The significance of intraventricular electrocardiogram in artificial heart pacing. Observations made on 232 patients. From 1972-1975, 232 consecutive patients suffering from A/V block were paced intravenously in the Cardiac Department. Medical School, University of Athens. Of these, 124 were female and 108 male. Their age range was between 49 and 85 years. Besides fluoroscopic and threshold control, the intraventricular electrocardiogram (E.C.G.)., recorded from the tip of the electrode, was used as a guide for the accurate positioning of the catheter-electrode in the right ventricle. An injury pattern with an elevation of the ST segment of at least 3 mV and characteristic and steady morphology was obtained when the electrode tip was satisfactorily impacted in the right position. As a consequence of this, an initial stimulation threshold below 0.7 mA was obtained in all cases and pacing failure, due to catheter displacement was noted in only 11 cases (5%), without any apparent increase in the incidence of right ventricular perforation.


Protein synthesis in heart mitochondria: mechanism and metabolic aspects. A short review is given with respect to the status quo of the knowledge of mitochondrial protein synthesis in mammalian tissues. The inhibitory effects of antibiotic such as chloramphenicol and thiamphenicol are discussed from the point of possible complications for cardiac metabolism. It is shown that a decrease of the activity of cytochrome c oxidase, the terminal enzyme of the respiratory chain, caused an increase in the production of lactate, if beating heart cells are cultured in the presence of chloramphenicol. In vivo treatment of rabbits with the chloramphenicol analogue thiamphenicol causes a strong fall in the cytochrome aa3 content of the hearts. The results are discussed in the light of the possible implications for cardiac function and metabolism in man.


Plasma levels of unconjugated steroids in male baboons (Papio hamadryas) and rhesus monkeys (Macaca mulatta). In an attempt to find suitable animal models to aid in the study of the reproductive processes of the human male, plasma levels of unconjugated pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 20alpha-dihydroprogesterone, 17-hydroxyprogesterone, androstenedione, testosterone, dihydrotestosterone, oestrone and oestradiol were measured in 18 male baboons and 10 male rhesus monkeys and the steroid levels were compared with those previously established in normospermic, middle-aged men. Significant species differences were found with regard to the three delta5-steroids studied; whereas the approximate relationship of pregnenolone to 17-hydroxypregnenolone and dehydroepiandrosterone was 1:2:4 in men, the corresponding relationship was 1:5:30 in rhesus monkeys and 1:10:10 in baboons. Similar levels of 20alpha-dihydroprogesterone were found in the three species. On the other hand, the 17-hydroxyprogesterone levels in baboons were much lower and the levels of androstenedione lower than those found in men and in rhesus monkeys. No species difference was found with regard to circulating testosterone levels. However, both rhesus monkeys and baboons exhibited much higher levels of dihydrostestosterone than did men. Oestrone levels were higher in baboons than in men and oestradiol levels were higher in rhesus monkeys than in men and in baboons. The significant differences in circulating steroid levels suggest that further studies (including i.a. steroid analyses in testicular tissue, seminal plasma and spermatic artery and vein following both stimulation and suppression of testicular endocrine function) are required before preference can be given to any of the two species studied as a suitable animal model for the study of new fertility regulating agents.


Temporal lobe epilepsy. Social conditions and rehabilitation after surgery. A social investigation was performed of 74 patients with temporal lobe epilepsy resistant to medication, who underwent unilateral temporal lobectomy 1960-1969. The patients were compared to their sibilings and to the general population in Denmark. Comparatively many patients were born out of wedlock. The level of schooling achieved was lower than expected, and this was most pronounced in patients with an early onset of epilepsy. The number of patients having received further education was also smaller than calculated. At the time of the operation all patients were socially incapacitated by their epilepsy; this was most pronounced in males, of whom 30 per cent were institutionalized and 32 per cent were receiving disablement pension; at follow-up the figures were 6 per cent and 52 per cent, respectively. Working capacity was markedly improved postoperatively, and at follow-up 39 per cent were in full-time employment. Relief from seizures (or almost complete relief), normal intelligence, normal psychiatric status, and operation before the age of 18 years were factors which favourably influenced the postoperative working capacity. The majority of the patients were unmarried or divorced, and few of the group had children. Their housing conditions were inferior to those of their siblings and of the general population. Parental social class distribution showed an excess in the highest and lowest social classes compared to the Danish population. The patients were subjected to downward social mobility, presumably caused by their illness, as their siblings displayed an upward mobility, which was most marked in the females.


Skeletal muscle fiber types in the adult mouse. The ATPase reaction and its pH lability demonstrate three fiber types in the adult mouse gastrocnemius; Type I (light staining with alkaline preincubation and dark with acid preincubation), Type IIA (dark after alkaline preincubation), type IIB (dark after alkaline and acid preincubation). The SDH and NADH-tetrazolium reductase reactions also demonstrate three types of fibers; those low (A), intermediate (B) or high (C) in oxidative enzyme activity. However, the use of both procedures in serial sections demonstrates that four different combinations occur; the IIB fibers are high in SDH activity, the I fibers are intermediate in SDH enzyme activity, while the IIA fibers are either low or intermediate in SDH activity. These fiber types are present within the gastrocnemius muscle in a distinct pattern of zones. The predominant fiber type, located in the superficial half of the muscle, is the IIA (A) fiber which is high in ATPase and low in SDH activity. This is consistent with the fact that the gastrocnemius is generally considered a white, fast muscle. The IIB and I fibers are fewer in number and are located deeper in the muscle.


Autoantibodies in myasthenia gravis: demonstration of anti-motor endplate antibody and anti-muscle membrane antibody using membrane immunofluorescence technique. The presence of specific serum antibodies in five myasthenia gravis patients was demonstrated against the motor endplates and muscle membranes of rats by membrane immunofluorescence technique. The immunologic specificity of the antibodies was confirmed. The clinical significance is discussed.


Adaptive changes in cardiolipin content of Staphylococcus aureus grown in different salt concentrations. Adaptive changes in cardiolipin content were examined in Staphylococcus aureus 209P using the 32P pulse-labelling method. Cardiolipin synthesis showed increased adaptation when cells grown in normal medium were transferred into high NaCl containing medium. When S. aureus cultured in 10% NaCl medium was transferred back to normal medium, cardiolipin concentration decreased to the normal level within 3 hours. The catabolic rate of cardiolipin in the cells was much slower in the 5% NaCl medium than in normal medium. The cardiolipin synthetase activity was examined by isolated membrane fraction from S. aureus grown both in normal and 10% NaCl medium. The activity was higher by two-fold in membrane fractions from cells cultured in 10% NaCl-containing medium than in membranes from cells cultured in normal medium.


Effect of sodium dodecyl sulfate on immuno-electrosyneresis between normal human erythrocyte membrane and sera of systemic lupus erythematosus patients. An anti-membrane antibody was present in the sera of systemic lupus erythematosus patients in immunoelectrosyneresis with sodium dodecyl sulfate (SDS) solubilized erythrocyte membrane as antigen. The SDS bound to protein was detected by chromatography at 10(-3)M concentration under U.V. light, at 10(-5)M concentration by the distilled water spray method and at 10(-6)M concentration by using rosaniline hydrochloride colorimetry. SDS was removed from the membrane protein at a concentration of 10(-3)M by the first gel filtration of Sephadex G-25 column and at a concentration of 10(-6)M by rechromatography of the same column. More than 99% of SDS in the solubilized erythrocyte membrane was removed by gel filtration. The antigenicity was still positive in the refiltrated fractions of systemic lupus erythematosus patients. Therefore, all precipitates in the gels were antigen-antibody aggregates.


Tissue distributions of 97Ru and 103Ru in subcutaneous tumor of rodents. Mice bearing Ehrlich tumor were administered 97Ru-chloride or 103Ru-chloride intravenously. Examinations of various tissues indicated similar distributions by the two radionuclides. The levels were higher in the lung, liver and kidney than in the tumor tissue. Rats bearing AH-130 tumor were administered 103Ru-chloride intravenously. The 103Ru distribution in rats was highest in the spleen, followed by the liver and kidney; however, the radioactive distribution in the tumor tissue exceeded the muscle level by about 5-fold. Tumors were delineated in rats by scintigraphy. The findings indicate that ruthenium radionuclides may be a useful clinical agent in the delineation of some types of tumors. Ruthenium-97 would be favored in possible clinical usage due to its shorter physical half-life and lower levels of gamma energy.


Preleukemia: hematological disorders prior to onset of leukemia. Published data on Japanese leukemia patients with a preleukemic hematological disorder were assessed. The reexamined cases were from the "Japona Centra Revuo Medicina" reported during the period from 1952 to 1971. Among preleukemic hematological disorders, hypoplastic anemia was the most frequently reported (41 of 62 cases). These "hypoplastic preleukemia" patients were rather elderly and terminated mostly in atypical myelocytic leukemia. The chief hematological feature of the hypoplastic preleukemia cases was the coexistence of a relative erythroid hyperplasia and a slight increase of myeloblasts in the bone marrow that was unusual in hypoplastic anemia. The presence of pancytopenia and hypocellular marrow with a relative erythroid hyperplasia combined with a slight increase of myeloblasts probably indicates hypoplastic preleukemia that terminates later in acute leukemia.


Primary biliary cirrhosis. Study of the action of mitochondrial antibody plus complement on mitochondrial membrane functions. It has been described that mitochondrial antibodies can be detected in the serum of primary biliary cirrhosis patients (over 90%) and that these antibodies are directed specifically against a component of the mitochondrial inner membrane. In the present study whole mitochondria isolated from rat liver were exposed to mitochondrial antibodies from patients with primary biliary cirrhosis, and to antibodies induced experimentally in rabbits to mitochondrial antigens of rat liver. This was an attempt to study the action of these antibodies and complement on mitochondrial functions. By studying respiratory control and oxidative phosphorylation of mitochondria, no significant, nor specific effect on mitochondrial membranes functions could be detected, after the incubation of suspensions of mitochdondria with normal or immune gamma-globulin (neither from rabbits nor from human) nor with the addition of complement. Furthermore, the respiration of fragmental mitochondria using succinate and NADH substrates was unaffected by the antibodies and complement. Similarly, mitochondrial APT-ase activity and swelling and contraction were not affected by antibody. Experiments are in progress to study the hypothesis of a lymphocyte dependent antibody mediated cytotoxicity in this system. In order to demonstrate that this autoimmune phenomenon might be associated with cellular immunity to a mitochondrial component, we have in a previous report demonstrated impairment of mitochondrial respiratory control by lymphocytes from rabbits sensitized in vivo with mitochondrial antigens. Subsequently we have recently shown evidence of sensitization. In-vivo of lymphocytes from patients with primary  biliary cirrhosis as demonstrated by an injurious effect on rat liver mitochondria by lymphocytes from patients with this disease. Further studies are necessary to clarify the involvement of this phenomena in the possible mechanisms responsible for the pathogenesis of the lesions.


A general cardiovascular risk profile: the Framingham Study. Persons at high risk of cardiovascular disease can be effectively identified from a measurement of their serum cholesterol and blood pressure, a smoking history, an electrocardiogram and a determination of glucose intolerance. One general function for identifying persons at high risk of cardiovascular disease is also effective in identifying persons at risk for each of the specific diseases, coronary heart disease, atherothrombotic brain infarction, hypertensive heart disease and intermittent claudication, even though the variables used have a different impact on each particular disease. The 10 percent of persons identified with use of this function as at highest risk accounted for about one fifth of the 8 year incidence of coronary heart disease and about one third of the 8 year incidence of atherothrombotic brain infarction, hypertensive heart disease and intermittent claudication. Hence the function provides an economic and efficient method of identifying persons at high cardiovascular risk who need preventive treatment and persons at low risk who need not be alarmed about one moderately elevated risk characteristic.


Acupuncture and transcutaneous electric stimulation in the treatment of chronic sacrolumbalgia and ischialgia. A comparison was made between 50 patients treated with acupuncture and 50 patients treated with transcutaneous electric stimulation. All patients suffered from chronic sacrolumbalgia or ischialgia of more than six months' duration. Two to 10 treatments were given at weekly sessions, the mean being 5 in both groups. Stimulation points were selected by the same principle in both groups: one point along the course of the nerve trunk affected, and one point at a dermatome proximal to the affected segment. The stimulation was given bilaterally. Needles were inserted as deep as the muscular layer and twirled at 5 min intervals. In the electric stimulation square-wave impulses of 1.0 msec duration and 50 Hz frequency were used. The electrodes were 0.9 cm in diameter. Each acupuncture and electric stimulation was of 20 min duration. Pain relief was complete or moderate in the acupuncture group in 58% of the cases, and in 46% in the electric stimulation group. After 2 months 30 patients in the acupuncture group and 23 patients in the electric stimulation group still reported satisfactory relief of pain. After 6 months 15 patients in the acupuncture group and 10 patients in the electric stimulation group still reported satisfactory relief of pain.


New instrument for automatic recording of clot lysis. An experimental instrument that determines and records automatically the end-point of clot lysis is described. The instrument is unique in that it measures the end product of lysis directly and quantitatively, unlike currently available indirect methods that rely on the optical or mechanical changes indicative of lysis. Data showing that the instrument is capable of yielding reliable, reproducible results in a variety of experimental conditions are presented.


Place and time aspects of the occurrence of Down's syndrome. Prevalence rates at birth for Down's syndrome were compared for Massachusetts communities of different population densities. Overall, there was a small positive association between the rate of Down's syndrome and population density, entirely attributable to a strong association for the children of older mothers. An analysis for space and time clustering of births of 2469 children born in Massachusetts with Down's syndrome revealed no aggregation of cases, except for a slight seasonal peak in the summer.


Comparative trial of influenza vaccines. II. Adverse reactions in children and adults. Commercially prepared zonally and chromatographically purified bivalent (A/England-B/Mass) and monovalent (B/Hong Kong) inactivated influenza vaccines were given to 438 individuals 6-33 years old. The vaccines had been examined for antigen content by chick cell agglutination (CCA) tests and electron microscopic particle count determinations. Endotoxin and pyrogen content were determined by limulus amebocyte lysate (LAL) and rabbit pyrogenicity assays; and egg-associated protein contamination was estimated by total protein and single radial immunodiffusion assays. Although great differences (10-200-fold) were found in the amount of endotoxin or pyrogen in the vaccines, no significant differences were found in the febrile responses they induced. Both bivalent and monovalent vaccines induced fever of greater than or equal to 38 C at a rate of approximately 3 1/2-4% above background. The febrile responses were most frequent at 24 hours after inoculation and a higher rate was observed in children than adults. Local reactions consisting of tenderness, erythema or induration were seen in from 20-57% of the recipients and also were unrelated to the pyrogenic or host-derived materials in the vaccines. Adults had higher local reaction rates than children and some vaccines containing larger amounts of viral antigen induced significantly higher rates of reactivity than did vaccines containing smaller amounts of antigen. Although 37-51% of all recipients experienced either a local and/or febrile reaction to influenza immunization, the reactions were in general mild and would not consitute a significant disadvantage in the immunization of children over 6 years and adults to prevent influenza infection and its sequelae.


Muscle damage produced by chronic alcohol consumption. The effects of chronic alcohol consumption on skeletal muscle, independent of nutritional factors, were studied. Chronic alcohol ingestion led to striking ultrastructural changes in skeletal muscle, including intracellular edema, enlarged and distorted mitochondria, dilatation of sarcoplasmic reticulum, and increased amounts of fat and glycogen. Actomyosin was isolated from skeletal muscle of baboons and volunteers fed alcohol. In this preparation, ATPase activity and the calcium sensitivity of ATPase were decreased. The isolated actomyosin displayed reduced contractility in vitro, measured by the association of actin and myosin and the response to adenosine diphosphate (ADP). In 2 of 3 volunteers, isolated membranes of the sarcoplasmic reticulum exhibited decreased calcium uptake. The pressure-rate product was increased in some of the volunteers after submaximal or maximal work. The changes decribed in this study were found after alcohol administration had been discontinued, and they may play a role in the development of alcoholic myopathy and cardiomyopathy.


Cardiac actomyosin ATPase activity after prolonged physical conditioning and deconditioning. Cardiac actomyosin ATPase was increased by making rats swim 150 min/day, 5 days/wk for 8 wk. Changes in Ca2+ -stimulated ATPase activity were then studied in these conditioned rats and in similarly conditioned animals in which swimming was subsequently discontinued (group A), reduced to 45 min/day (group B), or continued at the original level for an additional 8 wk (group C). After the 8-wk initial program actomyosin ATPase activity averaged 22% higher in hearts of conditioned rats than in hearts of sedentary controls (P is less than 0.001). In group A, actomyosin ATPase activity declined rapidly and reached the level found in sedentary controls by the 13th day. In group B, actomyosin ATPase activity declined to the control level by the 30th day. At the end of 16 wk the percent increase in actomyosin ATPase activity in group C over that in hearts of sedentary animals was approximately the same as after 8 wk. These results demonstrate that elevation in cardiac actomyosin ATPase caused by moderate physical training in rats is not maintained if the training program is decreased or discontinued. The training program must be continued at or near the initial level if the increases in cardiac actomyosin ATPase are to be sustained.


Pig reticulocytes: II. Characterization of density-fractionated maturing reticulocytes. A simple centrifugation technique initially developed for fractionation of human red cells in their own plasma has been found to be readily applicable to the separation of reticulocytes normally appearing in the pig soon after birth as well as to those induced in the adult pig by phenylhydrazine administration. The density of the naturally occurring reticulocytes, maximally amounting to 10-15% of total cells derived from a 7-day-old pig, varied from 1.073 to 1.101, in contrast to the mature cells, presumed to be the fetal cell type, whose density ranged in a narrower limit, from 1.101 to 1.106. In adult animals, the reticulocytosis amounting to more than 70% takes place in response to daily administration of phenylhydrazine for 7 days. The density of these reticulocytes varied widely from 1.068 to 1.094; in contrast, the density of the mature adult red cells ranged from 1.095 to 1.106. Among various physiological parameters examined, a marked decrease in cell size, cell water content, RNA, Na+ -K+ -ATPase, and Ca2+ -ATPase activities was observed in the course of reticulocyte maturation in vivo in the adult animal. All these physiological parameters were found to undergo a similar reduction from the top to the bottom fractions of the reticulocytes separated according to their density, suggesting that the separation technique employed here represents separation of reticulocytes according to their age.


The effort to rehabilitate workers' compensation. State workers' compensation laws have been subjected to criticism since their inception; pressure to change them is now increasing. Most of the current challenge arise from dissatisfaction with the level of benefits available to disabled workers or their survivors, and, to a lesser degree, with the extent of program coverage. In response to this challenge, changes will occur that my range from reform-simply raising benefit levels and extending coverage-to program redesign, implying major structural revisions or abolishment of the system. For several reasons, including public apathy, the role of interest groups, and experience with other social insurance programs, it seems likely that basic structural shifts will not occur in the near future. While the criticism of these state laws is widespread, the problems can be dealt with in the existing framework. One area, however, could conceivably arouse sufficient public and legislative interest to upset this forecast. If it develops that the system is excluding large numbers of individuals disabled or killed by occupational diseases, workers' compensation laws could be placed in jeopardy. While evidence on this is scarce, it is clear that the current system compensates only a small number of serious cases of disability arising from occupational diseases.


The Doppler and its use in axial flaps.

The Doppler and its use in axial flaps. The Doppler ultrasonic flowmeter has been used as an aid in locating blood vessels that supply axial flaps in several different clinical situations. It has also been of value in microvascular surgery in which axial vessels of island flaps can be located and continuous patency monitored after their transfer and anastomosis.


[The attack of different proteases on isolated zonular fibers (author's transl)]. Some proteases, i.e. trypsin, alpha-chymotrypsin, thermolysin, proteinase K, alpha-amylase, collagenase, and papain were investigated on their effect on isolated zonular fibers. All these enzymes but collagenase were zonulolytic active. An attack on the ground substance of the fibers by substances solving glycosaminoglycans and proteoglycans (hyaluronidase, EDTA, guanidinium chloride, H2O2) showed an increased effect of the enzymes used. These results suggest that the interfibrillar matrix has a protective function on the zonular fibers.


An evaluation of IL-404 oxygen alarm monitor. The accuracy of the IL404 oxygen alarm monitor has been tested against oxygen/nitrogen mixtures of known composition. The effects of inhalational anaesthetic agents and of changes in flow rate, PCO2 and humidity have also been investigated. The instrument was found to be sufficiently stable and accurate for clinical use and was unaffected by the presence of volatile anaesthetics, change in gas flow rate and the presence of nitrous oxide, carbon dioxide or water vapour. The instrument incorporates an efficient alarm system which gives both audible and visible warning should the oxygen concentration fall or exceed pre-set limits.


Constant negative pressure: an adjunct in the treatment of gastroschisis. Three cases of gastroschisis are described, managed surgically in the neonatal period by staged reduction employing a dacron reinforced silastic sac. All three cases were treated during the postoperative period with the application of constant negative pressure around the thorax and abdomen. Reduction of the eviscerated mass appeared to be accelerated and all three cases survived. The possible benefits of constant negative  pressure around the thorax and abdomen in the treatment of gastroschisis are discussed.


Tussockosis: reactions to Douglas fir tussock moth. An unusually heavy infestation of the tussock moth resulted in a high incidence of symptoms affecting the skin and mucous membranes of those exposed to high concentrations of particulate matter of this insect. Extensive epidemiological studies proved these manifestations to be both toxic and allergic. The authors have given this condition the name, Tussockosis. Clinical and immunoligical studies including in vitro procedures and direct patient testing confirmed the allergenicity, as well as the non-specific irritation of material from this moth.


Immunologic reactions in penicillin factory workers. One hundred sixty-nine employees of a synthetic penicillin plant participated in this study to correlate immunologic reactions, allergic symptomatology and dustiness of the work area. Statistically significant positive correlations existed among the following: (1)presence or absence of symptomatology and increasing dustiness of the work area; (2)presence or absence of symptoms and the presence or absence of benzyl-penicilloyl specific hemagglutinating antibody (BPO-specific antibody); (3)the absence, presence and level of titer of BPO-specific antibody with the dustiness of the work area. Because synthetic penicillin dust in the workroom air is able to evoke immunologic responses and produce symptoms among workers exposed to high levels, it is recommended that a reasonable air level for penicillin in factories be in the range of those demonstrated in the least symptomatic group in the study with measurements below 0.1 mg/m3.


Epizootic staphylococcal infections in subhuman primates after surgical operation. In late October, 1974, Staphylococcus aureus postoperative wound infection was recorded in a nonhuman primate (Macaca mulatta) which had recently undergone surgical operation. Infection in a second monkey appeared approximately 2 weeks later, and a clustering of 6 cases appeared over the next 3-week period. The clinical spectrum included septicemia in 2 monkeys and skin infection at the surgical incision site of several others. Investigation revealed a uniform and consistent association of a phage group II S aureus strain characterized as 3A/55/71. This strain was also found to be enzootic among other postoperative monkeys sharing or having shared a common postsurgical care unit with infected monkeys. Epizootiologic studies indicated that this unusually virulent S aureus strain probably was introduced by an infected monkey which underwent surgery earlier in the month and that additional monkeys became infected by animal-to-animal transmission. After appropriate control sanitary measures were instituted, no new infections occurred.


Prevention of swine dysentery with a combination of lincomycin and spectinomycin and resistance of swine dysentery to tylosin and sodium arsanilate. The addition of a combination of lincomycin and spectinomycin to feed at the total concentrations of 44 and 77 mg/kg, beginning at the time of exposure and continuing for 8 weeks, prevented experimentally induced swine dysentery in swine. The disease did not develop after the medication was withdrawn. In contrast, swine dysentery, similar to that seen in the nonmedicated swine, did develop in simultaneously exposed swine treated with feed containing either 44 mg of tylosin or 99 mg sodium arsanilate/kg. The swine fed sodium arsanilate and which developed hemorrhagic diarrhea had a more severe form of this type of diarrhea than did the nonmedicated swine. After reexposure to inefective inoculum of swine dysentery 86 days after initial exposure, all remaining swine previously medicated with either tylosin or sodium arsanilate and all nonmedicated swine were immune; whereas 17 of the 24 swine fed the combination of lincomycin and spectinomycin were susceptible to swine dysentery and developed diarrhea.


Clinical, histologic, and histochemical study of imidocarb diproprionate toxicosis in goats. The toxic effects of imidocarb diproprionate (3,3'-bis [2 imidazolin-2yl]-carbanilde diproprionate) were evaluated in adult goats given (intramuscular injection) a lethal dose (6.75 mg/kg). The immediate clinical signs of toxicosis were transient excessive salivation and diarrhea. Anorexia, dyspnea, recumbency, and death occurred between postinjection days (PID) 4 and 8, during which time 7 goats died and 4 moribund goats were euthanatized. There were marked increases in mean serum urea nitrogen concentration and significant increases in serum glutamic oxalacetic transminase activity and in the mean number of circulating neutrophils after PID 4. Renal hyperemia and enlargement were evident by PID1. Serosanguineous fluid in the trachea and major bronchi, pulmonary congestion and edema, hydrothorax, hydroperitoneum, and less frequently hydropericardium were observed on and after day 4. Microscopic renal tubular lesions rapidly progressed from pyknotic epithelial nuclei observed at 6 and 12 hours to acute tubular necrosis of epithelium of the proximal convoluted tubules on days 1 and 2. Pulmonary congestion and edema; hemorrhage into alveoli, bronchioles, and bronchi; and intracytoplasmic lipid vacuoles within the hepatocytes in the periacinar zones of the hepatic lobules were observed on or after day 4. Succinic dehydrogenase and adenosine triphosphatase activities decreased progressively in the epithelial cells of the proximal convoluted tubules. The decreases in cellular enzymatic activity occurred shortly after the appearance of microscopic lesions in the tubular epithelium.


The right ventricle in chronic airway obstruction: a clinicopathologic study. In men 40 or more years of age at death, the upper limits of normal (means plus 2 SD) cardiac ventricular weights were 69 g for the right ventricle and 203 g for the left ventricle plus septum. Right ventricular thickness, as usually determined at autopsy, was a relatively poor index of hypertrophy. When one ventricle hypertrophies as a result of stress, the other tends to enlarge simultaneously, even if no stress on it has been evident. Right ventricular weight correlated positively, although not strongly, with severity of emphysema and with the severity  of clinical chronic airway obstruction. Correlations between right ventricular weight and pathologic changes in the airways were weak or absent, except that subjects with abnormal large airways, but normal small airways, showed improved correlation between severity of emphysema and right ventricular hypertrophy, compared with the entire series. There was no correlation between left ventricular weight and severity of emphysema. The electrocardiogram was very reliable in the diagnosis of right ventricular hypertrophy (corpulmonale) due to chronic airway obstruction; the chest roentgenogram was somewhat less sensitive in this regard.


Surgical treatment of congenital defects in the abdominal wall. A series of 28 patients is presented with the two conditions of omphalocoele and gastroschisis treated over a five-year period . Improved survival can be obtained by the use of staged procedures with a silastic prosthesis plus intravenous alimentation with later definitive operation. If peripheral veins are used, serious complications are almost totally avoided. This combined form of therapy is the treatment of choice in infants with massive defects in the abdominal wall.


Drugs five years later. Spectinomycin.

Drugs five years later. Spectinomycin. A single intramuscular injection of 0.2 g of spectinomycin hydrochloride is highly effective for the treatment of uncomplicated anogenital infections with Neisseria gonorrhoeae. Spectinomycin hydrochloride is indicated for uncomplicated anogenital gonococcal infections in men and women who cannot receive penicillin or probenecid, and is the drug of choice for the retreatment of patients with uncomplicated anogenital gonococcal infection who have not responded to other antibiotics. A single dose of spectinomycin does not appear to be reliably effective in the treatment of gonococcal pharyngitis. Preliminary reports indicate that multiple-dose schedules of spectinomycin will prove to be effective in gonococcal pelvic inflammatory disease and disseminated gonococcal infection. In the dosage used for gonococcal infections, spectinomycin has little effect on infection with Treponema pallidum. Evaluation of this antibiotic against other microorganisms suggests little utility for this agent in conditions other than gonococcal infections.


[Study of the distribution of C14-variamycin and C14-mitramycim after intravenous administration to mice]. Distribution of antitumor antibiotics, i.e. C14-variamycin and C14-mitramycin in the organs of albino mice after their intravenous administration in single doses was studied. Similarity in the distribution dynamics of both the antibiotics with respect to the animal organs was found. However, the level of variamycin as compared to that of mitramycin was much higher in the liver and especially the spleen. In the experiments with variamycin the radioactivity of the kidney tissue decreased more rapidly than in the experiments with mitramycin. Chromatographic analysis of the urine of the mice treated with C14-variamycin was performed. The labeled Variamycin was detected in the animal urine within 48 hours from the moment of the antibiotic administration. Its portion in the total amount of the radioactive products in the urine was 30 to 40% at various stages of the study.


Improved method of assay for choline.

Improved method of assay for choline. A modified assay for choline is described which is shorter, yields more consistent responses, and requires considerably less time, space, and equipment than the existing assays.


[Further cytochemical researches on Microsporidia parasites of the Mediterranean shore crab, Carcinus mediterraneus Czerniavsky, 1884 (author's transl)]. A cytochemical study of Microsporidia in Carcinus mediterraneus points out the following data: acid or very acid intrasporoblastic mucopolysaccharids, are found in Thelohamia maenadis which react as sulfomucins in opposition to external asulfated mucosubstances rich in electronegative groups. In Nosema pulvis, the mucopolysaccharid compound is nearly equivalent of that of Nosema orthocladii. Both species are also characterized by the abundance of sulfured proteins in their spore walls and the lack of stock substances.


Topical use of tetracycline in the treatment of acne: a double-blind study comparing topical and oral tetracycline therapy and placebo. A group of 75 subjects with moderate or severe acne was divided by random selection into three treatment groups. One group was treated with a topically applied placebo liquid and with 500 mg of orally administered tetracycline hydrochloride daily; one group received orally administered lactose capsules and topically applied placebo liquid each day; and one group was treated with orally administered lactose capsules and with a topical preparation containing tetracycline hydrochloride and n-decylmethyl sulfoxide, an agent intended to enhance antibiotic penetration. At the conclusion of the 13-week study and at several points during the study, the conditions of the subjects receiving topically or orally administered tetracycline hydrochloride were significantly (P less than .05) more improved than the conditions of the subjects receiving lactose capsules and the topically applied placebo liquid. However, there was no significant difference between the effects of topically and orally administered tetracycline hydrochloride.


Acne vulgaris: double-blind trial comparing tetracycline and clindamycin. A double-blind prospective study was undertaken to compare low-dosage tetracycline hydrochloride and clindamycin hydrate hydrochloride in the treatment of patients with pustular acne. Clinical improvement was noted in 93.7% of those receiving tetracycline and in 92.8% of those receiving clindamycin. Of those patients who were receiving clindamycin, two patients developed diarrhea and one patient developed pseudomembranous colitis. We conclude, therefore, that clindamycin should not be used as a primary drug in the treatment of acne.


Subcutaneous fat necrosis after paracentesis: Report of a case in a patient with acute pancreatitis. A patient with acute pancreatitis developed subcutaneous fat necrosis of the anterior abdominal wall secondary to leakage of pancreatic enzymes through a rent in the peritoneum following paracentesis. The same patient also had another subcutaneous complication of pancreatitis, namely, nodular liquifying panniculitis of the lower extremities. The diagnosis was made by the typical histological findings of subcutaneous fat necrosis, foci of necrotic cells with a "ghost-like" appearance, and basophilic-staining calcium soaps deposited around the necrotic cells.


Hypopigmentation with punctate keratosis of the palms and soles. Generalized discrete hypopigmented macules forming a camouflage pattern appeared on the skin of a man. The condition has been present and has not changed since the age of 6 months. Five other members of his family are reported to have the same abnormality. All affected members also have punctate keratosis of the palms and soles. An autosomal dominant pattern of inheritance is suggested.


Progressive multifocal leukoencephalopathy in renal transplant recipients. Progressive multifocal leukoencephalopathy, a slowly progressive papovavirus infection of the CNS, has been reported in more than 110 patients to date, over half of whom have had either leukemia or lymphoma. Our patient is the fourth case of PML occurring after long-term immunosuppression for renal transplantation. We believe that PML is emerging as a potentially serious problem in renal transplant recipients.


[Dynamics of the cell membranes].

[Dynamics of the cell membranes]. The Author, after recalling the fundamental concepts of the function and structure of living cells, illustrate the functions characteristic of cellular membranes. He examines in detail the principal models which have been proposed for the interpretation of the structure of membranes, particularly those of DANIELLI and DAVSON and of ROBERTSON. He recalls his own biochemical experiments on the endoplasmic reticulum of the liver and spleen, from which useful information can be drawn on the locating of some catalytic proteins in the membrane. He then devoted particular attention to the relationships between proteins, lipids and glucides as constitutent parts of membranes and discusses the recent "fluid mosaic model" proposed by SINGER and NICOLSON. He concludes giving some examples of the functional flexibility of membranes and remarks that the collaboration between biochemists and electron microscopists has proved in the last few years to be a fertile point of encounter, promising results which will provide spectacular information on the structure and function of cellular membranes.


Disabled counselors: perception of their effectiveness in a therapeutic relationship. It has not been delineated how a disabled person is viewed when interacting with another person. The present study investigated subject perception of a counselor in a wheelchair who was seen in a video-taped counseling interview. Subject degree of body satisfaction was measured to assess the importance of this variable in the perception. Evaluation of the counselor was by the Barett-Lennard Relationship Inventory that measures four dimensions of a relationship: emphatic understanding, positive regard, unconditional regard and congruence. Results suggest that a counselor in a wheelchair is perceived more favorably than an able-bodied counselor along three of these dimensions and female subjects perceive him more favorably than male subjects do. Degree of body satisfaction does not seem to be a factor in this perception.


[Discovery of viroids and possible relationship with human and veterinary medicine]. The researches of DIENER and co-workers and those of the SEMANCIK'S group, have recently established that some plant diseases, such as potato spindle tuber, citrus exocortis disease and chrysanthemum stunt, are caused by a new class of pathogens, named viroids. These are the smallest known agents (they are smaller than viruses) having a molecular weight of ca 10(5) daltons, and composed of a highly structured RNA, rich in guanine-cytosine base pairs without a capsid. Little is known about the origin, replication model and pathogenic mechanism of viroids and until now only speculations are possible on these subjects. Some properties of the unknown agents of slow virus diseases (scrapie, Kuru, Creutzfeldt-Jakob disease and mink transmissible encephalopathy), suggest that these alterations in the central nervous system are caused by a sort of animal viroid.


[Cytologic diagnosis of stomach polyps]. Cytological and cytochemical studies of smears, taken during gastrofibroscopy in 36 patients with polyps of the stomach, with the aim to ascertain cytological and cytochemical characteristics of gastric polyps depending upon their histological structure were carried out. It was established that in the case of simple glandular polyps, because of nonspecificity of morphological changes in the stomachal epithelium, a cytological investigation in establishing clinical diagnosis plays a secondary role; the presence of goblet cells in smears makes it possible to verify polyps by means of enterolysis; identification in smears of cells of the proliferating epithelium, possessing a set of pathognomic signs, enables one to diagnose cytologically a corresponding form of polyps.


[Activity of lysosomal alpha-arylsulfatase and beta-glucuronidase enzymes in benign and malignant breast tumors]. The total activity per microgram of protein of alpha-arylsulphatase and beta-glucuronidase lysosomial enzymes has been determined in 20 cases of benign and malignant breast tumour. The activity of lysosomial enzymes of the normal breast tissue was always much lower than in neoplastic tissues. The difference is already fairly marked in the case of benign tumours and cystic fibroadenosis, but reaches its peak in malignant tumours where activity is 4-5 times higher than normal values. In the case of total activity, the reference is to one ml of homogenate in distilled water, and in the case of specific activity to mg of protein of the homogenate, in either case the findings are highly significant. Although these researches are at a preliminary stage, they confirm the importance of lysosomial enzyme modifications in the phenomenon of neoplastic growth in the breast.


Maturational arrest of fetal muscle in neonatal myotonic dystrophy. A pathologic study of four cases. Skeletal muscles from four infants with a severe neonatal form of myotonic muscular dystrophy showed histopathologic features of immaturity. Three of the infants died in the neonatal period and were studied at autopsy; one of these and the still-living infant had a gastrocnemius muscle biopsy. The most severely involved muscles were those associated with arthrogrypotic joints regardless of function as flexors or extensors. Pharyngeal muscles and the diaphragm were also severely involved. Immature features included irregularly distributed small, round muscles fibers with large vesicular internal nuclei and sparse myofibrils. Histochemical differentiation was incomplete and fiber types often could not be distinguished. Muscle fiber degeneration and other features of myotonic dystrophy in adult muscle were lacking. Electron microscopy showed fine granular chromatin and convoluted nuclear membranes of centronuclear fibers, dialated transvers tubules that were aligned longitudinally as in fetal myotubes, poorly formed Z-bands, simple mitochondria, and many satellite cells. We suggest that these features represent an arrest in fetal muscle maturation due to unresponsiveness of an abnormal sarcolemma to trophic influences of normal innervation.


Bromocriptine in Huntington chorea.

Bromocriptine in Huntington chorea. Following a recent report that apomorphine hydrochloride alleviates the involuntary movements of Huntington chorea, we have investigated another dopamine receptor agonist, bromocriptine, in this disease. A double-blind crossover study in six patients showed that rather than improving chorea, bromocriptine induced an exacerbation. This finding supports the view that choreatic movements correlate with overactivity in dopaminergic systems.


[Sex-linked juvenile retinoschisis].

[Sex-linked juvenile retinoschisis]. About 13 observations of sexe linked juvenile retinoschisis, the authors describe the ophthalmoscopic, fluorographic and functional aspects of the disease whose caracteristics are:--its sexe linked recessive heredity; --its clinical characterestics associating: a microcystic macular degeneration, peripheral retinal lesions, vitreous body alterations, --an electroretinogram of the negative type.


[Goldmann-Favre hyaloido-tapetoretinal degeneration]. In a sister and brother we found a case of vitreo-tapeto-retinal degeneration (macular retinoschisis, night-blindness, vitreous micro-fibrillose degeneration, abolished E.R.G., very pathological E.O.G.) and a "fruste" form of tapeto-retinal degeneration (De Lange's curve and flicker-E.R.G. both modified, E.R.G. subnormal and slight pathological changes in adaptometry). The father of these two patients suffered from tapeto-retinal degeneration which had caused complete blindness. Basing their suppositions on their personal experience and medical literature, the authors believe that the type of vitreo-retinal degeneration is best determined after examination of the mode of hereditary transmission. In the family which is presented, they believe that it is a form of Goldmann-Favre's disease with pseudo-dominance.


[2-year results of trabeculectomy at the ophthalmological clinic of Hôtel-Dieu (1973-1974)]. Trabeculectomy, an operation of relatively easy technique, is effective on the intra-ocular pressure in 93,5 p.100 of cases in our statistics. It does not alter the vision and in some cases improves it, and carries few post-operative complications. A flat anterior chamber, whose frequency varies according to the indications, is seldom severe. It appeared however as a frequent complication in closed angle glaucoma (30 p. 100), and in secondary glaucoma (14 p. 100), more frequently than in chronic open angle glaucoma (8 p. 100). Other complications are rare. Trabeculectomy, as a specific fistulising procedure, in fact appears to us to be one of the best antiglaucomatous surgical operations.


Human tear cholesterol levels.

Human tear cholesterol levels. Using a cul-de-sac sampling method, tear cholesterol concentrations were measured for a population of subjects varying widely in age and relative body weight. Under unregulated conditions tear and plasma cholesterol levels failed to correlate significantly; however, when both diet and sampling times were strictly regulated, a number of well defined correlations did emerge amongst age, relative body weight, tear and plasma cholesterol levels. No significant response differences were found between the sexes in either the unregulated or the regulated formats however.


[Intrathecal cortison injection in lumbar disc problems (author's transl)]. Intrathecal instillation of corticosteroid was used in treatment of 188 patients with persistent sciatica or lumbar pain caused by disc hernia or osteochondrosis and recurrent sciatica or lumbar pain after disc operation. 88 of 122 own patients were followed up. Indication, mechanism of steroid action, technic, complications and results are discussed. According to the good results in part of the patients, still after years, the authors believe, that intrathecal corticosteroid administration is a further useful method of conservative treatment of degenerative lumbar disc affections. This therapy can also be used in patients with recurrent, persistent lumbar or leg pain after disc operation.


The differentiation of T lymphocytes. Density characterisation of thymic and peripheral T cells responding in syngeneic and allogenic mixed lymphocyte reactions. Equilibrium density separation on continuous albumin gradients was used to separate and characterise the T cells responding by proliferation to both syngeneic and allogeneic stimulating cells in the one-way mixed leucocyte reactions (MLR). In CBA mouse spleen both light and dense T cells were capable of responding in an allogeneic MLR. No T cells responding to stimulation be syngeneic B lymphocytes could be isolated from adult or 7-day CBA mouse spleen. In adult CBA mouse thymus, cells responding to allogeneic stimuli were enriched in the light density region, along with the low theta subpopulation. Self-reactive cells, responding with proliferation when cultured with syngeneic adult CBA splenic lymphocytes, and found in adult and 4-day CBA mouse thymus, were also enriched in the light density zones. However, in adult thymus syngeneic MLR reactivity was also found in the dense zones, and the density distribution profiles of total syngeneic MLR responding cells revealed a series of peaks extending over the whole density range. It was suggested that these syngeneic MLR responders undergo a complete maturation process, including progressive density increases, within the thymus gland. Such a sterile differentiation pathway could be a censorship process, leading to death of self-reactive cells within the thymus.


Diphenylhydantoin sensitivity. a syndrome resembling infectious mononucleosis with a morbilliform rash and cholestatic hepatitis. A ten-year-old boy presented with an illness resembling infectious mononucleosis associated with an unusual skin rash and marked cholestatic hepatitis. This combination represents a rare reaction to diphenylhydantoin. Few reported cases have been published. The illness commences from three to seven weeks after starting  therapy. Although one death has been reported, other cases have shown complete recovery. Early recognition of the combination of symptoms and cessation of drug therapy is essential.


High altitude, indigenous origin, and continuous cardiac monitoring. Tape monitoring of the electrocardiogram among ambulant individuals with and without cardiac disease has been practicable for some years now. It has, however, found greater acceptance and utilization in diagnosis, early detection of silent ischemic heart disease (17), and the evaluation of the effectiveness of different dysrhythmia treatment modalities than as a means to examine differences in cardiovascular response to environmentally stressful situations. This study illustrates its practicability under field conditions substantially more rigorous than in most prior uses, and its applicability to our further understanding of the cardiovascular changes associated with adaptation to the hypoxia of altitude.


[Hypersensitivity to rubber].

[Hypersensitivity to rubber]. Occupational contact dermatitis caused by rubber chemicals is described in two groups of patients. The first group consisted of personnel from the operating rooms of a university hospital. In 12 persons the contact allergic reactions appeared to be mainly due to rubber chemicals of the thiuram group of compounds. The second group consisted of cattle farmers. In 6 persons patch tests could be performed. The main cause of the rubber contact on the farms appeared to be the milking machine. The antioxydants in the heavy duty rubber of these machines are of the paraphenylenediamine group of compounds. Positive patch tests were found to N-phenyl-N' -cyclohexylparaphenylenediamine (CPPD) and to the closely related N-phenyl-N'-isopropylparaphenylenediamine (IPPD). Their use in rubber of milking machines in Europe is based on the german "Mitteilungen aus dem Bundesgesundheitsamt" which permits the incorporation of IPPD in these kind of rubber parts to a percentage of 1,5%.


Immunoglobulin E (IgE), an aid in the classification of occupational dermatoses? During an 18-month period determinations of immunoglobulin E(IgE) in serum were made on all (631) new patients referred to the Department of Occupational Dermatology, Karolinska Sjukhuset, Stockholm. The mean for the entire series was 238 units/ml (U): 280 U for the 323 men and 196 U for the 308 women. The IgE values for the different age groups, clinical diagnoses and sexes are presented. About 20% of the patients with normal IgE (less than 250 U) had a history of atopy. On the other hand about 30% of the patients with pathological IgE value (greater than 1000 U) had no such history. No explanation of this rise of IgE without concurrent atopy was discovered despite detailed laboratory tests. Our impression is that the IgE value has a prognostic significance and that, especially for the question of choice or change of occupation in cases of dermatitis, the determination of IgE is of value.


[Oil keratoses and scrotal cancer, an avoidable occupational disease of the metal turner]. Report of a 39 year old lathe worker which suffered from oil acne 10 years ago. The disease was registrated as occupational dermatosis. It healed up after the patient changed to a plant with better conditions of work. Pitch warts on the scrotum remained and were failed to notice. Multiple scrotal carcinomas developed many years later. The case report illustrates the necessity of regularly control examinations of every patient which was suffering from oil acne, and the importance of occupational hygienic conditions for the development of oil acne and lathe turner cancer.


The regulatory principles of glycolysis in erythrocytes in vivo and in vitro. A minimal comprehensive model describing steady states, quasi-steady states and time-dependent processes. A simple mathematical model for glycolysis in erythrocytes is presented which takes into account ATP synthesis and consumption. The system is described by four ordinary differential equations. Conditions in vivo are described by a stable steady state. The model predicts correctly the metabolite concentrations found in vivo. The parameters involved are in agreement with data on the separate steps. The metabolite changes found in pyruvate kinase-deficient erythrocytes and the species variations among erythrocytes from different animals are described satisfactorily. The roles of the enzymes in the control of metabolites and glycolytic flux are expressed in the form of a control matrix and control strengths [R. Heinrich & T.A. Rapoport (1974) Eur. J. Biochem. 42, 89-95] respectively. Erythrocytes from various species are shown to be adapted to a maximal ATP-consumption rate. The calculated eigenvalues reveal the pronounced time-hierarchy of the glycolytic reactions. Owing to the slowness of the 2,3-bisphospho-glycerate phosphatase reaction, quasi-steady states occur during the time-interval of about 0.5-2h incubation, which are defined by perturbed 2,3-bisphosphoglycerate concentrations. The theoretical predictions agree with experimental data. In the quasi-steady state the flux control is exerted almost entirely by the hexokinase-phosphofructokinase system. The model describes satisfactorily the time-dependent changes after addition of glucose to starved erythrocytes. The theoretical consequences are discussed of the conditions in vitro with lactate accumulation and the existence of a time-independent conservation quantity for the oxidized metabolites. Even in this closed system quasi-steady states occur which are characterized by approximately constant concentrations of all glycolytic metabolites except for the accumulation of lactate, fructose 1,6-bisphosphate and triose phosphate.


Left ventricle contractile function in trained dogs with cardial hypertrophy. Eight mongrel dogs exercised for 8 weeks by treadmill running at 20 per cent incline 20 to 25 minutes twice daily, 4-5 days/week. Another eight dogs which were kept in the cages for a similar period served as controls. The exercise program was effective in inducing myocardial hypertrophy since the ratio left ventricular weight/body weight was significantly (P less than 0.001) higher in the trained dogs (5.04 g/kg) than in the sedentary animals (3.83 g/kg). In morphine-chloralose anesthesia the dogs were studied by left heart catherization and cineangiography at spontaneous heart rate (run I), at paced heart rate (run II), at paced heart rate following cardiac autonomic nervous blockade by bilateral vagotomy and the administration of propranolol (run III) and during acute pressure loading with methoxzmine at constant heart rate (run IV). Intergroup comparison yielded no significant difference in any hemodynamic or volumetric parameter throughout the entire study. However, with intragroup comparisons between run III and run IV a less significant increase in left ventricular end-diastolic pressure (from 5 to 15 mm Hg; P less than 0.05) was observed in the trained animals than in the control dogs (from 6 to 25 mm Hg; P less than 0.001). Left ventricular end-diastolic volume increased significantly only in the control dogs during acute pressure loading. Mean aortic pressure and left ventricular peak dP/dt increased to a similar extent in both groups. Since in the trained dogs the left ventricle encroaches less on the Frank-Starling mechanism than in normal animals for overcoming an acute pressure burden it is concluded that the development of hypertrophy concomitant with chronic exercise represents an adaptive mechanism with evidence of beneficial consequences for the intrinsic contractile function of the myocardium.


[Occurrence of spontaneous tumours in the rat strain Chbb: THOM (SPF) (author's transl)]. 400 albin rats (200 male, 200 female) of the strain Chbb: THOM (SPF) were investigated for the occurrence of spontaneous tumours over a period of almost three years. On day 750 of the study 78% of the male and 84% of the female animals were still alive. In 295 tumour hosts (73.8%) we discovered a total of 419 tumours. Several primary tumours were observed in 97 animals. The examinations revealed 240 tumours in the male and 179 tumours in the female rats. The highest tumour rate of 34.5% was established for adenomas of the interestial cells of Leydig in the testes. In female animals mammary tumours were the most frequent type of tumour, accounting for 31%. Talking into account the life expectation of the rats as well as the type and frequency of the tumours these results prove the suitability of this strain for carcinogenicity studies.


[Spontaneous Peripheral Proteolysis/1st Communication: method and results of clinical examinations (author's transl)]. With a modificated Astrup-fibrin plate-method also an inhibition of proteolysis can be registrated. In various medical areas a spontaneous peripheral proteolysis had been found, especially so in chronical bacterial infections.


Hereditary C2 deficiency: association with skin lesions resembling the discoid lesion of systemic lupus erythematosus. Two patients with hereditary homozygous C2 deficiency are described. They showed many similar clinical features. Both had discoid-like skin rashes and serologic abnormalities consistent with SLE, but neither had evidence of involvement of any organ other than skin. Although biopsy of these lesions revealed expected changes by light microscopy, typical immunofluorescent findings were not present. The presence of the HL-A haplotype 10, W18 was seen in both families and was associated with the C2 deficiency gene. The 2 patients were mutually nonreactive in MLC tests and both were found to be homozygous for the LD7a type.


[Multicenter clinical study of a novel steroid-free preparation in proctology]. In a multicentre study 15 physicians investigated the therapeutic efficacy and tolerance of Faktu suppositories and ointment (containing the active principle of Albothyl, a condensation product of m-cresolsulfonic acid and formaldehyde) in 585 patients with proctological affections. Highly satisfactory results were achieved in 486 patients (83.1%). The following were found to be the main indications: -treatment of wounds after proctological operations, -fresh and fissures, -bleeding internal haemorrhoids, -anal eczema and anal pruritus, -rhagades and perforated or prolapsed external haemorrhoids (perianal thrombosis). None of the investigators reported any persisting adverse side-effects. 16% of the patients complained of local discomfort of varying intensity such as pruritus, burning or irritation. The symptoms mostly appeared on commencement of the treatment and necessitated discontinuation of therapy in 5.3% only. The extremely favourable effect of Albothyl - the active principle of Faktu - is due to its unique mechanism of action: the markedly acid milieu of the substance. Furthermore the Faktu preparations do not contain any steroids and consequently they can be used without any misgivings over prolonged periods.


Mixed leukocyte reaction in rheumatoid arthritis. The mixed leukocyte reaction (MLR) responses of 29 patients with classic rheumatoid arthritis (RA) were compared with those of 24 age- and sex-matched healthy controls. Pools of stimulating cells were selected to include the major cross-reacting HL-A specificities. In pooled human serum the MLR response of the RA lymphocytes was significantly enhanced relative to the response controls (P less than 0.05). In autologous serum there was suppression of the MLR response in patients with RA which correlated with disease activity. The data suggest the presence of an intrinsically enhanced cellular reactivity of RA lymphocytes suppressed by serologic factor(s). The mechanisms of this enhancement of suppression are discussed.


Mechaism of neuromuscular blockade with some antiepileptic drugs. Effects of four antiepileptic drugs, viz., diphenylhydantoin, trimethadione, phenobarbitone and ethosuximide, were studied on different in vitro and in vivo skeletal muscle preparations which consisted of frog rectus, rat phrenic nerve diaphragm and cat gastrocnemius sciatic nerve preparations. A dose related blockade of neuromuscular transmission was seen with all the compounds tested. The blockade was mainly confined to the neuromuscular junction, although direct stimulation of muscle was slightly affected. The blockade was partially antagonized by physostigmine, adrenaline, succinylcholine, choline, tetraethylammonium and KCl and was additive to that due to tubocurarine. Moreover, the drugs were found to possess moderate local anaesthetic activity. The blockade was therefore considered to be partly due to curariform activity and partly due to their local anaesthetic activity.


Immunologic observations on 9 sets of twins either concordant or discordant for SLE. The influence of genetic and nongenetic factors on abnormalities of the immune response in systemic lupus erythematosus (SLE) was studied in 9 sets of twins in which one or both twins had SLE. Particular emphasis was placed on contrasting the results between the sibs of 3 monozygotic pairs discordant for clinical SLE. Depression of cell-mediated immunity, determined by lymphocyte blastogenic response to mitogens, was associated with the clinical expression of illness. In contrast, autoreactive antilymphocyte antibodies and lymphocyte tubuloreticular structures were found in both clinically affected and unaffected subjects and were more prominently associated with the presence of other serologic abnormalities. No evidence of antigens or cell surfaces determinants unique to affected sibs was encountered.


Toxic woods.

Toxic woods. Eighty-three cases of dermatitis caused by wood or sawdust have been seen at St John's Hospital for Dieases of the Skin, London, in the last 20 years. The clinical details and results of patch tests are reported. The literature on dermatitis, mucosal irritation, asthma and other toxic effects of woods of some 300 botanical species is reviewed at length, with an index of scientific, trade and vernacular names, chemical formulae of the known sensitizing substances, and a table of the 28 toxic woods most often encountered. Pathogenesis, diagnosis and prophylaxis are discussed.


Hypersensitivity to bacteria in eczema. I. Bacterial culture, skin tests and immunofluorescent detection of immunoglobulins and bacterial antigens. A study was made of the cytotoxic effect of antibacterial antibody and complement reacting with bacterial antigens firmly adsorbed to epidermal cells. It is believed that this phenomenon enhances the severity of the lesions and their spread in some cases of disseminated eczema. In this first part of the study it is confirmed that Staphylococcus aureus and micrococci are frequently present on lesions and 'unaffected' skin of patients with disseminated eczema. Intradermal skin tests with antigens of staphylococci and micrococci on 122 eczematous patients elicited immediate, or combined immediate and 4 h (Arthus-like) responses, in a large proportion, but few showed uncombined 4 h responses or delayed hypersensitivity, in contrast to findings reported by others. Immunofluorescence tests on skin of thirty patients showed that IgG and IgM diffused into the epidermis, sometimes to the skin surface, of lesional skin, and more immunoglobulin was found in skin of 'unaffected' areas than in skin of normal healthy persons, indicating that clinically unaffected skin in patients with disseminated eczema is abnormal. IgD was present in three of eight samples of unfixed, and six of eight samples of fixed eczematous skin. Staphylococcal and micrococcal antigen was shown on the skin surface and also diffusely in the cytoplasm of cells in the dermis beneath the surface deposits, indicating percutaneous absorption. Further small amounts of antigen were adsorbed to some epidermal cells. These results show that the predisposing conditions for a cytotoxic reaction mediated by hypersensitivity to bacteria do occur. Increased growth of staphylococci and micrococci on eczematous skin would result in increased deposits of antigen. Bacterial antigens are absorbed into the skin and bind with epidermal cells, and immunoglobulins diffuse into the epidermis. Furthermore, skin tests showed that many eczematous patients were hypersensitive to bacteria. Studies on the nature of the antibacterial antibody will be published in the succeeding reports.


A familial study of acne and eczema.

A familial study of acne and eczema. The incidence of eczema was assessed in acne patients and their first degree relatives and compared with control (non-acne) subjects and their relatives. It was found that there was a statistically decreased incidence of endogenous eczema in the acne patients.


Adenosine triphosphatase of rat liver mitochondria: detergent solubilization of an oligomycin- and dicyclohexylcarbodiimide-sensitive form of the enzyme. The hydrolytic activity of the ATPase bound to purified inner membrane vesicles of rat liver mitochondria can be increased threefold by washing extensively with a high ionic strength phosphate buffer. The specific ATPase activities of such phosphate-washed membranes are the highest reported to date for a mitochondrial membrane preparation (21-24 mumol of ATP hydrolyzed min-1 mg-1 in bicarbonate buffer at 37 degrees C). Deoxycholate (0.1 mg/mg of protein) extracts from these membranes a soluble, cold-stable ATPase complex which exhibits a specific activity under optimal assay conditions of 12 mumol of ATP hydrolyzed min-1 mg-1. This complex is not sedimented by centrifugation at 201000 g for 90 min, and readily passes through a 250-A Millipore filter. The ATPase activity of the soluble complex is inhibited 95% by 2.4 muM oligomycin. In addition, inhibitions of 60% or better are obtained in the presence of 1-8 muM dicyclohexylcarbodiimide, p-chloromercuribenzoate, venturicidin, and aurovertin. While a similar complex may be extracted with Triton X-100 this preparation is always lower in both specific activity and in inhibitor sensitivities than the complex extracted with deoxycholate. Detergents of the Tween and Brij series and other detergents of the Triton series are also much less effective than deoxycholate in solubilizing the oligomycin-sensitive. ATPase complex of rat liver. It is concluded that deoxycholate is superior to other detergents as an extractant of the oligomycin-sensitive ATPase complex of rat liver mitochondria, and that the complex extracted with deoxycholate possesses a closer similarity to the membrane-associated ATPase than does the complex extracted with Triton X-100. These studies document the first report of a detergent-solubilized, oligomycin-sensitive ATPase preparation from rat liver mitochondria.


The role of the carbodiimide-reactive component of the adenosine-5'-triphosphatase complex in the proton permeability of Escherichia coli membrane vesicles. Membrane vesicles isolated from wild-type and dicyclohexylcarbodiimide-resistant strains of Escherichia coli exhibit identical respiration-dependent transport activities, and in both cases, this activity is abolished by extraction of the vesicles with 1.0 M guanidine-HCl. Transport activity of extracted wild-type vesicles is completely restored by exposing the vesicles to lipophilic or water-soluble carbodiimides, while transport activity of the mutant vesicles is not restored by exposure to lipophilic carbodiimides. Strikingly, however, complete reactivation of transport in mutant vesicles is observed with water-soluble carbodiimides. Similarly, the Ca2+, Mg2+-stimulated ATPase activity of wild-type vesicles is inhibited by both classes of carbodiimides, while the ATPase activity of mutant vesicles is inhibited by water-soluble carbodiimides, but resistant to inhibition by lipophilic carbodiimides. The carbodiimide-reactive component of the membraneous Ca2+, Mg2+-stimulated ATPase complex in wildtype vesicles is readily labeled with N,N'-dicyclohexyl[14C]-carbodiimide, while the analogous component in mutant vesicles is not reactive. Alternatively, when vesicles are treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide [14C]methiodide, a water-soluble carbodiimide, the carbodiimide-reactive component is labeled to a similar degree in both preparations. The results suggest that the altered carbodiimide-reactive proteolipid in the dicyclohexylcarbodiimide-resistant mutant is specifically defective in its ability to react with lipophilic carbodiimides. In addition, these and other findings indicate that the increase in proton permeability observed on extraction of isolated membrane vesicles with chaotropic agents is due exclusively to an effect on the carbodiimide-reactive component of the Ca2+, Mg2+-stimulated ATPase complex.


Properties and function  of clostridial membrane ATPase. ATPase (ATP phosphohydrolase, EC 3.6.1.3) was detected in the membrane fraction of the strict anaerobic bacterium, Clostridium pasteurianum. About 70% of the total activity was found in the particulate fraction. The enzyme was Mg2+ dependent; Co2+ and Mn2+ but not Ca2+ could replace Mg2+ to some extent; the activation by Mg2+ was slightly antagonized by Ca2+. Even in the presence of Mg2+, Na+ or K+ had no stimulatory effect. The ATPase reaction was effectively inhibited by one of its products, ADP, and only slightly by the other product, inorganic phosphate. Of the nucleoside triphosphates tested ATP was hydrolyzed with highest affinity ([S]0.5 v = 1.3 mM) and maximal activity (120 U/g). The ATPase activity could be nearly  completely solubilized by treatment of the membranes with 2 M LiCl in the absence of Mg2+. Solubilization, however, led to instability of the enzyme. The clostridial solubilized and membrane-bound ATPase showed different properties similar to the "allotopic" properties of mitochondrial and other bacterial ATPases. The membrane-bound ATPase in contrast to the soluble ATPase was sensitive to the ATPase inhibitor dicyclohexylcarbodiimide (DCCD). DCCD, at 10(-4) M, led to 80% inhibition of the membrane-bound enzyme; oligomycin ouabain, or NaN3 had no effect. The membrane-bound ATPase could not be stimulated by trypsin pretreatment. Since none of the mono- or divalent cations had any truly stimulatory effect, and since a pH gradient (interior alkaline), which was sensitive to the ATPase inhibitor DCCD, was maintained during growth of C. pasteurianum, it was concluded that the function of the clostridial ATPase was the same as that of the rather similar mitochondrial enzyme, namely H+ translocation. A H+-translocating, ATP-consuming ATPase appears to be intrinsic equipment of all prolaryotic cells and as such to be phylogenetically very old; in the course of evolution the enzyme might have been developed to a H+-(re)translocating, ATP-forming ATPase as probably realized in aerobic bacteria, mitochondria and chloroplasts.


Lipoprotein lipase in rat lung. Effect of dexamethasone. The effect of hormone administration on the activity of lipoprotein lipase in the lung was studied in the rat. The following hormones were administered: dexamethasone, L-thyroxine, estradiol-17beta and progesterone. In addition, lung lipoprotein lipase activity was studied in diabetic and lactating rats. Lipoprotein lipase activity was measured in dried, defatted preparations of rat lung using double labeled ([14C]palmitate, [3H]glycerol) chylomicron triacylglycerol as substrate. Dexamethasone administration caused a rise of 70% in the level of activity of lipoprotein lipase in acetone powders of lung and a 100% increase in the amount of enzyme released during heparin infusion into isolated, perfused lungs. Enzyme activity was higher in lungs of females than of male rats; however; the level of activity was unaffected by estrogen or progesterone administration to either male or ovariectomized rats. Diabetes, hyperthyroidism or lactation did not change lipoprotein lipase activity in the lung. The constant presence of lipoprotein lipase activity in the lung suggests that this organ is able to maintain a steady supply of triacylglycerol-fatty acids under a variety of physiological and pathological conditions. Stimulation of enzyme activity by dexamethasone could lead to increased uptake of triacylglycerol-fatty acids by the lung and may thus be a contributing factor to corticosteroid-induced enhanced surfactant synthesis.


The susceptibility of the glycoprotein from the purified (Na+, K+)-activated adenosine triphosphatase to tryptic and chymotryptic degradation with and without Na+ and K+. Purified (Na+, K+)-activated adenosine triphosphatase ((Na+, K+)-ATPase, ATP phosphohydrolase, EC 3.6.1.3) has been subjected to trypsin and chymotrypsin hydrolysis. The glycoprotein is much more resistant to proteolysis than the large chain. This differential susceptibility to proteolysis is not due to differences in the number of trypsin or chymotrypsin sensitive bonds because the two subunits are equally susceptible to proteolysis after isolation by preparative gel electrophoresis in sodium dodecyl sulfate. It is also not due to steric "shielding" of the glycoprotein by the large chain or its proteolytic products: (1) The rate of digestion of the glycoprotein is not increased after 90% of the large chain is digested. (2) The majority of the large chain peptides are released into the supernatant upon degradation. It is concluded that the greater resistance of the glycoprotein to proteolysis is due to its native conformation. In the absence of the large chain, the susceptibility of the glycoprotein to tryptic degradation by K+ and Na+. The evidence suggests that this decreased susceptibility was due to conformational changes in the glycoprotein. These specific ligand effects on proteolysis of the glycoprotein suggests that the glycoprotein may participate in Na+ and K+ binding by (Na+, K+)-ATPase.


On the structure of heparitin sulfates. Analyses of the products formed from heparitin sulfates by two heparitinases and a heparinase from Flavobacterium heparinum. The analyses of the products formed from heparitin sulfates by the action of two heparitinases and a heparinase from Flavorbacterium heparinum is reported. Heparitin sulfates A and B are degraded by heparitinase I yielding two disaccharides, one of them composed of N-acetylucosamine and an unsaturated uronic, joined by alpha(1 lead to 4) linkage, and the other, with the same composition but with an O-sulfate at the hexosamine moiety. A third disaccharide is also formed from heparitin sulfate B, by the action of the same enzyme, composed of glucosamine N-sulfate and an unsaturated uronic acid joined probably by alpha(1 lead to 4) linkage. Besides these three disaccharides, heparitin sulfate B yields, by the action of heparitinase I, an oligosaccharide (with an average molecular weight of 6000) which is completely degraded by the heparitinase II yielding a disaccharide composed of glucosamine 2,6-disulfate and unsaturated uronic acid. All the disaccharides are further degraded by alpha-glycuronidase from Flavobacterium heparinum yielding the respective monosaccharides. Based on these and other analyses the possible structures of the heparitin sulfates are proposed.


Pathways of carbohydrate oxidation during thermogenesis by the spadix of Arum maculatum. 1. The aims of this work were to discover the pathways of carbohydrate oxidation prior to and during thermogenesis by the club of the spadix of Arum maculatum, and whether there was coarse control of these pathways. 2. 14C02 production from [1-14C]-, [3,4-14C]-, and [6-14C]glucose, the detailed distribution of 14C from [1-14C]- and [6-14C]glucose, and the maximum catalytic activities of phosphofructokinase, fructose-1,6-diphosphate aldolase, glucose-6-phosphate dehydrogenase, and phosphogluconate dehydrogenase were determined at different stages in the development of the spadix. The results indicate that in the early stages carbohydrate is oxidized via both the pentose phosphate pathway and glycolysis, and that a shift to glycolysis occurs during development so that just before and during thermogenesis glycolysis predominates almost exclusively. 3. During development the activities of phosphofructokinase and glucose-6-phosphate dehydrogenase per club increased 100- ans during spadix development, and indicated that the onset of rapid glycolysis at thermogenesis is regulated by fine control or availability of substrate.


Glycosaminoglycans and proteoglycans of human chondrosarcoma. The glycosaminoglycans and proteoglycans of a human chondrosarcoma have been studied. Glycosaminoglycans were fractionated and identified by cetylpirdium chloride (CPC) cellulose chromatography, ECTEOLA cellulose ion-exchange chromatography and electrophoresis on cellulose acetate. Proteoglycans were extracted by low ionic strength solutions and by 4 M guanidinium chloride and fractioned by equilibrium density-gradient centrifugation and gel chromatography on Sepharose 2B. The tumour matrix contained both the 4- and 6-sulphate isomers of chondroitin sulphate and a high concentration (12% of hexosamine) of hyaluronic acid. Proteoglycans were poor in carbohydrate moieties and proportion were capable of aggregation. Amino acid analysis of the fractionated proteoglycans suggested the presence of a single protein core. A substance with the characteristic amino acid composition of glycoprotein link was recovered from the top of the dissociative density gradient.


Tension development in skinned glycerinated rabbit psoas fiber segments irrigated with soluble myosin fragments. Single glycerinated rabbit psoas muscle fibers were skinned by splitting them lengthwise. The fiber segments thus obtained were more easily accessible to solutes in the surrounding medium than the intact fibers. Using such segments, active tension could be fully abolished by adding N-ethylmaleimide under conditions which lead to inhibition of actin activation of the ATPase activity of myosin. Such muscles could, however, develop tension after irrigation with myosin or with the water-soluble active myosin fragments heavy meromyosin (HMM) or its subfragment 1 (HMM-S1). The induced tensions increased with increasing protein concentration in the irrigating solution. At any given protein concentration, the tension generated by myosin was larger than that produced by HMM which was, in turn, greater than that induced by HMM-S1 e.g. at 15 mg/ml protein the tensions produced by these three myosin moieties were 44.0, 14.0 and 2.8 g/cm2, respectively. The tension was found to be intimately associated with ATP splitting; thus, HMM and HMM-S1 which have been treated with reagents abolishing actin-activated ATPase failed to induce tension development. A contractile force may thus be generated through the interaction with actin of the water-soluble, enzymatically active, myosin subfragments involving the splitting of ATP.


An inhibitor of DNA synthesis in erythrocyte-conditioned medium and its separation from haemoglobin. Erythrocyte-conditioned medium and erythrocyte lysate have been prepared from rat red blood cells. Molecular fractions of the conditioned medium and the lysate are used to test for the presence of erythrocyte chalone in short-term tissue cultures of mouse foetal liver cells. An inhibitor of erythroblast DNA synthesis has been found in the erythrocyte conditioned medium. The inhibitor is not haemoglobin, and it is not found in erythrocyte lysate soluble components.


Assembly of ATPase protein in sarcoplasmic reticulum membranes. Three specimen preparation techniques for electron microscopy were used to investigate the incorporation of the ATPase polypeptide chains in the membranes of fragmented sarcoplasmic reticulum (SR) obtained from rabbit skeletal muscle. Observations were made of both normal vesicles and vesicles exposed to trypsin, which is known to cleave the ATPase protein and to alter the ultrastructure of the vesicles in predictable ways. Freeze-fracture replicas reveal the typical 90-A particles on the concave (PF) faces with a density of 5,730 +/- 520/mum2. On the other hand both negatively stained and deeply etched preparations display outer projections, which are absent on trypsin-incubated vesicles. The etched specimens afford for the first time top views of the vesicles in the absence of any stain. These views reveal outer projections on the PS surface with a density of 21,000 +/- 3,900/mum2, a value nearly approximating the density of the ATPase polypeptide chains (106,000 mol wt) calculated on the basis of protein and membrane area determinations. On the other hand, this value is three to four times higher than that found for the density of the 90-A particles on the concave fracture faces. Since both outer projections and 90-A particles are identified with the ATPase protein, it is suggested that the ATPase polypeptide chains are amphiphilic molecules, with polar ends protruding individually as outer projections on the surface of the vesicles, and hydrophobic ends appearing as 90-A particles on the concave fracture faces. The discrepancy between the densities of the outer projections and the 90-A particles may be attributed either to variable penetration of the polypeptide chains into the membrane bilayer, or to formation of oligomers containing three or four hydrophobic ends and appearing as single 90-A particles. Each ATPase chain forms a complex with 20-30 phospholipid molecules. The remaining phospholipids (approximately 70% of the total SR phospholipids) account for less than half the membrane volume. It is proposed that the outer leaflet of the SR membrane is prevalently composed of the ATPase lipoprotein complex, and the inner leaflet is mostly a phospholipid monolayer.


[Calcium transport and ATPase activity of sarcoplasmic reticulum in normal and denervated rabbit muscles]. The properties of sarcomplasmic reticulum Ca-pump from normal and denervated rabbit muscles were investigated. Ca+2 ion transport in denervated muscle reticulum was subject to Michaelis-Menten kinetics. The rate of fast Ca2+ outflux from the vesicles was enhanced after denervation; this caused a decrease in the transport efficiency and an increase of the "basic" ATP-ase. At the same time the rate of Ca2+ accumulation and the Ca-ATP-ase transport activity were enhances by a factor of 1.5. Kinetic properties of the denervated sarcoplasmic reticulum proved to be closely related to the features of the excitation-contraction cycle in these muscles.


[Method of simultaneous determination of kallikrein, plasmin and thrombin precursors and inhibitors in human blood plasma]. Prekallikrein, plasminogen and prothrombin of human blood plasma have been separately activated by caolin streptokinase and thromboplastin. By measuring the TAME-esterase (N-d Tozy-L-arginine methyl ester) activity of each enzyme and its changes in the course of plasma incubation with the activator, it was possible to estimate the values of precursors of kallikrein, plasmin, thrombin and their inhibitors. Evidence is given that under conditions described the activation is specific of each enzyme and does not affect the level of the two other percursors. The method has been developed in two modifications, permitting to obtain the value of seven parameters in 0.4--0.7 ml of blood plasma.


Comparison of the actions of acebutolol, practolol and propranolol on calcium transport by heart microsomes and mitochondria. 1 The effects of acebutolol, practolol and propranolol (0,5-3 mM) on calcium uptake, calcium binding and ATPase activities of the rabbit and rat heart microsomal and mitochondrial fractions were investigated. 2 Dose-response and time course experiments revealed that propranolol greatly inhibited microsomal and mitochondrial calcium uptake whereas both acebutolol and practolol showed slight depressant effects. 3 The ATPase activities of microsomal and mitochondrial fractions were decreased by acebutolol, practolol and propranolol; however, the latter agent was more effective than the other two. 4 The inhibitory effects of acebutolol, practolol and propranolol on mitochondria and microsomes were not antagonized by adrenaline. 5 Propranolol decreased calcium binding by the microsomal fraction only, whereas acebutolol and practolol had no effect on microsomal or mitochondrial calcium binding. 6 The sensitivity of the rabbit heart subcellular fractions to the beta-adrenoceptor blocking drugs was similar to that of the rat heart; however, the calcium uptake and ATPase activities of microsomes were more sensitive to propranolol than mitochondria in both species. 7 Perfusion of rat hearts with 0.2-1 mM propranolol decreased contractile force, and microsomal and mitochondrial fractions obtained from these hearts accummulated less calcium in comparison to the control. On the other hand, acebutolol and practolol (0.2-1nM) had no appreciable effects on contractile force or subcellular fractions under similar conditions. 8 The negative inotropic effect of propranolol may partly be due to its inhibitory actions on calcium transport by subcellular organelles of the myocardium; the depressant action of propranolol on calcium transport is unlikely to be due to its beta-adrenoceptor blocking property.


Effect of experimental diabetes, food deprivation and genetic obesity on the sensitivity of pithed rats to autonomic agents. 1 The sensitivities of alloxan and streptozotocin diabetic and hereditary obese pithed rats to acetylcholine, isoprenaline and noradrenaline were compared to those of controls. 2 Blood pressure and heart rate recordings made before dosing was started showed the streptozotocin-treated animals to have a significantly reduced heart rate and increased pulse pressure as compared with controls. 3 Both diabetic groups were found to have reduced sensitivities to the pressor effect of noradrenaline, the depressor effect of acetylcholine, the positive chronotropic and inotropic effect of isoprenaline and the reduction in diastolic pressure induced by isoprenaline. The reduction in sensitivity was generally much greater in the streptozotocin diabetic animals. 4 The genetically obese rats were found to have similar sensitivities to all three agents as did their non-obese litter mates. 5 When either diabetic group was deprived of food for 24 h preceding the tests the sensitivities were found to be raised significantly towards normal in almost all cases. 6 The results are contrasted with previous in vitro results and possible causative metabolic factors discussed. It is suggested that sensitivity changes are unevenly distributed within the cardiovascular system.


Effects of phenobarbitone, cinnarizine, and zoxazolamine on the development of right ventricular hypertrophy and hypertensive pulmonary vascular disease in rats treated with monocrotaline. The results of this experiment suggest that the addition of zoxazolamine to the diet may prolong the survival and reduce the incidence of right ventricular hypertrophy and hypertensive pulmonary vascular disease in male rats given a single subcutaneous injection of monocrotaline. Phenobarbitone and cinnarizine were ineffective.


Biochemical changes associated with development and reversal of cardiac hypertrophy in spontaneously hypertensive rats. This study is the first report describing the sequence of biochemical alterations of myocardium during the progression of naturally occurring hypertrophy in spontaneously hypertensive rats (SHRs) and then with its reversal by alpha-methyldopa therapy. Changes in DNA, RNA, hydroxyproline, as well as incorporation of 14C lysine into cardiac myosin, were compared with the pattern found in suitably matched controls. A significant increase in RNA, hydroxyproline, and 14C incorporation was observed in SHRs. Antihypertensive treatment caused reversal of hypertrophy and normalization of all biochemical parameters except hydroxyproline, the concentration of which increased significantly as myocardial weight decreased. These compositional changes may help explain the conflicting result of the haemodynamic effects of cardiac hypertrophy.


Myocardial necrosis, fibrosis, and DNA synthesis in experimental cardiac hypertrophy induced by sudden pressure overload. The development of myocardial fibrosis as a result of cardiac hypertrophy was studied in 11 cats in which the pulmonary artery was banded, six rabbits in which the ascending aorta was banded, and eight cats with various congenital cardiac anomalies. Histological examination of the myocardium revealed multifocal areas of degeneration and necrosis with healing by fibrosis in the right ventricle of cats in which the pulmonary artery was banded and in the left ventricle of rabbits in which the aorta was banded. In five of eight cats with congenital anomalies, myocardial necrosis and fibrosis were not present in spite of heart weight to body weight ratios 2-4 times greater than in the experimental models. In the other three cats, fibrosis was subendocardial or diffuse rather than multifocal as in the banded animals. This suggests that the increased connective tissue found in animals with cardiac hypertrophy induced by banding the aorta or pulmonary artery is an artifact of the preparation. Autoradiographic studies of the myocardium of pulmonary artery-banded cats indicated that all newly synthesized DNA in this model is restricted to interstitial cell and endothelial cell proliferation.


Left heart volume characteristics following ventricular septal defect closure in infancy. Left ventricular and left atrial volume, left ventricular ejection fraction, and left ventricular muscle mass were determined preoperatively and postoperatively in 13 patients who underwent surgical closure of ventricular septal defects in the first two years of life. Left ventricular end-diastolic volume and systolic output averaged 255 +/- 19% (+/- SEM) and 240 +/- 19% of normal, respectively, before operation but fell to within normal limits postoperatively. Left ventricular ejection fraction was normal preoperatively (100 +/- 4% of normal) and remained so after correction (106 +/- 3%, NS). Left ventricular mass was mildly elevated at the preoperative catheterization (271 +/- 21%) and decreased significantly following repair (P less than 0.001). However, the postoperative left atrial volume (147 +/- 14%) remained abnormal (P greater than 0.05). These data suggest that when early surgical closure of a ventricular septal defect is necessary because of failure of medical management, good results with regard to postoperative left ventricular size and function can be expected.


Single film retrograde umbilical aortography in the diagnosis of hypoplastic left heart syndrome with aortic atresia. Single film retrograde umbilical aortography was used successfully in confirming the diagnosis of hypoplastic left heart in three neonates. The method involves injecting Renografin 75% (1.25 cc/kg body weight) into the umbilical artery catheter according to the following sequence. First, the tip of the catheter is positioned at the level of the ductus arteriosus. The infant heart beats are then counted from one to three. The contrast media injection is begun manually on the count of one and an anterior-posterior chest film is taken on the count of three. Thus the film is taken one diastolic period after completion of the injection. The proper timing of the contrast media injection and filming is essential for obtaining a diagnostic film. This procedure was diagnostic in the three infants studied and eliminated the need of transferring two sick infants from affiliated hospitals.


The coronary arteries and left ventricle in clinically isolated angina pectoris: a necropsy analysis. Certain clinical and morphologic observations are described in 27 patients with severe isolated angina pectoris of either the stable (five patients) or the unstable form (22 patients). Twenty-four patients died during or shortly after cardiac operations designed to relieve angina pectoris and three died during cardiac catheterization. During life none had had clinical evidence of acute myocardial infarction or congestive cardiac failure. At necropsy, each had diffuse, extensive coronary atherosclerosis with severe luminal narrowing: the lumens of at least two, an average of three, of the four major epicardial coronary arteries were narrowed greater than 75% in cross-sectional area by old atherosclerotic plaques. Despite the severe coronary narrowing, there was little myocardial damage. Left ventricular scarring (excluding papillary muscle) was observed grossly in only 14 (52%) of the 27 patients and in each it involved only a small portion of myocardial wall. The left ventricular cavity was of normal size in all except two patients. The hearts were of normal weight in 15 (56%) patients, and the average increase above the upper range of normal for the other 12 hearts was 19%. Thus, clinically isolated, severe angina pectoris is associated with severe, diffuse luminal narrowing but relatively little myocardial damage.


Tunnel subaortic stenosis: left ventricular outflow tract obstruction produced by fibromuscular tubular narrowing. The clinical and morphologic features of tunnel subaortic stenosis, an unusual form of obstruction to left ventricular outflow, are described in 11 patients. Although patients with tunnel subaortic stenosis demonstrate a variety of cardiovascular malformations, the most characteristic anatomic feature is fibromuscular tubular narrowing of the outflow tract that remains relatively unchanged during the cardiac cycle. The aortic anulus was abnormally small in six of the 11 patients, including one who also had a hypoplastic ascending aorta. Evidence of a small mitral orifice was present in two patients, and two other patients had asymmetric septal hypertrophy. Although operation was successful in significantly reducing the outflow gradient in two of the seven operated patients, all seven patients had gradients of 50 mm Hg or more at the most recent postoperative evaluation. Three patients (two with previous operation) died suddenly; each of these patients had mild or no symptoms. Because of the apparent ineffectiveness of current operative methods in patients with tunnel subaortic stenosis, it is important to differentiate this condition from obstructions to left ventricular outflow.