage at -25 degrees C) or by pooled lyophilized plasmas has been investigated. It was found that the thromboplastin sensitivity ratios (TSR's) assessed with pooled fresh plasmas show no divergence from those obtained with the original Biggs/Denson calibration procedure. With pooled lyophilized plasmas a small divergence can be found in particular with so-called PIVKA-insensitive rabbit-tissue thromboplastins. Since, in contrast to the original procedure, only a limited number of determinations with pooled fresh or lyophilized plasmas are needed to obtain an accurate TSR value, the modification substantially simplifies thromboplastin calibration. Moreover, the technique using lyophilized plasmas can be applied in laboratories where an insufficient number of patients are available or none at all. However, as long as pooled lyophilized plasmas display a more or less pronounced activation, it might be preferable to restrict calibration to qualified expert laboratories, i.e. national reference laboratories. The merits of pooled lyophilized plasma are those of good stability even under the condition of accelerated degradation. They might be just as useful as thromboplastins for use as (long-term) reference material in the standardization and quality control program of manufacturers of thromboplastins, and for laboratorians preparing their own thromboplastin for the anticoagulant control. Conditions for the preparation and use of lyophilized reference plasmas have been worked out and are presented.


The role of vitamins in hemostasis.

The physiological mechanism to prevent and control abnormal bleeding is dependent on three vitamins (C, K, and Q). Two of these are unequivocally established as essential for hemostasis while the existence of the third (Q) is supported by experimental evidence and by clinical and therapeutic observations (Quick 1972; Quick 1974). The interrelationship of these three vitamins has remained moot except for clue observations. Both vitamins C and K have a key structure in their molecules which supplies a redox mechanism, ascorbic acid and 2-methyl, 1,4-naphthoquinone, respectively. Both vitamins are concerned with growth. Lack of vitamin C, which clinically is the basic defect of scurvy, does not appear to cause a defect in blood coagulation while vitamin K affects the clotting mechanism by being essential for the production of four distinct clotting factors: prothrombin, factors VII, IX and X. In this presentation an attempt is made to correlate the action of the vitamin K-dependent clotting factors grouping them in a diagram to show how two systems of thrombin formation exist, one being essentially intrinsic, the second extrinsic requiring tissue thromboplastin and factor VII. The possible interlocking of vitamin Q in this mechanism is presented.


Haemophilia A in a patient with testicular feminization.

A case of typical haemophilia A in phenotypically "hairless" women aged 18 with complete testicular feminization (primary amenorrhea, absence of palpated gonads, negative sex chromatin, fluorescence of Y chromosome in interphase nuclei, caryotype 46, XY by common and fluorescent methods) is reported in this paper. Both diseases are of familial character with transmission through female line. The propositus' father did not suffer from haemophilia. Signs of Morris syndrome (delay of menses, absence of secondary hair) are present in the propositus' mother and sister. The propositus' niece, the daughter of her sister, also suffered from testicular feminization, but without any haemophilia, probably due to the crossing-over. The analysis of the pedigree gives no information in favour of sex-linked or autosome-dominant sex limited inheritance of testicular feminization. Haemophilia A in the propositus is characterized by the very low factor-VIII level-1.66%, and typical joints bleedings since 3 years. At the age of 18 the patient had major surgery for a haemophilic thigh pseudotumor. There was rapid consolidation of the fracture and contracture was erradicated. In spite of severe factor VIII deficiency the course of haemophilia in the propositus is clinically milder than in male haemophiliacs in her family and in the general population. The similar findings were reviewed in literature including the case of hemyzygous haemophilia with testicular feminization and described women-homozygotes. The suggestion is made that the course of haemophilia in the propositus is affected by the female phenotype. The psychologica status of the patient and the possibility of professional rehabilitation by surgical treatment is discussed. The need for detailed cytogenetical examination of the persons with "female" haemophilia or the other sex-linked diseases to establish the correct diagnosis and for exclusion of the possible mosaicism is discussed.


The effect of brinase on fibrinogen in vivo.

Brinase infusions in man cause, without excessive lowering of the inhibitor capacity, a slowing of the fibrin polymerization. This is combined with a degradation of the A alpha chain into two major fragments. Both fragments carry crosslinking sites. Brinase infusion also causes positive ethanol gelation. Evidence for the formation of gamma dimers was found.


Assay of brinase inhibitors with soluble and insoluble substrates.

Two methods for the assay of brinase inhibitors are compared. Neither provided a reliable means of brinase dose prediction. Overdosage can, however, be avoided by preinfusion inhibitor assay.


Sodium acetate buffer: a diluent of choice in the clot lysis time technique.

Sodium acetate buffer, 0.12 M, pH 7.4 as a diluent in the low temperature technique of dilute clot lysis time, is more effective in accelerating the velocity of lysis than phosphate buffer of similar pH and molarity. A uniform shape of the clot is maintained throughout the digestion in sodium acetate buffer and the end point of lysis is characteristically marked by an abrupt and sharply defined disintegration. Sodium acetate buffer can be employed advantageously in this technique not only to improve the observation but also to shorten the lysis times.


The inhibition of urokinase by aromatic diamidines.

1. Structure-activity  relationships have been established for the inhibition of urokinase by aromatic diamidines. In an assay system employing purified urokinase and human plasminogen the most potent inhibitor was found in 4',4''-diamidino-2-hydroxy-1,4-diphenoxybutane which proved 5600 times more active on a molar bases than epsilon-aminocaproic acid (E-ACA). 2. 4',4''-diamidino-2-hydroxy-1,4-diphenoxybutane behaved as a competitive inhibitor of the urokinase catalyzed hydrolysis of N-alpha-acetyl-L-lysine methyl ester. At pH 7.85 and 37 degrees C the K-1 value was determined as 3.18 times 10-6 M which compares with a value of 6.79 times 10-5 M for p-aminobenzamidine and 3.57 times 10-2 M for E-ACA. 3. In two fibrinolytic tests including urokinase as activator the superiority of diamidines over E-ACA was less marked than in the pure plasminogen activation system. This was due to the presence of certain plasma proteins in the fibrinolysis assays which augmented the inhibitory strength of E-ACA. The order of effectiveness of diamidines in the lysis tests was also different from the one in the activation test. In a human fibrin clot lysis test the most active inhibitor was 3',3''-diamidino-2-hydroxy-1,4-diphenoxybutane which was 1700 times more effective on a molar basis than E-ACA. In a human plasma clot lysis test the strongest inhibitor, 2-hydroxy-stilbamidine, was 70 times more powerful than E-ACA.


The effect of fatty-acid autoxidation products on blood coagulation.

Polyunsaturated fatty acids were allowed to autoxidise in air over 4 days. The water soluble oxidation products were extracted at daily intervals and tested for their effect on blood coagulation. After 1 day there was slight acceleration of the recalcification and RVV times, but from 2-4 days the extracts became increasingly inhibitory. The P.T. and P.T.T. were also inhibited. In the thrombin generation test the extracts delayed the appearance of thrombin, but the peak thrombin level was increased and its rate of decay was reduced. When added to phospholipid the extracts altered their coagulant activity. The presence of autoxidation products could account for some of the variable results obtained with different preparations of phospholipids.


Essential athrombia: study of a new case.

A constitutional platelet function disorder in a twelve year-old girl characterized by a lifelong bleeding tendency, prolonged bleeding time, normal platelet count, normal clot retraction, normal platelet factor 3 activity and impaired platelet aggregation was reported. Platelet aggregation, studied turbidimetrically, was absent in the presence of usual doses of ADP (1-4 MUM) although a small wave of primary aggregation was obtained by very large ADP concentrations (25-50 muM). The platelets were also unresponsive to epinephrine, thrombin and diluted collagen suspensions. But an almost normal aggregation response occurred with strong collagen suspensions. The platelets responded to Ristocetin. Release of platelet ADP was found to be normal by collagen and thrombin, but impaired by kaolin. Platelet fibrinogen content was normal. The present case, investigated with recent methods, confirms the existence of a type of primary functional platelet disorder characterized solely by an aggregation defect, described in 1955 and 1962 under the name of "essential athrombia."


The effect of noradrenalin infusion on plasma and platelet lipids and platelet function in man.

Noradrenalin was given as an intravenous infusion in a dosage of 0.1 mu-g/kg/h over a period of 30 minutes to 5 healthy male subjects. Blood samples were collected before, at the end of and 24 hours after the infusion. A significant increase in the number of circulating platelets and a marked increase of plasma FFA, reflecting an increase of all the main components of the FFA fraction were observed. No significant changes were observed in the similar lipid fraction in platelets and except for a moderate increase in platelet factor 3 activity, no significant changes in other platelet function tests were present.


Heterogeneity of rabbit platelets. IV. Thrombocytosis with absolute megathrombocytosis in phenylhydrazine-induced hemolytic anemia in rabbits.

Intravenous injection of phenylhydrazine into intact rabbits resulted in a thrombocytosis of 1.85 fold and megathrombocytosis (large platelets) of 2.30 fold. Splenectomy markedly impaired this response. The intravenous injection of red blood cell hemolysates gave a response similar to that of phenylhydrazine in both intact and splenectomized animals. Basal data obtained from intact and splenectomized animals; as well as kinetic data obtained following apparent splenic blockade secondary to phenylhydrazine hemolysis revealed the presence of a splenic platelet pool with preferential splenic sequestration of megathrombocytes. It is suggested that the thrombocytosis and absolute megathrombocytosis of hemolysis is due to splenic blockade by red blood cell hemolysate.


The effect of oral contraceptive estrogen on blood coagulation and fibrinolysis.

The changes of fibrinogen, antithrombin activity, spontaneous fibrinolytic activity, plasminogen and fibrinogen degradation products were studied in women, aged 18 to 30 years, who were using oral contraceptive preparations. Blood samples were obtained before use, as well as during the first month and again after several months of use. The results were divided into three groups based on the antiovulatory activity of the estrogen component of the oral contraceptive, ie. Mestranol, 50 mu-g, Mestranol 80 mu-g or Ethinyl estradiol 50 mu-g and Mestranol 100 mu-g. In each of the three groups there was a similar pattern of increase in spontaneous fibrinolytic activity and plasminogen but decrease in antithrombin levels during the monthly cycles. The fibrinogen level was increased in the first month of oral contraceptive use in the three groups but after several months of use the pattern of change seen in the first month was repeated with the lower estrogen compounds, but in the group using the preparation with 100 mu-g Mestranol, the fibrinogen level returned to that of the control month. The level of fibrinogen degradation products remained unchanged.


HL-A antigens in congenital rubella and the role of antigens 1 and 8 in the epidemiology of natural rubella.

Study of 87 patients (53 adults, 23 males; 34 children, 18 males) with congenital rubella revealed an increased incidence of several HL-A antigens, including HL-A5, HL-A1, HL-A3 and HL-A8, the frequency of HL-A1 being raised because of the statistically significant increase of this antigen in the adult female subjects compared with normal controls. Correlation of the level of seropositivity to rubella virus in 29 normal adult populations, according to racial origin and geographic location, with the frequency of various HL-A antigens revealed the most significant association with HL-A1 (r equals 0.71). It is suggested that the presence on the cell surface of HL-A1 or the combination of HL-A1 and 8 may fovour rubella virus infection.


The association between HL-A antigens ankylosing spondylitis and sacro-iliitis.

The second series antigen W27 has been found to have an increased frequency in ankylosing spondylitis (82 per cent of 17 patients) and juvenile rheumatoid arthritis (Still's disease) (29 per cent of 24 patients). Three family studies are presented, including one in which the antigen W27 occurs both in the absence and the presence of ankylosing spondylitis. It is suggested that this family illustrates that the relationship between W27 and sacro-iliitis is affected by non-HL-A genes. The development of clinical disease depends upon the coincidence of several factors in one individual, some of which are genetically controlled by two or more loci which are not necessarily linked.


The HL-A gene structure of Twareg populations. II. The Kel Dinig.

The HL-A groups of 138 Kel Diniq Twaregs were determined by the platelet complement fixation microtechnique. Their HL-A characteristics, compared to those of Caucasoid populations, are: decrease in HL-A2, 9, W17 and W15; increase in W28, W32, HL-A7, W5, W10 and second locus blank; absence of Da25 (W30 plus W31), HL-A13, W15, W18, W27. This genetic structure is in accordance with the isolated condition of this population. The most frequent haplotypes are W28,HL-A7, common to both the Kel Diniq and the Kel Kummer Twaregs previously studied; W32,W10 and HL-A3, HL-A5, Kel Diniq only. These two populations are both isolates, with a common origin the seventeenth century, but separated as from that date. Genealogical studies have enabled the haplotype W28,HL-A7 to be attributed to the two brothers who founded the populations in the seventeenth century. A comparison of these two populations constitutes a model for the study of genetic drift and the founder effect.


Comparative immunogenicity of HL-A antigens: a study in primiparas.

A comparison of immunogenic strength among 23 HL-A antigens was made by studying HL-A antibodies formed in primiparous women. In this setting of single pregnancies, each one of the incompatible fetal antigens would have an equal opportunity (one gestational period) to sensitize the mother. Three hundred pairs of primiparous women and newborns were HL-A typed and the serum of each mother was tested for antibody activity against the child's lymphocytes. The test was positive in 24 instances; 19 sera were reactive with only one antigen of paternal origin, one serum was reactive with both antigens, and in four instances the children's incompatible antigens were identified. When the frequencies of different antibody specificities were statistically analysed, HL-A5 and W14 were found to be distinctly more immunogenic than the other antigens.


HL-A  antigens and thyrotoxicosis.

HL-A phenotypes were determined in 60 patients with primary thyrotoxicosis and in 60 age-sex  matched controls living in the same region in order to establish the frequencies of ten HL-A antigens in the two populations. HL-A1 was present in 28 patients and 18 controls (X2 equals 2;86, P greater than 0,05); HL-A13 was present in eigth patients and only one control (X2 equals 4.32, 0.05 greater than P greater than 0.025). These findings suggest that HL-A phenotypes may be of value in studies on the aetiology of primary thyrotoxicosis. The statistical significance of these results is discussed as these findings may be due to chance deviations.


Production of anti-W24 xenoantisera in rabbits.

One out of four rabbits injected with partially purified soluble HL-A antigen from serum produced cytotoxic antibodies to human lymphocytes. These antibodies appear to be directed to the specificity W24 as determined by correlation studies with HL-A alloantisera and by absorption-inhibition experiments with human platelets and with serum soluble HL-A antigens. In the sera from the other three immunized rabbits, no antibodies to human lymphoid cells could be detected by the cytotoxic test, blocking of T cell rosette formation, stimulation of DNA synthesis and inhibition of mixed lymphocyte reaction.


Burkitt's lymphoma and HL-A antigens.

Studies were carried out on the distribution of HL-A antigens in 33 patients with Burkitt's lymphoma from several tribal groups in Kenya. The frequency of distribution of the HL-A antigens was not significantly different in these patients from that in a selected control population. Difficulty was experienced in the precise identification of some HL-A antigens in Africans using a Caucasoid serum panel, in particular those associated with HL-A7 and to a lesser extent, the "W19" complex.


HL-A and Burkitt's tumour--a study in Uganda.

Thirty-one Burkitt's patients and forty-eight matched controls from Uganda were HL-A typed to investigate possible antigen frequency differences which could suggest association of an HL-A antigen with disease susceptibility. Cells were shipped in tissue culture medium from Uganda to Oxford where they were HL-A typed using sera from the Fifth International Histocompatibility Workshop in the cytotoxic fluorochromatic assay. No significant frequency differences between patients and control were found.


Combined analysis of three studies of patients with Burkitt's lymphoma.

Data from the three preceding studies on the possible relationship of HL-A type with Burkitt's lymphoma were combined to see whether any trends in the data, not significant in the individal studies, would show significance when the three groups were combined. A statistical method for combining data from different studies is developed. Although in this analysis even the combined data failed to show any significant association of HL-A type with  disease, it is suggested that the statistical methods used will be helpful in analysing other sets of data where it seems desirable to combine information from several studies.


Papain-solubilized Ag-B antigens. I. Isolated and characterization of two components composing Ag-B antigens.

Ag-B antigen molecules of about 59,000 daltons were partially purified from papain digests of liver cell membranes of Fischer and ACI rats. These preparations were radioiodinated and the labeled Ag-B antigen molecultes were isolated as specific immune complexes with alloantibodies directed to Ag-B1 or Ag-B4. These specifically purified Ag-B antigen molecules were found to give two fragments of 37,000 and 11,000 daltons on sodium sulfate-acrylamide gel electrophoresis. The two fragments (or very similar ones) were isolated from the radioiodinated partially purified Ag-B antigen preparations by acid dissociation and subsequent gel filtration. The 37,000-dalton fragment retained the same Ag-B alloantigenic specificity as the parental 59,000-dalton Ag-B antigen molecules, whereas the 11,000-dalton fragment did not carry any detectable Ag-B alloantigenic activity. In the reaction with rabbit antisera raised against rat cell membranes, each fragment was shown to be antigenically distinctive.


Lymphocyte stimulation with skin cells. A function of maturation.

Cell monolayers grown from trypsin dispersions of whole rat embryos were tested for their capacity to stimulate allogeneic rat thymus cells in mixed cell cultures. Cells from whole embryos of only 15-days gestation were virtually ineffective at stimulating allogeneic thymus cells. Cells from 19-day-old whole embryos produced definite stimulation and stronger stimulation was obtained with skin cell monolayers prepared from these embryos. The average amount of allogeneic stimulation obtained with rat skin cells increased with the age of the donor animals. The greatest degree of stimulation occurred when the skin cells were obtained from rats about 1 week postpartum. Thereafter, the stimulating potential of allogeneic skin cells declined and was found to stabilize at the levels observed when adult skin cells were used as the stimulator cells. Neither rat brain cells nor rat kidney cells (taken from embryos, neonates, and adults) were capable of inducing allogeneic rat thymocytes to undergo significant transformation in culture. We conclude that the in vitro lymphocyte response to skin cell stimulation is a function of skin cell maturation, and that the inability of kidney cells or brain cells to provoke the same sort of stimulation is not attributable to antigen loss during or after foetal development, but exists as a feature of these cells at the earliest stages of differentiation.


Radiology and disease patterns in Malaysia.

The organisation of the radiological services in Malaysia is described and those diseases in which radiology plays an important part in diagnosis are discussed. As radiology embraces all specialities a pattern of diseases emerges which is different from that seen in the West. The control of infectious diseases, the general improvement in health care and the more sophisticated radiological investigations now available mean that in future radiology will play a much more important part in diagnosis and management of patients.


Pulmonary embolism in Africans.

The clinical and autopsy records of 54 cases of pulmanary embolism seen at the Lagos University Teaching Hospital over the period 1966-1972 are analysed. The incidence of pulmonary embolism during this period was 0.1 per cent of all patients admitted, and there was a 78 per cent mortality. The primary medical condition associated with pulmonary embolism is heart disease. Sex has little influence on the liability to pulmonary embolism. Age has a pronounced influence, the incidence increases steadily after the age of 40. Medical cases are more liable than surgical cases to suffer from pulmonary embolism in each age group. The view is expressed that pulmonary  embolism is not rare in Africans. Our results support the opinion that the possession of the haemoglobin S predisposes although the final veridct must await the result of a larger prospective study.


Resistance-factors in the hospital and non-hospital environment.

The enteric flora of a group of antibiotic-treated patients and two groups of non-antibiotic-treated individuals were studied for antibiotic resistance patterns and presence of transferable R-factors. The former group consisted of 100 hospitalised patients, the latter two groups consisted of 200 hospitalised patients and 200 individuals from rural communities in Jamaica. The occurrence of multiple-resistant organisms with transferable R-factors was significantly higher in the antibiotic-treated group. R-factors were also more common in the hospitalised, non-treated group than in the non-hospitalised, non-treated group. Follow-up studies on hospitalised patients showed a tendency to increased occurrence of R-factors with duration of hospitalisation, whether the patients were treated with antibiotics or not. These studies have shown that both antibiotic treatment and hospitalisation promote the occurrence of R-factors.


Arbovirus studies in two towns in western state of Nigeria.

Three hundred and fifty-one persons were tested for HI antibody to arbovirus Groups A, B and Ingwavuma viruses in Ilesha and Oshogbo, two towns in western Nigeria. Chikungunya accouted for most Group A infections (39%). Antibodies to Group B virus were distributed as follows: Dengue 22%, Yellow Fever 25%, West Nile 28% and Wesselsbron 30%. Few sera 5% were positive to Ingwavuma. No virus was isolated from 188 blood specimens processed for virus isolation.


Structural identification of haemoglobin E in a group of Thai subjects.

Among 1052 women from Northern Thailand whose bloods were examined for haemoglobin variants by starch gel electrophoresis, 84 (8.0 per cent) had variant with the doubly-slow mobility associated with Haemoglobin E. Seventy-nine of those slow variants were examined by chemical structure studies and all were confirmed to have the change, beta26 Glu leads to Lys, associated with Haemoglobin E. These results indicate that other variants with mobilities like that of Haemoglobin E are uncommon in Thairs.


Long survival in sickle cell anemia.

A nearly 72-old black male with sickle cell anemia suffered from heart failure, hypertension, chronic impaired kidney function with hyperuricemia and gout. Anoxemia due to refractory anemia of the sideroachrestic type most probably precipitated the sudden heart failure.


A directional quantifying Doppler system for measurement of transport velocity of blood.

A transcutaneous Doppler device has been developed that measures primarily the directional transport velocity of blood, averaged over the vessel diameter, irrespective of its flow in adjacent vessels. Directional information is obtained by high or low-pass filtering of frequency converted versions of the received Doppler signals, applying low-cost, sharp filters in a superheterodyne system. Upper and lower channel signals are quantified separately to average directional velocity. Linear results from in vitro measurements are obtained.


[Determination of the rate constants for the interaction of enzymes with substrates and inhibitors during a short incubation time].

Kinetics of enzymatic reactions was studied using equipment which permitted to decrease the time of incubation of an enzyme with substrate or inhibitor up to two sec; principles of action, design and experimental procedure are described. A method of pipetting under pressure was employed to accelerate an addition of suitable reagents to the enzyme solution and for rapid stirring of the reaction mixture. Time of incubation was automatically measured with a precision of plus or minus 0.01 sec using an electronic stop-watch. Start and stop of the watch were made by means of electric gauges with platinum electrodes, placed into the channels through which the substrate or inhibitor solutions were supplied to the reaction mixture.


[Overall activity and isoenzymatic spectrum of liver lactate dehydrogenase in hypobiotic rats].

A total activity and isoenzyme spectrum of LDH from liver tissue were studied in rats, which were cooled down to the body temperature of 18-22 degrees and were kept in conditions of artificial hypobiosis for a long time (24 and 30 hrs). In cooled rats an increase in total LDH activity was observed. The increase might be a reflection of a stress-reaction to cooling since the method of developing of a hypobiosis involved an incomplete depression of thermoregulation. Subsequent extention of hypobiosis caused a gradual decrease in the total activity of LDH from liver tissue. The LDH activity reached values which were lower than the initial level. This phenomenon was probably due to attenuation of the stress-reaction and to a decrease in metabolic processes under effect of hypothermia. The alterations noted in the total LDH activity were determined by changes in the activity of a prevailing isoenzyme--LDH5. The increase in the LDH5 activity was assumed to be associated with activation of neoglucogenesis and determined by an orientation of the LDH-reaction in the direction of pyruvate.


[Effect of a malic acid load on the blood and urine content in animals of the products of a malate dehydrogenase reaction and the correlation of reduced and oxidized forms of ascorbic acid].

Addition of 150 mg of malic acid per a day to food of rabbits caused an increase in content of reduced ascorbic acid and pyruvic acid in blood; at the same time the content of oxydized forms of ascorbic acid was decreased. Similar alterations were observed in urine of guinea-pigs, which received 100 mg of malic acid per a day. The data obtained suggest that under these conditions the increased reduction, of ascorbic acid was due to increased formation of NADP with H2 in the course of reaction, catalyzed by malate dehydrogenase.


[Isolation and some properties of rat skeletal muscle polysomes].

Possibility was investigated to prepare polysomes from microsomal fraction of rat sceletal muscles. Centrifugation in sucrose gradient showed that approximately 60 percent of UV-absorbing material in the preparation obtained was in polysomic region of the gradient. Mild treatment with pancreatic ribonuclease led to disintegration of polysomes and respective increase in content of monosomic component. The use of combined gradient permitted to obtain two fractions of polysomes, one of which was readily sedimented by centrifugation. This fraction contained significant amount of protein and incorporated relatively low quantity of 32-P within 2 hrs after administration of the label in vivo. The data obtained suggest that the fraction of polysomes carried out the biosynthesis of myosin.


[Serotonin metabolism in acute renal ischemia in rabbits].

In tissue of ischemic kidney of rabbits a 5-hydroxytryptophan decarboxylase activity was decreased at first 15 min of ischemia; in contralateral kidney it was slightly increased. Then, within all the studied periods (24 hrs), activity of the enzyme was gradually decreased in both kidneys. The monoamine oxidase activity (substrates serotonin and p-nitrophenyl ethylamine) changed alternatively in early periods of ischemia; it tended to increase, especially in contralateral kidney, within 3 hrs after constriction of kidney artery.


[Characteristics of the energy metabolism in the kidneys in analgesic nephropathy].

Effect of prolonged treatment with acetyl salicylic acid (100 mg/kg) on energy metabolism was studied in dog kidney. Functional conditions of kidney were altered, which was manifested by an increase in excretion of sodium and by impairement is osmotic concentrating of urine. Studies of energy metabolism revealed uncoupling of oxidation and phosphorylation and also some decrease in the activity of glycolytic processes. The observed alterations in bioenergetics of kidney tissue are considered as important factors in development of analgetic nephropathy.


[Study of some properties of rat myocardial pyruvate kinase in adrenaline myocarditis].

Adrenaline myocarditis in rats was accompanied by a decrease in relative activity of pyruvate kinase from hyaloplasm of heart muscle, especially pronounced within 6-13 hrs after adrenaline administration. This phenomenon was probably due to an increase in content of protein in hyaloplasm, but not to an alteration in the enzyme activity. This conclusion was confirmed by studies of some properties of pyruvate kinase. Under these pathological conditions the Km of phosphoenol pyruvate was of the same order of magnitude as in normal state; 1-phenylalanine was characterized as an inhibitor of non-competitive type tomards phosphoenol pyruvate, and palmitate did not exhibit the inhibitory effect on pyruvate kinase as it was found in normal state. The effectiveness of the enzyme inhibition by L-phenylalanine, protection of the enzyme against this amino acid effect by L-alpha-alanine, L-serine and L-cysteine, and also the degree of activation of pyruvate kinase by the amino acids under adrenaline myocarditis were similar to those phenomena observed in normal state.


[The place of ultrasonic diagnosis in radiotherapy].

1. Before starting radiotherapy ultrasonic investigation of the abdominal, retroperitoneal and pelvic area is mainly used to determine the stage of the disease, the tumour size and its relation to adjacent organs, as well as in the diagnosis of metastases. 2. During treatment, ultrasonography is useful in controlling the correct position of the treatment fields and the response of the tumour to treatment. 3. During follow up echography is helpful in controlling therapeutic results and in the early detection of tumour recurrence. At this point the procedure frequently replaces diagnostic X-ray control. 4. In regard to treatment planning, the outlines of the organs are directly transferred from the B-mode scan to the treatment plan. Hence, the position of the treatment fields and the isodose distribution can be exactly adjusted to  e patient's anatomical requirements. Several examples are given to illustrate this procedure.


[Effect of L-thyroxine on the activity and isoenzymatic spectrum of liver hexokinase in intact and insulin-resistant rats].

Administration of L-thyroxine into intact rats caused a distinct increase in the activity of hexokinase in liver tissue. In the isoenzyme spectrum of hexokinase the activity of hexokinase II was increased significantly. After repeated administration of insulin, liver tissue cells lost their capacity to respond to the hormone administration by induction of hexokinase. Administration of L-thyroxine into animals caused a distinct increase in the hexokinase activity in liver tissue. In isoenzyme spectrum of hexokinase under effect of L-thyroxine a significant increase in the hexokinase II activity was also observed.


[The place of ultrasound diagnosis in gynaecology].

The indications for the implementation of ultrasonic diagnosis in gynaecology is discussed. Whereas the differential diagnosis between cystic and solid tumours is relatively simple in those tumours which have extended beyond the true pelvis, a profound knowledge of the examination technique is necessary to diagnose smaller lesions confined to the true pelvis. Knowledge of the ultrasonic anatomy of the female pelvis is not only the basis for the diagnosis of tumour recurrence following operation and irradiation of genital tumours, but, moreover, for the exact planning of radiotherapeutic management and follow up evaluation of therapeutic success. It is also shown that echotomography enables the demonstration of physiological changes within the ovary during the menstrual cycle.


[The place of ultrasound diagnosis in urology].

Ultrasonic diagnosis is used in urology, as in other fields, for the differentiation between cystic and solid tumours and in the planning of radiotherapeutic management. A particularly valuable application of ultrasound is in the determination of prostatic size, which provides essential information of which the preoperative decision as to surgical procedure is based. Ultrasonic tomography also has a limited application in the examination of the scrotum.


[Effect of dexamethasone and arecoline on the 5-methylcytosine and pyrimidine blocks in the DNA of certain sections of the brain, the liver and the spleen of rats].

In DNA of rat brain and liver tissues content of 5-methylcytosine increased by about 25 percent after dexamethasone administration; arecholine decreased content of 5-methylcytosine by about 20 percent. No other essential changes (GC content, amount of different pyrimidine isoplits) were found in these DNA. These data suggested that changes in 5-methylcytosine content in DNA studied were due to difference in DNA methylation rather than to alteration in DNA molecular population. The changes in DNA methylation, induced by the hormone or the alkaloid, were tissue-specific (brain, liver but not spleen). The level of DNA methylation was different in various parts of brain and correlated with the functional activity of the corresponding cells or genes. The alterations in DNA methylation, induced by the hormone or by the alkaloid, corresponded to changes in RNA synthesis. Thus, DNA methylation may be one of possible control mechanisms of transcription.


[Isolation and properties of cytoplasmic 21S and 7.5S RNP-particles from rat M-1 sarcoma cells].

RNP-particles, containing components with coefficient of sedimentation 119 S, 78 S, 60 S, 40 S, 21 S and 7.5 S were prepared from cells of sarcoma M-1. After separation in sucrose gradient, physico-chemical properties of 21 S and 7.5 S particles were studied. RNA of the particles was shown to belong to the GC-type. More than 10 protein fractions were found in polyacrylamide gel electrophoresis of these particles in presence of sodium dodecyl sulphate. Some of the proteins possessed electrophoretic mobility similar to that ribosomal proteins. In CsCl2 floating density of 21 S and 7.5 S particles was equal to 1.355 g/cm-3. By means of immunodiffusion method it was shown that light RNP-particles were analogous to the ribosomes of rat liver tissue and sarcoma M-1. Incorporation of 14-C-leucine into protein and 32-P-ortophosphate into RNA within 4, 7 and 12 hrs after administration of the isotopes demonstrated metabolic stability of RNA and high activity of the protein in the RNP-particles studied.


[The place of echoencephalography in neurolgy].

A short survey is given of the use of ultrasound examinations in neurology. Special attention is paid to the original immersion technique of Dussik, the A-scan echoencephalographic technique and the non-directional and directional Doppler technique, which are described with particular reference to their applications in the field of neurological diagnosis.


[Effect of 2-phenyl-3-methyl-3-hydroxypentanoic and 2,3-diphenyl-3-hydroxypentanoic acids on the lipolytic activity of rat adipose tissue].

Aromatic derivatives of mevalonic acid (2-phenyl-3-methyl-3-hydroxy pentanic and 2,3-diphenyl-3-hydroxy pentanic acids) decreased the yield of unesterified fatty acids from adipose tissue by about 28-36 percent after subcutaneous administration into rats within one or two weeks and under conditions of incubation of the adipose tissue in vitro. Distinct decrease in the yield of glycerol was cause by 2,3-diphenyl-3-hydroxy pentanic acid (1 with 10-minus 3 = 5 with 10-minus 3 M) under conditions of lipolysis stimulated by adrenaline. Antilipolytic effect of the preparation was more pronounced than that of well-known hypolipidemic drug clofibrate (p-chlorophenhydroxy isobutyrate).


[The place of ultrasound diagnosis in obstetrics].

A review is presented of the diagnostic applications of the ultrasonic scan technique in obsterics. In the 1st trimester of pregnancy the demonstration of the gestational sac and of an embryo is most important. During the further course of pregnancy the growth of the gestational sac and motions of the fetus can be observed. A disturbance in the development of the pregnancy can be deduced from these parameters. The various types of abortion can be differentiated by means of the scan. In the 2nd trimester the biometry of the fetus is most important. The motion behaviour of the fetus seems to be a good indicator of its well-being. The location of the placenta and the evidence of twins are easily demonstrable. In the 3rd trimester the biometry of the fetus is a good parameter of its maturity. The diagnosis of the fetal position is important for the management of delivery. Apart from these applications of ultrasound in obstetrics, the procedure is of great value in the diagnosis of tumours and the measurement of the true pelvis in pregnancy.


[The place of ultrasound diagnosis in paediatrics].

Ultrasound as a diagnostic technique is of rapidly increasing value in paediatrics. The great advantages of this procedure are that it is without risk of the patient and, hence, may be repeatedly carried out. Furthermore, ultrasound yields information which cannot be obtained by other methods.


[Acid phosphatase activity in the organs and tissues of rats after the administration of beta-mercaptopropylamine].

Effect of beta-mercaptopropylamine on the activity of acid phosphatase was studied in liver, brain, spleen, thymus and blood of intact rats. The effect was observed within three days after the administration of beta-mercaptopropylamine. At the same time the weight of lymphoid organs (spleen and thymus) was distinctly altered. The alteration in the weight of the organs correlated with alteration in the enzymatic activity.


[The place of echoencephalography in neurosurgery].

The different results of A- and B-mode echoencephalography, as well as the problems arising in the use of these techniques are discussed in the light of experience gained over many years in the investigation of numerous cases at a large neurosurgical department. The different indications for each method must be borne in mind, both techniques being useful in neurosurgical in mind, both techniques being useful in neurosurgical practice. The zscan technique is almost entirely confined to the domain of infant and childhood neurosurgery. Moreover, new aspects and future applications of echography in neurosurgical diagnosis are briefly discussed.


[New development trends in ultrasound diagnosis].

The first application of ultrasonics in medical diagnosis was attempted with a material testing apparatus. It is a pulse method which has remained essentually unchanged till the present day. New developments are primarily concerned with improvement of the deep and lateral resolution of the diagnostic apparatus. Useful improvements have already beeh achieved. It is realistic to look for new improvements with the application of modern electronics to this field.


The structure of N-[3-phenyl-5-(1,2,3,4-oxatriazolio)]-phenylamide at 105 K.

The crystal and molecular structure of the meso-ionic title compound, C13H10N4O, have been determined by X-ray methods using 2667 reflections above background level collected by counter methods at 105 K. The crystals are monoclinic, space group P2a/c, with cell dimensions: a=5.233(2) A; b=18.846(6) A; c=11.643(2) A, beta=105.71  degrees(2), with 4 molecules per unit cell. The structure model was refined to an R-factor of 0.047. In order to reduce the influence of the valence electrons all reflections with sin theta/lambda smaller than 0.5 A- minus 1 were excluded in the last stages of the refinement procedure (leaving 1658 Fo'S, R=0.058). The central five-membered ring is found to be planar and the bond lengths within this ring indicate a resonance stabilized system, as has been found for sydnones. The planes of the two benzene rings are tilted 11.7 and 8.0 degrees, respectively, with respect to the plane of the central oxatriazolio-ring.?


Enzymic decarboxylation of s-adenosyl-l-methionine in rat liver: possible interaction of putrescine with the prosthetic group.

S-Adenosyl-L-methionine decarboxylase (EC 4.1.1.50) has been purified more than 1000-fold from rat liver. The molecular weight of the decarboxylase was calculated to be 68 000. No evidence was obtained indicating that pyridoxal phosphate acts as the prosthetic group of the enzyme. On the other hand, the decarboxylase apparently contains some carbonyl group(s) participating in the catalysis as supported by the inhibition of S-adenosyl-L-methionine decarboxylation in the presence of NaBH-4, phenylhydrazine or NaCN. Putrescine, the specific activator of mammalian S-adenosyl-L-methionine decarboxylase, might interact, directly or indirectly, with the carbonyl group(s) of the enzyme as suggested by the protection of the decarboxylase activity against borohydride reduction by the diamine.


Structural studies of the extracellular polysaccharide produced by the diatom chaetoceros curvisetus cleve.

Methylation studies and partial acid hydrolysis have been carried out on the extracellular polysaccharide produced by the diatom Chaetoceros curvisetus. The polysaccharide contains the sugars galactose, rhamnose, and fucose and is partially sulfated. The presence of fucose in both furanose and pyranose forms within one molecule is reported for the first time. The fucofuranose is present as end groups, 1,2-linked and as branch points. Fucopyranose is mainly present as branch points in the polysaccharide, some being 1,3-linked, and a small fraction as end groups. The main part of rhamnose is 1,2-linked and galactose is mainly 1,3-linked.


Studies on the fluorophore forming reactions of various catecholamines and tetrahydroisoquinolines with glyoxylic acid.

Strongly fluorescent 2-carboxymethyl-3,4-dihydro-7-hydroxyisoquinolin-6-ones are formed in high yields when catecholamines are reacted with glyoxylic acid. Formation of the fluorophores has been found to take place in two steps; i. e. via virtually non-fluorescent tetrahydroisoquinoline-1-carboxylic acids, which react to give the fluorophores in a subsequent, rapid reaction with glyoxylic acid. The rates of reaction (pseudo first-order) with glyoxylic acid for 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid, and 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3- carboxylic acid show that introduction of a carboxyl group at either C-1 or C-3 in a tetrahydroisoquinoline highly facilitates the reaction with glyoxylic acid. This behaviour is discussed in terms of a mechanism involving both intramolecular acid catalysis by the C-1 or C-3-carboxyl groups during dehydration of the carbinolamine intermediate, and facilitation of the prototropic shifts of the resulting Schiff's base by decarboxylation.


The crystal and molecular structure of delta-9-tetrahydrocannabinolic acid b.

The crystal and molecular structure of the title compound C-22H-30O-4, has been determined by X-ray methods using 1106 reflections above background level collected by counter methods. The crystals are orthorhombic, space group P2-12-12-1 with cell dimensions a equals 16.514(2) A; b equals 14.324(2) A; c equals 8.744(1) A; there are four molecules per unit cell. The structure was refined to an R of 0.084 (weighted R-w equals 0.068). The cyclohexene and the pyran part of the molecule occurs in the half-chair conformation. The bond distances and angles, and a slight twist of the benzene ring, indicate considerable stains in the aromatic system. Both the phenolic and carboxylic group are significantly out of the plane through the aromatig ring. The angle between this plane and a plane through the cyclohexene ring is 37.7 degrees. The pentyl sidechain occurs in an extended gauche conformation, and the thermal parameters of this part of the molecule are very high. The molecules are held together by van der Waals forces in the c-directions, and hydrogen bonds (2.688 A) from phenolic to carboxylic groups in the a-b plane. There is a short ultra-molecular hydrogen bond (2.490 A) from the carboxylic group to the pyran oxygen.


Intracranial esthesioneuroblastoma. A light and electron microscopic study.

A 31 year-old  black woman with unilateral facial dysesthesia was found to have an intracranial parasellar mass that extended into the sphenoid sinus. By light microscopy, the neoplasm appeared as nests of poorly differentiated neuroblasts in a finely fibrillary stroma and was diagnosed as an esthesineuroblastoma. Electron microscopy confirmed the neuroblastic nature of the tumor with demonstration of neurites containing neurofilaments and neurotubules, synapses and dense cored biogenic amine granules in perikarya and processes. This neoplasm was further characterized by the presence of numerous dystrophic axons that were evident only by electron microscopy.


Infantile neuroaxonal dystrophy (Seitelberger's disease). A light and ultrastructural study.

The findings in a case of infantile neuroaxonal dystrophy are presented. Light microscopy shows wide distribution of spheroids, cerebullar atrophy and striatal degeneration. Electron microscopy shows numerous spheroids consisting of tubulo-vesiculo-membranous profiles. The dystrophic changes appear first in the axon seem to be modified by axostasis and/or transneuronal degeneration in addition to the dystrophic changes. The participation of the endoplasmic reticulum and microtubules in spheroid formation and their relation to the malformation of the synaptic vesicles have been discussed. Diverse mitochondrial abnormalities and Hiranolike body are also described.


Congenital myopathy with "reducing bodies" in muscle fibres.

A muscle biopsy of a boy of 14 years presenting clinically a benign congenital myopathy showed granular intrasarcoplasmic bodies exhibiting reducing activity. The resemble the bodies described by Brooke and Neville in muscle of two children with severe congenital myopathy which they referred to as "reducing body myopathy". If the reducing bodies are the characteristic morphological feature peculiar to this newly recognized congenital myopathy, the case reported here would be therefore a benign form of reducing body myopathy. The origin and nature of the granular material forming the bodies is doubtful. The close relationship between this material and the myofilaments may suggest that the granules arise from some myofibrillary component.


[The effect of piromen on the flial-mesenchymal scar in the cortex of hamsters].

In the present work the effect of Piromen is studied on the formation of the glial-mesenchymal scar in the experimentally injuried cortex of hamsters. The uniform effect of the bacterial polysaccharide is suggested in a strong and lasting stimulation of proliferating reactive cells in the traumatic area. The excessive proliferation is combined with a decrease of differentiation in the reactive cells. A reduction of specific activities (phagocytosis, production of collagen and glial filaments) of these cells was also observed. Finally a porous mesenchymal scar develops with a great many of dedifferentiated cells. On the other hand a spongy glial scar is formed, which is due to a desintegration of astrocytic processes in the peritraumatic area. A so far not precisely understood transformation of reactive astrocytes plays an important role herein. The changes of the glial-mesenchymal scar after administration of Piromen, reported in the literature, were on the whole confirmed.


Electron microscopic study of the developing capillaries of human brain.

The ulstrastructural characteristics of the cerebellum and olfactory bulb capillaries were studied in 12 human specimen measuring 25-200 mm. Type I capillaries, whose lumina were wider than 8 mu, contained no pores of fenestrations. The basement membrane was sometimes discontinous. In that case, junctions without quintuple-layered zones could be observed. Such capillaries may correspond to primary vessels in which the sinusoid character has disappeared. Elsewhere, the basement membrane was continuous and the interendothelial junctions always contained quintuple-layered zones. Type II capillaries, whose lumina measured between 2 and 8 mu had basement membranes  that were either discontinuous or continuous. They were identical to the immature capillaries described previously in numerous species including man. Type III caillaries, rarely observed, were characterized by the presence of several endothelial cells with abundant cytoplasm, which limited the  mina from 0.5 --3 mu in diameters. They had continuous basement membranes. Type IV and V capillaries has small or non-patent lumina. The basement membrane was absent or rudimentary. These  capillaries appeared to correspond to simple and complexendothelial sprouts. In Types II, III, V and most Type IV capillaries, the interendothelial junctions contained quintuple-layered zones. No mature capillaries were observed. The hypothetical pathways of development of cerebral capillaries and the degree of permeability of immature interendothelial junctions are discussed. The long duration of maturation in man probably accounts for the diversity of capillary formations observed as compared with animals. The co-existence over along period of time of several capillary types with probably  varying permeability may play a significant role in the maturation of the blood-brain barrier.


Aspartylglycosaminuria: a generalized storage disease. Morphological and histochemical studies.

Aspartylglycosaminuria (AGU) is a hereditary metabolic disorder characterized by slowly progressive mental deterioration from infancy, urinary excretion of large amounts of aspartylglycosamine, and decreased activity of the lysosomal enzyme aspartylglcosamine amido hydrolase in various body tissues and fluids. The nature and distribution of the morphological and histochemical alterations in AUG are described in the light of the first AGU patient investigated post mortem and brain and liver. Most nerve cells and hepatocytes contained  large vacuoles without any histochemically demonstrable lipid or carbohydrate material. Ultrastructural studies revealed numerous electron-lucent vaculoles, limited by a single, membrane, in the cytoplasm of these cells. In addition to evenly disperesed finely granular or reticular material the vacuoles contained small electron-opaque "lipid" droplets and polymorphic membraneous or granular aggregates. Similar vacuoles were also seen in a number of other cell types, particularly in the kupffer cells and brain macrophages, as well as in the capillary pericytes. Biochemical studies suggest that the principal storage material consists of aspartylglycosamine itself; glycoasparagines of higher molecular weight are present as only minor components. Correlated morphological and biochemical studies thus definitely establish that AGU is a generalized storage disorder. The condition is apparently due to decreased activity  of aspartylglycosamine amido hydrolase, with accumulation of products of flycoprotein carabolism in cytoplasmic vacuoles in both epithelial and mesenchymal cells.


Effect of hypoxia, ischemia and carbon monoxide intoxication on in vivo protein synthesis in neuron and glia cell enriched fractions from rat brain.

The dynamics of changes in the in vivo amino acid incorporation into proteins of the neuron and glia cell enriched fractions of rat brain following application of a number of hypoxic conditions were investigated. The experimental models include: a) simple hypoxia, b) ischemic-hypoxic hypoxia and c) carbon monoxide intoxication. Irrespective of the experimental model used, neuronal protein synthesis was more markedly inhibited than glial, maximal inhibition being observed 2 hrs after cessation of the experimental procedure. The changes were of transient character, whereby 24 hrs after the experiment the glial synthesis appeared activated above the control value. The higher sensitivity of the neuronal protein synthesis to the applied experimental procedures produced more significant changes of the protein/total radioactivity ratio in neurons than in glia, the ratio expressing the extent of radioactive amino acid utilisation in the synthesis.


Traumatic production of an intracranial berry-like aneurysm in a monkey.

A berry-like dissecting intracranial aneurysm resulted from inadvertent puncture of the internal carotid artery during trans-palatal section of a monkey's optic nerve. The light and ultrastructural features are rather similar to those of human berry aneurysms supporting the notion that the latter are degenerative rather than congenital in origin.


An autopsy case of classical Pelizaeus-Merzbacher's disease.

A  girl aged 8  years and 10 months at death had shown signs of a slowly progressive neurological disease  with onset in early infancy. The main clinical features were nystagmus, spastic paraplegia, amd mental deterioration. Pathological examination of the brain showed severe demyelination with perivascular preservation of mylein islands, presenting a tigroid pattern. The patient is  the second case of classical Pelizaeus-Merzbacher's disease in Japan proven by autopsy.


Male breast cancer.

The disease male breast cancer has been evaluated on the basis of data concerning 265 cases registered in Denmark over the period from 1 January 1943 to 1 July 1972. The data were obtained by review of hospital records, survey of microscopic preparations and examinations of surviving patients. The results are compared to results reported in the literature. The recent material is the second largest series hitherto published. Male breast cancer comprises 0.8 per cent of all cases of breast cancer in Denmark. The average age at establishment of diagnosis was 65.2 years in 257 cases of breast carcinoma, which is considerably higher than that found in women. The duration of symptoms in breast cancer is considerably longer in males than in females, 16 per cent having a duration of symptoms of 2 years or more. In only 13 per cent was a palpable tumour the only symptom on admission. Twenty-seven percent had ulceration. Ulceration and fixation to the underlying tissue are not, as commonly presumed, early symptoms in male breast cancer. According to the TNM classification, 35 per cent of 253 cases were in clinical stage I, 11 per cent in stage II, 42 per cent in stage III, and 12 per cent in stage IV. Duration of symptoms and histological grade of malignancy were of significant importance or the stage on admission. Assessed on the basis of the distribution into stages, the clinical appearance of the disease showed a significant improvement from the period 1943-1957 to the period 1958-1972. Attempts should be made to differentiate the disease from gynecomastia which is much more frequent. Only during the early stages of breast cancer, however, will there be differential diagnostic problems as the majority of patients do not present themselves until unequivocal clinical signs of malignancy are present. The series has been reviewed with regard to the presence of gynecomastia. Certain facts appear to support the theory that gynecomastia may be a premalignant state. A series of 30 patients with breast cancer were screened for the Klinefelter syndrome. One positive case was found. By pooling series of male breast cancer, in which such screening has been made, it was found that the incidence of the Klinefelter syndrome is higher among men with breast cancer than in the normal male population. Calculated on the basis of the general public were better informed about the existence of this disease and the value of its early diagnosis and treatment, the prognosis should undoubtedly by improved.


Solitary autonomously functioning thyroid lesions. Diagnosis, clinical features and pathogenetic considerations.

One hundred sixty-four patients with autonomously functioning thyroid lesions (AFTL), 140 with nontoxic and 24 with toxic lesions, were studied over 12 years. To avoid pitfalls in diagnosis of nontoxic AFTL, a suppression procedure should precede the repeat scan after the administration of thyroid stimulating hormone. Women outnumbered men by 13 to 1 for nontoxic AFTL and 3.8 to 1 for toxic AFTL. Larger and toxic lesions were found in older patients, suggesting their derivation from smaller nontoxic lesions. Serum triiodothyronine (T3) and thyroxine concentrations exhibited parallel deviations from average normal levels for most of 29 patients with hot AFTL. T3 toxicosis  was not seen. Ultrasound was more sensitive than scanning in detecting cystic degeneration. Observation was advised for patients with nontoxic AFTL unless toxicity appeared imminent. Of 51 such patients, followed from 1 to 12 years, none became hyperthyroid, but 10 AFTL increased from slightly to fourfold in size or showed evidence of degeneration. Of 24 patients with toxic AFTL, 20 were treated with radioiodine and the remaining 4 surgically; surgery is the preferred treatment for patients under 40 years of age. Three of 29 patients who were treated surgically had thyroid cancer. Since AFTL have histologic and pathophysiologic features characteristic of benign endocrine neoplasms, the association with cancer may be more than coincidental.


Lymphocytic choriomeningitis in university hospital personnel. Clinical features.

Clinical manifestations of lymphocytic choriomeningitis (LCM) virus infection in 15 patients are described. These patients were University Hospital personnel who had had contact with hamsters, subsequently shown to harbor the virus. Fever with striking myalgias, headache and rigors were the most common symptoms. Only 2 of the 15 patients had clinically overt and documented aseptic meningitis. Leuikpenia was observed in 10 of 11 patients and thrombocytopenia in 8 of 8 patients tested. A biphasic illness was seen in eight patients. In a patient who has been exposed to laboratory animals, particularly to hamsters, a nonspecific influenza-like febrile illness accompanied by leukopenia and thrombocytopenia may represent LCM virus infection.


A relationship between impaired cellular immunity humoral suppression of lymphocyte function and severity of systemic lupus erythematosus.

Eighteen newly diagnosed, untreated patients with systemic lupus erythematosus (SLE) were divided into two groups based on the severity of the disease. Patients with very active disease were nonresponsive to skin test antigens used to assess delayed hypersensitivity. Skin test reactivity was intact in most patients with mildly active disease. Lymphocytes from subjects in both groups responded normally to phytohemagglutinin (PHA) when the results were expressed as counts per minute per million small lymphocytes. Serum from patients with severely active disease markedly suppressed lymphocyte responsiveness of autologous and allogeneic lymphocytes. Serum from patients with mild disease had significantly less suppressor activity. Lymphocytotoxic antibodies and suppressor activity were not correlated. Suppressor activity in immunoglobulin G fraction paralleled that found in whole serum. The present studies suggest that impaired delayed whole serum. The present studies suggest that impaired delayed hypersensitivity in SLE is a consequence of disease activity rather than an inherent feature of this disease. The strong correlation between serum suppression of PHA reactivity and anergy suggests that the humoral immunosuppressive effects described may be responsible, in part, for impaired delayed hypersensitivity in this disease.


Clinical features of chorea associated with systemic lupus erythematosus.

Neurologic complications of systemic lupus erythematosus (SLE) are common, but chorea is rare. Three cases of chorea associated with SLE are presented as well as a review of 28 cases from the world literature. Chorea may be the first and at times the only sign prior to the establishment of diagnosis of SLE. Under such conditions the establishment of the correct diagnosis is difficult, and the chorea may be attributed to a more common etiology, Also the SLE-related chorea may recur in the same subject during the course of the disease. Finally, the chorea associated with SLE can be brought under control by use of haloperidol (HALDAL).


Hepatic disease in erythropoietic protoporphyria.

Two sisters had erythropoietic protoporphyria and a spectrum of liver disease. One (F.B.) died in hepatic failure within 3 months after the development of jaundice. Only 10 months before she died, she had exhibited only bromsulfalein retention and a borderline increase in serum transaminase. Surgical exploration because of the jaundice revealed patency of the bile ducts which was confirmed at autopsy. Wedge biopsy and autopsy specimens of liver showed an active cirrhosis with massive amounts of protoporphyrin in Kupffer cells, portal histiocytes, bile canaliculi and parenchymal cytoplasm. The other sister (L.R.) had never had symptomatic liver disease and only a slight increase in serum transaminase and bromsulfalein retention. On needle biopsy, the liver specimen showed portal inflammation with erosion of limiting plates, occasional bridging between triads and central areas of cell dropout. Protoporphyrin pigment was present in portal histiocytes, areas of central collapse and, more rarely, in parenchymal cytoplasm. These studies demonstrate that significant, progressive hepatic disease may occur insidiously in erythropoietic protoporphyria, and that once jaundice appears it may be followed rapidly by fatal hepatic failure.


Osteosclerosis in primary hyperparathyroidism.

Osteosclerosis in adults with primary hyperparathyoidism is rare; the usual skeletal manifestation, when presented, is diffuse osteropenia. We describe a patient with generalized osteosclerosis in association with primary hyperparathyroidism. The findings are documented by conventional and fine-detail radiography, absorptiometric bone mineral analysis, quantitative microradiography and histologic examination of bone. The unique features are contrasted with the manifestations recorded in a recently studied group of 87 hyperparathyroid patients. The data presented here support a causal relationship in this patient between parathyroid hormone excess and the development of densely sclerotic bones.


Familial renal amyloidosis. Case reports, literature review and classification.

Three siblings (two brothers and a sister) of Polish origin, presented in late middle age with the features of the nephrotic syndrome and hypertension. Glomerular deposition of amyloid was found in all on renal biopsy. No amyloid was seen on rectal or gingival biopsy. Their mother and a maternal aunt died in middle age with a clincally similar disease. These cases are compared with other forms of hereditary amyloidosis which are briefly reviewed. The hereditary amyloidoses are classified with particular emphasis on neural and renal involvement.


Cell wall-deficient bacterial variant cultural surveillance. A useful laboratory aid.

A cell wall-deficient variant of Corynebacterium species was isolated from the blood of a patient with a chronic febrille illness of unkown etiology. He was given antimicrobial therapy, to which both variant and reverted bacterial forms of this organism were sensitive, and he recovered. Cultural surveillance for cell wall-deficient organisms was not only helpful in confirming the presence of infection in our patient but also in following his clinical course once antimicrobial therapy had been instituted.


Left ventricular dyskinesia in infarction and angina.

In 29 patients, the site and extent of coronary artery obstruction were related to the position and area of abnormally contracting segments of the left ventricle, both in patients with a history of angina without myocardial infarction (group I) and in patients with prior documented myocardial infarction (group II). The degree of coronary artery obstructive disease was estimated in the standard manner and also by a coronary artery index which considered not only the degree of obstruction but also the total length of the obstructed segment. A kinetic or dyskinetic segments were present in 22 of the 29 patients. An abnormally contracting segment was present in 12 or 18 patients without prior myocardial infarction in comparison with 10 of the 11 patients with prior infarction. Complete obstruction of a coronary vessel and resultant dyskinesia were more frequent in the right coronary artery than in either the left anterior descending or the circumflex artery. There was a significant correlation between total per cent of vessel obstruction and degree of ventricular asynergy in both groups; consideration of length of obstructed segment did not improve this correlation.


Mitral valve disease of systemic lupus erythematosus. A cause of severe congestive heart failure reversed by valve replacement.

Libman-Sacks endocarditis caused progressive life-threatening mitral regurgitation necessitating mitral valve replacement in an 18 year old woman with systemic lupus erythematosus (SLE). Although Libman-Sacks endocarditis is frequently seen at autopsy in patients with SLE, hemodynamically significant valvular disease due to that lesion is quite rare. We found no previous reports describing mitral regurgitation in a patient with SLE which has necessitated surgical intervention.


Pseudohypoparathyroidism. Disappearance of the resistance to parathyroid extract during treatment with vitamin D.

Serum immunoreactive parathyroid hormone (iPTH) levels were increased in a 15 year old girl with pseudohypoparathyroidism, hypocalcemia, hyperphosphatemia, and minimal phosphaturic and absent hypercalcemic responses to exogenous parathyroid extract (PTE). Following normalization of the serum calcium concentration with vitamin D, serum iPTH and phosphate concentrations returned to the normal range, and phosphaturia could be clearly stimulated and hypercalcemia induced by PTE. On the other hand, the urinary cyclic adenosine 3',5'-monophosphate (cyclic AMP) excretion could not be stimulated, suggesting that in this case, there appears to be no relationship between the urinary excretion of cyclic AMP and the phosphaturic effect of PTE. The minimal phosphaturic effect and the lack of hypercalcemic effects of PTE in untreated pseudohypoparathyroidism can be explained by the secondary hyperparathyroidism causing elevated iPTH levels rather than by a defect at the level of the receptor sites. A requirement of pharmacologic amounts of vitamin D per se, however, for the responsiveness of patients with pseudohypoparathyroidism to PTE cannot be ruled out.


Left ventricular ejection fraction in severe chronic obstructive airways disease.

The subject of left ventricular involvement in chronic obstructive airways disease is controversial. We measured left ventricular ejection fraction (LVEF) in 120 patients with severe chronic obstructive airways disease, 92 of them acutely decompensated and 28 stable. A bedside radionuclide technic using a scintillation probe was used to measure LVEF. Of the 28 patients with acute respiratory failure, LVEF was normal (larger than or equal to 55 per cent) in 60 and subnormal in 32. Of the 28 patients with stable chronic obstructive airways disease, LVEF was normal in 12 and low in 16. Coronary artery disease could be demonstrated clinically or at autopsy in 13 of the patients with acute and in 7 of the patients with stable chronic obstructive airways disease. LVEF was 28 plus or minus 10.4 per cent (average plus or minus SEM) in the patients with acute chronic obstructive airways disease and coronary artery disease which was significantly different (P smaller than 0.001) from LVEF in patients without coronary artery disease (61 plus or minus 1.9 per cent). In the patients stable with chronic obstructive airways disease and coronary artery disease, LVEF was (42 plus or minus 3.5 per cent), significantly different (P smaller than 0.001) from LVEF in those without coronary artery disease (55 plus or minus 2.1 per cent). There was no relationship between LVEF and arterial oxygen, or carbon dioxide tension, or pH. Results suggest that LVEF is normal in patients with severe lung disease alone and that reduced LVEF in patients with chronic obstructive airways disease can reasonably be ascribed to coronary artery disease.


Cardiac conduction in myotonic dystrophy.

Cardiac conduction abnormalities are frequent in myotonic dystrophy and can result in complete heart block. In a study of 26 patients with myotonic dystrophy, first degree heart block was found to precede clinical presentation of the disease in 7 patients. His bundle electrocardiography in 11 patients demonstrated abnormalities throughout the entire conducting system, even in patients with only first degree heart block. In patients with block of the right bundle branch or anterior fascicle of the left bundle branch, slowing in the remaining fascicles was always present. Therapy of myotonia with procainamide significantly lengthened the P-R interval, and treatment with diphenylhydantoin significantly shortened the P-R interval suggesting that diphenylhydantoin may be preferable for therapy of myotonia in patients with myotonic dystrophy.


Reversibility of pulmonary function abnormalities in smokers. A prospective study of early diagnostic tests of small airways disease.

A prospective study of the reversibility of pulmonary function abnormalities in cigarette smokers was performed. Base line studies of 50 otherwise healthy cigarett smokers included lung volumes, static volume-pressure curves, closing volume, slope of phase III and maximum expiratory flow-volume curves while the subjects breathed air and while they breathed an 80 per cent helium-20 per cent oxygen mixture (He). Ten subjects, seven women and three men, ages 29 to 61, were restudied 6 to 14 weeks after they had stopped smoking. Two of these people had an abnormal closing volume, four had an abnormal slope of phase III and five had an abnormal response to helium. Static volume-pressure curves, slope of phase III and airflow rates were not improved on the repeat studies. There was increases in maximum expiratory flow rates with He at 50 and 25 per cent of vital capacity, reductions in the lung volume at which the maximum expiratory flow rate of air and He became identical, and decreases in closing volume. These reversible functional changes in smokers are thought to indicate improvement of peripheral airways obstruction.


A heterozygote for Hb S beta, Hb C beta and Hb G Philadelphia beta in a family presenting evidence for heterogeneity of hemoglobin alpha chain loci.

A child heterozygous for the genes for hemoglobins S, C and G alpha Philadelphia presented with a clinical picture similar to sickle cell anemia. Her hemoglobin electrophoretic pattern contained three components with the mobilities of hemoglobins S (35 per cent), C (47 per cent) and a more slowly migrating hybrid G/C molecule (15 per cent). Seven relatives were heterozygous for Hb G beta and Hb S beta and five were heterozygous only for Hb G alpha. Among the latter, three had approximately 30 per cent and two had 40 per cent of Hb G. These proportions are consistent with the hypothesis that the American Negro genome contains two types of chromosomes bearing structural loci for alpha chains, some possessing one Hb alpha locus, others having two loci. Hb G alpha-Philadelphia presumably arose as a mutation on a chromosome with a single locus. Those heterozygotes having 30 per cent and 40 per cent Hb G presumably have two loci and only one locus, respectively, on the homologous chromosome.


Relation of ventricular arrhythmias in the late hospital phase of acute myocardial infarction to sudden death after hospital discharge.

To determine the prognostic significance of ventricular arrhythmias persisting during the hospital ambulatory phase of acute myocardial infarction, 64 patients with acute myocardial infarction underwent continuous 10-hour Holter monitoring an average of 11 days after discharge from the coronary care unit (CCU). Patients were categorized according to the results of ambulatory monitoring: 27 patients had ventricular extrasystoles, which were complicated (multifocal, R on T, paired, more than 5/min), or ventricular tachycardia; 22 had uncomplicated premature ventricular contractions; and 15 exhibited no ventricular arrhythmias. The 64 patients were followed prospectively for an average course of 25.8 months; 12 died suddenly; 8 died of other causes, and 44 survived. In all patients who died suddenly, ventricular ectopy was recorded on Holter monitoring before their discharge from the hospital (complicated premature ventricular contractions, eight patients; uncomplicated premature ventricular contractions, four patients); there were no sudden deaths in the patients without ventricular arrhythmias. Patients who died suddenly and those survived were similar in respect to age (60, 62 years), sex, location of infarction, presence of coronary risk factors, severity of acute myocardial infarction (Q waves, cardiac enzymes), serum cholesterol levels, evidence of cardiomegaly on roentgenograms, presence of ventricular gallop and drug therapy received. The occurrence of acute arrhythmias in the CCU did not separate patients who died suddenly from those who survived; there were no differences in ventricular tachycardia or ventricular fibrillation (3 or 12 patients who died suddenly, 6 of 44 patients who survived) or complicated premature ventricular contractions (4 or 12 patients who died suddenly, 18 of 44 patients who survived). Electrocardiograms obtained late in the hospital course revealed no differences in the extent of Q or T wave changes between these two groups. However, the extent of S-T segment abnormality was greater in patients who died suddenly than in patients who survived (5.6 compared to 1.8 leads/standard tracing, p smaller than 0.02) suggesting that the arrhythmias in the former were related to persistent ischemia or segmental ventricular dyssynergy. Thus, in this relatively small number of patients, ventricular arrhythmias persisting late in the hospital course of patients admitted for acute myocardial infarction are shown to predispose to subsequent sudden death.


Endotoxin, prekallikrein, complement and systemic vascular resistance. Sequential measurements in man.

Eighteen patients were studied prior to and again within 6 hours after transurethral resection or cystoscopy. In addition to hemodynamic measurements, detection of endotoxin by limulus assay and bacteriologic sampling; prekallikrein, C3, C3 proactivator and lysosomal enzyme levels were measured. In five patients limulus assays were positive, and in one, gram-positive bacteremia developed but limulus assay remained negative. All six had significant decreases in prekallikrein, C3 or C3 proactivator. Systemic vascular resistance fell in all six. Four additional patients who had a decrease in systemic vascular resistance were not endotoxemic or bacteremic; one of these had a decrease in prekallikrein only. In the remaining eight patients with neither bacteremia nor endotoxemia, systemic vascular resistance did not change or increase after instrumentation. One had a decrease in C3 proactivator, another in prekallikrein. There was no significant difference in age, disease, antibiotic therapy or bactermia in the two groups of patients. Four of the five resectional procedures were performed in the group that showed decreases in systemic vascular resistance. The data suggest that acute endotoxemia or gram-positive bacteremia in man is associated with depletion of prekallikrein, decreased peripheral resistance and, in some instances, activation of the complement system.


Clinical, microbiologic and therapeutic aspects of purulent pericarditis.

Twenty-six patients with purulent pericarditis were seen at the Massachusetts General Hospital between 1960 and 1974. The diagnosis was made in 18 of them during life, but only 6 survived, with an over-all mortality rate of 77 per cent. In eight patients, purulent pericarditis developed in the early postoperative period after thoracic surgery. In seven, purulent pericarditis was the result of contiguous spread of infection from a pleural, mediastinal or pulmonary focus in nonsurgical patients. In five patients, it was the result of direct spread to the pericardium from an intracardiac infection. In the remaining six patients, purulent pericarditis developed as the result of a systemic bactermia. Immunosuppressive therapy, extensive thermal burns, lymphoproliferative disease and other systemic processes affecting host resistance were present in at least half the patients. Staphylococcus aureus was the etiologic agent in the largest number of patients (8 of 26 in this report). However, in contrast to previous studies, in a significant number of the patients (five), purulent pericarditis was the result of fungal infection (in three patients subjected to thoracic surgery and in two immunosuppressed patients). This report confirms that purulent pericarditis is an acute disease with a fulminant course. The diagnosis is easily missed since classic signs of pericarditis (including chest pain, friction rub and diagnostic electrocardiographic abnormalities) may be absent. The echocardiogram shows considerable promise in allowing earlier diagnosis of the pericardial effusion which accompanies purulent pericarditis. Optimal therapy consists of prolonged antibiotic therapy and aggressive drainage of the pericardium. In this series, there were 6 survivors among the 11 patients (55 per cent) who received appropriate therapy.


Hematogenous candida osteomyelitis. Report of three cases and review of the literature.

Candida osteomyelitis of the spine and intervertebral disc developed in three patients without evidence of back trauma of overlying cutaneous infection. Two patients were prone to the development of disseminated candidiasis by the use of multiple antibiotics and other predisposing modalities following abdominal surgery. One patient had no identifiable cause for development of the infection. The diagnosis was established in all three cases by x-ray evidence of osteomyelitis and culture from needle aspirate. Two patients had bone scans consistent with infection. Each patient received different therapy. One was treated with amphotericin B, one with spinal fusion and 5-fluorocytosine, and one with no antifungal therapy. All patients had complete healing of the involved vertebrae. Candida organisms have the potential to cause destructive bone infection following hematogenous dissemination. The presence of Candida osteomyelitis may be helpful in diagnosing disseminated candidiasis.


Silicon nephropathy.

A patient with excessive industrial exposure to silicon and an elevated silicon content in his renal tissue was found to have a distinctive nephropathy, characterized pathologically by changes in the glomeruli and proximal tubules, and manifested clinically by albuminuria and hypertension. Proximal tubular function was intact. From a biochemical standpoint, this finding correlates with the demonstration in vitro that, in contrast to cadmium, a known cause of Fanconi syndrome, silicon does not inhibit renal cortical sodium-potassium-adenosine triphosphatase (Na-K-ATPase).


[High doses of fentanyl as the sole anaesthetic agent and naloxone as its antagonist (author's transl)].

In 70 patients (maxillo-facial-, neurosurgical-, abdominal- and gynaecological operations) the technique of "analgetic anaesthesia" using high doses of fentanyl (0.025 mg/kg body weight) and naloxone as its antagonist (0.02 mg/kg body weight) has been employed. All patients were artificially ventilated with N2O/O2 in a 3:1 ratio. Muscle relaxation was achieved with pancuronium-bromide (0.08 mg/kg). The patients had no apparent heart or lung disease. The youngest patient was 4 years of age, the oldest 82 years of age (average age 48.9). The necessity for a reinjection of fentanyl (half the initial dose) was determined by continously monitoring heart rate. This variable appeared to be the most subtle index indicating a reduction in analgesia. Sufficient analgesia was maintained once the heart rate stayed 20% below preanaesthetic levels. At the end of the operation naloxone reversed the respiratory depression. There was no evidence indicating postoperative pain, which may have required administration of additional analgesics. If deep analgesia was maintained up to the last surgical procedures no emesis appeared in the post operative period. The incidence of emesis was higher 10% compared to the classical neuroleptanalgesia with droperidol this was often noted in cases where blood accumulated in the stomach (maxillo-facial operations) (70%). In 3% of all cases psychomotor agitation with delirium appeared right after the injection of naloxone. This lasted for about 15 minutes. We suspect that due to the sudden and powerful effect of naxolone, in replacing fentanyl from its receptor site, acute withdrawal symptoms may be precipitated.


[On the pressure-volume relation of the central and the peripheral vascular bed of the low pressure system (author's transl)].

The effect of hemorrhage amounting 420 ml in relation to the behaviour of the pressures and volume of the intrathoracic and extrathoracic compartment was studied on 10 young male adults. The volume elasticity coefficient E' and the vascular compliance 1/E' of the intrathoracic, extrathoracic and the total circulation were calculated as a result of the change in pressure and volume after the 420 ml hemorrhage. The coefficient of the volume elasticity for the intrathoracic compartment was found to be 23 dyn-cm-minus 5, for the extrathoracic compartment 15 dyn-cm-minus 5 and for the total circulation 9 dyn-cm-minus 5. The compliance of the intrathoracic compartment was 0.8 ml/mm Hg/kg BW, that of the extrathoracic compartment was 1.2 ml/mm Hg/kg BW and that of the total circulation was 2.0 ml/mm Hg/kg BW. These findings support the thesis of the large distensibility of the intrathoracic compartment.


[Bloodgas changes during heart catheterisation in children under basal sedation (author' transl)].

A form of basic sedation for cardiac catheterisation in children with congenital heart disease is described. The drugs used (Toronto cardiac mixture, papaveretum--hyoscine respectively) offer a true alternative to general anesthesia. Blood gases and acid-base status of 32 children aged two days to twelve years were investigated. The observed tendency towards metabolic acidosis is believed to be related to the angiographic contrast medium.


[Gas exchange and pulmonary mechanics under anaesthesia and artificial ventilation (author's transl)].

During general anaesthesia with controlled ventilation and normocapnia the A-a DO2 and pulmonary shunt were investigated in a group of 7 patients undergoing a parotidectomy or laryngectomy. In a second group of 21 patients the behaviour of the total, lung- and thorax compliance was investigated. Within the first 1 1/2 hours after induction of anesthesia the A-a DO2 and shunt increased. During the time the thorax compliance did not change, whereas the total and lung compliance decreased significantly. After 1 1/2 hours no further change occured.


Massive aspiration during surgery for a hydatid cyst of the lung.

A case of massive aspiration of hydatid liquid during an operation for excision of hydatid cyst of the lung is presented. Some considerations about the treatment and the anaesthetic approach to the problem are given. An analysis of 42 operations performed during 1963-1973 in the Rambam Hospital is discussed. Rupture of cyst with cyanosis and fall in blood pressure occurred in only 5 of these cases and among them, only one patient died.


[Study on the time requirements of nursing care in an intensive care unit (author's transl)].

We have studied the high nursing requirements of an intensive-care unit. We report concerning the size of the staff required and the consequences for the hospital.


[Tension pneumothorax as anaesthesia complication - report on 3 cases (author's transl)].

Three cases of tension pneumothorax during anesthesia are reported. The symptoms, difficulty to ventilation, unusual, decreased or absent chest movements and breath sounds, rapid onset of circulatory collapse. Decompression of the pleural cavity by puncture or thoracotomy is lifesaving.


[The usefulness of system analysis to reduce the anaesthetic risk (author's transl)].

The attempt is made to increase the safety of anaestesia by the method of categorizing separate risk factors. It is very important to minimize these risk factors, but I do not think this is the way to do it. I propose to tackle this problem by the method of systems analysis. Systems analysis would also result in a certain levelling out of the demands made on both the staff and the equipment of an anesthesiology department and help to build a bridge between us and our industrial supplies. Systems analysis rejects the examination of separate risk factors in order to study the system as a whole and the functional cohesion of the various elements within it. In anesthesia, there are 3 different systems to be studied: the induction phase, the phase of true anesthesia, the recovery phase. The induction phase is discussed in this paper as an example of the thought processes and steps involved in a study by means of systems analysis.


Increased platelet aggregation in early diabetus mellitus.

In view of the tendency toward vascular disease in diabetes mellitus, we studied platelet aggregation in 15 normal, 7 prediabetic, 12 latent, and 20 frankly diabetic subjects. Platelets from latent and frank diabetics showed increased platelet aggregation 4 minutes after adding adenosine 5'-diphosphate (60% verus 29% at 1.0 mu-M), epinephrine (46% versus 14% at 0.25 mu-M), and collagen (72% versus 17% at 0.25 mu-g/ml). Three prediabetics had increased platelet aggregation. Platelet sensitivity to aggregating agents was most marked in frank diabetics, intermediate in latent diabetics, and least in prediabetics. Second-phase platelet aggregation was reversed with acetylsalicylic acid, intravenous tolbutamide, and oral glucose administration. We conclude that platelet aggregation may be increased early in diabetes mellitus and may be involved in the genesis of diabetic microangiopathy. Prospective studies on the effect of therapeutic agents such as acetylsalicylic acid on the natural course of diabetic vascular disease are indicated.


Prosthetic valve endocarditis.

From January 1963 until January 1974, 45 patients had prosthetic valve endocarditis. Symptoms of prosthetic valve endocarditis developed within 2 months after operation (early onset) in 16 patients (36%) and more than 2 months after operation (late onset) in 29 patients (64%). Overall mortality among the 45 patients was 56% (88% among those with early onset and 40% among those with late onset). Medical therapy alone was curative in 60% of the surviving patients. Combined medical and surgical therapy was curative in 40% of the survivors. The most frequent isolates in the early-onset group were Staphylococcus aureus (44%) and Gram-negative bacilli (38%); associated mortality was 86% and 83%, respectively. The most frequent isolates in the late-onset group were viridans streptococci (41%) and Gram-negative bacilli (31%); the mortality was 25% and 22% respectively. Suggestions are offered for operative antimicrobial prophylaxis and for medical and surgical treatment of prosthetic valve endocarditis. Prompt surgical replacement of an infected prosthesis is necessary when medical therapy fails.


Effects of guanethidine and methyldopa on a standardized test for renin responsiveness.

A standardized test for renin responsiveness, employing the dual stimulus of upright posture and the loop diuretic furosemide, was applied to 19 hypertensive patients in the untreated state and during therapy with the antihypertensive agents guanethidine and methyldopa. During therapy with guanethidine, 6 of 10 patients with "low-renin essential hypertension" experienced elevations of plasma renin activity to levles ordinarily diagnostic of "normal-renin" hypertension (P less than 0.05), whereas methyldopa had no significant effect on plasma renin activity in either "low-renin" or "normal-renin" patients. It is suggested that methyldopa has a negligible influence on renin responsiveness when stimulated under the above conditions and that it may be used during assessment of plasma renin activity in hypertensive patients whose blood pressure is too severely elevated for temporary withdrawal of therapy.


Cost and yield of the hypertensive evaluation. Experience of a community-based referral clinic.

During the first 5 years of a community-based referral hypertension clinic, 331 ambulatory patients referred for diagnostic evaluation. Thirty-four patients were judged to be normotensive on the basis of resting blood pressures on 3 separate days. In 51 patients the diagnosis was borderline hypertension and 220, essential hypertension. Twenty-six patients (10.6%) had secondary hypertension. Twenty-one patients with secondary hypertension were first recognized from the data of the history, physical examination, and routine urinalysis. The main cost per patient of the initial and further evaluations was computed for each group of patients. The average cost to identify one case of secondary hypertension in the clinic was $2083. Because of the large problem with hypertension in the United States today, the cost-effectiveness of various approaches to the evaluation of patients with hypertension requires thoughtful reappraisal.


Familial neutrophil chemotaxis defect, recurrent bacterial infections, mucocutaneous candidiasis, and hyperimmunoglobulinemia E.

A 20-year old women and her infant daughter had recurrent bacterial infections and chronic mucocutaneous candidiasis and were found to have extreme hyperimmunoglobulinemia E, defective neutrophil chemotaxis, and diminished lymphocyte responses to Candida antigen. Studies of members of the mother's family showed mild increases of IgE and mildly depressed chemotactic activity of neutrophils in a brother, the father, and the paternal grandfather. The recurrent bacterial infections in these two patients can be explained by the defective neutrophil chemotaxis. It is not known whether the mucocutaneous candidiasis is related to the neutrophil chemotaxis with the lymphocyte defect being secondary to the Candida infection or, alternatively, the Candida infection being secondary to the lymphocyte defect. Furthermore, the family data suggest a familial pattern of hyperimmunoglobulinemia E and defective neutrophil motility.


Staphlococcal endocarditis in parenteral drug abusers: source of the organism.

Because approximately one third of persons injecting illicit drugs carry Staphylococcus aureus in their nose and throat or on the skin, we wondered if the carrier was the person in the drug-injecting population at risk of developing endocarditis. If so, patients with drug-related, staphylococcal endocarditis should have a very high carriage rate of the organism when first admitted to the hospital. Ten such patients were studied within 3 days of admission, and all were carriers of S. aureus. In each case, the phage type of the carried organism matched that of the organism recovered from the blood.


Diagnosis of pancreatitis masked by hyperlipemia.

It is often difficult to confirm a diagnosis of acute pancreatitis in the presence of hyperlipemic serum because the serum amylase and lipase and the urinary amylase are frequently normal. We were able to substantiate the diagnosis of pancreatitis in seven patients with hypertriglyceridemia (greater than 1200 mg/100 ml) by the use of the simple amylase/creatinine clearance ratio and by the serial dilution of hyperlipemic serum. The amylase/creatinine clearance ration in the hyperlipemic pancreatitis patients (10.0%) was significantly (P GREATER THAN 0.001) higher than in normal patients (3.1%) and essentially the same as in nonlipemic pancreatitis patients (9.2%). The calculated serum amylase activity after serial dilution of the serum showed up to a tenfold increase in hyperlipemic pancreatitis, with no significant increase in normal controls, hyperlipemic controls, and nonlipemic pancreatitis.


Low blood pressure in young adults with cystic fibrosis: an effect of chronic salt loss in sweat?

Young adults with cystic fibrosis have lower blood pressures than control subjects of similar age and sex. The low blood pressure may be related to the excessive loss of salt in the sweat of these patients. A beneficial effect of the cystic fibrosis gene may be protection against developing hypertension in both the homozygous and heterozygous states, especially if the heterozygote has borderline elevation of sweat electrolytes.


Guidelines for the management of hospitalized narcotics addicts.

Opiate-dependent patients who are hospitalized for medical, surgical, or obstetrical reasons require proper management of their addiction to care of their presenting illness. Guidelines are offered for methadone support during hospitalization for the patient enrolled in a treatment program and for the street addict. The important clinical features of withdrawal reactions are outlined, and a method is presented for establishing an initial and supportive dose of methadone for street addicts. The use of analgesics in the addicted patient, the treatment of methadone overdose, and some problems in the management of mixed-drug abuse are discussed.


The community and medical education: organization and function of a board of concerned citizens.

A Board of Concerned Citizens was organized in 1971 to facilitate the resolution of problems between the College of Medicne and Dentistry of New Jersey at Newark and the community in which it is located. The board has provided an orderly imput by consumers, representatives of community organizations and nonfaculty employees into decisions on policies and programs of the medical and dental schools. It has aided in the resolution of employee grievances and student problems, given support needed to assist the development of quality health care services, helped improve the climate for clinical research, and served as an intermediary between the community and college on issues of special concern to local residents. An opinion poll conducted 3 1/2 years after its organization shows c ontinued support by citizenry, nonfaculty employees, faculty, and students for a Board of Concerned Citizens. Experiences of the board indicate that investigations and recommendations of a properly organized and motivated group of community residents and leaders can provide an effective bridge between a community and a medical or dental school.


[New tetraene antibiotic, abkhazomycin].

The cultures of Act. L10-0740 and L10-0772 were isolated from a soil sample. By their morphological and cultural features they were close to Act. badiocolor and differed from the latter by their antibiotic properties. Because of this they were classified as a new variant of Act. badiocolor var. abhasus var. nov. The cultures produced a new tetraen antibiotic, named abkhazomycin. Its physico-chemical properties are presented.