Some factors influencing metabolism and distribution of fibrinogen in man and rabbits. To shed some light on the homeostatic regulation of plasma fibrinogen, metabolic studies were made in healthy females, and in normal, thyroidectomized, and thyroxine-treated rabbits. In females, compared with normal males, plasma fibrinogen concentration, plasma and interstitial fibrinogen decreased consequent to an increased fractional catabolic rate and a normal fibrinogen synthesis rate. The interstitial/plasma fibrinogen ratio remained unchanged. In normal rabbits, with increasing body weight fractional catabolic rate and catabolic rate decreased, while fibrinogen concentration and plasma fibrinogen remained constant owing to a simultaneous decrease in fibrinogen synthesis. In addition, fractional transcapillary transfer rate and transcapillary flux also decreased resulting in a shrinkage of interstitial fibrinogen. Thyroidectomy and thyroxine-injection markedly altered fibrinogen metabolism: thyroid hormone accelerated fibrinogen catabolism but also stimulated synthesis. The net result was an increase in plasma fibrinogen and fibrinogen concentration. The interstitial/plasma fibrinogen ratio decreased in thyroxine-treated, and increased in thyroidectomized animals. This study defines the variations of the fibrinogen system parameters in these physiologic and pathologic conditions, and illustrates some patterns of alterations in fibrinogen metabolism.


The stability of glutardialdehyde-stabilized 35-heparinized surfaces in contact with blood. Heparin can be bound to polymer surfaces by precipitation of an ionic heparin-amine complex which can be stabilized against dissolution by treatment with glutardialdehyde. The aim of this investigation was to study the degree and course of desorption of heparin from such a heparinized surface on contact with blood. This desorption must be considered when analysing the interaction between the heparinized surface and blood. Different heparinized surfaces were prepared by using 35S-labelled heparin, and the desorption of heparin on exposure in vitro to citrated plasma or heparinized blood as well as during exposure at in vivo conditions was quantified. During in vitro experiments, the glutardialdehyde stabilized surface became stable with no further desorption of heparin after an initial loss of about 3% of the initial surface-bound heparin. Under in vivo conditions, there was an initial loss of about 12%. There was no further loss from surfaces inserted into the circulation of the dog for seven days as compared to those inserted for one hour.


Prevention of platelet adhesion and aggregation by a glutardialdehyde-stabilized heparin surface. A stable heparinized surface was prepared by sequential treatment of polyethylene with water solutions of hexadecylamine hydrochloride, heparin and glutardialdehyde. In order to explain the "non-thrombogenic" properties of this surface, it was evaluated with regard to prevention of platelet adhesion and aggregation. Human heparinized blood (2 and 10 IU/ml) with 51Cr-labelled autologous platelets was rotated for 60 minutes in untreated and heparin-treated circular tubings. The surface area/blood volume ratio was varied and an air-blood interface was present. In untreated tubings, platelet adhesion and aggregation increased in proportion to the size of the surface area/blood volume ratio, irrespective of the heparin concentrations of the blood. In the heparin-treated tubings, there was no measurable platelet adhesion to the surface and no platelet aggregation in the blood. The difference between the heparinized and the untreated surfaces with regard to platelet adhesion was discernible even after 10 minutes storage of stagnant blood. It is concluded that platelet adhesion and aggregation induced by exposure of blood to a foreign surface in an in vitro experimental model can be prevented by a stable heparin coating of the surface.


Kinetic parameters of platelet aggregation as an expression of platelet responsiveness. The kinetics of platelet aggregation induced by collagen and by ADP were studied. The maximum aggregation (deltaLTmax) and the ADP and collagen concentrations required to produce half-maximum aggregation (Kd) were determined using platelets obtained from normal individuals, individuals who ingested aspirin and individuals whose platelet-rich plasma (PRP) demonstrated spontaneous aggregation. The Kd and deltaLTmax for ADP-induced platelet aggregation were variable and markedly affected by the citrate concentration. Conversely, kinetic parameters of collagen-induced aggregation were more reproducible and less affected by citrate. The Kd for collagen in platelet aggregation was increased following aspirin ingestion and decreased in samples of PRP that demonstrated spontaneous aggregation. These results suggest that kinetic parameters of platelet aggregation may be useful to express the responsiveness of platelets.


Cyanide insensitive oxidase in platelets of newborn infant. The authors studied the behaviour of neonate platelet O2 consumption after the addition of pyridine nucleotide compared to adult controls. O2 consumption of neonate platelets after NADH addition was 103,2 millimicronmol O2/10(9)/hr (SE = 24,74) and in adult controls 188,8 millimicronmol O2/10(9)/hr (SE = 36,46). After the addition of NADPH O2 consumption was, respectively, 233,5 millimicronmol (SE = 46,29) and 218,3 millimicronmol (SE = 30,01).


Ethanol-induced microaggregate formation in pig and rabbit blood. An in vitro study. Increased microaggregate formation was found after mixing ethanol with blood from pig and rabbit in vitro, measured with Swank's Screen Filtration pressure method. Final ethanol concentrations were in the range found in ethanol-intoxication in man. No rise in SFP was noticed when plasma with 10,000 platelets/microliter was used. It is therefore doubtful that altered plasma proteins caused the rise in SFP. It is suggested that if a direct effect of ethanol upon platelet aggregation exists in vivo, it may be of importance in acute ethanol intoxication and in chronic alcoholism.


[Regarding the effect of bromhexine metabolite VII on lecithin synthesis in fetal lungs (author's transl)]. With the help of incorporated amounts of radioactively labeled choline, it was shown that bromhexine metabolite VIII in vivo (10 mg, 5 mg, 1 mg/kg body weight) and in vitro (100 microgram to 0,01 microgram/g fetal lung tissue) does not stimulate lecithin synthesis in fetal lungs of rats.


[Effect of storage on the vitamin B6 activity of foods (author's transl)]. In a study of the effect of storage on the vitamin B6 activity of foods, the vitamin B6 content of different foods of plant and animal origin and also of a mixed feed with added pyridoxine were analyzed microbiologically using Saccharomyces carlsbergensis as test organism. Vitamin B6 activity was determined initially, in some of the specimens after storage for 10 months and again in all foods after 40 months. The storage period of 10 months caused a loss of the natural vitamin B6 content of about 25--30%. This loss increased to more than 50% after 40 months storage. The diet containing the high level of synthetic pyridoxine lost 85% of its vitamin B6 content.


Analysis of rabbit and guinea pig complement efficiency in cytotoxicity tests against fibrosarcoma and lymphosarcoma cells. In a complement-dependent 51Cr cytotoxicity assay, using as target murine fibrosarcoma or lymphosarcoma cells, the rabbit complement (RC) was more efficient than guinea pig complement (GPC) when tested either with strong antisera, such as antihistocompatibility sera, or with weak sera, such as wera from normal mice shown previously to posses a natural antitumor response. The high efficiency of RC was not due to activation by antibodies of a different class or specificity than those activating GPC. In fact, both 2-mercaptoethanol (2-Me)-sensitive or-resistant immunoglobulins could activate both RC and GPC, and the results of absorption tests indicated that the antibodies detected using either of the 2 complements were directed against the same specificities. In addition, the results of tests searching for cooperative antibodies excluded that a cooperative effect might be responsible for the high efficiency of RC. With weak antisera, sera of different rabbits were found to have different complement activity.


[New strategies for prevention in adolescents and young adults]. For various reasons, it is justified to revise the classical strategies of intervention concerning medical and social action to help young people. New behaviours such as drug addiction, for instance, have emphasized the inadequacies of the conventional means of treatment. Since 1970, Youth Advisory Services have appeared in Europe. Their aims may be various: information, counselling, lodging, social and educative help, medical assistance. These services which were created by the community have such ethical and organizational features that it is easy to discern them among the conventional administrative services. Their users are mainly teenagers and young adults whose reasons for consultation are due to various causes. The originality of the methods, facilities and principles of these innovating services may be considered as a decisive contribution to the research of new prevention strategies to help young people.


Lactose malabsorption in preschool black children. One hundred sixteen healthy black children ages 13 to 59 months, representing high and low socioeconomic deciles, were studied for lactose malabsorption. A fasting lactose tolerance test using 2 g of lactose/kg of body weight was carried out. Glucose was determined at 0, 15, 30, and 60 min. Of the 116 preschoolers 34 (29%) evidenced lactose malabsorption as determined by a blood glucose rise of less than 26 mg/100 ml. Clinical signs of diarrhea, gas, and cramps were noted singly or in combination in 18% of the 34 lactose-malabsorbing children. Of the 82 lactose absorbers, 12% demonstrated similar signs. The nature and length of the initial infant milk feeding failed to show any relationship to the onset of malabsorption. Current milk drinking patterns were reported as being similar. Eight-seven percent of the malabsorbers and 92% of the absorbers report drinking 240 ml or more of milk/day. Socioeconomic status, education, marital status, and medical assistance of the parent is similarly distributed between lactose absorbers and malabsorbers.


Selected beverage consumption patterns among Mormon and non-Mormon populations from the same geographic location. This study presents data from a mail questionnaire survey designed to determine the daily beverage consumption patterns of Mormon and non-Mormon households in Utah and southern Idaho. Mormons differed significantly from their non-Mormon counterparts in both their low intake of coffee, tea, and beer, and increased daily consumption of milk and water. A high percentage of Mormons adhere to Church doctrin in their beverage intake habits and the results would appear to substantiate previous preliminary studies of the dietary habits in this religious group.


Amniotic fluid analysis in assessment of fetal maturity. Sixty samples of amniotic fluid were analyzed for their surfactant level by measuring the lecithin-spingomyelin ratio and performing the "shake" test. Cytologic examination of the sediment was also performed using Nile blue sulfate staining. The lecithin-sphingomyelin ratio was found to be the best method to predict fetal maturity and assess the probability of subsequent respiratory distress syndrome. The "shake" test proved to be a valuable screening tool in assessment of fetal pulmonary maturity when the fetus is mature, but of little value when the fetus is immature. The estimation fetal fat cells seemed to be of lesser value in predicting fetal maturity.


Early functional closure of the ductus arteriosus associated with decreased severity of respiratory distress syndrome in preterm infants. It has been shown that a patent ductus arteriosus may complicate the course of the respiratory distress syndrome (RDS) in preterm infants. In this study, an attempt is made to answer the question: Is there any relationship between RDS and patency of the ductus arteriosus in preterm infants, that is, do preterm infants without the RDS have early functional closure of the ductus arteriosus? Clinical observations were made on 144 preterm infants 25 to 34 weeks' gestation. Infants were included in the study if the status of the ductus arteriosus (open or closed) could be established either by clinical examination or retrograde aortography. The ductus arteriosus was closed in 59 infants within 48 hours of birth and open in 85. None of the infants with a closed ductus had severe RDS and only three had mild RDS. In contrast, 50% (43 of 85) of infants with open ductus had severe RDS. These findings suggest that early functional closure of the ductus can occur even in very immature infants, and this early closure appears to be associated with a decreased incidence of RDS.


Molluscum contagiosum venereum in a women's outpatient clinic: a venereally transmitted disease. Molluscum contagiosum in a venereal distribution (MCV) was identified as an incidental finding in 14 patients in a women's outpatient clinic at a general hospital. The lesions were frequently overlooked both by patients and physicians. The lesions of MCV are frequently asymptomatic. The sexual history of the patients and the genital distribution of the lesions provide circumstantial evidence that MCV is a veneral disease. Management of cases of MCV should include a culture for the gonococcus and a serologic test for syphilis.


Effects of hydrocortisone on lecithin-sphingomyelin ratio. An intravenous infusion of hydrocortisone succinate was given in four divided doses during a 24 hour period to 17 high-risk pregnant women to accelarate fetal pulmonary maturity. Amniocentesis was performed before and 48 to 72 hours after treatment in all 17 patients. Comparisons were made of lecithin/sphingomyelin (L/S) ratios before and after treatment. The L/S ratio rose in 12 or 17 cases and was not influenced by the type of severity of maternal disease. Neither lenght of rupture of the membranes nor gestational age at the time of treatment affected the change in L/S ratio. Pretreatment L/S ratios (1.21 +/- 0.435 S.D.) were found to have a statistically significant difference from posttreatment values.


Lecithin/sphingomyelin ratio in pregnancies complicated by diabetes mellitus. The amniotic fluid lecithin/sphingomyelin (L/S) ratio was determined in 182 pregnancies complicated by Classes B and C diabetes and in 28 patients with Classes D, F, and R diabetes. These data were retrospectively correlated with the occurrence of the respiratory distress syndrome (RDS) or hyaline membrane disease (HMD). Only four cases of RDS and two cases of HMD were observed in 200 patients with an L/S ratio of 2.0 or greater prior to delivery. This 3 per cent incidence of complications is no higher than that of the nondiabetic population in our institution. Seven of 10 neonates with an antenatal L/S ratio of 1.5 to 1.9 developed RDS. An L/S ratio of 2.0 or more appears to be reliable predictor of fetal pulmonary maturity even in pregnancies complicated by diabetes mellitus.


Serum immunoglobulin concentrations of cattle in a herd with bovine leukosis. Consistent relationship was not found between the serum concentrations of immunoglobulin IgM and IgG and the concentration of blood lymphocytes (Bendixen index) in 289 Holstein-Friesian heifers and cows from a dairy herd in which bovine lymphoma had been identified repeatedly. Serum IgM was present in all cattle, and those cows with highest concentrations of blood lymphocytes generally had higher levels of IgM.


Malignant tumors of the intestine: a review of 37 cases. Malignant tumors of the small bowel are rare but carry a grave prognosis. Thirty-seven cases from the Tumor Registries of Brooke Army Medical Center. Fort Sam Houston, Texas, and Fitzsimons Army Medical Center, Denver, Colorado, were retrospectively studied. Twenty-nine males and eight females ranging from five to 86 years were included in the combined series. Thirteen carcinoid tumors, eight adenocarcinomas, seven lymphosarcomas, five leiomyosarcomas, two reticulum cell sarcomas, one liposarcoma, and one mesenchymal cell sarcoma were found. Symptoms included intermittent crampy abdominal pain, intestinal obstruction, intestinal bleeding with anemia, and weight loss. The diagnosis was made on the basis of the clinical picture in addition to physical findings and pertinent x-ray contrast studies. The overall survival rate was 25%. The treatment of choice is surgical extirpation of the tumor whenever possible followed by appropriate adjunctive modalities.


Association of immunoblastic lymphadenopathy and Hashimoto's thyroiditis. A 75-year-old white woman with a supraclavicular mass and primary hypothyroidism was found to have immunoblastic lymphadenopathy and Hashimoto's thyroidits. Peripheral blood contained normal percentages of T and B lymphocytes, but there was a markedly decreased response to phytohemagglutinin and to skin testing for delayed hypersensitivity. Since lack of suppressor T cells, B-cell proliferation, and decreased immunosurveillance may be causative factors in these diseases, it was of interest to document this rare association of immunoblastic lymphadenopathy and Hashimoto's thyroiditis.


Single-step gastric aspirate shake test: bedside predictor of neonatal pulmonary morbidity. A simplified, single-step shake test has been performed on gastric aspirate samples from 85 preterm infants and a control group of 214 term infants. Respiratory symptoms were seen in 25 of 30 preterm infants with a negative or intermediate test, but in only 2 of 55 infants with a positive test (P less than 0-001). No infant with a positive test developed respiratory distress syndrome (RDS) while RDS developed in 66% of those preterm infants with a negative test. False-negative results were not seen in the preterm group. The gastric aspirate shake test had better sensitivity and selectivity in prediction of clinical outcome than did the amniotic fluid lecithin/sphingomyelin ratio in 37 preterm infants in whom both results were available. Serial shake tests were performed on samples from a number of infants with RDS and the results were seen to change in parallel with clinical recovery. This and other observations suggest that the result of the gastric aspirate shake test depends more upon direct swallowing of fetal lung liquid than on swallowing of amniotic fluid.


Unusual events preceding hyperthyroidism with diffuse goiter. Two unique patients with hyperthyroidism are presented here. A 48-year-old woman with a family history of Graves' disease was first evaluated and treated for a toxic adenoma with radioactive iodine. Three months later, she was again hyperthyroid, was found to have a diffuse thyromegaly, and was treated with radioactive iodine for the second time. This patient represents, to our knowledge, the first reported case of two sequential forms of endogenous hyperthyroidism. The second patient, a 64-year-old woman, had well-documented hypothyroidism that was presumably primary. She was admitted in thyroid storm and subsequently died. The autopsy disclosed characteristic changes in the thyroid of hyperthyroidism and a normal pituitary gland. The timing of the onset of Graves' disease with hyperthyroidism cannot be accurately determined.


Peliosis hepatis. Twelve cases associated with oral androgen therapy. Peliosis hepatis was encountered in 12 patients treated with high-dose oxymetholone or fluoxymesterone therapy. In three cases liver failure was the primary cause of death. In one case, the diagnosis was established by biopsy, the androgen therapy was discontinued, and the lesion was absent at autopsy two years later. In eight cases peliosis hepatis was an incidental finding at postmortem examination. The clinical and anatomic features of these cases are described, and previously reported cases of peliosis are briefly reviewed. A hypothesis is offered to explain the association of this peculiar lesion with anabolic androgen therapy.


Fatty metamorphosis of the liver associated with jejunoileal bypass. Report of five cases. Detailed postmortem examination was carried out on five patients who died three months to four years after jejunoileal bypass for obesity. A spectrum of histological changes was observed in the liver, with pericentral fat deposition being a common feature. Evidence of previous and/or ongoing liver cell dropout with accompanying polymorphonuclear and mononuclear infiltration was seen in all cases, but Mallory hyalin was not detected. Liver function abnormalities included decreased plasma protein levels, decreased prothrombin activity, increased serum alkaline phosphatase levels, and variable elevations of the serum transaminases, bilirubin, and ammonia concentrations. The pattern of the hepatic disease does not resemble protein deficiency. An uncharacterized hepatotoxin or toxic effect of hepatic fat accumulation may play a significant role in the changes observed in these patients.


Congenital extrahepatic biliary atresia. Ten cases of congenital extrahepatic biliary atresia were studied ultrastructurally. Samples of liver were obtained from each and in six of the cases, fibrous tracts, which we hoped would contain extrahepatic bile ducts, were also secured. The observed extrahepatic biliary structures were real, but hypoplastic, bile ducts. In places, necrosed epithelial cells, without obvious inflammatory processes, could be observed. The ductular cell cytoplasmic changes and the inflammatory reaction are different according to whether extrahepatic or intrahepatic sites are considered. These differences, as well as the cytoplasmic modifications of liver parenchymal cells, seem to be the result of impaired bile flow. On the contrary, extrahepatic bile duct hypoplasia and necrosis seem to be directly related to the unknown origin of this disease. Whether the nuclear changes of hepatocytes are the expression of direct injury of the liver is another important question. If there is direct injury, it is possible that the disease might evolve as an independent liver disease despite a correctly performed and uncomplicated surgical intervention.


Ultrastructure of chronically inflamed human submandibular glands. The structure of chronically inflamed submandibular glands from four patients was examined by electron microscopy. The patients were free of the sicca syndrome and lacked other symptoms of Sjögren's syndrome or related autoimmune diseases. The affected glands were characterized by a reduction in acinar elements, by ductular proliferation and hyperplasia, and by large numbers of inflammatory cells in the stroma. This study indicates that many of the ultrastructural changes in salivary glands previously attributed to autoimmune diseases may also occur in patients who are free of such afflictions but whose salivary glands have undergone intermittent obstruction or infection.


Extraskeletal Ewing sarcoma. An ultrastructural study. Soft tissue tumors with the characteristics of Ewing sarcoma of bone have thus far only been studied by light microscopy. A pelvic tumor of this type in a 13-year-old girl was examined by electron microscopy. Comparison of its ultrastructural features with those of reported cases of bony Ewing sarcoma reveal much similarity. It is believed that they are probably identical and that the tumor cells are of immature mesenchymal type. However, their site of origin and the direction of their potential differentiation remain obscure.


Ruptured mycotic aneurysm: a complication of parenteral drug abuse. Mycotic aneurysms occurred in five narcotics addicts treated between 1969 and 1975. Fever, localized tenderness, swelling, loss of distal pulses, and leukocytosis were common findings. The aneurysms were located in the femoral (two patients), brachial (two), and superior mesenteric arteries (one). They occurred at the site of arterial injection in three patients. In one patient with subacute bacterial endocarditis, an aneurysm of the superior mesenteric artery developed. In one patient, the pathogenesis was uncertain. All patients had rupture of the arterial wall, with hemorrhage contained by adjacent muscle or soft tissue. Four patients were treated by ligation and debridement. One, with preexisting ischemia, required amputation below the knee. One patient underwent repair with autogenous artery. Recurrent hemorrhage necessitated ligation of the artery. In all patients, extensive sepsis and tissue necrosis precluded repair with prosthetic material. All patients survived, without evident of ischemia.


Improved assay of neurotoxic esterase for screening organophosphates for delayed neurotoxicity potential. The assay of neurotoxic esterase (NTE) in brains taken from dosed hens enables potential neurotoxicity of organophosphate pesticides, plasticers, etc. to be assessed. The original assay [Johnson, M.K. Biochem. J. 114, 711-717 (1969)] has been simplified to eliminate centrifugation and transfer steps and both the selectivity and the sensitivity have been increased. The procedures necessary to obtain stable reagent stocks are described.


Propoxyphene overdosage: a study of cases involving analgesic preparations containing dextropropoxyphene. Propoxyphene and paracetamol concentrations have been determined in blood, urine, liver blood and stomach contents from 17 post mortem cases in which Distalgesic (a propoxyphene and paracetamol compound preparation) was involved. Five patients admitted to hospital with suspected Distalgesic poisoning have also been investigated. In most cases the propoxyphene concentrations, but not the paracetamol concentrations, exceeded the minimum lethal levels reported. On the basis of our results it appears that of the constituents of Distalgesic, propoxyphene has a far more immediate and dangerous effect than paracetamol.


Suicide by an overdosage of N-propylajmalinium bitartrate. The toxicological findings after suicidal poisoning with N-propylajmalinium bitartrate (NPAB) are presented. For isolation of NPAB the biological material was homogenized and the drug was isolated by adsorption on Amberlite XAD-2. After column chromatographic purification on Sephadex LH-20 quantitative determinations were carried out by gas chromatography of the trifluoroacetate. The identity of the material finally obtained was checked by various chromatographic and spectrometric methods. The following concentrations of NPAB were found: liver 58 microgram/g, kidney 32 microgram/g, brain 16 microgram/g, muscle less than 10 microgram/g, heart less than 5 microgram/g, blood less than 5 microgram/g, gastric contents 600 mg (total). 1200 mg of NPAB had been swallowed; thus the amount of NPAB, that had crossed into blood, was approx. 500-600 mg corresponding to a dose of 9-11 mg/kg body weight.


Determination of cadmium in human milk during lactation. During lactation, Cd-levels in human milk were determined by means of flameless atomic absorption spectrophotometry. The levels in colostrum were some 50-65% higher than in transitional and mature milk.


Biochemical and morphological changes in some organs of rats in nickel intoxication. Biochemical and histological alterations in liver, kidney, testis and myocardium of albino rats were investigated at various intervals after daily administration of nickel sulphate. No significant changes were observed during the initial periods of the treatment, but longer exposures produced marked enzymatic and histopathological alterations in all the four organs examined. The severity of the histological lesions was found to be directly related to the duration of the treatment.


[Teratologic-neurotoxicologic studies on biglumide (K-2004) and thalidomide]. Comparison of the teratogenic and neurotoxic influence of thalidomide with the new hypnosedative preparation Biglumide (K-2004) revealed significant differences. Malformations could be seen only after treatment with thalidomide. Some results concerning the thalidomide-treated group of animals could be interpreted as a retardation of development in the posterior root ganglia.


Fatal poisoning with verapamil.

Fatal poisoning with verapamil. The toxicologic findings in a case of fatal poisoning with verapamil (Isoptin) are are presented. For isolation of verapamil the biologic material was subjected to protein precipitation. The aqueous solutions were acidified with hydrochloric acid, prepurified by extraction with ether, and subsequently the basic drug verapamil was isolated by ion pair extraction with chloroform. Quantitative determination of verapamil was carried out by gas chromatography using a nitrogen specific flame ionization detector. The following concentrations of verapamil were measured: liver 5500 ng/g, kidney 2000 ng/g, blood 590 ng/g, urine 250 ng/g, gastric contents 3 mg (total). During examination by the police it was claimed by a witness that two tablets of Isoptin had been taken before death. After application of a therapeutic dose of Isoptin peak concentrations of 11 and 30 ng/g of blood cells and of 30 and 65 ng/g of plasma were measured in two healthy subjects; the latter figures corresponded well to previous findings of other authors, who investigated plasma concentrations of verapamil after therapeutic administration. In the case presented here, the blood concentration of 590 ng/g clearly demonstrated that an extreme overdose must have been taken before death.


[Enzyme studies of synovial fluid from osteoarthritis knee joints (author's transl)]. In 40 patients who were operated on for meniscopathy, accompanied by more or less severe arthroses of the knee joints, the total activity of LDH-T and of the LDH-H isoenzyms could be evaluated. The data show that severe arthroses without any synovitic reactions as well as  cases with inactive chronic synovitis showed small total activities of LDH, whereas cases with clinical and macroscopic-anatomically active synovitis (including the so-called activated arthroses) showed a great total activity of LDH. Furthermore the dominance of LDH-H isoenzyms has been found to indicate an aerobic situation of the metabolism.


Middle ear mucosa and secretory otitis media. Recent investigations have identified the viscous middle ear effusion in secretory otitis media (S.O.M.) as being of the same nature as true mucus--the "backbone" of which is glycoprotein. The source of the mucus is mucus-producing cells in greater number than found in the normal middle ear lining. The pathological state which leads to excessive mucus production and maturation of numerous mucus cells is an inflammation associated with deficient ventilation of the middle ear. In the presence of inflammation, especially when CO2 tension is high, mucosal stem cells differentiate metaplastically into numerous mucus-producing cells, as demonstrated by us in tissue cultures. The higher CO2 tension in S.O.M. is due to eustacian tube insufficiency (not blockage) which is a smaller than normal amount of air introduced into the middle ear per unit of time. Ventilating tubes restore CO2 tension to normal and equalize the slight barometric negative pressure (average 3.35 H2O)--the latter being related to mucociliary clearance. Evidence for an allergic factor as a pathogen is also not available. The mucus in the middle ear is probably not noxious by itself and ears should be ventilated surgically only when hearing is below social level perception. Most S.O.M. ears will clear sooner or later spontaneously. A minority of these ears will progress with time into atelectatic ears and some might perforate later on.


Ectopic muscle in the middle ear.

Ectopic muscle in the middle ear. An ectopic muscle was found in the hypotympanum of a 31-year-old Japanese male. The muscle produced symptoms quite similar to those seen in cases of glomus jugulare tumor: a red mass visible through the ear drum, conductive deafness, a compressed jugular bulb demonstrable by retrograde jugulography, and VIIth and IXth nerve paresis. However, the audible pulsating tinnitus of glomus jugulare tumor was absent. The mass proved to be a muscle speculated as being a part of the levator veli palatini muscle. In view of our findings, ectopic muscle should be included in the differential diagnosis of glomus jugulare tumor.


Filter function of the guinea pig cochlea after degeneration of outer hair cells. After kanamycin induced degeneration of outer hair cells from  guinea pigs the tuning properties of primary auditory nerve fibres are compared with those of normal untreated guinea pigs. The existence of fibres with no alteration of the tuning properties leads to the conclusion that there is no neural interaction between inner and outer hair cells needed to enhance the frequency selectivity.


Does promethazine (Atosil) influence the human's early acoustically evoked potentials in the same way as the late potential N1? In a former investigation the effect of promethazine (Atosil) on the late acoustically evoked potential component N1 was examined. Now the cochlear and the brain-stem potentials were registered by the earlobe-vertex pick-up with i.m. application of 0.8 mg/kg (body weight) promethazine. There was no influence of promethazine either on the compound action potential (NAP) or on the brain-stem potentials (Pot. II-V), but sedation improves significantly the signal-to-noise ratio, therefore we sedate all patients when registering the five early acoustically evoked potentials.


[Influence of different fixation buffers on the quantitative cytoarchitecture of the cochlear spiral ganglion. A morphometric study (author's transl)]. The influence of two fixation buffers on the quantitative cytoarchitecture of the cochlear spiral ganglion in guinea pigs was evaluated morphometrically. After fixation with phosphate buffered 1.3% OsO4 granular spiral ganglion cells lost 45% of their average individual volume as compared to the volume after fixation with s-collidine buffered 1.3% OsO4. Using the two fixatives there was no significant difference of the volume proportion of cell nuclei, mitochondria, lysosomes and rough endoplasmic reticulum per unit volume cytoplasm of the granular spiral ganglion cells. The volume proportion of their ribosomes and their Golgi apparatus per unit volume cytoplasm increased 3.5fold after fixation with phosphate buffered OsO4. The volume density of the granular ganglion cells decreased by 30%, the volume density of the interganglionar space (= space between granular ganglion cells) showed an increase of 50% using phosphate buffer. Mostly the extracellular space was participating in this relative increase of the interganglionar space. As a result fixation of the spiral ganglion for morphometric studies should be performed using s-collidine buffered OsO4. The morphometric findings underline the presumption of semicompact myelin being a fixation artefact.


[Detection of noise-induced physiological stress and hearing loss in guinea pigs by means of an electro-cochleographic method (author's transl)]. One of the most essential prerequisites to the suitability of test animals used for studying the damage effect of noise on audition is the threshold determination with reasonable expenditure. Mention is made of an electro-cochleographic method to determine the click threshold and click threshold shift [TTS(C) and PTS(C)], resp., after an uninjured guinea pig has been subjected to noise. The temporary threshold shift following a short-term sonic exposure and the permanent threshold shift following a permanent sonic exposure reveal a far heavier effect on the guinea pig ear than on the human ear. However, the trends in stress and affection are so much alike in guinea pig and man that the former's involvement in studying the effects of audition-affecting noise on the human ear seems to be primising.


Intraoral nerve block for glossopharyngeal neuralgia. Glossopharyngeal neuralgia was treated by a new method of intraoral block. The procedure consists of block for the tonsillar branch and block of the lingual branch by the injection of 5% Phenol in Glycerin. This can be applied for neuralgia with a trigger zone around the tonsil. The result is quite satisfactory. This is extremely safe and simple, and can be performed repetitively when recurrences occur. Also, this procedure does not preclude later operations as a final step.


Aerodynamic pattern of Eustachian tube dysfunction. Detailed aerodynamic patterns for various disorders of the Eustachian tube function were reported. Simultaneous recording of the pressure in the ear canal and the pharyngeal cavity during Valsalva's maneuver and deglutition permitted an objective evaluation of different tubal dysfunctions. The patient with occluded tube showed either disturbance of the air flowing into the tube or outflowing from the tympanum to the pharynx. Depending on the degree of patency, the patulous tube showed either a synchronous change of the tympanal pressure with that of the pharyngeal cavity or an early and sudden drop of the tympanal pressure without deglutition. Through this rather simple aerodynamic technique, evaluation of different tubal dysfunction is possible.


[Changes of the motility of the pillar in case of intrathoracical affections (author's transl)]. It is shown that in the light of relevant cases the intensified movements of the pillar and the vocal cords during the respiration can indicate a pulmonary or cardiac respiratory insufficience. The increased appearance of respiratory movements of the pillar after the stress of motion goes to prove a reduced cardiorespiratory efficiency. The unilateral or bilateral reduction of motility, the ataxy and tremor of the pillar as well as disturbances of coordination of the automatically steered respiratory movements of the pillar may indicate lesions of the distal, thoracical and abdominal vagus trunk by neoplasms and operative traumas, even if this damage was done far below the offset of the Rr. pharyngici. An interpretation of these retrograde losses of motility of the pillar is given, which is also important for understanding the median and intermediary position of the paralysed vocal cord.


[Congenital torticollis with dislocation of the larynx and trachea caused by contracture of one omohyoides muscle (author's transl)]. Report on a boy with congenital torticollis by contracture of one omohyoid muscle with lateral displacement of the larynx and trachea, marked asymmetry of the face. Since surgery this asymmetry has nearly totally regressed, and the larynx is in median position.


[Determination of the perilymph density in the cochlea of guinea pigs (author's transl)]. The perilymph density of the sc. tympani, sc. vestibuli and the density of liquor cerebrospinalis in guinea-pigs are measured by determination from mass and volume of the fluid column in a glass capillary tube. For the density of perilymph in sc. vest. a value of (formula: see text) in sc. tymp. a value of (formula: see text), and for liquor a value of (formula: see text) was obtained.


[Model building in pharmacokinetics/Part I: General strategy (author's transl)]. A repetitive cycle: hypothesis-experiment-analysis is typical for construction and evaluation of models in pharmacokinetics. A general strategy is outlined to meet the requirements of correct modelling, proper experimental design, careful experiments, valid parameter estimation and model identification.


[Model building in pharmacokinetics/Part II: Generalized theoretical presentation of complete integration of linear compartment models of optional structure (author's transl)]. The method of Laplace transformation is used to obtain the integral of linear differential equations for pharmacokinetic models. A general solution uniform in structure for all types of models (mammillary, catenary, mixed) was established. Choice of one more application compartments, of kinetics describing the input procedure and of elimination pathways is free.


[Model building in pharmacokinetics/Part III: Simplified rules for the deduction of analytical solutions for linear compartment models (author's transl)]. Analytical solutions for any linear compartment model are obtained empirically by use of simple rules. Set up of differential equations and tedious integration procedures are thus avoided. The procedure is suited for automation by a calculator. Integrated equations are accessible then even more simply and rapidly.


Model building in pharmacokinetics/Part V: Simulation of blood level curves following repetitive dosing and their experimental verification (author's transl). An equation is given to describe the plasma level curve of any linear compartment model following multiple dosing of various doses after various time intervals. The equation is especially suitable to be used with desk top computers equipped with a plotting device. A dosage regimen can be simulated using the parameters derived from single dose experiments. Experimental check-up of the predicted curves is necessary and illustrated by two examples. Systematic deviations from the prediction indicate changes in the biological system, e.g., in absorption, by enzyme induction, saturable processes, etc.


[Effects of reserpine and its derivatives on release of biogenic amines. Comparative study of the activity of reserpine and diethylaminoethyl-1-reserpine as bitartrates (author's transl)]. A comparative study of the activity of reserpine and its salt of diethylamineothyl on the central nervous system was performed. Palpebral ptosis in the mouse and depletion of catecholamines in the rat served for comparison. The reserpine salt of diethylaminoethane is a new derivative of reserpine the depleting activity of which on the central nervous system is considerably diminished.


Ibuproxam and ibuprofen. A pharmacological comparison. The anti-inflammatory, analgesic and antipyretic effects and the tolerability of 2-(4-isobutylphenyl)-propionic acid (ibuprofen) were compared with those of its derivative 2-(4-isobutylphenyl)-propiohydroxamic acid (ibuproxam, Ibudros. Our experiments show that the interfering action of the two drugs with the reactive processes of the tibio-tarsic articulation, brought about by carrageenin, serotonin, dextrane and formalin is of the same intensity. Also, the analgesic activity is perfectly consistent with the antipyretic one. However, the tolerability of the two molecules is different; the acute toxicity is consistent in the case of the single parenteral administration and it differs in the case of a single or repeated oral treatment. When used under these conditions, ibuproxam is considerably less damaging to the gastroenteric tube than is ibuprofen. The hypothesis is put forth that the greater tolerability of ibuproxam is due to its pharmacokinetics: it is, as such, little or not toxic for the mucous membrane of the digestive apparatus, and it progressively releases ibuprofen, whose concentrations in the blood  would remain below those levels that cause systemic lesions in the gastroenteric tract.


Determination of ibuproxam and its metabolites in the plasma and urine of rats. The metabolism of 2-(4-isobutylphenyl)-propio-hydroxamic acid (ibuproxam, Ibudros), a new molecule with anti-inflammatory, antipyretic and analgesic activity was studied by its administration orally and rectally to the rat. The analysis, carried out with gas chromatographic method and thin-layer chromatography, showed that the drug is present in blood as 2-(4-isobutylphenyl)-propionic acid (ibuprofen), an anti-inflammatory drug which is commonly used and the metabolites of which are already known. Using the same methods, it was observed that only a few traces of the hydroxamic acid appear in the urines of rats treated with ibuproxam, whilst the ibuprofen metabolite is absent. Therefore, we conclude that the drug ibuproxam changes rapidly into ibuprofen, following afterwards the same known metabolic process as the latter drug.


Charge-transfer complexes of hematoporphyrin having a pharmacological interest. Complexes formed by hematoporphyrin with donor molecules were prepared and isolated. Among these complexes particular attention is given to that formed by reacting dimethylaminoethanol with hematoporphyrin. Some data are reported on the chemical evidence of formation like u.v. spectra. The product, named Hematodeanol, determines some sufficiently specific effects on the CNS; it remarkably cuts down the depression induced by pentobarbital, moderately hinders convulsions by metrazole, delays hypothermia by reserpine, facilites the learning of conditioned avoidance response (CAR) and improves the learning of a sound discrimination at variable interval. The actions become evident when tests are carried out after a continuous treatment for 7 days and according to the data of the investigation of pharmacokinetic kind, the phenomenon may be attributed to the fact that the drug concentration in the nervous tissue, when it is administered several times at intervals of 24 h, inclines to increase progressively.


[Diuresis and natriuresis following application of bemeticide and triamterence in rats on normal and low-potassium diet (author's transl)]. The investigations were carried out under identical conditions and were aimed at determining the effects of different doses of the two diuretics: 3-(alpha-methylbenzyl)-6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide (bemeticide) and 2,4,7-triamino-6-phenylpteredine (triamterene) as well as for their joint administration at ratios of 1:2 and 1:4, resp., with regard to renal elimination of sodium and potassium as well as to urinary output in normally and low-potassium-fed rats. The 1:2 combination of bemeticide and triamterene resulted in an optimum diuretic and sodium elimination effect with potassium values within normal range, both in the normally and in the low-potassium-fed animals. An increase of the triamterene component from the 1:2 to the 1:4 ratio did not yield additional advantages.


Effect of temperature of perorally administered phenol red solution on gastric emptying in the rat. Phenol red solutions of 5,25 and 45 degress C were administered perorally to rats. 15, 30 and 45 min after administration the rats were sacrificed and the residue of phenol red in the stomach and in the small intestine determined. Precent phenol red dose recovered from the stomach versus time was found to follow first-order kinetics. The data show a decrease of gastric emptying with increasing temperature of the phenol red solution administered.


[Pharmacological studies on the antiphlogistic effect of pentosanpolysulfate in combination with metamizol]. In the present study we investigated the antiinflammatory effect of pentosanpolysulfate (SP 54) in combination with metamizol using different forms of rat paw edema (induced by dextrane, hyaluronidase, trypsin, formaldehyde, carragenine or kaolin). After s. c. application Probaphen, a new drug containing pentosanpolysulfate, metamizol, and lidocaine, proved in our experiments to exert an antiphlogistic effect about 40% stronger than the equivalent amount of SP 54 alone. Since pentosanpolysulfate by itself has no analgetic activity, its combination with metamizol results in a formulation which is not only a more potent antiinflammatory drug but will aslo counteract pains which accompany most edematous reactions. Probaphen may therefore be suggested for the treatment of rheumatoid arthritis and similar inflammatory and edematous processes. First clinical studies and reports on Probaphen fully support our pharmacological results.


Rutosides and radiation induced regression of experimental tumours. The effect of some flavonoids like O-(beta-hydro-xyethyl)-rutoside, alone and in combination with X-rays, was investigated on three transplantable mouse tumours. The growth characteristics of the tumours depending on the sex of the host animal and the application of flavonoids are described. Under the different experimental conditions exployed involving 1500 mice, flavonoids did not alter the radiation effect on the tumours as neither a protective nor a sensitizing effect was observed.


Variations in acid and neutral protease activity of rats with thermal oedema together with the influence of various benzopyrones. The benzopyrones are known to be very effective in reducing thermal oedema. It is believed they do this by enhancing protoelysis of the abnormal accumulated protein. However, the enzymes which are affected were not known. The effect of the benzopyrones was examined on both acid and neutral proteases in normal and thermally injured animals. In normal animals the benzopyrones at first enhanced serum acid protease levels, while serum neutral protease levels were depressed. Acid and neutral protease levels of the skin were not altered. The effect of thermal injury was to elevate serum acid protease activity and to depress neutral protease activity. Additional treatment with the benzopyrones further enhanced the former and depressed the latter. Acid and neutral protease activity of the skin was depressed by burn, but enhanced by benzopyrone treatment. The enhancement of proteolytic activities by the bezopyrones is indicative of increased phagocytosis and digestion. The resulting small protein fragments can rapidly leave the injured region thus freeing the osmotically attracted fluid, which is the cause of oedema.


Vasotropic drugs--a survey based on a unifying concept of their mechanism of action. A group of vasotropic drugs was surveyed using a new assay method based on the inhibition of endothelaemia increases after a standard vascular lesion in rats. The new test is considerably more sensitive than all previous ones. It provides a common link between all tested vasotropic drugs and points also to their common mechanism of action. All of them have a protective effect on endotherlium based, in some of them at least, on the preservation of the consistency of endothelial cement. The effect is probably mediated by their influence on calcium availability.


[Biopharmaceutic investigations with D-norpseudoephedrine. 2nd communication: Bioavaliability of a depot preparation (author's transl)]. The concentrations of D-norpseudoephedrine in the plasma of five healthy male subjects were measured after oral administration of either two Fugoa depot aragees or of a standard of 60 mg D-norpseudoephedrinehydrochloride in a hard gelatin capsule. Areas under curves (AUC) were calculated with the trapezoidal-rule for blood levels to compare bioavailability. The medium bioavailability of Fugoa depot dragees was 95% compared to the standard. With the paired t-test no significant difference in the bioavailability occurred.


[Experimental investigation of psychophysiological effect of a new antidepressant (lofepramine) as compared to imipramine and placebo (author's transl)]. Using 24 non-selected healthy male students the effects of imipramine (single dose of 100 mg orally) and 4'-chloro-2-[3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-propyl]-methylamino]-acetophenone-hydrochloride (lofepramine, Gamonil) (single dose of 140 mg orally) in comparison to placebo (doubleblind) on subjective, physiological and performance variables were examined. All subjects (Ss) received the three drugs in a completely counterbalanced sequence. On the basis of their scores on the Depression Scale of the Freiburger Personality Inventory (FPI, Fahrenberg) Ss were divided into two groups of 12 Ss each, "high depression" and "low depression" group. Two-way analyses of variance were computed. Imipramine and Lofepramine elevate scores in the mood scale, but only for the "high depression" group. For the Ss scoring lower in depression no such effect can be demonstrated. The physiological effects are similar. Reported side effects are less for lofepramine than for imipramine.


Laser photolysis and fluorescence studies on pyrene-thiazide and pyrene-diazoxide systems. The laser photolysis studies on pyrene, pyrene-thiazides and pyrene-diazoxide systems in acetonitrile revealed that thiazides and diazoxide can scavenge the photoejected electron. It was found that the pyrene fluorescence is quenched by the present diuretics and related compounds and both static and dynamic quenching constants were obtained. Thiazides quench the fluorescence through both static and dynamic mechanism, while the small static quenching constant and no lifetime shortening of pyrene were observed in the case of diazoxide quencher. This difference may correspond to the difference of their diuretic activity.


[Antiviral agents / 9th communication: virustatically active N-(1-adamantyl)-thiourea derivatives based on cyclic secondary amines (author's transl)]. By nucleophilic addition of pyrrolidine (2a), piperidine (2b), 3-hydroxypiperidine (2c), and 4-hydroxypiperidine (2d) on 1-adamantyl-isothiocyanate (1), the N',N'-disubstituted N-(1-adamantyl)-thiourea derivatives 3a, 3b, 3c, and 3d are accessible. Particularly 3d exhibits remarkable antiviral activity vaccinia and herpes virus.


[Anticoagulant activity of triiodinated x-ray opaque media (author's transl)]. The anticoagulant activity of the triiodinated X-ray opaque media iodipamide, iothalamate and diatrizoate on standardized normal human pool plasma was investigated in vitro. We found a dose dependent lengthening of the thrombin time, the reptilase time and the partial thromboplastin time together with a dose dependent drop of the calcium thromboplastin and factor V activity. Iodipamide proved to exert the most pronounced anticoagulant activity of the 3 contrast media tested. The results are interpreted as latent disseminated intravascular coagulation with hyperfibrinolysis following the direct interaction of contrast media with the coagulation enzymes.


[Phytopharmacological study on proadiphene, amiphenazole and bemegride in association with phenobarbitone (author's transl)]. The capacity of 2-diethylaminoethyl-alpha, alpha-diphenylvalerate (proadiphene), 2,4-diamino-5-phenyl-thiazole (amiphenazole) and 2,6-dioxo-4-methyl-4-ethyl-piperidine (bemegride) of stimulating or stopping the growth of seedlings of Lepidium sativum L. was tested. Only bemegride shows a weak stimulating effect between 10(-3) and 10(-2) moles/l. In combination with phenobarbital these compounds counteract the stimulating effect and increase the inhibiting one of this barbiturate on the growth of the seedlings.


[Exchange of aromatically bound halogen for OH- and SCH3-groups in metabolising clozapine in the human organism (author's transl)]. 8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo-(b,e)(1,4)-diazepine (clozapine, 1) is metabolized in humans by exchange of the aromatic halogen for a hydroxy- or a methylthio-group (compounds 2 and 3). Further metabolites are the N-demethyl derivatives of 2 and 3, the compounds 4 and 5. In addition a clozapine metabolite with the structure 6 with an oxidized piperazine ring was found. The presence of a metabolite with an oxidized sulfur atom is suggested. Possible ways for the formation of these metabolites are discussed.


[Biotransformation and pharmacokinetics of grandiflorenic acid [kauradiene-9(11),16-oic acid-18] / 1st communication (author's transl)]. Grandiflorenic acid is oxidized by several partial-synthetic ways. The spectroscopic properties of the resulting compounds are compared in mass-, IR- and 1H-NMR-spectrometer.


Isolation of apoprotein from bovine lung surfactant material by sodium deoxycholate. Aqueous solutions of bovine lung surfactant material were solubilized with a high concentration of sodium deoxycholate and the protein moiety could then be separated from the mixed lipid-sodium deoxycholate micelles by gel filtration in the presence of a micellar concentration of sodium deoxycholate of 10 mM. The lipid-free protein showed only one detectable peak in the gel filtrate and the sedimentation rate of this protein was 12.1 S. Sodium dodecyl sulfate disc gel electrophoresis showed essentially the same pattern as did the protein extracted directly from the bovine lung surfactant material with organic solvents, of which the major component has a molecular weight of 36 000. This protein should be the main apoprotein of lung surfactant material, and the main band in the sodium dodecyl sulfate disc gel electrophoresis, with a molecular weight of 36 000, would constitute the major protein subunit.


On enzymatic clotting processes. I. Kinetics of enzyme-triggered coagulation reactions. The kinetics of enzymatic clotting reactions such as the clotting of blood or milk, is analyzed. The appearance of a lag phase in the clotting is shown to be due to the difference in reaction order of enzymatic production and flocculation. The weight-average particle weight of the product formed is found to be a quadratic function of the reaction time. The condition for the clotting time is t square root of ksV/2 = C, where t is the clotting time, ks the flocculation rate constant, V the maximum rate of enzymatic product formation and C a constant. In agreement with this result double-logarithmic plots of t versus enzyme dilution are always observed to be linear over a wide range of enzyme concentrations. No statistical evidence could be produced for the widely held belief that the clotting time should be inversely proportional to the enzyme concentration. Varying exponents of the latter in its relation to the clotting time are discussed in terms of von Smoluchowski's theory of the slow coagulation of colloidal particles.


Combination intrathecal therapy for meningeal leukemia: two versus three drugs. The comparative effectiveness of intrathecal (IT) combination chemotherapy using two agents, methotrexate (MTX) and hydrocortisone (HDC), and three agents, MTX, HDC, and cytosine arabinoside (CA), in treating meningeal leukemia was determined in a randomized Southwest Oncology Group study. Following central nervous system (CNS) remission induction the same regimen was used for periodic maintenance until CNS relapse supervened. Complete CNS remission was achieved in 100% of 43 children given two-agent therapy and in 96% of 48 children given three-agent therapy. Length of CNS remission for two-agent therapy was 1-150+ wk, median 47.2 wk; for three-agent therapy, remissions were 1-190+ wk, median 64.6 wk. Differences in length of remission curves were not of statistical significance (p=0.71). Toxicity of combination IT chemotherapy in the two- and three-agent regimens was reduced compared to that of IT MTX alone for CNS remission induction and maintenance. The additive effects of the IT drug combinations have been less than expected. The cytocidal activity of these agents when administered simultaneously of sequentially is not fully understood. Further studies are clearly indicated to determine optimum doses, schedules, and sequences for the chemotherapeutic agents which can be given intrathecally in combination.


Is milk a coronary health hazard?

Is milk a coronary health hazard? Epidemiological and clinical evidence is presented on an association between the quantity of milk consumed and the incidence of ischaemic heart disease. It is suggested that the daily intake of liquid milk for adults should be at most one-third of a pint (less than 0-21).


Antitumor effects of RNA isolated from murine tumors and embryos. We describe the antitumor effects of a certain RNA(s) isolated from murine tumors and embryos. A single i.v. injected of 10 to 30 microgram of this RNA(s) induces necrosis, hemorrhages, and regression of solid tumors in the strain of origin; in pregnant mice it is embryotoxic, causing resorption of the embryos, but has no toxic effect upon the tumor-bearing or pregnant host. Its action is highly specific, and its presence in both tumors and embryos suggests that it may result from reexpression of embryonic genes in tumor cells.


Perilymph penetration of methotrexate in cats. The perilymph of the inner ear has recently been suggested as a site of frequent leukemic or lymphomatous infiltrates. Experimental evidence supports the existence of barrier mechanisms and explains the attenuated entry of several substances, including chemotherapeutic agents, from either the cerebrospinal fluid or blood into theperilymph. The present study describes the attenuated entry of methotrexate into the perilymph compartment of experimental animals following intrathecal or iv administration.


Clinical pharmacology of intrathecal methotrexate. I. Pharmacokinetics in nontoxic patients after lumbar injection. Cerebrospinal fluid (CSF) and plasma methotrexate (MTX) concentrations were measured in 76 children and adults who received intrathecal MTX, 12 mg/m2 body surface area, without developing symptoms of lumbar puncture syndrome or drug-induced neurotoxicity. After an initial rapid redistribution of the injected drug, the mean antifolate value in the lumbar CSF declined in a biphasic manner with half-lives of 4.5 and 14 hours. In the plasma the mean MTX concentration reached a peak of 2 X 10(-7) M between 3 and 12 hours after injection and decreased biexponentially thereafter with half-lives of 5.5 and 24 hours. Pharmacokinetic analysis suggested that the predominant mode of MTX transfer from the central nervous system to the systemic circulation is bulk flow absorption of CSF with entrained drug. The two phases of disappearance from the lumbar CSF appear to result from interaction of the convective transport and diffusion between the CSF and brain extracellular fluid (and perhaps some intracellular sites).


Reduction of plasma triiodothyronine (T3) induced by propranolol. The effect of propranolol on plasma triiodothyronine (T3), thyroxine (T4) and triiodothyronine uptake by Sephadex G-25 (RT3U%) was studied in fourteen thyrotoxic patients and eight normal volunteers. 40 mg of propranolol as a single oral dose caused significant reduction in total serum T3 which began 60 min after administration. No significant changes were observed in T4 and RT3U% values. Plasma T3 levels remained suppressed during a 5 day course of treatment with propranolol. These results suggest that propranolol has a direct effect on peripheral metabolism of T3 rather than on thyroid hormone secretion.


Development of a lymphocytic lymphoma during immunosuppressive therapy with azathioprine for systemic lupus erythematosus with renal involvement induced by phenylbutazone. A case of systemic lupus erythematosis (SLE) with renal involvement after the administration of phenylbutazone is described. The patient subsequently developed a lymphocytic lymphoma following two years treatment with azathioprine and prednisone. Although the association between SLE, immunosuppressive therapy and the development of lymphomas is well documented, the increased incidence of malignant disease in uremic patients is less well recognized. The varied factors that may have contributed to the development of the lymphoma in this case are discussed, together with a review of the literature.


Genital herpes: the newest venereal disease. Report of a case associated with aseptic meningitis. A case of genital herpes associated with aseptic meningitis is presented. The current concepts regarding epidemiology and pathogenesis, with special attention to involvement of the central nervous system, are discussed. The various clinical and laboratory aspects of the disease are briefly discussed. A review of the literature revealed only forty-four cases of proved herpetic infection of the cerebrospinal fluid in patients other than neonates. The concept of genital herpes as a new and serious public health problem is presented. With the present state of our knowledge and technology, genital herpetic infections will be a major problem for some time to come.


[Intraamnial application of 14C-labeled lecithine at man 13 hrs. ante partum (author's transl)]. It was examined, whether by intraamnial applicated lecithine an approaching respiratory distress syndrome could be prevented. This possibility of therapy was tested on a fetus unviable of life. It was shown by examining the lavage-fluid of the fetal lung, as well as the organ homogenates of lung; liver and gut, that the intraamnial applicated lecithine was metabolised and resynthesised in the organism. In the lung the lecithine was present as a complete molecule.


[Studies on the relationship of maturity to the tolerance of ischemia]. In newborn rabbits during asphyxia caused by ligature of the trachea circulation was maintained 2-3 times as long as in adult rabbits because in contrast to the adults myocardial energy loss in asphyxia is rather low caused by a small energy consumption for circulatory work. In the cerebral cortex of newborn rabbits glycolysis is able to meet a good part of energy demand, with the energetic situation predominantly depending on glucose supply by maintenance of circulation. Thus in addition sufficient blood glucose levels deliberated from glycogen stores in liver and lung are an important factor for the central nervous revivability. Kidney and skeletal muscle tolerate anaerobic periods for rather long time because of their high glycogen stores and low metabolic activity but do not contribute to glucose supply of other tissues.


Pharmacokinetics of carfecillin and carindacillin. The pharmacokinetics of carfecillin and carindacillin was compared in 10 volunteers. The pharmacokinetic parameters of both antibiotics were also determined using an analog computer. From the pharmacokinetic point of view, no significant differences between the two carbenicillin esters were found.


Factors affecting the bioavailability of phenytoin. The bioavailability of seven phenytoin (DPH) formulations, five brands of tablets and two suspensions, was measured in a cross-over study with six healthy volunteers. Single doses of 600 mg of DPH were used and the bioavailability was determined as the area under the serum DPH concentration-time curve (AUC). Highly significant differences between the bioavailability of various products were found. The highest bioavailability was obtained with suspension prepared from the micronized raw material of DPH and the lowest bioavailability (26% of that of the former suspension) with the tablets having the largest particle size of DPH. The in vitro dissolution rate of the products in borate buffer at pH 9 showed a significant (p less than 0.01; r=0.93) correlation with the in vivo bioavailability of the DPH products. In addition to the particle size, several other formulation factors are important for dissolution rate and absorption characteristics of DPH products. The properly performed measurement of the in vitro dissolution rate can be used as a preliminary screening test in predicting the bioavailability of DPH products.


Pulmonary surfactants in pulmonary oedema induced by head injury in mice. A study has been carried out to examine the role of pulmonary surfactants in pulmonary oedema induced by head injury. Pulmonary oedema was induced by head injury in mice by the method of Mackay (5). There was no change in surface tension as well as total phospholipid concentration of the lung between control and test groups suggesting that there was no involvement of lung surfactant sytem in pulmonary oedema induced by head injury. Since the animals in the test group died within a few minutes, possibly there may not have been sufficient time for alteration of lung surfactant system.


Photography of peripheral pulmonary airway expansion as affected by surfactant. Edges of excised lungs from twenty 27-day-old rabbit fetuses were photographed as tracheal pressure was raised and air entered alveoli. Lungs from two littermates were expanded simultaneously with pressure up to 50 cmH2O. The effect of surfactant (SA) on peripheal airway expansion was assessed by depositing 25 mul of SA suspension in the trachea of one pair of lungs. The suspension was obtained by washing the lungs of young adult rabbits and concentrating the SA by centrifugation. In 9 of the 10 experiments, the SA-treated lung was the first to become expanded. When pressure was lowered to 10 or 0 cmH2O, peripheral airways of treated lungs usually maintained expansion; air in control lung alveoli disappeared, or was trapped. High surface tension tended to collapse the cylindrical respiratory bronchiole rather than the spherical alveolus, causing air trapping, if the radius of the cylinder was less than half of the sphere. SA lessened collapsing tendency in the respiratory bronchiole.


Dysthyroid ophthalmopathy: orbital evaluation with B-scan ultrasonography. B-Scan ultrasonography was used to show muscle enlargement in all patients with Graves' disease and positive eye signs even when the clinical signs were minimal (lid lag and stare only). In addition, in cases of Graves' disease without clinical eye signs, 63% of orbital examinations showed ultrasonic evidence of muscle enlargement, often to a marked degree. This occurred more frequently in euthyroid patients after ablation of the thyroid by surgery or radiation, than in frankly thyrotoxic patients. The presence of subclinical ophthalmopathy in the fellow eye is a useful diagnostic aid in cases of uniocular proptosis.


Use of litmus milk agar for presumptive identification of cutaneous propionibacteria. Presumptive identification of cutaneous propionibacteria can be achieved with litmus milk agar as medium.


Aortic mycotic abdominal aneurysm involving all visceral branches: excision and dacron graft replacement. A 41 year-old patient with an aortic mycotic abdominal aneurysm involving all visceral branches is presented. Excision and dacron graft replacement involving limbs to the coeliac axis, superior mesenteric, and both renal arteries was accomplished successfully. The rationale for employing dacron material in infected tissue is reviewed. In our opinion, an integral aspect of its usage includes the debridement or removal of the aneurysm in conjunction with prolonged antibiotic coverage postoperatively. The patient is alive and free of apparent infection one year following surgery.


Milk consumption by black and by white pupils in two primary schools. It is heartening to note that relatively well nourished black children in the United States, a number of whom are, in all probability, lactose intolerant and most of whom are destined to become lactose intolerant adults, are able to consume nutritionally valuable quantities of milk with meals and, on the whole, do not report suffering from any abdominal pain or discomfort. It is also encouraging that this population of over two hundred primary school children consumed, on the average, 75 per cent of the 1/2 pt. milk served with lunch, reported drinking an average of three glasses of milk daily, and the vast majority reported liking milk and a number of other dairy products which are important nutrient sources in their diets.


The management of infected arterial aneurysms. Infected aneurysms involve the aorta, visceral and peripheral arteries and are associated with a high morbidity and mortality. Prompt confirmation of the suspicion of infection, resection of all infected tissue, and prolonged antibiotic therapy based on appropriate sensitivity studies are crucial to successful management. Patients whose aortic aneurysms grew Gram negative organisms were more likely to suffer early rupture of an aortic aneurysm, and had a higher mortality. Superior mesenteric aneurysms are preferably treated by resection. Upper extremity aneurysms can often be excised without distal ischemia. Lower extremity aneurysms were more likely to require reconstruction which can be accomplished through non-infected tissue planes, preferably with autogenous tissue.


Studies on the ecology of the tick Amblyomma hebraeum Koch in the Eastern Cape Province of South Africa. II. Survival and development. Quantitative data are given on the survival and rate of development of Amblyomma hebraeum Koch in relation to temperature and humidity, in laboratory and field conditions. By comparison with other ixodid species the developmental periods of A. hebraeum are extremely long. Development is most rapid at 30 C, and the duration of the developmental periods increases exponentially with decreasing temperature. Oviposition occurs successfully at 15 and 30 C, egg incubation at 20 to 30 C, and larval and nymphal molting at 15 to 35 C. The ability of the developing stages to survive in dry conditions increases with increasing size, i.e. from egg to engorged larva. Mortality in the developing stages increases at low humidities as temperature decreases, due to the longer periods over which water is lost. The conversion efficiency of ovipositing females is influenced by both temperature and atmospheric humidity. Longevity of unfed larvae is correlated directly with saturation deficit. Longevity of unfed nymphs and adults is dependent on both temperature and saturation deficit.


Interaction of hydrocortisone with model membranes containing phospholipid and cholesterol. Pure and mixed monolayers of lecithin and cholesterol were spread on substrates of dissolved hydrocortisone at 25 and 37 degrees. The presence of hydrocortisone increased the surface pressure of dipalmitoyl and egg lecithin films that were in head contact. The increase in surface pressure was dependent on steroid concentration. There were no significant interactions with coherent cholesterol monolayers. Penetration of hydrocortisone was decreased by the addition of cholesterol to the monolayer system. These model membrane systems indicate that hydrocortisone interacts with the hydrated polar head group of the phospholipid and not with films whose molecules are in hydrocarbon tail contact.


Selection of breast cancer patients for adjuvant chemotherapy. Another look at the prognostic importance of involved lymph nodes. To aid in the selection of breast cancer patients for adjuvant chemotherapy, 263 patients with primary breast carcinoma undergoing curative surgery at the Yale-New Haven Medical Center were examined with respect to axillary lymph node involvement and prognosis. Thirty-five percent of patients with one to three axillary nodes histologically involved with cancer relapsed within five years, as did 61% of patients with four or more cancer-positive nodes. Equally important was the clinical stage. Stage III patients had a poor prognosis (71% relapse rate) regardless of their axillary status. Stage I patients with metastasis to one to three axillary nodes did just as well as stage I patients with no nodal involvement (13% relapse rate). Relapse rates within the nodal categories are significnatly less (P less than .05) than those reported by the National Surgical Adjuvant Breast Project.


Gray-scale ultrasonography and thin-needle cholangiography. Evaluation in the jaundiced patient. Gray-scale ultrasonography (GSU) and thin-needle cholangiography (TNC) were performed in 35 consecutive patients with unexplained jaundice. The status of the biliary tree was correctly assessed by GSU in 33 of 35 cases (94%); in two patients technical difficulty prevented definitive assessment. Neither false-positive nor false-negative results were encountered. There were no discrepancies between the results of GSU and TNC. We conclude that GSU provides a safe, highly reliable method of assessing the jaundiced patient and should be the preferred initial procedure in the diagnostic evaluation of patients with jaundice when the major differential lies between the medical and surgical types. If GSU does not demonstrate a dilated biliary system, TNC is unnecessary, and other diagnostic studies should be undertaken.


Lightning-strike disaster among children. A lightning strike involving 47 children is described. Four cases demonstrate the most common and serious resulting pathology: burns, myocardial infarction, and neurological symptoms varying from feelings of fear and nightmares to brain death. The pathophysiology of lightning injury is described. The importance of immediate resuscitation of the victim who appears dead after a lightning strike is emphasized, and procedures to prevent lighting injury are presented.


Insulin-dependent diabetes mellitus. Sudden onset following hypophysectomy in an acromegalic patient. A euglycemic woman with acromegaly contracted conspicuous hyperglycemia two hours following transphenoidal hypophysectomy. Insulin therapy was initiated and has by necessity been continued. The development in the immediate postoperative period of blood glucose levels ranging from 300 to 500 mg/dl was totally unexpected, as the levels on the preoperative oral glucose tolerance test were normal. No explanation for this sudden development of hyperglycemia is apparent. Therefore, frequent monitoring of the blood glucose level is necessary in all acromegalic patients following hypophysectomy, even if they are euglycemic prior to surgery.


Pop bottle explosions.

Pop bottle explosions. To our knowledge, there are only two brief reports in the medical literature of injury sustained as a result of a carbonated soft-drink (pop) bottle explosion. We report three such cases and review pertinent data on this hazard.


Serum ferritin level. Determinant of iron requirement in hemodialysis patients. Seventeen patients without renal failure and 14 patients receiving long-term hemodialysis were studied. Serum and bone marrow ferritin determinations were made at the time of bone marrow aspiration. A good correlation was found between serum ferritin levels and bone marrow iron stores, as well as between bone marrow ferritin levels and iron stores. Serum ferritin determinations appear to give an accurate estimation of bone marrow iron stores, thereby providing a reliable guide for iron replacement therapy and reducing the need for repeated bone marrow aspirations. Serum ferritin levels of less than 105 ng/ml suggest decreased iron stores, and values greater than 120 ng/ml indicate adequate or increased iron stores. Preliminary data also suggest that bone marrow ferritin determinations may be useful in quantitating bone marrow iron stores.


Salt substitutes as a source of potassium. Chemical analysis of commercially obtained potassium-containing salt substitutes was performed. The potassium content was remarkably uniform from sample to sample of each brand and even among different brands. When hypertensive outpatients ranked these products, several were shown to differ considerably in taste characteristics and in overall preference. A cost comparison showed salt substitutes to be less costly than prescription (pharmaceutical) potassium supplements.


Sudden catatonic stupor with disastrous outcome. Catatonic stupor occurred in two psychiatric inpatients, predisposing them to staphylococcal pneumonia, venous thrombosis, and pulmonary embolism. Disastrous outcomes ensued. Catatonic stupor can lead to fatal complications, and aggressive medical and psychiatric therapy is indicated.


Diabetes insipidus following cardiorespiratory arrest. Diabetes insipidus following cardiac arrest and hypoxemic encephalopathy occurred in two patients. In both, severe hypoxemic brain damage was followed within three days by clinical and laboratory features of diabetes insipidus, which were corrected by administration of exogenous vasopressin. Hypothalamic injury resulting in diabetes insipidus should be considered in the differential diagnosis of polyuria and dehydration occurring in critically ill patients who have suffered cardiorespiratory arrest.


Patterns of blood pressure in Milwaukee. Blood pressure measurements were obtained among 92,074 persons in Milwaukee between 1974 and 1976 by the Milwaukee Blood Pressure Program. Systolic hypertension was more prevalent in young white men than blacks below 25 years of age, was more common in middle-aged blacks than whites, and was equally prevalent among all persons past 65 years. Diastolic hypertension was more prevalent in blacks than whites of all ages. Whereas the prevalence of systolic hypertension in the population increased with age and was present in a majority or near majority of persons past 65 years, the prevalence of diastolic hypertension rose until the sixth decade, after which it declined. Hypertension was primarily of a diastolic variety in young blacks, whereas systolic hypertension was a prominent feature in young whites.


Treatment of Bechçet's syndrome with transfer factor. Six patients with Behçet's syndrome were treated with transfer factor (TF) from randomly selected donors. Mucocutaneous symptoms and signs were predominant at the time that TF injections were started. Three patients showed great improvement, one moderate improvement, and one was unresponsive to multiple injections of TF from different donors. One case was uninterpretable because of concomitant administration of high doses of prednisone and chlorambucil and brief treatment with TF. These results indicate that TF therapy may be beneficial in some patients with Behçet's syndrome and that a trial of TF is warranted at least in the absence of severe ocular or neurologic manifestations.


Mammographic screening. Value in diagnosis of early breast cancer. Analysis of the two-year results of a project screening asymptomatic women for breast cancer is presented. There were 10,008 women examined and 490 biopsies completed. There were 97 cancers found, of which 55 were nonpalpable; 36 of the 97 cancers were in women under 50 years of age. The incidence of axillary metastasis was 7% in the nonpalpable lesions. We suggest that mammography is useful in discovering curable breast cancer, even among younger women at least down to the age of 40. The potential benefit seems to greatly outweigh the theoretical carcinogenic hazard. Selection of candidates for mammography should be based on all risk factors, not just age. An attempt is made to correlate the results with the theoretical risks as proposed by others.


A planned system of patient education.

A planned system of patient education. A planned system of patient education is now used in more than 70 group clinics, hospitals, and other health care institutions. Essential features of this system are (1) a patient education center, (2) a patient educator, and (3) patient education programs. Structured programs are especially useful in the management of chronically ill patients. Patients have responded enthusiastically to this planned system. The response of physicians has ranged from enthusiastic to resistant.


Angiotensin II inhibition. Treatment of congestive cardiac failure in a high-renin hypertension. A patient with intractable congestive cardiac failure secondary to renovascular hypertension and severe coronary artery disease was infused with the competitive antagonist of angiotensin II, saralasin acetate. The infusion produced an impressive increase in cardiac output and left ventricular stroke work index in parallel with a striking decrease in the systemic and pulmonary vascular resistance, the coronary resistance, and the myocardial oxygen consumption. It is suggested that angiotensin inhibition may present advantages over other forms of treatment of congestive cardiac failure in selected cases.


Quinidine-induced agranulocytosis.

Quinidine-induced agranulocytosis. In a 75-year-old man, agranulocytosis and septicemia developed after eight weeks of quinidine sulfate therapy. An IgG antibody requiring the presence of quinidine was shown by complement-dependent leukocytotoxicity and leukoagglutination reactions. The antibody did not cross-react with quinine and was active against WBCs obtained from normal subjects and from the patient himself.


Adaptive coping mechanisms in adult acute leukemia patients in remission. The adult leukemia patient in a drug-induced remission possesses a unique set of emotional responses as he adjusts to an altered life-style and a life-threatening disease. Six patients, ranging in age from 24 to 62 years and being treated with monthly maintenance chemotherapy, were interviewed over a six-month period. The adaptive coping mechanisms most frequently identified were denial of being sick, identification with fellow patients to form a "hospital family," and anticipatory grief of one's own losses by participation in grieving another patient's death. The means of adjustment was to adapt to the "hospital family" and benefit from the therapeutic milieu established on the ward. The patient's total response to remission in acute leukemia can be influenced positively by appropriate intervention based on an assessment of his previous and present patterns of coping.


Occupational hazards for operating room-based physicians. Analysis of data from the United States and the United Kingdom. Comparative analysis of data from three large retrospective surveys in the United States and the United Kingdom reaffirms an increased incidence of spontaneous abortion among female physicians working in the operating room. The live-born children of female physicians exposed in the operating room also had substantially more congenital abnormalities. Male anesthetists, compared with nonanesthetist physicians, had an increased incidence of hepatic disease; there was also an increased frequency of congenital abnormality in their children. The incidence of spontaneous abortion in wives of male anesthetists and in the rate of cancer among exposed male anesthetists was similar to control. Despite differences in survey methods and analysis, there was remarkable agreement in conclusions to be drawn from the independent studies.


The Minnesota Rural Physician Redistribution Plan, 1971 to 1976. The Rural Physician Associate Program was developed by the University of Minnesota Medical School faculty in an attempt to meet the demands of the citizens of Minnesota to improve the distribution of primary physicians to rural areas. The program is offered to students who have completed 2 2/3 academic years of medical school. There were no regulations requiring the students' return to rural areas after completion of training. Thus far, 163 students have completed the program. Forty-three have continued in medical school and another 27 are in residency-training programs. Primary care residencies have been chosen by 68; another 31 have completed their medical education and are in rural practice. Of the 22 practicing in Minnesota, 21 have returned to rural communities.


Confirmation of brain death at bedside by isotope angiography. Documentation of the absence of cerebral circulation is useful as a confirmatory test of brain death. Intravenous isotope angiography performed at the bedside with a mobile gamma camera is a safe, convenient, rapid, reliable, and easily understood method of proving the absence of cerebral blood flow that occurs in brain death.


Comparative study of bowel lymphosarcoma in childhood. Five cases of lymphosarcoma of the bowel in Nigerian Igbo children are presented. They were found to be similar to an Australian series in the following respects: boys were more commonly affected than girls; affected children were all aged over two years; and the two main modes of presentation were intussusception and a localized abdominal mass. Unlike Australian children, Nigerian Igbos did not present with features suggestive of acute appendicitis.


[Etiopathogenesis of mycotic aneurysms]. In a patient after operation for metastatic bronchogenic brain abscess presence of aneurysm was demonstrated during control carotid angiography. In previous angiography the aneurysm had not been seen. During further observation the size of the aneurysm decreased. The patient died 5 weeks after the operation due to rupture of lung abscess into the pleural cavity. Microscopic examination showed that the lesion was in fact pseudoaneurysm. The authors discuss the mechanism of development of mycotic aneurysms and their possible role in the pathogenensis of metastatic brain abscesses.


Renal cell carcinoma with erythrocytosis and elevated erythropoietic stimulatory activity. A case study is presented of a 55-year-old man who had clear cell renal carcinoma with pulmonary metastases and erythrocytosis. The increase in red blood cell mass was associated with an elevation in erythropoietic stimulatory activity in serum, pleural fluid, and tumor-cyst fluid as determined by the exhypoxic polycythemic mouse assay. It is postulated that the increased erythropoietic stimulatory activity represents autonomous tumor secretion of erythropoietin or an erythropoietin-like material. Electron microscopic studies confirmed the proximal tubular origin of this tumor.


Neurosurgical complications of heroin addiction: brain abscess and mycotic aneurysm. Few neurosurgical complications occur as the result of heroin addiction. One case of brain abscess and another of brain abscess associated with mycotic aneurysm caused by such addiction are presented.


[Electrolyte metabolism in toxic goiter]. The author presents the results of parallel studies of potassium, sodium and calcium in the blood plasma and the 24-hour urine of 146 patients suffering from toxic goiter of different severity (mild course in 43 patients, of moderate severity in 59, and severe in 44). Investigations were carried out before and after the treatment with thyrotoxic preparation and in some of the patients (24) after strumectomy. Before the treatment patients with mild and moderately severe forms of the disease showed a tendency to increase of potassium and calcium and a fall of sodium level in the blood. Patients with a severe course of thyrotoxicosis displayed an opposite tendency in the changes of plasma electrolyte composition--the majority of the patients showed hypokaliemia, hypocalciemia and hypernatriemia. A tendency to normalization of plasma ionic composition was noted after the treatment with thyrotoxic preparations during the euthyroid state. Sodium and calcium plasma level became normal after strumectomy; potassium content remained lowered. Correction of electrolyte metabolism should be carried out in the patients with a severe form of toxic goiter; potassium and calcium administration is recommended.


Respiratory health and dust levels in cottonseed mills. Four cottonseed mills in the southern United States contained high levels of total and respirable dust. A survey of 172 workers showed low prevalences of byssinosis (2-3%) and chronic bronchitis (4%). Mean baseline (out of dust) lung function values were normal. Mean functional declines over the working shift were present on Monday and absent on Friday, indicating an acute bronchoconstrictor response. Despite limitations in translating measured dust levels into estimates of individual exposures, the overall dose-response relationship seems to differ from that found in the cotton textile industry.


Calcium electrode--a method for the continuous monitoring of the platelet release reaction. The calcium electrode is a convenient, inexpensive, and non-traumatic method for measuring changes in the extracellular calcium which accompanies a platelet release reaction. With this instrument, the temporal pattern of release by platelets in a buffered-saline medium following thrombin stimulation was observed as follows: an initial time lag phase, followed by a maximum release phase, and finally a slow release phase.


Potentiation by alpha and inhibition by beta-adrenergic stimulations of rat platelet aggregation. A comparative study with human and rabbit platelets. Epinephrine, known to potentiate and elicit aggregation of human platelets, was shown to inhibit thrombin-induced aggregation of rat platelets, delaying the onset of aggregation from 2 to 12 times. Incubation of rat platelet suspensions with propranolol (1.25--30 micrometer), inactive by itself, totally prevented the inhibitory effect of epinephrine and also permitted a potentiation effect to show up. On the contrary, phentolamine (1.25--30 micrometer) potentiated the inhibitory effect of epinephrine on rat platelets and unmasked an inhibitory effect on human platelets. Finally, isoproterenol (0.25--9 micrometer) produced a marked inhibition of aggregation induced by thrombin, ADP and collagen in the three species studied, but most particularly in the rat. From these results, we conclude that stimulation of the platelet adrenergic receptors may either result in promotion (alpha-stimulation) or inhibition (beta-stimulation) of platelet aggregation. Furthermore, differences in the ratios or responses of alpha/beta receptors may account for species variations in the platelet aggregation response to catecholamine challenge.


Cigarette-smoking effect on platelet function. The immediate effect of cigarette-smoking on ADP-induced platelet aggregation and on platelet adhesiveness was investigated in 12 normal subjects aged 20 to 40, in 10 normal subjects aged 43 to 72 and in 10 patients with cerebrovascular disease aged 45 to 75. All the subjects were heavy smokers (more than 20 cigarettes a day). After smoking 2 cigarettes a significant increase in ADP aggregation and platelet adhesiveness was found in the group of young heavy smokers, while in the old subjects with or without cerebrovascular disease the increase in platelet activity was never significant. These data were discussed and some hypotheses for this higher reactivity of platelets from young people were suggested.


The plasminogen activator of the arterial wall. The plasminogen activator in 645 specimens of various human arteries--thoracic, abdominal aorta, carotic, pulmonary, renal, basilar, coronary - was studied using Todd's histochemical method. 92 cadavers were used, 1--18 hours post mortem from subjects aged from 272 days to 83 years. 45 specimens of pulmonary, renal and splenic arteries were obtained during surgery. The greatest fibrinolytic activity was within the adventitia. Intima occasionally showed very little fibrinolytic activity, or none at all. No statistically significant differences in plasminogen activator activity were found between the various arteries examined. A statistically significant increase in fibrinolysis in adventitia of atherosclerotic arteries was established. No correlation was found between the fibrinolytic activity of the arteries and their alkaline phosphatase content. Some properties of the plasminogen activator of the arterial vessel wall were evaluated. Influence of storage, inactivation with epsilonaminocaproic acid and extracted with potassium thiocyanate was studied.


Marathon run I: effects on blood coagulation and fibrinolysis. Blood coagulation and fibrinolysis were assessed in 13 Finnish amateur runners aged 31 to 48, and one 65-year old taking part in a non-competitive marathon (42.2 km). After the run the mean values of partial thromboplastin time showed a very significant shortening, whereas the mean values of the prothrombin time and of plasma fibrinogen were not significantly altered. The mean values of euglobulin lysis time were significantly shorter and the mean values of fibrin degradation products increased highly significantly. After the run, protamine sulphate was positive or strongly positive in all subjects, whereas the ethanol gelation test was negative in all runners; no cryofibrinogen was detected in any participant. Thus, running a marathon race affects the haemostatic balance and activates the fibrinolytic mechanism. The effects of training and physical fitness on the above parameters are discussed.


Marathon run II: Effects on platelet aggregation. Platelet count and aggregation were assessed in 9 Finnish amateur runners aged 34 to 48, and one 65-year old taking part in a non-competitive marathon race (42.2 km). After the run the mean value of platelet count showed a very significant rise (p less than 0.001). The platelets were markedly more sensitive to both ADP and collagen-induced aggregation. A highly significant increase (p less than 0.001) was noted for both the intensity and velocity of platelet aggregation. The finding of platelet by hyperaggregability after prolonged strenous exercise even in trained subjects is discussed. It is concluded that a through medical examination of the haemostatic balance is recommended before a marathon race.


A method for the measurement of fibrinolytic activity based on one dimensional diffusion using small glass tubes. II. With special reference to the differences between the use of plasminogen-rich fibrinogen and that of plasminogen-free fibrinogen as the substrates. The optimal conditions for the measurement of the fibrinolytic factors of plasma were examined using human and bovine plasminogen-rich fibrinogen or plasminogen-free fibrinogen as the substrates using the one dimensional diffusion method. The results were as follows: 1. There was no essential difference found between using human or bovine fibrinogen. 2. The levels of proactivator-plasminogen and plasminogen could be measured while using either plasminogen-rich or plasminogen-free fibrinogen. But, in using the latter, the proactivator-plasminogen level could not be measured, if a final concentration of more than 2,000 Christensen units of streptokinase were employed. 3. When using plasminogen-rich fibrinogen, anti-plasmin(s) and anti-activator(s) could be measured while using urokinase and plasmin, but not while using streptokinase. However, further study should be given to the measurement of the inhibitors, when using plasminogen-free fibrinogen.


Characterisation of serum fibrinogen degradation products using gel chromatography and radioimmunoassay. Fibrin(ogen) degradation products (FDP) are detected by radioimmunoassay in the serum of all subjects. Some of these FDPs have considerable biological activity in vivo, and hence may play a significant part in the process of coagulation. Chromatography of serum samples from patients including those with pulmonary emboli and deep venous thrombosis indicates that the majority of non-clottable fibrin(ogen)-related antigen present is of high molecular weight--greater than that of fibrinogen--and that in pathological situations there is a quantitative increase not a qualitative alteration in the molecular species present.


Early venous thrombosis: A scanning electron microscopic study. The passage of a minimal electric charge was used to initiate thrombosis in rabbit femoral veins, and the events occurring during formation of the thrombus were observed using scanning electron microscopy. Thrombosis began to occur within ten minutes after passage of the charge, upon an apparently unaltered endothelium. The first event was the laying down of a fibrin meshwork and this was shortly followed by the appearance of regularly arranged platelet clumps.